An examination of interference effects in infants' memory for faces.

2 experiments with 18-week-old infants employed an interference paradigm to study infant visual memory. The infants were habituated to a repeated stimulus, given several trials with 1 or more interpolated stimuli, and then tested for recognition of the original stimulus. In Experiment 1, both amount of exposure and the similarity of the potentially interfering material to the original habituation stimulus were manipulated. Neither produced a significant interference effect, although some effect may have been shown by subjects who habituated to the interference stimult did demonstrate more clearly long-term retention of the originally remembered material. It was concluded from both studies that infant visual memory is a robust phenomenon, relatively immune to interference under most conditions.


Coordination of vision and prehension in young infants.

Infants aged 3, 5, and 7 months were shown solid objects and comparable intangible images of objects both within and beyond possible arm's reach. The infant's emotional reactions and reaching behavior in the presence of the image stimuli were very similar to their responses to the solid objects. The results do not support the reports of previous studies using a similar tactual-visual conflict situation that young infants become emotionally distressed when presented with discordant visual and tactual information. It was concluded that the initation of reaching attempts by young infants is predominantly visually controlled and any tactual-kinesthetic feedback from prehension seems to produce very little modification of young infants' reaching behavior.


[A method for the extraction of high serum-gastrin concentrations for the quantitative differentiation of human gastrin types].

By selective investigation of human antral venous blood, concentrations of gastrin are sufficiently elevated for the quantitative differentiation of the various forms. The results of comparative determinations of gastrin from antral and peripheral venous blood are shown.


[Preoperative reduction of intestinal bacteria through orthograde lavage of the large intestine].

The orthograde colon lavage, suggested by Crapp, is a new method for the preoperative preparation of the colon. On the day prior to surgery, the sitting patient receives for 4 h through a stomach probe, 101 of physiological saline solution warmed up to 37 degrees C. The result is a complete evacuation of the bowel. If a bactericidal antibiotic with a broad spectrum of activity (neomycin) is added, the suppression of the microflora amounts to 92%. The regeneration of the intestinal flora could be observed after a few days. A complete evacuation of the colon is guaranteed by this procedure, so that all operations can be performed under optimal conditions. From the clinical as well as from the microbiological point of view this method is without any risk. -- The orthograde colon lavage is indicated in every case of colon, rectum and anal surgery, but it is contraindicated in patients with highly stenosing tumors.


[Traumatic cysts of the spleen].

During a routine clinical examination of a 7-year-old girl and a 17-year-old man a large tumor was discovered in the left upper quadrant of the abdomen. Large splenic cyst were found in the spleen at splenectomy. The traumatic etiology of the cysts can be assumed on the basis of histologic results, as well as of a significant history of previous trauma. The etiology, differential diagnosis, therapy, and classification of splenic cysts are discussed.


[Comparative studies on preoperative skin disinfection].

The antibacterial effects of Sepso-tincture, Kodan, Dibromol, and 70% ethanol as disinfectants were compared on the skin of 34 patients of the first surgical department of the general hospital in Hamburg-Barmbek. Special attention was paid to the regeneration of microorganisms in relation to time. The result was that the tested substances showed an almost equal effect after 2 min. However, after 10, and 60 min the tests showed considerable divergencies. In comparison, therefore, with the other substances, it could be proved that the least regeneration of microorganisms was observed after application of Sepso-tincture (significance after 10 min: P less than 0.01, after 60 min: P less than 0.05).


The preoperative diagnosis of hepatic metastases in cases of colorectal carcinoma.

Preoperative LDH, CPK, alkaline phosphatase and liver scan results were compared with the presence or absence of hepatic metastases at operation in 124 laparotomies in 123 patients with colorectal carcinomas during a three-year period. The overall accurcy rates for the four tests ranged from 74 to 84 per cent. The false-negative rates were acceptably low (9-13 per cent) for all but the CPK determination. The false-positive rates were unacceptably high for all four tests (38 to 60 per cent). A 'metastatic score' for reducing the high false-positive rate is described. In view of the high false-positive rates of preoperative screening tests, laparotomy is presently the most accurate method of diagnosing hepatic metastases.


Ileorectal anastomosis for inflammatory disease of the colon.

We have reported long-term results in the cases of 42 patients following total colectomy and ileorectal anastomosis for inflammatory bowel disease. In this group, 35 patients had Crohn's disease and seven had ulcerative colitis. Five of those seven patients with ulcerative colitis had carcinoma of the colon at the time of colectomy. A diverting loop ileostomy was constructed in 14 of the 35 patients who had Crohn's colitis at the time of operation, and none of these patients had any anastomotic leakage either before or after the ileostomy was closed. However, there patients with Crohn's colitis in whom anastomotic leaks developed postoperatively; all three patients died. In the group with ulcerative colitis, one patient had an anastomotic leak but there was no operative nortality. Of the 29 patients with Crohn's disease followed for one to 18 years, 12 (41 per cent) developed recurrences in the ileum and/or rectum, and seven of these patients had to have their anastomoses taken down.


Acute perforations of the colon.

A retrospective study of acute perforations of the colon is presented. Sites, causes, morbidity, mortality, and treatment are discussed. Comparison with several large series is made.


Adenocarcinoma of the appendix: a clinicopathologic study.

Clinicopathologic correlation and survival were evaluated in 11 patients with adenocarcinomas of the appendix. This extremely rare tumor was seen most often in patients in the fifth decade of life. Acute appendicitis was the most common mode of presentation (8/11). A few patients (3/11) showed signs of distant metastases from an occult primary tumor in the appendix.


Leiomyosarcoma of the colon: report of a case.

A case of leiomyosarcoma of the colon is reported. Only 33 other cases have been reported. The course of the disease is insidious. The prognosis seems favorable. An attempt is made to stage the disease for better documentation and evaluation for the sake of better management.


Giant condyloma of the rectum: report of a case.

The case of a woman who had a giant condyloma arising in the rectum and manifesting with a rectovaginal fistula is described. Radical surgical excision was performed. The clinical and pathologic features of this locally malignant condition are described and a plea is made for early radical surgical excision.


[Pregnancy in ulcerative colitis and Crohn's disease (author's transl)].

Between 1967 and 1973 15 women with ulcerative colitis had 20 pregnancies. 14 ended with normal deliveries, 4 with spontaneous abortions, and 2 with therapeutic abortions. Fertility was normal. Malformations in the children were not observed. In the case of conception during remission or a latent phase of the disease in general a normal pregnancy is to be expected (12 out of 14). On the other hand conception during an active phase can lead to an unpredictable threat to the life of mother and child. Therapeutic abortion should be seriously considered when ulcerative colitis and pregnancy begin simultaneously. In the same period of time in 15 comparable patients with Crohn's disease (12 with ileo-colitis and 3 with terminal ileitis) who were not taking ovulation inhibitors 4 pregnancies were observed. Fertility is not significantly reduced in terminal ileitis whereas in ileo-colitis it is highly significantly reduced (bilateral tubal irritation). As in ulcerative colitis a normal pregnancy can be expected after conception in an inactive phase (2 out of 4).


[Occupational lung cancer after inhalation of alkylating compounds: dichlordimethyl ether, monochlordimethyl ether and dimethyl sulphate (author's transl)].

A 42-year-old chemist died from extensive pulmonary carcinoma, having inhaled for over seven years dichlordimethyl ether, monochlordimethyl ether and small amounts of dimethyl sulphate. This exposure took place in circumstances which, in animal experiments, have led to the development of cancer. A causal connection between the occupational exposure to these chemicals and carcinogenesis has to be accepted.


[The effect of treatment on circulating immune complexes in rheumatoid arthritis (author's transl)].

Immune complexes were demonstrated by leucocyte phagocytosis assay in 37 of 55 patients with rheumatoid arthritis. After treatment with gold salts, penicillamine, alpha-mercaptopropionylglycine, immunosuppressive agents or levamisole a substantial fall or elimination of demonstrable circulating immune complexes occurred. In-vitro studies revealed that gold salts in therapeutic concentrations inhibited the phagocytosis of immune complexes, while other drugs - penicillamine, levamisole and all anti-inflammatory agents including corticosteroids - lack this effect. The reduction in circulating immune complexes under basic therapy may be due to a beneficial effect of these agents on the disease process itself. This test may, therefore, be of value in assessing the efficacy of drug treatment.


[Results of angiographic investigations in basilar artery insufficiency (author's transl)].

Angiographies were performed in 75 selected patients with basilar artery insufficiency. In only one case was there an indication for vascular surgery to the vertebral artery, and in two cases for an uncoforaminectomy, whereas in 13 cases prophylactic desobliteration of the internal carotid artery was performed. Thus vascular surgical consequences of angiography of the supraaortic vessels in basilar insufficiency are minimal. However, personal observations and reports in the literature indicate that the indications for surgery to the vertebral artery or the cervical spine will increase if functional investigations can be performed in various positions of the cervical spine by means of selective catheter angiography.


[The diagnosis of traumatic haemobilia and bilhaemia (author's transl)].

A case of bile passage into the portal vein (bilhaemia) and two cases of haemobilia are reported. The former is a hitherto undescribed complication of liver injury, in the reported case first noted two weeks after trauma. Serum-bilirubin concentration was 560 mg/l (958 mumol/l). Bilhaemia or haemobilia may occur when a fistula has been formed between the bile duct system and the circulatory system, depending on pressure differences between the two. The diagnosis and exact localisation of bilhaemia or haemobilia can be made by endoscopic retrograde cholangiography, a useful complementary test to selective angiography.


[The "locked-in" syndrome: pseudocoma in thrombosis of the basilar artery (author's transl)].

In pontine lesions with tetraplegia and cranial-nerve disturbances--including trismus--and with speech disability paralytic akinesia and loss of reactivity may be misinterpreted as coma. "Pseudocoma" of this kind may be associated with normal consciousness or relatively mild psychological disorders. This explains the discrepancy between a normal EEG (only minor abnormalities) and presumed unconsciousness. The term "locked-in" expresses the patient's inability to communicate. In typical cases there may be only vertical eye movements and blinking. Using remaining innervation facilities, those examining and treating the patient must try to communicate with him. The locked-in state may be mistaken for coma particularly if there had been a preceding episode of unconsciousness. Moreover, the "locked-in" syndrome often passes into a state of unconsciousness or coma. The degree of communication can markedly differ from hour to hour. Most of the cases of this syndrome are caused by basilar artery thrombosis.


[Serum-complement factors in the pseudo-LE syndrome (author's transl)].

