Experimental Biology and Medicine

Subplantar injections of Freund's complete adjuvant (M. butyricum) were used to induce a typical adjuvant polyarthritis in rats. The lungs of the arthritic rats exhibited histological and biochemical changes characteristic of an emphysema-like condition. The lung pathology included markedly enlarged alveoli and septal fibrosis as well as numerous granulomatous foci. Serum trypsin inhibitory capacity was reduced. An adjuvant prepared with E. coli in place of M. butyricum failed to induce either polyarthritis or emphysema-like changes. Neither the polyarthritis nor the lung pathology was as severe in rats treated simultaneously with M. butyricum and the immunosuppressant, cyclophosphamide, as in rats treated with M. butyricum alone. The data thus suggest that inappropriate immunological responses to M. butyricum antigens may be related to the production of the pulmonary disease as well as the polyarthritis.

The number of Na⁺, K⁺-ATPase enzyme (EC 3.6.1.3) units in skeletal muscle and liver of 14-day-old lean and obese (ob/ob) mice was assayed from the concentration of high-affinity [³H]ouabain-binding sites in the tissue preparations. The number of [³H]ouabain-binding sites in forelimb and hindlimb muscles of obese mice was 28% lower than in lean littermates. In contrast, livers of lean and obese mice possessed equal numbers of [³H]ouabain-binding sites. The lower number of Na⁺,K⁺-ATPase enzyme units observed in skeletal muscle of the 14-day-old obese mice represents one of the earliest reported developmental alterations in an enzyme system in these mice and may be associated with the lower energy expenditure of young obese mice.

The digestion and absorption of elastin was studied in rats by feeding intact or elastase-predigested elastin labeled with ¹⁴C or ³H. Radioactive elastins (59.3-71.5%) remained in feces whether feeding intact or predigested elastins. Of the absorbed products, 3.2-3.5% and 24.8-27.8% appeared in urine for [¹⁴C]- and [³H]elastin, respectively. However, desmosine-containing degrative products were not found in the urine. The absorption of [³H]desmosine was also studied following oral and intraperitoneal administration. Given orally, ³H appeared predominately in the feces, but when injected intra-peritoneally, ³H was mostly in the urine. Therefore, even if elastin were completely digested, desmosine would not be absorbed.

The replacement of choline ions by Na⁺ ions in the secretory solution of the frog gastric mucosa of Rana pipiens in Cl^--free media increases the resistance, the PD, and the H⁺ secretory rate. The replacement of Na⁺ by choline ions produces generally the reverse changes of the three electrophysiological parameters. The experimental data involving the PD and H⁺ secretory rate can be explained in terms of a Na⁺ emf in a Na⁺ conductance pathway opposing the H⁺ emf in a H⁺ conductance pathway on the secretory (apical) membrane.

The role of elevated renal phosphate-dependent glutaminase activity in enhancing ammonia excretion in response to an acute acid load was evaluated in adult rats. Although enzyme activity was approximately threefold higher in “adapted” rats, ammonia excretion rate during the 24 hr following administration of an acute acid load was not significantly greater than from rats with normal enzyme activity. This observation represents an example of dissociation between elevated phosphate-dependent glutaminase activity and ammonia excretion response to an acute acid load.

The relationships of age and reproductive state to hypothalamic LHRH content and gonadal steroids was studied in young and old female rats. LHRH content in the medial basal hypothalamus (MBH) of young female rats was maximal on the morning of proestrus (PE), but fell to a nadir on PE afternoon. MBH-LHRH rose again on the morning of estrus (E) and then dropped by 1000 hr on diestrous Day 2 (DE-2). Old constant estrous (CE) rats had MBH-LHRH levels that were significantly lower than in young E rats, while old pseudopregnant-like (PP) rats had intermediate MBH-LHRH levels, not significantly different from those in young E or DE-2 rats. LHRH content in the MBH of old anestrous (AN) rats was lower than in any other group. Anterior hypothalamic (AH)-LHRH in old CE, PP, and AN rats were similar and did not differ from those in young E or DE-2 rats.

Serum estradiol and progesterone peaked at PE in young cycling rats, but showed no cyclic variations in old rats. Old CE and PP rats had moderate estradiol levels comparable to those in young DE-2 rats, and AN rats had low estradiol levels comparable to those in young E rats. Old PP rats had higher progesterone levels than old CE or young E rats. Old AN rats had progesterone levels lower than in any other group. In general, these observations suggest that sufficient LHRH is present in old CE or PP rats to maintain basal LH secretion, but that the stimulus for cyclic LHRH release is lacking. Low to undectable LH levels seen in old AN rats may be the result of the low LHRH levels seen in these rats.

High intracellular concentrations of ATP have been observed to protect human erythrocytes against the loss of K⁺ and gain of Na⁺ induced by h-LPS. This protection was abolished by ouabain, indicating that red cells treated with h-LPS are competent for cation transport mediated by Na⁺,K⁺-dependent ATPase. In addition, the failure of h-LPS to stimulate glycolysis by fragmented erythrocytes suggests that the increased glycolytic rate of intact h-LPS-treated red cells is a secondary effect of h-LPS. Thus, the cation redistribution induced by h-LPS appears not to be due to a primary effect of h-LPS on red cell energy metabolism. Since h-LPS demonstrates neither an obvious inhibitory effect on Na⁺,K⁺-ATPase activity nor a direct stimulating effect on erythrocyte glycolysis, it is proposed that a primary action of h-LPS on human erythrocytes is to increase plasma membrane permeability toward Na⁺ and K⁺. The cation redistribution resulting from increased membrane permeability would explain the secondary increase in energy metabolism observed for the h-LPS-treated intact cells. Additional studies are now required on rapid effects of h-LPS on transmembrane fluxes of cations in intact mammalian cells, and the possible role played by such effects in the biological activation of cells by h-LPS.

Experiments were performed to determine the extent to which thoracic translocation of blood and abdominal compression contribute to the diuresis and natriuresis during head-out water immersion in the anesthetized nonhuman primate. Neither a diuresis nor natriuresis occurred in animals immersed in the recumbent posture to a depth such that the abdomen was subjected to the same water pressure as during head-out upright immersion. It is concluded that the abdominal compression observed during upright immersion does not contribute per se to the renal responses and that the immersion-induced translocation of blood to the thorax may be the causal factor during this volume stimulus.

The correlation between circulating catecholamines and ventricular vulnerability during psychologic stress was examined in conscious dogs. The repetitive extra-systole (RE) threshold was used to assess vulnerability to ventricular fibrillation. Exposure of the animals to a stressful sling environment compared to that of nonstressful cage setting resulted in a significant 41% (P < 0.01) reduction in the RE threshold. Plasma levels of norepinephrine and epinephrine increased twofold (P < 0.05) and fourfold (P < 0.01), respectively. It is concluded that the elevation in circulating catecholamine levels correlates closely with enhanced ventricular vulnerability during psychologic stress and that the model for psychologic stress employed results in substantial increases in plasma catecholamine levels which is in large part due to release of epinephrine from the adrenal medulla.

Isolated rat hepatocytes were found to adsorb (nonspecific binding) as well as to absorb chlorpromazine. The linearity of chlorpromazine adsorption was dependent on the drug concentration in the incubation medium. Also, the absorption of chlorpromazine was linear with respect to the drug concentration, suggesting an unsaturable uptake process which was considered to represent simple diffusion, with a diffusion coefficient of 0.15 nmole chlorpromazine/mg protein/min/μM. Chlorpromazine uptake was not inhibited by the action of a series of metabolic inhibitors present in the reaction medium. The drug is rapidly and to a large extent adsorbed onto hepatocellular membranes.

Thyroidal, pituitary, and hypothalamic hormones in the plasma and tissues of newborn young of rats fed diets containing 24 or 4% casein as the sole source of protein were quantitated by radioimmunoassay. Circulating levels of total plasma triiodothyronine (T₃) were significantly reduced and the free fraction of T₃ was lower in young of protein-deprived rats than in control pups. Total plasma T_4, free T_4, plasma TSH, pituitary TSH per milligram of pituitary, the metabolic clearance rate of exogenous TSH per 100 g of body weight, and the TRH content of the hypothalamus were not significantly affected by the maternal diet.