In contrast to the situation in disseminated lupus erythematodes, in pseudo-LE syndrome the serum-complement factors C'3 and C'4 are elevated and not decreased in the active stage of the disease. Although both diseases are defined and easily distinguished by the demonstration of the specific pathognomonic autoantibodies, at least in the active stage, they can also be distinguished by determining these two complement factors. The finding also demonstrates a different pathogenesis of the two diseases. The serum concentration of C'3 activator is elevated both in LE and pseudo-LE. In the former, determining C'4 is a more sensitive test than that of C'3.


[The diagnosis of medullary carcinoma of the thyroid (author's transl)].

The pentagastrin stimulation test was given to ten brothers and sisters of two patients who had previously undergone total thyroidectomy for medullary carcinoma of the thyroid. 5 microng pentagastrin/kg body-weight were injected as an intravenous bolus and calcitonin levels determined before and after. The test was positive in four members of the family and the presence of a medullary carcinoma was subsequently confirmed in them histologically.


[Theophylline blood levels after administration of Euphyllin retard (author's transl)].

The plasma theophylline concentration gradually increases after oral administration of Euphyllin retard, followed by a slower fall, than is the case after Euphyllin tablets have been taken, in which case maximal theophylline levels are reached 1 1/2 hours after administration. When Euphyllin retard is given, one to two tablets (350-700 mg) eight or twelve hours apart, there is a progressive rise of theophylline plasma levels to a plateau. This plateau can be maintained and is dependent upon dosage and the half-life of theophylline, which varies amongst individuals. Patients with obstructive airway disease treated with one tablet of Euphyllin retard every twelve hours for several weeks had a mean plasma theophylline level of about 6 microng/ml. In these patients the airway resistance, measured by body-plethysmography, improved by about 30%, without any side-effects. Six and twelve hours after administration of two tablets of Euphyllin retard the mean plasma concentration was 13 and 9 microng/ml, respectively. About half the patients receiving the larger dose of two tablets every twelve hours had gastro-intestinal or CNS disturbances. Long-term administration of Euphyllin retard provides a constant blood level of the drug.


A biologic and genetic study of 40 cases of severe pure mental retardation.

The family history of 40 patients with severe "pure" mental retardation (MR) was studied to determine the incidence of mental retardation and dull-normal intelligence among relatives, probable etiologies and an empiric recurrence risk. Significant findings include: (1) an increased sex ratio (69% males) of propositi, (2) a significant proportion of patients with clinical manifestations besides MR, (3) virtually no consanguinity among parents, (4) a "positive" family history for over 1/2 of the propositi--about 37% of all children in the sibships were affected; about 21% of the full sibs were affected, (5) a higher number of offspring produced by dull persons and a lower number of offspring from retarded persons compared to two normal persons (6) a proportionately large number of affected children produced from matings involving one or two dull persons, (7) a tendency for dull to have additional dull children and mentally retarded parents to have further retarded children while normal parents with more than one affected child usually had further retarded children, (8) an incidence of affected parents of about 32%, and (9) an overall empiric recurrence risk of 14%. Several etiologies were discussed as possible causes of the condition(s) in this group: (unrecongized) environmental damage and/or maternal/fetal interaction; unrecognized chromosome abnormalities; the homozygous state of several different autosomal recessive gees: X-linked recessive mutations; autosomal dominat new mutations; and mutifactoral inheritance. It was concluded that the group was etiologically heterogeneous and although none of the probable etiologies could be excluded, it seemed reasonable to assume that autosomal recessive inheritance plays an important role in the etiology of severe "pure" mental retardation.


Absence of spermatogonia in the Prader-Willi syndrome.

Bilateral testicular biopsies in an 81/2 year old boy with the Prader-Willi syndrome showed total absence of spermatogonia. Similar findings in postpubertal cases (Wannarachue et al., 1975) suggest that testicular dysplasia is one of the reasons for hypogonadism in males with the Prader-Willi syndrome.


A metabolic disorder similar to Zellweger syndrome with hepatic acatalasia and absence of peroxisomes, altered content and redox state of cytochromes, and infantile cirrhosis with hemosiderosis.

A patient with a cerebro-hepato-renal syndrome was investigated. The visceral manifestations were those of the Zellweger syndrome (ZS); however, the child exhibited muscular hypertonia and survived into the 2nd year of life. Ultramicroscopically, hepatocytes were lacking peroxisomes, but, contrary to findings in one patient with ZS [2], contained smooth endoplasmic reticulum. No catalase was found by histochemistry or spectroscopy. Mitochondria showed normal succinate and glutamate respiration, and normal coupling of respiration to the phosphorylation potential. The cytochrome (cyt) content was diminished to one-third with an abnormally inversed redox pattern of the respiratory chain in the controlled state, cyt b being 5%, cyt c 23% reduced. The oxygen affinity of cyt a3 was normal. These findings exclude a defect in the nonheme iron protein region of the respiratory chain as described in ZS [2], but point to a functional abnormality of cyt b in out patient.


The age-dependence of intestinal absorption using d-xylose as an example.

In 40 infants the serum concentrations of D-xylose were measured from capillary blood samples up to 300 min after an oral dosage of 0.5 g of D-xylose per kg body weight. The parameters of the absorption kinetics, which are calculated by a digital computer program, showed an age-dependent behavior. Infants up to the age of 2 months have lower maximal serum concentrations compared to older ones because of a larger volume of distribution. The rate constant of invasion k1, which serves as a measure for the rate of intestinal absorption and the rate constant of elimination k2 were significantly lower in infants up to the age of 2 months compared to older ones. The quotient of k1:k2 was independent of age. The time it took to reach maximal serum concentration was significantly longer in young infants. By adding metoclopramide simultanously to the oral D-xylose doses it could be demonstrated that the slower motility of the gastrointestinal tract in newborns and young infants is not exclusively responsible for the slower rate of absorption of D-xylose. Comparing the absorption rates in 26 infants after different D-xylose dosages a saturation kinetics may be supposed.


Continuous blood velocity and flow measurements by intravascular elutherm probe.

A device for measuring the mean blood velocity (by means of a thermal equilibrium method) and the intravascular electrical impedance, which determines the mean sectional area of the vessel, have been mounted on the same probe (french catheter 7F). The validity, of the method has been confirmed in vitro and by 100 measurements carried out in dogs and compared with flow measurements by means of the cardio-green method. The correlation coefficient is found to be 0.98.


Microembolism in experimental septic shock. Distribution of platelets and fibrinogen after intravenous injection of disintegrated Pseudomonas bacteria to dogs.

Platelets were labelled with 51Cr, fibrinogen with 125I and erythrocytes with 59Fe. Disintegrated Pseudomonas bacteria were injected intravenously and radioactive measurements were made on whole blood; tissue biopsies and clottable fibrinogen. After the infection there was an immediate but transient increase of 51Cr activity in the lung concomitant with a decrease in platelet count and 51Cr activity of blood. In the liver there was a less pronounced increase of 51Cr activity. The fibrinogen concentration decreased slightly, paralleled by the 125I activity of whole blood and of clottable fibrinogen, whereas the 125I activity in the lung and liver remained fairly constant. There was no changes of 51Cr activity or 125I activity in biopsies from muscle, pancreas, small intestine, kidney or spleen. During the experiment (3h) there were no signs of significant disseminated intravascular coagulation other than platelet aggregation. A consumption of fibrinogen related to the formation of fibrin plugs could not be detected. After injection of disintegrated Pseudomonas bacteria reversible platelet aggregates were formed and temporarily trapped in the pulmonary microcirculation. This microembolism might induce tissue damage and could be of importance for the development of septic pulmonary complication.


Hypoxanthine and urate levels of plasma during and after hemorrhagic hypotension in dogs.

The plasma hypoxanthine concentrations increased during hemorrhagic hypotension in dogs. A venous-arterial hypoxanthine difference was found indicating metabolism of hypoxanthine in the lungs. A maximal hypoxanthine level was found during the hypotension, then the level decreased. This probably reflects peripheral vasoconstriction. During reinfusion of the blood, a new hypoxanthine peak was observed. The urate levels also increased during the hypotension. An arterial venous difference was found. This probably illustrates that hypoxanthine is metabolized to urate in the lungs. It is concluded that the increase of plasma hypoxanthine concentrations might reflect tissue hypoxia.


Interaction between acute gastric ulcer and epinephrine-induced mucosal erosions in the rat.

Gastric mucosal erosions were produced in rats by pyloric occlusion and intraperitoneal injection of epinephrine. Gastric ulcer was induced by the application of acetic acid to the anterior wall of the stomach. The gastric lesions were photographed and examined microscopically. 5 h after pyloric occlusion alone, the gastric mucosa looked essentially normal. After pyloric occlusion and injection of epinephrine, superficial mucosal erosions were observed in the major portion of the fundus. The presence of an acute acetic ulcer was found to inhibit partly or completely the development of mucosal erosions usually induced by pyloric occlusion and injection of epinephrine. It is suggested that this might be due to a local release of inflammatory mediators around the ulcer.


Suppression of generation of human cytotoxic effectors by lectins or lectin-activated peripheral blood lymphocytes.

The lectins phytohemagglutinin, pokeweed mitogen and concanavalin A used at their optimal mitogenic concentration, or human lymphocytes activated by the same mitogens, were found to suppress the in vitro generation of cytotoxic effectors when added to a cell-mediated lympholysis (CML) mixture during the first 48 h of culture. The data suggest that the suppressive mechanism is mediated to a greater extent by an allogeneic interaction between lectin-activated cells and the allogeneic cells present in the CML mixture than by suppressor cells induced by the lectin. Since partial suppression was observed with supernatants of activated lymphocytes cultured for 18 h with allogeneic stimulating cells (but not activated lymphocytes alone), a soluble mediator may be involved in the suppressive mechanism. The mechanism of suppression therefore may be identical to the preemption phenomenon recently described in primary and secondary CML.


Studies on the lymphocytes of sheep. III. Destination of lymph-borne immunoblasts in relation to their tissue of origin.

Lymph-borne immunoblasts were labeled in vitro with 125I[]iodo-deoxy-uridine, washed and returned by intravenous injection to the sheep from which they had been collected. Twenty h later the sheep were killed and the distribution of the immunoblasts was determined by assaying the radioactivity in various organs. Immunoblasts from the efferent lymph of peripheral somatic lymph nodes (PSLN) went mainly to the spleen, lungs and other PSLN, while immunoblasts from intestinal lymph went mainly to the small gut. This ability of intestinal immunoblasts to home to the gut was demonstrated also in the sterile environment of fetuses in utero; apparently the migratory behavior of immunoblasts, like that of small lymphocytes, is not primarily "antigen-driven". A technique was devised for the collection of peripheral (i.e. afferent to the mesenteric node) intestinal lymph which was found to contain 10-20 times the numbers of small lymphocytes that occur in the peripheral lymph from other tissues. Immunoblasts from peripheral intestinal lymph also homed to the gut. The immunoglobulin content of immunoblasts was studied by making detergent extracts of lymph cells, by applying immuno-peroxidase techniques to cell films and by investigating the incorporation of 14C-labeled amino acids into immunoglobulins by immunoblasts in vitro. Immunoblasts from both somatic and intestinal lymph contained and made IgG and IgM, but many intestinal immunoblasts contained and made IgA. It is not known whether this immunoglobulin mediates the extravasation of immunoblasts into the gut. Nonetheless, there is compelling evidence that there are two major migratory pathways for lymphoid cells; one through the gut-associated lymphoid tissue and the other through the somatic-splenic lymphoid tissues.


Autoimmune murine thyroiditis IX. Relationship of humoral and cellular immunity to thyroiditis in high and low responder mice.

Good responder (C57/Br/cd) and poor responder (C57BL/10) mice were immunized with mouse thyroid extract in Freund's complete adjuvant. The good responder mice first showed antibody to thyroglobulin on the seventh day while the poor responder animals had slightly lower titers and antibody did not appear until day 12. The first signs of thyroid infiltration appeared on day 4 in the responder strain, and severe lesions were seen between the third and fifth week. In contrast, the poor responder mice showed almost no evidence of infiltration. The macrophage disappearance reaction, a measure of cell-mediated immunity, was similar in the responder and nonresponder strains.


Dihydroxyphenylacetic acid conjugate: natural occurrence and demonstration of probenecid-induced accumulation in rat striatum, olfactory tubercles and frontal cortex.

Methods for the synthesis of 14C-dihydroxyphenylacetic acid (DOPAC) conjugate and for the fluorometric determination of both free and conjugated DOPAC in the same tissue sample are described. Both free and conjugated DOPAC were demonstrated to occur endogenously in the rat corpus striatum, olfactoy tubercles and frontal cortical area, and the ratio of conjugated DOPAC to free DOPAC was 2-3 times greater in the olfactory tubercles and frontal cortical area than in the striatum. Probenecid administration (200 mg/kg, i.p., 4 and 2h before sacrificing) significantly increased the levels of DOPAC conjugate in all 3 brain areas studied. The levels of free DOPAC were also increased in the olfactory tubercles and frontal cortex by the probenecid treatment, but this increase was much less than that seen for DOPAC conjugate in these regions. Free DOPAC levels in the striatum were unaffected by the probenecid treatment. In all 3 brain areas studied, therefore, probenecid treatment resulted in a significant accumulation of conjugated DOPAC relative to free DOPAC. The magnitude of this effect varied, and was most marked in the frontal cortex. These results suggest that, in order for DOPAC to be transported from the central nervous system via a probenecid-sensitive transport system, it must first be conjugated. Additionally, it appears that the rates of synthesis, metabolism, and transport for both free and conjugated DOPAC may vary greatly among different dopamine-containing brain regions.


Effect of bumetanide and furosemide on the thick ascending limb of Henle's loop of rabbits and rats perfused in vitro.

Direct effects of bumetanide and furosemide on the thick ascending limb of Henle's loop (TALH) were compared by using the isolated tubules of rabbits and rats perfused in vitro. Both drugs, applied to the lumen, reversibly suppressed the lumen positive potential (PDt) of the rabbit TALH. Bumetanide also suppressed the PDt in the absence of Na+ where the NaCl of the artificial solutions was replaced by choline chloride. The efflux of 36Cl was also reduced by the addition of bumetanide to the perfusate. The dose-response analysis disclosed that bumetanide was 14 times as potent as furosemide. The onset and duration of bumetanide action was significantly longer than that of furosemide. Bumetanide also suppressed the PDt of the rat TALH when it was added to the perfusate.


Inhibition of [3H]norepinephrine uptake in peripheral organs of some mammalian species by ouabain.

In order to demonstrate the possible involvement of (Na+ + K+)-ATPase in the high affinity uptake of [3H]-norepinephrine in the sympathetic nerve endings, the effect of ouabain on [3H]norepinephrine uptake in spleen and heart slices of five mammalian species was examined. The ouabain sensitivity of [3H]norepinephrine uptake in the heart slices form various species, as determined by the estimation of IC52, was, in increasing order, lamb (2,3 muM) less than calf (2.5 muM) less than guinea pig (4 muM) less than rabbit (10muM) less than rat (greater than 500 muM). The IC50 values in the spleen slices were: lamb (1 muM) less than calf (3.2 muM) less than rabbit (9.5 muM) less than guinea pig (25 muM) less than rat (greater than 500 muM). The IC50 values for the inhibition of specific [3H]ouabain binding in the microsomal fractions of spleen and heart of the five mammalian species by ouabain were similar to the IC50 values for the inhibition of [3H]norepinephrine uptake by the cardiac glycoside. Since ouabain is known to bind exclusively to (Na+ + K+)-ATPase of a microsomal fraction, these results suggest that the inhibition of [3H]norepinephrine uptake in the sympathetic nerve endings by ouabain is mediated by the inhibition of (Na+ + K+)-ATPase.


Effect of metabolites of chlorpromazine on plasma prolactin levels in male rats.

Since prolactin secretion is under vigorous dopaminergic inhibition, neuroleptic drugs can, because of their capacity to block dopamine receptors, produce large increases in plasma prolactin levels in man and laboratory animals. The capacity of intramuscular (i.m.) chlorpromazine and 6 of its metabolites to increase plasma prolactin levels in male rats was compared. 7-Hydroxychlorpromazine produced increases in plasma prolactin equivalent to those produced by chlorpromazine. The following metabolites had no effect on plasma prolactin levels after i.m. injections of 5 mg/kg: 8-hydroxychlorpromazine; 7,8-dihydroxychlorpromazine; 8-hydroxy-7-methoxychlorpromazine; 7-methoxychlorpromazine; and chlorpromazine sulfoxide. 8-Hydroxychlorpromazine, 7-methoxychlorpromazine, 7,8-dihydroxychlorpromazine and chlorpromazine sulfoxide had no effect even after 25 mg/kg i.m. The capacity to increase rat plasma prolactin correlates highly with other methods of determining potential antipsychotic activity of chlorpromazine and its derivatives.


The contribution of renal and extrarenal mechanisms to hypokalemia induced by glucagon.

Other investigators have shown that infusion of glucagon causes the concentration of potassium, [K+], in the arterial plasma to increase rapidly, then to decrease to less than the beginning value. In studies on anesthetized dogs, we found that the magnitude of the initial, rapid rise of [K+] was increased by nephrectomy but not affected by pancreatectomy. The subsequent decline of [K+] and the persistent hypokalemia were not affected significantly by nephrectomy. Plasma [K+] decreased in the nephrectomized-pancreatectomized dogs, as it did in the nephrectomized and the control groups, but the effect was temporary, and [K+] began to increase again, even though the infusion of glucagon continued; after the infusion was ended, plasma [K+] became significantly higher than the beginning value. These data suggest that the hypokalemia caused by infusion of glucagon initally depends on extrarenal factors other than insulin, and, later, depends on insulin.


Tolerance to the increase of striatal homovanillic acid elicited by several anorectic drugs.

Several anorectic drugs affect dopamine metabolism in the rat striatum, increasing the concentration of homovanillic acid (HVA). However 1- and d-amphetamine and mazindol develop a tolerance to the HVA increase. On the contrary, the effect of fenfluramine and S 992 is not reduced by sub-chronic treatments. Moreover, a cross-tolerance to this biochemical effect develops between amphetamine and mazindol, but pretreatment with fenfluramine or with S 992 does not induce cross-tolerance to amphetamine.


Prevention by drugs of tachyphylaxis at nicotinic receptors in the cat superior cervical ganglion in situ.

A new compound, AF3 (4-ethyl-6-oxa-1-azatricyclo)4.2.2.02,7)dodecan-5-one), and its 4-phenyl analogue, AF6, embodying the structural elements of acetylcholine in a highly rigid framework, were shown to evoke nicotine-like responses in the nictitating membrane (NM) and blood pressure when applied to the superior cervical ganglion in anaesthetized cats. In this respect, their equiactive molar ratio was (nicotine : 1),20-30. However, at doses that were too low to evoke any response, AF3 appeared to potentiate the responses to nicotine or tetra-methylammonium (TMA) by preventing or abolishing tachyphylaxis to the two latter drugs, the effect being dose-dependent with AF3. DMPP which produces much less tachyphylaxis, or preganglionic nerve stimulation, was little or not potentiated in presence of AF3. It is proposed that potentiation to nicotine or TMA occurs following occupancy by AF3 of a regulatory subsite, thereby preventing further access to it by nicotine or TMA. In this respect, AF3 plays the role of a "neutral" molecule.


Studies on the contribution of active metabolites to the anticonvulsant effects of propranolol.

The anticonvulsant activity of propranolol and two selected metabolites, propranolol glycol and N-desisopropylpropranolol were compared in mice against 4 types of experimentally induced seizures: pentylenetetrazol, strychnine, low frequency and maximal electroshock. Both metabolites possessed significant anticonvulsant activity with propranolol glycol being 1/2 to 1/3 as potent and N-desisopropylpropranolol being 1/6 as potent as propranolol. The possible contribution of these two active metabolites to the acute anticonvulsant efficacy of propranolol was assessed in time course studies. Maximal anticonvulsant activity occurred between 2.5--10 min after propranolol (5-20 mg/kg, i.v.) and was significantly diminished after 30 min. Following propranolol, brain levels of both metabolites were extremely low ( less than 10 ng/g) at the onset of anticonvulsant action and reached peak levels between 15-30 min at which time anticonvulsant activity was already declining. In contrast, brain levels of propranolol were similar in time course to that observed for its anticonvulsant effect and there was significant positive correlation between these two parameters in 3 of the 4 seizure models. These data indicate that although these two metabolites are pharmacologically active, they do not contribute significantly to the acute anticonvulsant actions observed after propranolol administration.


Antidepressant drugs and dopamine uptake in different brain regions.

The effect of trycyclic antidepressants on 3H-dopamine uptake into synaptosomes obtained from rat striatum and mesolimbic cortical areas was examined. Chlorimipramine was found to be the most potent uptake inhibitor (IC50 of 3.2-3.8 X 10(-6) M) in both brain regions. Desmethylimipramine, protryptyline and iprindole were approximately one-half as potent (IC50 of 5.9-8.5 X 10(-6) M) in both brain areas. Kinetic constants obtained from Line-weaver-Burk plots in both areas revealed no alteration in Km for transport and a decrease in V max thus indicating a non-competitive inhibition. The effect of chlorimipramine on the release of 3H-dopamine from striatal synaptosomes required a concentration 10(-5) M for 50% release in 5 min. It is suggested that dopamine uptake inhibition may play some role in the action of tricyclic drugs, e.g., activation of schizophrenic psychopathology but that this action can not be solely responsible for their antidepressant properties.