Human pulmonary macrophages were able to phagocytize BP-ferric oxide particulates in a time-dependent manner. BP was eluted from the engulfed particulates and released into the extracellular space either as free BP or as metabolites of BP. Some of the released products were mutagenic for Chinese hamster V-79 cells. A higher binding level of BP to bronchial DNA was found when bronchial explants were coincubated with PAM containing BP-ferric oxide than when incubated with BP-ferric oxide alone.

Disodium cromoglycate (DSCG) is absorbed from the lungs of the 6-day-old rat in part by a carrier-type transport process and in part by diffusion. The carrier process is saturated at DSCG concentrations greater than 25 mM and is inhibited by certain other organic anions including phenol red, benzylpenicillin, and p-aminohippuric acid. Although the carrier-mediated absorption process is present in the lungs of rats as young as 1 day of age, the process does not appear to become quantitatively mature until an age of 6 days when the transport rate is two to three times greater than that seen at the age of 1-3 days.

The antral gastrin concentration of female Snell dwarf mice (dw/dw) was 30% the concentration of normal female littermates. In addition, the mutants had an abnormally thin duodenal mucosa, having significant reductions in the number of mitoses/crypt, crypt length, and villus height. Because crypt length was reduced to a greater extent than villus height, the villus/crypt ratio was significantly higher in mutants than in normal mice. It was determined that antral gastrin concentration in both mutants and normal mice could be significantly increased over a 16-day period by transplantation of a normal pituitary under their renal capsule. Ectopic pituitary transplantation in mutants also significantly increased the number of mitoses per crypt as well as crypt length but did not influence villus height, resulting in a decrease in the villus/crypt ratio to normal levels. Administration of exogenous prolactin to mutants (125 μg/day) over a 2-week period did not significantly influence antral gastrin levels and had a marginal growth-promoting effect on the duodenal mucosae.

Possible effects of adrenalectomy (adx) on light-dependent changes in the timing of the preovulatory LH surge have been investigated. In the first experiment, female rats were maintained on a standard light schedule of 14 hr light: 10 hr dark (lights on 0500-1900 hr). Intact and adx rats showing at least two consecutive 4-day estrous cycles were bled at 1400, 1600, 1800, or 2000 hr on proestrus. The timing and amplitude of the preovulatory surge of LH were very similar in intact and adx animals. In a second experiment, intact animals were maintained under standard lighting conditions (lights on 0500-1900 hr) until the establishment of regular 4-day cycles. Intact rats and experimental animals immediately after adx were then transferred to an altered light regime in which the 14-hr light period was advanced 7 hr (i.e., lights on 2200-1200 hr). After 3 weeks or more in the altered light environment, animals showing regular 4-day estrous cycles were bled at 0700, 0900, 1100, 1300, or 1500 hr on proestrus. Both intact and adx rats showed an approximately 7-hr shift in the timing of the preovulatory surge of LH. However, the adx animals required a longer period of time to reestablish regular cycles when placed in the altered light environment than did the intact rats. The results indicate that the primary synchronizing effects of light on the timing of the preovulatory LH surge in the rat operate via mechanisms independent of the pituitary-adrenal system.

Bumetanide, when infused into one renal artery at 0.05 μg/kg/min in the dog, produced a significant ipsilateral increase in the excretion of sodium and water without affecting the rate of glomerular filtration. At this dose, these responses were limited to the infused kidney. When probenecid (50 mg/kg, iv) was given prior to bumetanide to inhibit tubular secretion of this drug, the natriuretic and diurectic actions of bumetanide were blocked. The inhibition of bumetanide-induced natriuresis and diuresis by probenecid indicates that adequate luminal concentration is a prerequisite to the natriuretic-diuretic actions of this drug.

Monocytes isolated from patients with active rheumatoid arthritis had elevated hexose monophosphate shunt (HMP) levels. Metabolic activity of blood monocytes incubated with rheumatoid sera was assessed by measuring hexose monophosphate shunt (HMP) levels. Sera from patients with rheumatoid arthritis enhanced HMP shunt activity of normal monocytes. These findings suggest that blood monocytes may be activated by circulating components present in rheumatoid sera.

The effect of direct electric current (EC) on the tissue K⁺ concentration ([K⁺]_t) of inhibited and secreting frog gastric mucosa was studied in order to investigate further our previous observation that a high K⁺ concentration in the secretory solution prevents the inhibitory effect on H⁺ secretion of EC passed from secretory (S) to nutrient (N) side. No differences in the [K⁺]_t of resting, secreting or inhibited mucosae bathed with K⁺-free S solutions (120 mM NaCl) was observed. All N solutions contained 5 mM K⁺. A significant increment in [K⁺]_t of secreting mucosae bathed on S with 100 mM KC1/20 mM NaCl was observed when EC was passed from S → N through this solution. Addition of Ba²⁺ (1 mM) to the N solution had no effect on [K⁺]_t, but did prevent complete inhibition of H⁺ secretion by EC passed through a K⁺-free S solution. A mechanism whereby EC exerts its inhibitory action and the “rescue” effect of K⁺ on S is postulated. Interference with intracellular conductance pathways by Ba²⁺ on N is suggested.

The effect of SRIF on GH release was studied in monolayer-cultured cells of rat anterior pituitary with respect to Ca²⁺ and cAMP metabolism. Both the basal GH release and the DBcAMP- or PGE₁-stimulated GH release showed the requirement for Ca²⁺ in the medium but were not affected by increasing Ca²⁺ over 1.8 mM. On the other hand, GH release induced by high K⁺ or A23187 also required the presence of Ca²⁺ but showed a different dependency on Ca²⁺ concentration, being increased by high Ca²⁺. SRIF inhibited almost completely both the basal and DBcAMP- or PGE¹-stimulated GH release. Although SRIF showed a partial inhibitory effect on the increment of GH release induced by high K⁺ during a short-term incubation at both 1.8 mM and high Ca²⁺, little inhibitory effect of SRIF on that was observed in 3-hr-incubation experiments. Similar results were obtained when A23187 was used in the presence of 5.4 mM Ca²⁺. In the presence of 1.8 m^M Ca²⁺, however, the increment of GH release induced by A23187 was inhibited partly during the incubation of both 30 min and 3 hr. When high K⁺ or A23187 was added together with DBcAMP or PGE₁, an additional increase in GH release occurred. Inhibition by SRIF of GH release enhanced by DBcAMP or PGE₁ was almost completely reversed by the simultaneous presence of high K⁺. Similar tendency, but less potently, was observed when A23187 was used instead of high K⁺. In regard to dependency on extracellular Ca²⁺ concentration and sensitivity to SRIF, high K⁺ and A23187 appear to enhance GH release by a mechanism different from that of DBcAMP and PGE₁. Moreover, our results confirm the previous findings that SRIF seemed to inhibit the hormone release by acting distal to the cAMP-dependent process(es) of the releasing pathway.

The effect of four components of laetrile (mandelonitrile, amygdalin, cyanide, and a neoamygdalin-amygdalin mixture) on guanylate cyclase activity in a variety of tissues was examined. Mandelonitrile and cyanide, which can be released from mandelonitrile, stimulated the activity of rat guanylate cyclase (EC 4.6.1.2), an enzyme thought to be important in normal and abnormal cell growth, Amygdalin and neoamygdalin had no effect in these same tissues. The activation of guanylate cyclase by mandelonitrile was observed over the concentration range 0.001 to 3 mM, while cyanide stimulated the activity of guanylate cyclase in concentrations of 0.1 to 3 mM. Since many nitrosamine and nitrosamide carcinogens also stimulate guanylate cyclase activity, the present investigation suggests that possible carcinogenicity of laetrile used in man needs further study.