Effects of phentolamine, phenoxybenzamine and desipramine on clonidine-induced blockade of cardiac acceleration in the dog.

Clonidine reduced cardiac acceleration induced by low frequency electrical stimulation of cardiac sympathetic nerve fibers in anesthetized and vagotomized dogs. This effect of clonidine was abolished by short periods of high frequency electrical stimulation. The inhibitory effect of clonidine was observed with 10- as well as with 90-sec periods of electrical stimulation of sympathetic nerve fibers; it was antagonized by phentolamine, phenoxybenzamine and desipramine. This suggests the presence of alpha-adrenoceptors at the peripheral sympathetic nerve ending in the dog.


The effect of tamoxifen on the in vitro production of prostaglandins F by the guinea pig uterine tissue.

Tamoxifen, a drug widely known as an antioestrogen is shown to depress the in vitro yield of PGF from pro-oestrus guinea pig uterine homogenates. The possibility that this is a novel antioestrogenic effect of tamoxifen is discussed.


Haloperidol blocks the discriminative stimulus properties of lateral hypothalamic stimulation.

Haloperidol was shown to block the discriminative stimulus properties of electrical stimulation in the lateral hypothalamus, and this effect to be related to train frequency. This finding is relevant to the relation between discriminative and reinforcing properties of stimuli exerting internal stimulus control of behavior.


Nomifensine and its derivatives as possible tools for studying amine uptake.

An experimental antidepressive drug, nomifensine, was tested in simultaneous experiments as an inhibitor of the uptake of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) in rat brain synaptosomes. The drug was found to be a very potent inhibitor of NA (Ki 4.7 X 10(-9) M) and DA (Ki 2.6 X 10(-8) M) uptake, but relatively weak inhibitor of 5-HT uptake (Ki appr. 4 X 10(-6) M). According to kinetic studies on dopamine uptake, the inhibition was competitive. Time course studies indicated that the percentage inhibition did not increase with time. This finding suggests that inhibition of membrane uptake rather than inhibition of storage is the mechanism of action of this drug. 3 metabolites of nomifensine were also tested as inhibitors of NA and DA uptake. The addition of a 4-hydroxy group to the phenyl ring of nomifensine slightly decreased the potency, and addition of hydroxy and methoxy groups to the positions 3 and 4 in the phenyl ring, clearly decreased the potency. The structure of nomifensine is compared to that of chlorimipramine. It is suggested that the differences in selectivity as to dopamine and 5-HT uptake mechanisms might be due to 2 conformational differences: one of the phenyl rings is freely rotating in nomifensine but not in chlorimipramine, and the tertiary amine group is in a flexible side chain in chlorimipramine but rigidly tied in nomifensine.


Dual inotropic effect of harmaline on the rat heart atrial muscle.

The effect of harmaline (HME) was analyzed in rat atrial strips superfused in vitro. A dual inotropic action was found: the positive component was due to a transient catechol-mediated enhancement of the velocity of development of tension (dT/dt) and to a prolongation of the duration of the rising phase of the contraction (TPT). The negative component was due to a depression of dT/dt, which overcame the persistent TPT-prolonging effect of HME, and it was abolished by rising the [K]0. It is concluded that: (1) the positive inotropic effect of HME depends on its actions on the dT/dt and TPT; (2) the enhancement of dT/dt is due to an adrenergic mechanism, which stimulates the Ca2+-dependent slowly activated current (Is); (3) a negative inotropic effect becomes evident whenever the dT/dt is depressed by the drug, regardless of the persistence of the TPT-prolonging effect; (4) the depression of the dT/dt is not due to an inhibition of Is.


The effect of the narcotic antagonists naloxone, naltrexone and nalorphine on spinal cord C-fiber reflexes evoked by electrical stimulation or radiant heat.

C-fiber reflexes were recorded from an S1 ventral root in the acute decerebrate low spinal cat following stimulation of the ipsilateral superficial peroneal nerve or application of radiant heat to the metacarpel footpad. Naloxone when administered i.v. increased the electrically evoked C-fiber reflex to 158% (+/- 23.8% S.E.M.) of control 10 min after administration; whereas, naltrexone, 0.0025 mg/kg, increased the C-fiber reflex to 206 +/- 26.1% (S.E.M.) of control. Naloxone in a dose of 0.050 mg/kg increased the radiant heat evoked ventral root reflext to 161 +/- 19.5% of control. Nalorphine, 1 mg/kg, facilitated the electrically evoked C-fiber reflex to 282 +/- 75% of control. These findings that naloxone and naltrexone facilitated these reflexes in doses too small to have non-specific excitatory effects and that nalorphine facilitated the C-fiber reflex at a dose level that is depressant to the flexor reflex in the chronic spinal dog are consistent with a hypothesis that these effects are due to antagonism of a naturally occurring opiate-like inhibitory substance.


Increase of striatal dopamine turnover by drugs: interference with granular storage or receptor blackade?

Apomorphine completely antagonized the reserpine-induced enhancement of the striatal 3,4-dihydroxyphenylalanine (dopa) accumulation seen after administration of the decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD 1015). Reserpine-like drugs, e.g. Ro 4-1284 and Ro 4-9040, markedly enhanced the striatal dopa accumulation (due to NSD 1015) in normal animals but not in rats treated with reserpine plus apomorphine. Haloperidol enhanced the striatal dopa accumulation to a similar extent in normal and in reserpine-apomorphine-treated animals. Chlorpromazine also caused an enhancement of striatal dopa accumulation in both types of animals, but its potency was somewhat higher in normal rats than in those treated with reserpine plus apomorphine. In conclusion, reserpinized animals treated with apomorphine appear to be useful models for differentiating whether a drug enhances striatal DA turnover by interference with granular DA storage or by blockade of DA receptors. The latter seems to be the main mechanism of action of neuroleptic drugs.


On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs.

3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in the corpus striatum, nucleus accumbens and tuberculum olfactorium of the rat brain, 4 antidepressants, 4 anesthetics, dipropylacetate, ethosuximide and metoclopramide induced a rise of DOPAC and HVA levels in the 3 brain regions. No change was observed after carbamazepine, diazepam or propranolol treatment. Combined treatment with a maximally effective dose of haloperidol and morphine, oxotremorine or probenecid produced an additional rise of DOPAC and HVA levels, while no additional rise was seen with chloral hydrate, chlorimipramine, ether, halothane, metoclopramide or sulpiride. The potency of drugs to increase DA metabolism in corpus striatum relative to mesolimbic structures was estimated. Atypical neuroleptics such as sulpiride could be differentiated in this respect from classical neuroleptics such as chlorpromazine, fluphenazine and thioridazine, by their ability to produce a relatively large increase of metabolite levels in the mesolimbic regions. The heterogeneous group of 14 non-neuroleptics however produced regional changes which were very similar to those of the atypical neuroleptics. DA metabolism in mesolimbic regions, in contrast to striatal tissue, seems to respond more to atypical neuroleptics and non-neuroleptics than to typical neuroleptics.


Colony growth of normal human bone marrow in agar-gel.

A study of the colony forming ability of 99 normal human bone marrows using the semi-solid agar technique is presented. Feeder layers of 10(6) normal human peripheral white blood cells were used as the stimulus, and were overlaid with 2 X 10(5) bone marrow cells. The presence of human plasma either in feeder layers or bone marrow overlays inhibited colony formation when compared with studies performed with cells washed free of plasma. The number of colonies grown varied, but not significantly when the same marrow was grown on feeder layers from different donors. The inhibitory effect of normal human plasma was also demonstrated when unwashed and washed bone marrow cells were plated over feeder layers with no stimulus. Further confirmation of the inhibition by normal human plasma was made in 10 cases by the addition of 0.1 ml plasma to cultures of washed marrow over washed feeder layers. These data suggest that optimum results from in vitro culture of normal human bone marrow can be obtained only when all plasma is washed from both the feeder layer cells and the marrow cells before culturing.


Radiation induced hemopoiesis in adult mouse liver.

Repeated whole-body irradiation of adult mice induced hemopoiesis in liver, as shown by the presence of stem cells (CFUS), progenitor cells of granulocytes and macrophages (CFUC) and foci of granulocytic cells. The largest numbers of CFUS (up to 700) were found 24 to 47 days after four doses of 450 rad x-rays given at 24 day intervals and 15-17 days after 2310 rad gamma radiation given at a low dose-rate (70 rad per day). CFUS were still present (although in smaller numbers) up to 210 days after four doses of 375 rad x-rays or 225 rad neutrons. CFUC were also present in liver after four doses of 450 rad x-rays, but their numbers could not be calculated accurately because of the marked inhibitory effect of liver cells on in vitro colony growth. Irradiation with one dose of 450 rad x-rays did not result in the appearance of CFUS in liver, suggesting that hepatic hemopoiesis can be induced by radiation only after repeated or prolonged bone marrow injury.


Erythropoietic precursors in mice under erythropoietic stimulation and suppression.

Using a methylcellulose clonal cell culture technique, we examined serial changes in erythropoietic precursors in the femur, spleen, and blood of mice prepared with bleeding, erythropoietin injections, or hypertransfusion with packed red blood cells. Significant changes were observed for all hemopoietic organs in the number of erythropoietic burst-forming units (BFU-E) and erythrocytic colony-forming units (CFU-E). In mice prepared with bleeding or erythropoietin injections, the serial changes of BFU-E and CFU-E were similar to but less striking than those seen in mice with phenylhydrazine-induced anemia. The transient decline in the femoral BFU-E coincided with the temporary increase in the splenic and blood BFU-E. A more pronounced increase in CFU-E was noted in the femur and spleen of these mice. In hypertransfused mice, the direction of the changers in the erythropoietic precursors was opposite. While femoral BFU-E increased mildly, a significant drop was noted in the splenic and blood BFU-E. Both femoral and splenic CFU-E declined and remained low while erythrocytosis presisted. Next, we examined the proliferative state of the erythropoietic precursors in the marrow and spleen using short-term incubation with high specific tritiated thymidine. In the marrow and spleen of normal mice, the BFU-E and CFU-E in the DNA synthetic phase was about 36 and 74%, respectively. Neither induction of anemia with phenylhydrazine hydrochloride nor polycythemia with hypertransfusion caused changes in the proliferative state of the precursors. These results indicate that the serial changes in the number of BFU-E represent migration of BFU-E from marrow to spleen rather than BFU-E proliferation. Marrow CFU-E increased in anemic mice and decreased in polycythemic mice without changes in their proliferative state. It is possible that the target of erythropoietic stimulation in mice may be cells at maturational stages intermediate between BFU-E and CFU-E.


Effect of furosemide on plasma fibrinolytic activity and urokinase excretion.

Plasma fibrinolytic activity, as measured by the fibrin-plate method, is enhanced after a single intravenous administration of 40 mg of furosemide. This effect becomes evident within 30 min and a peak response is attained 6 h after i.v. administration. On successive administration of furosemide, the fibrinolytic effect persists and the second peak becomes manifest again after 6 h. Following the parenteral administration of furosemide there is an initial decrease of urinary urokinase excretion which returns to a normal level after 3 to 6 h. Possible mechanisms which may explain the enhanced fibrinolytic activity after furosemide administration are discussed.


Comparison of the inhibition of avian and mammalian bone alkaline phosphatases by levamisole and compound R8231.

Alkaline phosphatases from mammalian bone are inhibited much more than chick bone alkaline phsophatase by levamisole and compound R8231. Doses of R8231 (10(-4) to 10(-5) M) that almost completely inhibit mammalian alkaline phosphatases do not inhibit the growth of embryonic rat femurs in vitro. R8231 should be an excellent biological probe for the function of alkaline phosphatase in bone metabolism.


Effect of germination on the glycoprotein of mash (Phaseolus mungo) seeds.

The soluble carbohydrates and insolube proteins of Phaseolus mungo seeds decreased considerably up to 96 h of germination, whereas the soluble proteins remained nearly constant. The carbohydrates content of glycoprotein also remained constant. This suggests that a negligible change took place in the glycoprotein during the initial period of mash seed germination.


Enzymic basis for the nutritional requirement of arginine in insects.

The fat body of the cockroach, Blaberus cranifera, and the silkmoth, Hyalophora gloveri, has been tested for some enzymes of the urea cycle. While ornithine transcarbamoylase and argininosuccinase activities could not be detected, arginase is present in the fat body of these insects. These results explain the essentiality of arginine in the diet of insects.


The role of sialic acid in determining the survival of circulating interferon.

Rabbit interferon has been extensively desialytated and its metabolic behaviour has been evaluated in the rabbit. The half-life of asialointerferon is significantly shorter than the native interferon and its urinary excretion becomes negligible. Moreover the rapid uptake of asialointerferon by the isolated and perfused rabbit liver, suggests a hitherto unsuspected catobolic pathway for this glycoprotein.


Fertile diploid drones in africanized honeybees, Apis mellifera adansonii.

59 diploid drones of Apis mellifera adansonii, 12-37 days old, were tested for the presence of semen after provoked ejaculation; 13 drones ejaculated semen enough to be used in an instrumental insemination, but only three on them (5%) furnished 1 mm3 of semen. The problems referring to the attainment of descendants from the 2n drones are briefly discussed.


Spontaneour Robertsonian fusion leading to karyotype variation in the house mouse - first report form Asia.

The occurrence of spontaneous Robertsonian fusion leading to 2n=39 chromosomes (NF=40) in the house mouse (Mus musculus domesticus) has been reported for the first time from Asia. 3 phenotypically normal female mice collected from 2 distantly located populations of India (Tripura and Calcutta) show centric fusion in somatic chromosomes between pairs 2 and 16, and 8 and 14 respectively. C-banding analysis revealed that the (sub)metacentric has been originated by fusion between the broken/eroded centromeres of 2 telocentric chromosomes.


On the location of the tetrapyrrole macrocycle of chlorophyll a in phospholipid vesicles and in hexadecane.

The state of chlorophyll a in phosphatidylcholine vesicles was examined. The results indicate that the chlorophylls are present in monomeric form. A kinetic study of chlorophyll reactions with K2S2O8 and piperidine showed that these substances react with the porphyrin rings of pigments located on both vesicle faces, most probably within the polar headgroup region.


[Methodical investigations concerning the measurement of red cell deformability dependent on plasma viscosity, plasma proteins, hematokrit, filtration pressure as well as osmolarity (author's transl)].

The measurement of red cell deformability (flexibility or fluidity) according to the method of filtration strongly depends on the suspension medium, the hematokrit, filtration pressure as well as osmolarity and is hard to differentiate over the influence of red cell aggregation. Therefore, data concerning the flexibility of red cells have to be established under standardized conditions, e.g. suspension medium, such as albumin, stabilized hematokrit, constant osmolarity and pressure.


Crossing between nondiapausing and diapausing races of Sarcophaga peregrina.

The temperate race (D) of S. peregrina undergoes pupal diapause in response to certain environmental conditions of photoperiod (13L:11D-11L:13D) and temperature (under 20 degrees C). The tropical race (ND) does not do so under the same circumstances. The tendency toward diapause was suppressed 30-40% of the hybrids of crossings D female x ND male and ND female x Dmale even under such short day and low temperature conditions as 11L:13D-9L:15D, 20 DEGREES C. For entering diapause, the hybrids rrequire a shorter day length (13L:11D) than that of (D) parents (15L:9D).


Peroxidase activity in mitochondria of Prototheca moriformis.

Peroxidase activity was investigated by the use of diaminobenzidine method in fixed cells of Prototheca moriformis. A strong peroxidase activity was observed in the mitochondria. DAB staining was unaffected by KCN, aminotriazole and antimycin A, but it was completely inhibitied by methanol-nitroferricyanide.


Benzoyl cyanide in the defensive secretion of polydesmoid millipeds.

A novel cyanogenetic compound benzoyl cyanide, was isolated from the defensive secretion of 3 polydesmoid millipeds (Pseudopolydesmus seratus, Apheloria corrugata and A. trimaculata). The secretion of the 3 species also contains mandelonitrile and benzaldehyde, and that of P. serratus contains mandelonitrile benzoate, benzoic acid, isovaleric acid, myristic acid and stearic acid.


Fungitoxic properties of Rosa chinensis Jacq.

During a systematic survey of higher plants for their fungitoxicity, the flowers of Rosa chinensis Jacq. were found to exhibit strong antifungal properties. On chemical investigation the antifungal priniciple was isolated as a shining, needle-shaped cyrstalline substance. It was identified as gallic acid. It exhibited fungistatic action against as many as 17 fungi at 3% concentration.


Differential effects of disuse preceding denervation on the onset and development of fibrillation in fast and slow muscles.

Section of the sciatic nerve, performed after a week of muscular disuse, is followed by fibrillation earlier in the soleus (S) than in the anterior tibialis (AT) muscle of the rat. The subsequent development of fibrillation, which is different in the control denervated S as compared with the control denervated AT, tends to become similar in the disused-denervated muscles.


Thiamine transport by human intestine in vitro.

Surgical specimens of human gastrointestinal mucosa and mucosa and muscle were incubated in vitro with thiamine-thiazole-214 C. Labelled thiamine uptake was uphill in mucosal tissues and downhill in muscle. Small intestinal mucosa accumulated labelled thiamine in a phosphorylated form, while gastric and colonic mucosa, as well an muscular layers of all gastrointestinal segments studied, did not.


Intensification of amphetamine-induced excitation by methysergide, a serotonergic receptor blocker.

Methysergide, a serotonergic receptor blocker, was studied to determine its effects against d-amphetamine-induced excitation as measured by convulsions elicited by handling in mice. Significant intensification (p less than 0.01) of the action of d-amphetamine was observed in mice. These results indicate that reduction in serotonergic activity in the central nervous system enhances excitation induced by d-amphetamine.


[Repercussions of hyperthyroidism on the total cerebellar DNA contents in the rat at 6 and 35 days of age. Comparative effects of LT3 and DLT4 (author's transl)].

The total cerebellar proteins RNA and DNA contents from DLT4-and LT3-treated rats was studied at 6 and 35 days of age. The effect of injections of 5 microng/j of DLT4 is comparable to that of 25 microng of LT3 at birth, followed by 0.5 microng every 2 days. On the other hand, injection of 0.5 microng of LT3 every 3 days does not induce any significant modification of the total DNA contents in the cerebellum.


Induction of an intestinal epithelial sugar transport system by high blood sugar.

Intravenous infusion of glucose produces a marked increase of the mucosal-to-serosal sugar flux in the isolated everted small intestine of rats. The phenomenon is partially substrate specific, is inhibited by phloretin but not by phlorizin and is completely abolished by cycloheximide. The results suggest that sustained hyperglycemia may stimulate the synthesis of new transport receptors (carriers).


Electrically excitable excitable neurosecretory cell bodies in the periphery of the stick insect, Carausius morosus.

Intracellular recordings have been made from the cell bodies of both neurosecretory and non-neurosecretory multipolar neurons in the periphery of Carausius morosus. The neurosecretory neurons have cell bodies which are electrically excitable and produce overshooting action potentials, whilst the cell bodies of the non-neurosecretory neurons are electrically inexcitable.


[Moulting of insects without moulting gland: reseults with larvae of Periplaneta americana (author's transl)].

The course of moulting of Periplaneta americana larvae of which the prothoracic gland were exstirpated, was investigated in 2 succedding series. It could be proved that all animals underwent 1 or 2 moulting processes inspite of the absence of the moulting gland. These results demonstrate that the generally accepted classical schema of the endocrine control of the insect moulting must be renewed.


On the possible mode of action of neurohormones on cholinesterase activity in the ventral nerve cord of scorpion, Heterometrus fulvipes.

It is shown that Km of ChE is not affected by the neurohormones but Vmax is increased and decreased in presence of acceleratory and inhibitory neurohormones respectively. Hence it is suggested that the neurohormones might modulate the enzyme activity be altering the maximal velocities (Vmax) rather than affecting the enzyme affinity (Km) towards the substrate.


Auditory and visual perception of simultaneous verbal and nonverbal stimuli.

In an auditory experiment, digits and tonal sequences were presented simultaneously to both ears. In a visual experiment, words and nonsense figures had to be compared in both visual half-fields. The verbral stimuli were better reported from the right ear and right visual half-field. The nonverbal stimuli were reported equally well from both ears and visual half-fields. It appears that the processing of stimuli presented to both input channels depends on the type of the stimuli. These results point to a cerebral mechanism classifying incoming information to the brain and yielding an optimal processing of verbal and nonverbal stimuli by the cerebral hemispheres.


Arousal-induced increase of cortical [K+] in unrestrained rats.

Changes of extracellular concentration of brain potassium [K+]e were studied in lightly anesthetized unrestrained rats with ion-selective K+-microelectrodes introduced into the cerebral cortex with a head-mounted microdrive system. Nociceptive stimuli elicited EEG arousal lasting for 47 sec on the averag which was accompained by an increase of [K+]e from 3.0 mM to 3.31 +/- 0.04 mM.


Modification of effects of biologically active peptides, caused by enzyme treatment, on the excitability of identifiable giant neurones of an African giant snail (Achatina fulica Férussac).