The frequency of the various types of acute sporadic viral hepatitis was studied in a sample of 222 consecutively hospitalized, adult patients. Sera at admission and discharge from the hospital as well as feces were available in 26 out of the 69 cases negative for hepatitis B surface antigen (HBsAg) by passive hemagglutination assay. These were selected for more intensive serologic investigation by solid-phase radioimmunoassay methods. IgM antibodies to HAV (anti-HAV) were detected in 9 cases. In 3 (33%) of them HAV was demonstrated in feces. In 10 cases evidence of current hepatitis B virus (HBV) infection was demonstrated. The remaining 7 cases were characterized as non-A, non-B hepatitis by exclusion because of serologic evidence of past HAV and HBV infection. It appears from the studied sample that in Greece almost 80% of the acute sporadic cases among adults are caused by HBV, 11% by HAV, and about 9% by non-A, non-B virus.

Rats were depleted of adrenal corticosteroids by adrenalectomy and orchidectomy, as evidenced by determination of blood levels 1 week later, and by failure of the animals to survive without supplementary NaCl. When 7-day adrenalectomized-orchi-dectomized rats were partially hepatectomized, incorporation of [³H]thymidine into hepatic DNA, indicative of rate of liver regeneration, differed insignificantly from the rate in similarly treated controls, and diverged at only one time point (30 hr) from the rate in regenerating livers of normal rats. The divergence was due to the saline-dextrose injections, not to adrenalectomy-orchidectomy. Administration of adrenal cortical hormones in near physiologic doses did not alter [³H]thymidine incorporation in experimental or control rats. The evidence does not support an important role for these hormones as physiologic regulators of liver growth during hepatic regeneration.

The effects of N-acetylprocainamide (NAPA) and procainamide (PA) on myocardial force of contraction were compared in open-chest, vagotomized, pentobarbital-anesthetized dogs, with the use of a Walton-Brodie strain gauge sutured to the right ventricle. NAPA increased myocardial force of contraction, particularly at the high dose level (40 mg/kg). PA, on the other hand, had a negative inotropic effect that was equally apparent at all doses (10-40 mg/kg). In addition, both NAPA and PA had a negative chronotropic effect and caused a reduction in mean arterial pressure. The mechanisms of the inotropic and hypotensive actions of NAPA require elucidation. Some of the implications of these findings for the clinical use of NAPA as an antiarrhythmic agent are discussed.

The collagen Types synthesized during early wound healing have not been quantitatively analyzed. Therefore, open wounds were made on the backs of Sprague-Dawley rats and analyzed at various times for newly synthesized collagen Types I and III. Biopsies were incubated in tissue culture medium with [³H]proline and collagen was extracted and purified prior to separation on an A5-M column. Type III collagen was increased significantly at 10 hr compared to all other times through Day 12. By 24 hr, the percentage Type III collagen returned to a normal skin value of 20%. The early appearance of Type III collagen is associated with an early increase in collagen synthesis and may function in providing initial wound structure and support for subsequent healing events.

C57B1/6 mice were immunosuppressed with antilymphocyte globulin and prednisolone around the time of infection with cytomegalovirus (CMV) or from 18 to 30 days after infection. Mice immunosuppressed around the time of CMV infection developed humoral immunity (HI) but not cell-mediated immunity to CMV. The ability of spleen cells to transform to nonspecific mitogens was also depressed in immunosuppressed mice. If mice were immunosuppressed from 18 to 30 days after infection, a time they are known to have CMI to CMV, the CMI disappeared and remained low for the duration of the study (67 days after infection). However, HI was not affected. Transformation of spleen cells to nonspecific mitogens similarly remained low. These studies demonstrate that immunosuppression can abrogate CMI but not HI to CMV.