Physalaemin, which excites an identifiable mooluscan giant neurone (the TAN, tonically autoactive neurone), lost the effect after the trypsin treatment. Unexpectedly, this peptide shows an inhibitory effect on the same neurone after chymotrypsin treatment. Deamino-dicarba-(d-d-)oxytocin and d-d-Arg-vasotocin, which excite another identifiable neurone (the PON, periodically oscillating neurone) continue to show the effect after chymotrypsin treatment (6 h). But d-d-Arg-vasotocin losts the effect on the PON after trypsin treatment.


Acidic metabolite of prednisolone.

The metabolic fate of the 17beta-ketol side chain of (21-3H) prednisolone was studied with an enzyme preparation from male golden hamster liver. The acidic metabolite of prednisolone was identified by mass spectrometry as 11beta, 17alpha,20epsilon-trihydroxy-3-oxo-1,4-pregnadien-21-oic acid. The enzyme showed substrate specificity, depending on the nature of substituent on the steroid nucleus.


Alpha-and- beta-activity of O-methylated derivatives of norepinephrine and epinephrine.

Metanephrine, iso-metanephrine, normetanephrine and isonormetaephrine were tested for alpha- and beta-activity on various tissues obtained from rats, guinea-pigs and cats. It was found that methylation of the hydroxyl groups of norepinephrine or epinephrine in either the 3- or 4-position markedly reduces or abolishes alpha- and beta-activity with the exception of the nictitating membrane of the cat. This receptor seems to show a tissue difference.


[Metabolism of fluorinated mescallins by Pieris brassicae (Insect, Lepidoptera) (author's transl)].

The action of alpha-fluorinated mescalins on induction of diapause in the cabbage butterfly, Pieris brassicae, has been studied. The introduction of fluorine into mescalin has no influence on this activity. This result suggests solvolysis of fluorine and in vivo formation of a common ethylimine intermediate. Activity decreases, however, with substitution of the nitrogen.


Effect of irradiation on electrophoretic properties of enzymes in haemopoietic cells of opossum.

5-month-old male opossums were exposed to 5000 rads whole body 60Co radiation and sacrificed at 16, 40 and 90 h following irradiation. Stract gel electrophoretic studies of dehydrogenases of lactate, malate, 6-phospho-gluconate and glucose-6-phosphate and alpha-esterases and acid phosphatase were conducted on the homogenates of spleen and bone marrow cells. Expressions of LDH and G6PD were affected by irradiation in bone marrow and spleen cells.


Nitrate fertilizers as environmental pollutants: positive correlation between nitrates (NaNO3 and KNO3) used per unit area and stomach cancer mortality rates.

Since a significant positive correlation between nitrate fertilizer exposure and stomach cancer mortality has been found, a study of nitrate fertilizer pollution in arable land in terms of amount of nitrates used per unit area (kg/ha) and stomach cancer death rates was carried out. The regression of death rates for stomach cancer, standardized for age, on the nitrates used per unit area, by province (N = 25), exhibited a significant association between the 2 variables (p less than 0.004). When industrialized provinceds (N = 3) were not considered, a highly significant association was found (F = 16.47; d.f. = 1, 20; p less than 0.0006). The correlation coefficient was + 0.672.


So-called annular gap junctions in bone cells of normal mice.

Spherical bodies consisting of a granular matrix and a pentalaminar limiting membrane were found in cells from the proximal tibial metaphysis of normal mice. The structures measured about 280-570 min in diameter and were located mainly in the cytoplasm of osteoblasts and occasionally in preosteoblasts. The granules within the bodies resembled ribosomes. The multi-layered composition of the limiting body membrane was identical with that of intercellular gap junctions.


Turnover of 5-hydroxydopamine in adrenergic nerves.

In adrenergic nerve endings of the guinea-pig vas deferens the population of small granular vesicles increases from 19% in control animals to 80-90% 1-3 h after the administration of 5-hydroxydopamine, and gradually declines to control values in 10 days. Large granular vsicles were also loaded but the loss of enhanced granulation was more rapid than in the small granular vesicles.


Erythrocyte 2,3-diphosphoglycerate in anaemic sheep.

Experimental anaemia resulted in an increase of red cell 2,3-DPG from 0.11 micronM/g Hb to 0.99 micronM in haemoglobin A sheep and from 0.21 micronM in haemoglobin B sheep. Production of haemoblobin Cas a result of anaemia was confined to haemoblobin A only. The results, therefore, appear to suggest that the rise in 2,3-DPG in the red blood cells of different haemoblobin types is independent of haemoblobin C.


Sexual and contraceptive experience of young unmarried women in the United States, 1976 and 1971.

The prevalence of sexual activity among never-married U.S. teenage women increased by 30 percent between 1971 and 1976; so that by age 19, 55 percent have had sexual intercourse. The increase, which has occurred at all ages and among all races, has been accompanied by a dramatic increase in the use of contraception, the use of the most effective methods, and the more regular use of all methods. Nevertheless, few teenagers begin use of contraception at the same time that they initiate intercourse--and many wait until after they have experienced pregnancy.


New estimates of mortality associated with fertility control.

Recent data on mortality related to pregnancy and to use of various contraceptive methods show that up to age 30 the risk to life among noncontraceptors from pregnancy and childbirth is far in excess of that experienced by users of any method. After age 30, the mortality risk experienced by pill users who smoke rises dramatically, but among nonsmokers the risk remains relatively low--and is lower than the risk of death among noncontraceptors even after age 40. Safest at all ages is condom or diaphragm backed up by abortion.


Cholinergic compounds. VIII Synthesis and biological activity of epiallo-desethermuscarine.

The synthesis of epiallo-desethermuscarine (I) is reported. Its pharmacological activity has been tested and compared with the other carbocyclic analogs of muscarine and its derivatives.


[New analogs of papaverine: synthesis, pharmacological and conformational study of benzyl-4-isoquinolines substituted in the 1 or 3 position].

The synthesis of p-chlorobenzyl-4-isoquinolines variously substituted in the 1 and 3 positions by condensation in an acid medium of the diethyl acetal of a substituted N-veratrylaminoacetaldehyde with p-chlorobenzaldehyde is described. Pharmacological and conformational tests have been carried in comparison with papaverine and p-chlorobenzyl-4-isoquinoline. The basicities of these derivatives have been measured and compared.


[Synthesis of 1,4-benzodiazepine and 1,5-benzodiazocine through oxidative fission of the double bond of indole derivatives].

A simplified new synthesis of some 5-phenyl-1,4-benzodiazepines and 6-phenyl-1,5-benzodiazocines, in satisfactory yields, by oxidation with sodium periodate of 1-alkylamino-2-methyl-3-phenylindoles, is described.


[Chemical and pharmacological research on pyran derivatives. VII. Derivatives of naphto/1',2':5,6/pyran/2,3-c/pyrazole and of 12H-naphto/1',2':5,6/pyran/2,3-d/pyrimidine].

Reaction of substituted 1-oxo-3-dialkylamino-1H-naphtho[2,1-b]pyrans with N,N-dimethylformamide in the presence of phosphorus oxychloride afforded the corresponding substituted 1-oxo-2-formyl-3-dialkyl-amino-1H-naphtho[2,1-b]pyrans. Condensation of substituted 1-oxo-2-formyl-3-dimethylamino-1H-naphtho[2,1-b]pyrans with hydrazine or monosubstituted hydrazines led to the formation of 11-oxo-8H,11H-naphtho[1',2':5,6]pyrano[2,3-c]pyrazole derivatives through the intermediate hydrazones and subsequent cyclization. Similarly, condensation with acetamidine or guanidine gave rise to the formation of 12-oxo-12H-naphtho[1',2':5,6]pyrano[2,3-d]pyrimidine derivatives. Some of these compounds were tested for their pharmacological properties, but no noteworthy activity was observed.


[N-acylindoline with phytotoxic activity. II].

A series of N-acyl derivatives of indoline (A) was prepared and studied for phytotoxic activity. The substances studied (Tables I and II, substanes I leads to XXXVIII) were mostly new compounds and were prepared from the appropriate indoline by condensation with acid chlorides and isocyanates. The biological tests consisted in pre- and post-emergence treatment in doses of 6 kg/ha or less of six common weeds and for two substances (XVIII, XIX) of other species of agricultural importance (Table III). The results show that N-methylcarbamoyl and N-dimethylcarbamoylindolines in which the indoline nucleus bears a halogen or alkyl substituent are highly active on absorption via the roots of foliage and have a wide spectrum of action. The compounds showing the highest phytotoxic activity in both pre- and post-emergence tests were 5Cl-N-(methylcarbamoyl)indoline (XVIII), 5Cl-N-(dimethylcarbamoyl)indoline (XIX) and 2CH3-N-(methylcarbamoyl) indoline (XXXIII).


Radiopaque contrast media XXXI-Glucoside conjugation of iodophthalein in rabbit.

Report is given on the identification of the metabolites of the iodophthalein sodium (TIP) in rabbit. After i.v. administration two meabolites (S1 and S2) were excreted mostly in the bile, but both were also found in the urine. The TIP glucoronide (S1) is formed in much greater yield than the glucoside (S2). This latter is a further example of glucoside conjugation in mammals.


Factors involved in heavy metal poisoning.

The heavy metals include at least 40 elements but cadmium, lead, and mercury have been most extensively studied. The biological properties of heavy metals are discussed in terms of three important characteristics: the ability to form, irreversibly, complexes and chelates with organic ligands; the properties to form organic-metallic bonds; and the potential to undergo oxidation-reduction reactions. The formation of complexes and chelates within the body is shown to influence greatly the dynamics of transport, distribution, and excretion of several important metal cations. The excretion of uranium is influenced by acid-base balance in the body because uranium forms complexes with bicarbonate anions that are filtered by the kidneys. The biliary excretion of methylmercury depends on the formation of small molecular weight complexes with sulfur-containing amiono acids and the peptides in the liver. The degree of enterohepatic recirculation of a variety of heavy metals appears to depend on the chemical nature of the bilary complexes. The oxidation of elemental to divalent ionic mercury is the crurial step in the retention and tissue deposition of inhaled mercury vapor. That the oxidation process is, at least in part, catalyzed by the enzyme, catalase, explains the effects of ethanol, aminotriazole and the state of acatalasemia on the metabolism of inhaled vapor in man and animals. The formation of covalent bonds between metal cations and the carbon atom usually greatly modifies the biological properties of the metal. Methylarsenic and methylmercury compounds both differ from the inorganic forms in accumulation in animals.


Regulation of drug metabolism in man by environmental chemicals and diet.