Three inbred strains of mice, AKR/J, SWR/J, and C57BL/6J, showing differential response to dimethylhydrazine (DMH)-induced colorectal tumors, were given SC injections once a week for 10 weeks with 20 mg methylazoxymethanol (MAM) acetate/kg body wt. Colorectal tumors occurred in nearly 100% of the SWR/J mice and 77% of C57BL/6J mice that survived 20 or more weeks after the first injection. Three C57BL/6J mice and 1 SWR/J mouse developed anal tumors. None of the AKR/J mice developed colorectal or anal tumors; a possible factor here could have been the earlier deaths of animals, mostly from leukemia. The influence of genetic background on the susceptibility to MAM acetate-induced colorectal tumors is discussed.

An aerosol generator suitable for administration of a small-particle aerosol of amantadine for treatment of influenza A infection in man is described. As currently operated, the usual daily recommended oral dose of amantadine of 120 to 200 mg can be given in 8 to 10 hr of inhalation of the aerosol. Limited clinical study indicates the safety and probable efficacy of this method of treatment.

The stimulatory actions of prolactin on RNA and casein synthesis in mouse mammary gland explants were shown to be significantly reduced or abolished by incubation with p-bromphenacyl bromide (BPB) at concentrations of 0.05 mM or greater. Since BPB has been shown to be an inhibitor of phospholipase A₂ activity, the inhibition of prolactin's actions by BPB provides further support for the proposal that at least certain of the actions of prolactin in the mammary gland may be initiated by a stimulation of membrane-associated phospholipase A₂ activity.

The C3 Nephritic Factor (C3Nef) from two patients with partial lipodystrophy was partially isolated in order to study the role of early classic C-complement components in C3Nef activity. Both C3Nef preparations were C2 dependent for C3 inactivation, although one C3Nef was C2 dependent only following dilution of the C3Nef preparation. Reconstitution of C2-deficient sera with either human or guinea pig C2 restored C3Nef activity in C2-deficient sera. C3Nef prolonged the decay of the classic complement C3 convertase (EAC142gp) in a dose-dependent manner, and this function of C3Nef may explain, in part, the role of C2 in C3Nef activity.

In an earlier paper (1) we have described an augmentation of acid and pepsin secretion from both innervated gastric mucosa and a Heidenhain pouch following cooling of the mucosa of an innervated pyloric pouch. β-Adrenergic receptors seem to play a part in this. Debas et al. (2, 3) have described vagally mediated pyloro-oxyntic reflexes which result in elevations of blood gastrin and/or acid secretion.

In our first series of experiments cooling a Heidenhain pouch in animals with a gastric fistula did not augment pentagastrin-stimulated secretion from the fistula; on rewarming the pouch, however, the fistula secretion was significantly diminished (1). The data reported here are a reexamination of this phenomenon

Methods. The animals used were five dogs with Heidenhain pouches, four of which in addition had innervated antral pouches of the Pavlov type, and finally six animals which 18 months previously had had their left gastric, right gastroepiploic arteries and accompanying nerves ligated and cut. Three of these animals had Heidenhain pouches and three Pavlov (4). All six of these responded normally to PG.

The fundic pouches were irrigated with water for 60 min at 37°, for a further hour at 5° and finally at 37° again while secretion was stimulated submaximally either with methacholine or pentagastrh 2 The irrigation system consisted of a rubber tube attached to the pouch cannula instead of the Malecot catheter used earlier (1). The outflow end of the catheter was always 1 cm above the point where the pouch cannula emerged from the abdominal wall. Gastric juice was collected from the fistula only.

The same warm-cool sequence was used in the main stomach without any stimulus, during methacholine and pentagastrin stimulation and also in four animals during irrigation of the antral pouch with 0.5% acetylcholine. In this case water was circulated through a 10-m loop of polyethylene tube which had been inserted through the gastric cannula.

A method is described for determining plasma flow velocity in microvessels of the cat mesentery. Time-concentration curves of FITC-dextran were recorded from the video-tape-recorded images of fluorescent dye as it passes through the vessels. The plasma velocity in arterioles, capillaries, and venules were determined during control periods and during isoproterenol vasodilation. Vasodilation reduces the mean transit time of the indicator from the point of injection to the arterioles, capillaries, and venules. Plasma velocity is markedly increased by isoproterenol vasodilation. There is evidence of reduced dispersion of indicator by the microvessels with vasodilation.