Studies in animals have shown that many environmental pollutants induce the synthesis or inhibit the activity of microsomal mixed-function oxygenases that metabolize drugs, carcinogens and normal body constituents such as steroid hormones. These effects on microsomal enzyme activity alter the duration and intensity of action of foreign and endogenous chemicals in animals, and such effects on metabolism may influence the carcinogenicity of some pollutants in man. Studies on the effects of environmental chemicals on drug metabolism in man are sparse. Exposure of humans to DDT or lindane in a pesticide factory results in an enhanced rate of metabolism of antipyrine and phenylbutazone and an increased urinary excretion of 6-beta-hydroxycortisol. Polycyclic aromatic hydrocarbons present in cigarette smoke, in charcoal-broiled meats, and in polluted city air are potent inducers of drug-metabolizing enzymes in animals. In humans, cigarette smoking stimulates the activity of placental enzymes that metabolize several drugs and carcinogens. In addition, cigarette smokers metabolize phenacetin, theophylline, and other drugs more rapidly in vivo than nonsmokers. Dietary factors are important in the regulation of drug metabolism in animals and man. Feeding rats brussels sprouts or cabbage stimulates the intestinal and hepatic metabolism of drugs in animals. This effect is caused, at least in part, by certain indoles normally present in these vegetables. The feeding of a charcoal-broiled beef diet to rats stimulates the metabolism of phenacetin in vitro, and a similar diet stimulates the in vivo metabolism of phenacetin in man. It is likely that polycyclic aromatic hydrocarbons are the major inducers in charcoal-broiled beef.


Responses to the thermal environment.

Human responses to the thermal environment and to internal heat production serve to maintain a narrow range of internal body temperatures of 36-38 C. There are two categories of responses: voluntary or behavioral responses, and involuntary or physiological autonomic responses. Voluntary or behavioral responses consist generally of avoidance or reduction of thermal stress by modification of the body's immediate environment by modification of clothing insulation or by comfort conditioning of his microenvironment. Physiological responses consist of peripheral vasoconstriction to reduce the body's thermal conductance and increased heat production by involuntary shivering in the cold, and peripheral vasodilation to increase thermal conductance and secretion of sweat for evaporative cooling in hot environments. Autonomic responses are proportional to changes in internal and mean skin temperatures. Repeated exposures to heat, humidity, and exercise will modify the physiological response mechanisms by acclimation to produce more effective responses. Physiological responses also depend on the point in a diurnal cycle, on physical fitness, and on the sex of the individual. Behavioral responses rely on thermal sensations and thermal discomfort. Thermal discomfort appears to be closely related to the level of autonomic responses so that warm discomfort is closely correlated with skin wettedness, and cold discomfort similarly relates to cold extremities and shivering activity.


Nutrition and the responses to extreme environments.

The calorie requirements of adequately clothed men living and working in a cold environment are not increased, except for the 2-5 percent increase in matabolic rate due to the "hobbling" effect of the heavy clothing. The energy requirements in the cold, as in a temperate environment, are primarily a function of body weight and level of physical activity. The discrepancies between studies of persons living in a hot environment are explainable and are primarily due to the level of protection from the heat. The increased requirements are probably due to the increased heat load imposed on the body by solar radiation and the extreme heat. The increased requirements, in all likelihood, are a combination of increased action by blood in heat transport, increased ventilation and heart rate, and increased action of the sweat glands plus the increase in metabolic rate due partially to elevation in body temperature. In view of some strong new evidence, the energy requirements are increased for individuals living and working in extremely hot environments. There is no evidence showing that modification of macro nutrient composition of the diet will enhance either heat tolerance or cold adaptation in humans. Recent studies indicate that high carbohydrate diets will improve tolerance during high altitude exposure.


Nutrition and responses to zero gravity.

Prior to the Mercury program, extensive efforts were undertaken to find ways of minimizing the mass of in-flight food systems. Such efforts were directed to the use of dehydrated, energy-dense foodstuffs and to the possibilities of nutrient recyclization. As the space program became a reality, nutritional scientists were more concerned with the mechanics of food consumption in weightless flight and with the problems of structuring convention foods in a way that would facilitate their use in weightlessness. It soon became clear that there was no substantial impediment to normal gastrointestinal function in flight, and attention was shifted to more subtle metabolic phenomenons. It became apparent that slight changes occurred in skeletal density, muscle mass, and overall body composition. Recognition of these changes led to extensive ground-based simulation studies and carefully designed in-flight experiments. Data are presented on the requirements for metabolic energy in flight and on the losses that have been observed in the major elemental constituents of the body. It is concluded that convincing evidence is not yet avialable on the ability of man to adapt to long-term weightless flight. Although his nutritional requirements are qualitatively similar during flight, the sophisticated manipulation of nutrient profiles shows promise of counteracting some of the deteriorative processes that are known to occur.


Modification by fiber of toxic dietary effects.

There is evidence that type of diet may affect the course of chemical carcinogenesis. In experiments with acetylaminofluorene, rats maintained on stock diet exhibit fewer tumors than do rats fed semi-purified diets. Rats fed stock diet augmented with high levels of sodium cyclamate (2.5-10%), amaranth (5%) or Tween (15%) showed normal weight gain, whereas addition of these toxicants to a fiber-free basal diet caused severely restricted weight gain and decreased survival. The latter effect can be overcome by addition of 10% pectin, alfalfa or cellulose to the basal diet. On the other hand, mice fed a fiber-free diet survived pneumococcal infection better than did mice fed modified stock diets. The mechanism(s) by which fiber affects carcinogenicity or toxicity are unelucidated. The effect of fiber and other aspects of diet on drug action is an area of research that should be developed.


Some effects of nitrogen dioxide on the lung.

Nitrogen dioxide (NO2) when inhaled in different concentrations and for varying times produces pulmonary injuries which are dependent on the anatomic site in the lung and the duration of exposure. Single exposures to high concentrations of NO2 for 5-6 hr produce an intense cellular proliferation which regresses within 48 hr in all lung regions except the terminal respiratory bronchiole region and the alveoli where the proliferation persists for 4-7 days. This same delayed response is also observed in more chronic exposures. Histologically, the lesion in the terminal and respiratory bronchioles may resemble an obliterative bronchiolitis, but the lesion clears if further exposure is terminated. Prolonged exposure to 2 ppm NO2, 20-22 hr per day for 7 days per wk, produces an increase in total pulmonary upstream resistance in animals killed immediately after exposure; this resistence returns to normal values within 3 mo after removal from exposure. The internal surface area (ISA) is decreased after 12 mo exposure to NO2, but this loss of surface progresses during the recovery period in air, suggesting an autonomous progression of the tissue destructive process. Exposure to 3.64 ppm NO2 with and without fly ash for periods of 12-14 mo causes no increase in pulmonary resistance and no alteration in lung surface. Lung phospholipids and protein synthesis appear to be depressed following exposure to NO2. Lecithin is significantly increased. The synthesis of proteases by alveolar macrophages is increased during NO2 exposure. Pigmented alveolar macrophages present in animals exposed to NO2 simulate those found in human lungs of young cigarette smokers in the terminal and respiratory bronchioles. The mechanism of tissue injury by oxidants such as NO2 may involve free radical formation, and peroxidation of lipids or proteins.


Allergic responses to airborne allergens and insect venoms.

Exposure to environmental allergens leads to human sensitization and disease by two different routes: inhalation (i.e., pollen allergy) and parenteral administration (i.e., insect sting anaphylaxis). In both, the pathogenesis of disease involves specific IgE antibodies and mediator release from mast cells and basophils. The relevant allergens have been characterized and found to be proteins with a molecular mass that ranges from 15,000 to 40,000 daltons. Appropriate diagnostic methods, skin testing, basophil histamine release and IgE antibody measurements (RAST), have been developed. Appropriate immunotherapy (immunization with the relevant allergens) leads to an increase in IgG (blocking) antibody. This therapy has proved to be useful in inhalational allergy and is potentially curative in parenterally induced anaphylaxis.


Urticaria, angioedema, and mediator release in humans in response to physical environmental stimuli.

The activation of mast cells by immunologic or physical stimuli leads to the generation of unstored intermediates (mediators) such as slow reacting substance of anaphylaxis (SRS-A) and platelet activating factor (PAF), and to their release along with performed mediators, histamine, eosinophil chemotactic factor of anaphylaxis (ECF-A), and neutrophil chemotactic factor (NCE), and macromolecular heparin. The internal regulation of mast cell-dependent phenomenons occurs at at least four levels: 1) the intensity and nature of the activating stimulus, 2) the regulation of mediator generation and release of cellular levels of the cyclic nucleotides, 3) the capacity of target cells to bind and respond to primary mediators, and 4) the rate at which mediators undergo biodegradation. Inasmuch as the mast cell is present at cutaneous and mucosal surfaces about venules, it seems likely that the initial or humoral phase of its response achieves an influx of plasms proteins, such as immunoglobulins and complement components, whereas the subsequent cellular phase augments local host defense through the entrance of neutrophils and eosinophils that terminate the humoral phase. The activation of mast cells is considered herein in terms of defined physical stimuli that are characterized by urticaria and angioedema.


Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes.

The lymphocyte response to phytohemagglutinin (PHA) as measured by [13H]thymidine incorporation is equally inhibited by 10(-5) to 10(-4) M concentrations of delta8, and delta9-tetrahydrocannabinol (THC), their 11-hydroxymetabolites, cannabidiol, cannabinol, cannabichromene, cannabicyclol. A similar inhibiting effect is produced by olivetol, which has the structure of the C ring common to all of these cannabinoids and their metabolites that accumulate in tissues. THC inhibits intracellular and intramolecular incorporation of thymidine, uridine, and leucine. This inhibition can be observed within 15 min after addition of THC to the culture medium. The cytotoxicity of THC is a function of the concentration of serum in the culture medium. The higher the concentration of serum, the more the cells are protected against the toxicity of THC. The cytotoxicity of THC is reversible by washing, after the cells have been incubated for 24 hr with the drug. Lymphocytes incubated with THC or olivetol present a significantly larger number of hypodiploid cells and a significant increase in segregational errors of chromosomes. The inhibitory effect of THC on macromolecular synthesis might be mediated by an alteration of the plasma membrane by the drug.


Intrauterine contraception in diabetic women.

The results of intrauterine contraception using four different types of Antigen devices in 118 insulin-treated diabetic women are reported. The patients were followed for a total of 24 months. Cumulative closure rates for the 1st year were as follows: pregnancy, 3.5; expulsion, 13.1; removal for bleeding and/or pain, 7.9; and planned pregnancy, 1.2, giving a continuation rate of 74.3. Cumulative closure rates after 24 months were as follows: pregnancy, 6.5; expulsion, 14.4; removal for bleeding and/or pain, 17.1; and planned pregnancy, 8.3, giving a continuation rate of 56.7. These results are not significantly different from those found by us in nondiabetic women, No serious side effects occurred, in particular no pelvic inflammations or perforations. Intrauterine contraception using the Antigon appears to be a well-suited method for diabetic women.


Accuracy of endometrial biopsy dating in relation to the midcycle luteinizing hormone peak.