The residues obtained from single-donor plateletphereses are a reproducible and convenient source of CFU-C as detected by a double-layer agar culture technique. Enrichment of CFU-C is achieved by sequential sedimentation on LSM, macrophage depletion by adherence to plastic, and isopycnic centrifugation on BSA gradients. The final preparation from a single-donor contains approximately 3 × 10⁸ cells, sufficient for 150 quadruplicate cultures. Enrichment of CFU-C was about sixfold and the yield of CFU-C was 76%. Cells from the macrophage-depletion step were suspended in 10% dimethyl sulfoxide, frozen, and stored at —70°. After thawing at 37°, CFU-C were enriched by centrifugation on BSA. Frozen cells retained full CFU-C activity for at least 4 weeks.

Copper was found to be a normal constituent of the amniotic fluid in high-risk pregnant women at the level of 0.14 ± 0.004 ppm (n = 138). Copper in the amniotic fluid was positively correlated (P < 0.001) to maternal serum copper levels at r = 0.43. During the 13-19 weeks of early pregnancy, copper levels in the amniotic fluid and serum were not appreciably influenced by gestational age. There was no significant correlation between copper and zinc in serum or amniotic fluid. Copper levels in serum and amniotic fluid during this period were not altered in pregnant women having an increased risk of producing a child with a fetal anomaly.

In summary these studies have demonstrated that chronic nicotine consumption by oral administration elicits a reduction in vascular resistance within the iliac circulation of the rat. The mechanism appears to involve a change in the vascular architecture as opposed to modification of vascular tone. By contrast long-term consumption of an equivalent amount of nicotine via tobacco smoke had no significant effect.

The production of antibodies in cell cultures from the draining lymph nodes of rabbits injected in the foot pads with two to four different protein antigens was studied. Antibodies against all of the immunizing antigens were produced simultaneously when aliquots of the cells were cultured 4 to 8 weeks after immunization in the absence of further antigen exposure. In vitro exposure to a single immunizing antigen always resulted in an anamnestic response to the added antigen and a general enhancement of antibody production against cross-reactive determinants on other immunizing antigens. However, antibody production against unrelated immunizing antigens was always significantly suppressed by this exposure. This suppression was not the result of antibody feedback and could not be induced unless the unrelated antigen had been used as a priming antigen.

In 10 dogs with chronic (>4 weeks) one-kidney perinephritic hypertension and in 10 uninephrectomized normotensive control dogs anesthetized with pentobarbital we measured mesenteric pressures, flows, and venous pressure-volume relationships in the collateral-free, innervated, naturally-perfused ileal loop preparation. In hypertensives, compared to normotensives, arterial pressure (P < 0.001) and mesenteric blood flow/100 g (P < 0.02) were elevated, and venous compliance was decreased. In contrast, there were no significant changes in venous pressures and total and segmental resistances in hypertensives. Mesenteric pressures, flows, resistances, and compliances in these chronically hypertensive dogs did not differ significantly (P > 0.05) from values in dogs with early (<2 weeks) perinephritic hypertension that we previously reported. Together these results indicate that in the mesentery the normal vascular resistance and increased blood flow occurring in the early stages of perinephritic hypertension in dogs persist for several weeks into the established stages, without the development of increasing resistance and decreasing flow as would have been expected if “long-term autoregulation” had taken place.

The iron-chelating agent desferrioxamine caused approximately 10-fold reductions in ⁶⁷Ga vascular concentrations and substantial (~ × 2) reductions in ⁶⁷Ga concentrations of other tissues when injected iv into mice at 2 hr after ⁶⁷Ga injection. Given 48 hr post ⁶⁷Ga however, its only noteworthy effect was on the vascular compartment. Tumor was distinguished from other soft tissues by high concentrations of cell-bound ⁶⁷Ga, of which an appreciable fraction could be chelated and cleared by desferrioxamine given 2 hr after ⁶⁷Ga. This fraction diminished with time and, at 48 hr, desferrioxamine caused no significant clearance of tumor-bound ⁶⁷Ga.

The Halle strain of SSPE virus was found to consist of a heterogeneous population with regard to temperature sensitivity. Ten of 16 purified virus populations isolated from this strain were temperature sensitive (ts). The Halle strain was able to initiate persistent infection (PI) of HEp-2 cells at restrictive temperature but not at permissive temperature. The proportion of virus with ts properties did not increase with the passage of the persistently infected cells. No ts virus was detected in a strain of Edmonston measles virus, and this strain did not initiate PI at any temperature.

The HF (factor XII) activity in plasmas of 18 mammalian species has been studied by immunological means and gel filtration. All HFs had the same approximate size as human HF. Primate HF activity was most susceptible to inhibition by antihuman HF serum, ungulate HF activity by antibovine HF serum, and rodent HF activity by anti-rat HF serum. Immunodiffusion studies were consistent with these inhibition studies. These data suggest that mammalian HFs in the same taxonomic order share common antigenic sites.

A rapid, reproducible, noninvasive technique which allows repeated determinations of blood pressure in the rabbit is described. With the rabbit in the supine position, hind legs extended, a pediatric blood pressure cuff was placed around the upper thigh. A Doppler ultrasound probe, placed over the femoral artery, was used to determine the systolic and diastolic pressures. The average pressures obtained were 132 ± 3/65 ± 1 mm Hg (± SEM) (n = 93). These correlated well with direct intraarterial recording of the blood pressure. This technique was also used to measure the elevated pressures in hypertensive rabbits. Pressure measurements varied very little from one observer to another. Repeated determinations from the same rabbit were also relatively constant. This modified auscultatory method provides an efficient method for blood pressure determination in the rabbit over a period of time.

Prolactin in sera of four cows subjected to 30 min of continuous milking increased from 28 ± 9 ng/ml before milking to a peak of 290 ± 29 ng/ml at 20 min, and averaged 229 ± 32 ng/ml at 30 min. In comparison with 25 cows maintained in the absence of their offspring on Day 2 postpartum, 23 cows maintained immediately adjacent to their calves (suckling not permitted) decreased basal-, milking-, and TRH-induced release of prolactin by 68, 69, and 29%, respectively, on Days 3 to 5 postpartum. We conclude that direct tactile stimulation of teats maintains increased secretion of prolactin, whereas presence of the calf immediately adjacent to their mothers but without suckling, does not stimulate secretion of prolactin. Indeed, the presence of the calf may be inhibitory to the secretion of prolactin in lactating cows.

Pinealectomized cockerels (PX) were individually exposed to a thermocline (20 to 34°) throughout both phases of the light-dark cycle (12L:12D). Twelve birds from each surgical treatment, including sham operated (PN) and unoperated controls (C), were singly placed in the thermocline for 100 min during photophase and scotophase in 4-hr segments designated early (E), middle (M), and late (L). Prior to placement in the thermocline, PX birds had a lower mean T _r (40.15°) than PN and C groups (40.64°). During photophase, PX birds selected a higher T _a during the E and L segments, but preferred a T _a similar to PN and C cockerels for M photophase (23°). This produced an interaction (P < 0.05) between pinealectomy and T _a selection during photophase. The PX group had a T _a preferendum of 29.7° for scotophase in contrast (P < 0.05) to 25.4° selected by PN and C birds. The average T _a preferred by PX birds across both phases of the light-dark cycle was 28° (P < 0.05) while on the average, PN and C groups selected 24°.

The two mouse myeloma globulins, MOPC-104E IgM and J558 IgA, have antibody specificity to α-1,3-dextran and represent two idiotypes of antidextran antibodies. The results of the reported experiments indicate that idiotype suppression could be achieved by prior immunization of BALB/c mice with either 104E IgM or J558 IgA. After this immunization antibodies to dextran were only of the other idiotype. The absence of cross-reactivity strongly suggests that the idiotypes of antidextran antibodies are directed against different epitopic groups on the antigen.