The accuracy of endometrial biopsy dating was evaluated in a selected group of apparently normal women in whom the basal body temperature (BBT), the onset of subsequent menstruation, the midcycle luteinizing hormone (LH) peak, and the 17beta-estradiol peak were determined. Forty-two women with regular cycles, normal ovaries at laparoscopy, and luteal phases of 12 to 15 days were studied. In group I (n=20), the infertility could be explained satisfactorily by either tubal occlusion or infertility of the husband, while in group II (n=22) no explanation was found for the infertility. In group I the duration of the luteal phase, defined as the interval between the LH peak and the onset of subsequent menstruation, was 13.4+/-0.7 days. The plasma 17beta-estradiol concentration declined (P less than 0.01) on the day of the LH peak in both groups of women, while the first significant rise (P less than 0.05) in BBT occurred in groups I and II, respectively, 1 and 2 days following the LH peak. Dating of the endometrial biopsy correlated with the LH peak with standard deviations of 1.2 and 1.3 days, respectively, in groups I and II. It is suggested that, in women with a progressive rise in BBT over several days, the localization of the LH peak can be helpful for correct interpretation of the endometrial biopsy.


Absence of circulating HL-A lymphocytotoxic antibodies in men 21 to 44 months after vasectomy.

Nineteen vasectomized men were followed for 21 to 42 months after surgery, and their sera were tested for the presence of HL-A lymphocytoxic antibodies. In a previous study, the sera of two of these men had shown a definite increase in serum reactivity 6 to 12 months after surgery. Only one of the nineteen tested in the study demonstrated, a single, weakly positive, reaction 24 months after surgery. It was considered that the initial stimulus for lymphocytotoxic antibody production was related to surgery. There was no evidence of antibody stimulation 21 to 44 months postoperatively.


The immunologic effects of husband's semen on donor spermatozoa during mixed insemination.

Artificial insemination was performed on four women with the husband's and donor's semen mixed. No pregnancies resulted after several inseminations. One woman also received artificial donor insemination without success. Seminal plasmas from the husbands were allowed to react with donor semen and were observed to produce immobilization and agglutination of the donor's spermatozoa. Two of the husbands' seminal plasmas had high levels of immunoglobulin A, and all contained complements C-3 and C-4, which suggests that the mechanism is immunologic. Artificial donor inseminations were performed, and in addition the couples were advised to refrain from sexual intercourse for 2 days prior to insemination, in order to eliminate the risk of husband's seminal plasma being on the wife's cervix. Within 1 month, three of the four women became pregnant. As a practical measure, it is proposed that the effect of husband's semen on donor spermatozoa be determined prior to performing mixed inseminations and that couples refrin from sexual intercourse for 2 days prior to donor inseminations.


Effect of metal ions on the binding of 17beta-estradiol to human endometrial cytosol.

The influence of zinc and other metal ions on the binding of 3H-17beta-estradiol to human endometrial cytosol was studied. Zn2+ began to interfere with estrogen binding when its concentration in the cytosol exceeded 50 micronM. At a concentration of 5 mM, all of the specific binding of 17beta-estradiol, including more than 50% of the nonspecific binding of the hormone, was destroyed. Analysis of the binding data revealed that one possible site of action of the cations on the binding protein might be the sulfhydryl group(s) of the 17beta-estradiol binding site. The inhibition of 17beta-estradiol binding brought about by Zn2+ was partially abolished by dithiothreitol. Among the metal ions tested, Cu2+ was found to be the most potent inhibitor, followed by Cd2+, Zn2+, and Pb2+. At 1 mM, Mn2+, Ba2+, Ca2+, and Mg2+ had little effect, but at 5 mM, their inhibitory action became more appreciable. K+ and Na+ had no effect on 17beta-estradiol binding. The stimulatory effect of 5 mM Zn2+, Ca2+, Mg2+, and K+ on the binding of 3H-17beta-estradiol to a macromolecular fraction from bovine endometrium was not observed in human endometrial cytosol.


Studies on the effects of pharmacologic doses of cortisone acetate and several nonsteroidal anti-inflammatory compounds on ovo-implantation, early pregnancy, and the deciduomal response in the rat.

Cortisone acetate (10 mg/day), alone or in combination with progesterone (4 mg/day); progesterone (4 mg/day); progesterone (4 mg/day) plus estrone (1 microng/day); indomethacin (0.75 mg/day); phenylbutazone (20 mg/day); flufenamic acid (10 mg/day); and Compound 83161 (tetrazolo less than 1,5-alpha greater than s-triazolo less than 3,4-c greater than quinoxoline) (8 mg/day and 12 mg/day) were each given to intact rats during early pregnancy (days 1 and/or 2 through day 8). Only cortisone acetate treatment caused a true delay in ovo-implantation. Both progesterone treatment beginning on day 1 and cortisone acetate treatment beginning on day 1 or 2 caused an increased postimplantation fetal death rate. Compound 83161, at doses causing signs of general toxicity (12 mg/day), caused a marginal inhibition of implantation. Treatment with indomethacin, phenylbutazone, or flufenamic acid caused some inhibition of the traumatic deciduomal response in spayed rats treated with progesterone, while treatment with cortisone acetate and Compound 83161 did not.


Further studies of inhibitors of in vitro mammalian oocyte maturation.

Studies of luteinizing hormone (LH)-mediated serum inhibition and of follicular fluid and granulosa cell inhibition of in vitro porcine, ewe, and cow oocyte meiotic maturation have been carried out. A porcine serum inhibitor or inhibitors with a molecular weight above 15,000, similar to the ewe and cow serum inhibitor(s), have been demonstrated. An LH-inactivated inhibitor or inhibitors in fluid from medium-sized ewe and cow follicles have been shown and a minimally effective porcine follicular fluid inhibitor has been confirmed. The estimated molecular weight of these inhibitors is below 1,000. Granulosa cells from the three species were not found to be dramatically inhibitory. It is postulated that the follicular fluid inhibitor(s) may be derived from the larger serum molecule(s) by an action of LH within an intermediate cell type.


Effect of calf thymus histone and its fractions F2 and F3 on human lymphocyte stimulation by phytohaemagglutin.

The effect of exogenous calf thymus histone and its fractions F2 and F3 on blastic transformation of human lymphocytes stimulated by phytohaemagglutinin was investigated. It was found that histones can not only inhibit, but also potentiate phytohaemagglutinin-induced blastic transformation of lymphocytes. This effect depends on the amount of histones in the medium and most probably also on individual sensitivity of lymphocytes. The arginine-rich histone fraction (F3) displayed the greatest inhibitory effect on lymphocyte stimulation.


Absorption and metabolism of fructose in the small intestine of conventional and germ-free piglets in vitro.

The aerobic uptake and metabolism of D-fructose in the rings of the small intestine of conventional and germ-free piglets during development was studied. No accumulation of fructose in the intracellular water against its concentration gradient was found. In both groups of animals the intracellular concentration of fructose decreases with increasing age, being highest in the newborn intestine and the sharptest decrease being observed on the first two days of post-natal life. Lactic acid was found to be the main metabolic product of fructose; a considerable amount of it was formed also from endogenous sources of the small intestine. In the newborn piglet fructose does not affect the formation of lactic acid, on the first two days after birth this effect of fructose is already apparent and more pronounced in germ-free piglets than in conventional ones. Conventional and germ-free animals differ markedly in endogenous lactic acid production. While in the former with increasing age endogenous lactate formation decreases, in the latter it rises after a sharp drop on the first post-natal day.


Neuropsychic factors in physical urticaria.

Psychosomatic investigations were made in 18 patients with dermographism, 17 with cold urticaria, and 13 with cholinergic urticaria, and 13 with cholinergic urticaria. The Maudsley Personality Inventory was used and electroencephalograms were recorded from most patients. In the majority of cases of dermographism first symptoms coincided with frustrating situations and psychic stress-intensified manifestations. 81.8% of the patients with dermographism had abnormal electroencephalograms. In cold urticaria the role of psychic factors could not be demonstrated, whereas in cholinergic urticaria 'brief' emotions provoked symptoms in three-quarters of the patients, although no other signs of the role of psychic factors were detected,


Psoriasis: case rate--HL-A antigen frequency correlations.

HL-A antigen B17, associated with a high familial frequency of psoriasis, is significantly correlated (r=0.8242) with psoriasis case rates in several countries but HL-A antigen B13 alone, associated with 'early age onset' cases of psoriasis, is not significantly correlated (r=0.4299) with case rate. A sum of the B13 and B17 antigen frequencies, since either antigen has been associated to psoriasis, is correlated with case rate in the populations surveyed (r=0.7405) and is statistically significant.


Erythema multiforme in association with active ulcerative colitis and Crohn's disease.

Erythema multiforme of vesiculo-bullous type is described in one patient at the onset of ulcerative colitis and in another during an exacerbation of Crohn's disease. Inflammatory large bowel disease should be once more accepted as a cause of erythema multiforme in its own right, presumably mediated through an immunological reaction.


'Atypical' blue nevus--a benign variant of cellular blue nevus. Presentation of three cases.

Three cases of 'atypical' blue nevus presented almost identical histological findings differing from both benign cellular blue nevus and malignant blue nevus or malignant melanoma, and suggesting malignancy. Long-term follow-up--in one case 19 years--indicates that this pigmented tumor is a benign variant of blue nevus.


Congenital ichthyosis and medulloblastoma.

Occurrence of ichthyosis and malignancy together is unusual. An 18-year-old patient suffering from congenital ichthyosis was found to have a medulloblastoma of cerebellum. A short review of the literature of cases of tumors with ichthyosis, and neurological syndromes with ichthyosis is presented.


Effect of ultraviolet light therapy, given over a period of several weeks, on the amount and composition of the skin surface lipids.

Ultraviolet (UV) light therapy was given over a period of several weeks to 19 test persons on one side of the back. The duration of the treatment was gradually increased from 30 sec to 7 min. After conclusion of the treatment quantitative lipid determination was made on both the treated and the untreated sides of the back, using the direct extraction method and the paper absorption method. The lipids obtained in this way were analysed by thin-layer chromatography. The following were the most important results: (1) The amount of skin surface lipids was significantly increased by UV irradiation. This results goth from an increase in the epidermal lipids as well as in the lipids of the sebaceous blands. (2) The percentage of free cholesterol in the skin surface lipids was significantly increased by UV irradiation. This increase is probably connected with a thickening of the stratum corneum. (3) The percentage of free fatty acids in the skin surface lipids is significantly increased by UV therapy. This shows that the living conditions of the saprophyte skin flora, which set free lipases, are improved as a result of this treatment or that this treatment leads to an increase of the activity of the bacterial lipases in the excretory ducts of the sebaceous glands.