Acute hemodynamic alterations after aortic valve replacement with the glutaraldehyde-treated porcine heterograft prosthesis.

Twenty-two patients underwent aortic valve replacement for acquired valvular heart disease with the porcine heterograft prosthesis. In the immediate postoperative period, a transient decrease in the cardiac index (CI) (preoperative 3.0 +/- 0.14 to 2.45 +/- 0.16 L. per minute per square meter, p less than 0.05) and an increase in the systemic vascular resistance (SVR) (preoperative 1,078 +/- 62 to 1,287 +/- 103) dynes/sec./cm.-5, p greater 0.05) were seen; these values returned to preoperative levels by the first postoperative day. After valve replacement, an elevation in the heart rate (HR) (preoperative 75 +/- 2 to 87 +/- 4 beats per minute, p less than 0.05) and a reduction in the stroke volume (SV) and stroke work index (SWI) (preoperative 35 +/- 2 to 26 +/- 2 Gm.-M. per square meter, p less than 0.05) occurred which persisted throughout the study. The endocardial viability ration (EVR) increased after valve replacement. These findings suggest that, following aortic valve replacement, (1) an increase HR is the mechanism utilized to maintain cardiac output, (2) subendocardial perfusion is enhanced as indicated by an increase in the EVR, and (3) the hemodynamic alterations following insertion of the porcine heterograft prosthesis are not different from those observed when other valves are placed in similar patient populations.


Filter paper disk techniques for assay of nucleotidase.

A DE filter disk technique for assaying the activity of nucleotidase is described. This method is based on the observation that nucleotides bind to the filters at 5 mM Tris-HCl (pH 7.8) while nucleosides do not. As parameter for the nucleotidase activity the decrease of bound nucleotides is determined. In parallel experiments the amount of the product (nucleoside) formed can be measured by DEAE Sephadex column chromatography. The filter disk technique can be applied for the determination of vmax and Km of a nucleotidase by using different ribonucleosidase monophosphate substrates.


Immunochemical assay for information in cytoplasmic polysomes.

Only very small amounts of informatin could be detected in cytoplasmic polysomes with the aid of antiinformatin antibodies. This low amount of informatin cannot represent a structural component of polysomes or polysomal mRNP.


[Vaginal reflux during miction-cystourethrography in girls (author's transl)].

The cases of 57 girls with reflux of radioopaque iodin solution into the vagina during mictioncystourethrography are reported. In 52.6% (30 cases) no signs of anomalies of the urinary tract or of pyelonephritis were found. For this group of 30 girls pyuria (leucocyturia) was typical (in 86.6%). In contrast, a urinarty-tract infection was found only in a few cases (16.6%). The authors discuss the clinical importance of vaginal reflux and its role in the pathogenesis of urinary-tract infections.


Induced abortion and subsequent outcome of pregnancy in a series of American women.

We studied the effect of induced abortion on outcome of subsequent pregnancy in a sample of 4896 parturients in Seattle, Washington, from July, 1972, through June, 1976. We used a matched-pair analysis for 571 women with histories of prior abortions. In addition to analyses involving all women with histories of induced abortions, separate analyses were done for 97 black women and 277 primiparas. Histories of prior induced abortions were not related to low birth weight, premature delivery, stillbirth, neonatal death, miscarriage or congenital malformations in subsequent pregnancies. The termination procedure and weeks of gestation at time of termination were not related to the later occurrence of low birth weight or premature delivery.


The effect of osmotic pressure and salinity of the medium on the growth and sporulation of Aspergillus niger and Paecilomyces lilacinum species.

The effect of osmotic pressure and salinity on the production of conidia and growth of Aspergillus niger and Paecilomyces lilacinum, isolated from the soil, have been studied in this investigation. The maximum production of conidia in both species was observed in the nutrient medium containing 1% NaCl wheras maximum growth was recorded in the nutrient medium containing 3% NaCl. It has been thus observed that the salinity and the osmotic pressure related to it effect the reproductive as well as the vegetative development of both species, and these effects have been observed to be different. The sensitivity of both fungal species to the salt was also investigated. Conidia were not observed in the P. lilacinum species grown in nutrient medium with 5% NaCl whereas conidial development did take place in the case of Aspergillus niger grown in the nutrient medium containing 5% NaCl.


[Different behavior of 22 strains of Emmonsia Cifferi and Montemartini 1959, a monilial fungus, in the lungs of laboratory mice in comparison with their parasitic morphology in vitro].

The 22 strains of Emmonsia Ciferri & Montemartini 1959, inoculated intranasally to laboratory mice are not equally virulent. One month after the inoculation, 15 of the strains had produced adiaspores 120 t9 190 micrometer in diameter in the lung. Another strain produced adiaspores measuring 44 micrometer and 2 others measuring 20 micrometer or 10 micrometer. The remaining 4 strains did not develop in the lung tissue. Four thermophilic strains, which in vitro have adiaspores measuring 8 to 15 micrometer, had adiaspores reaching 120-180 micrometer in vivo. Neither budding nor endosporulation could be observed in any adiaspore.


[Familial multiple hemangioblastomas--report of two cases in a family (author's transl)].

The authors reported their experience with two cases in a kindred with multiple hemangioblastomas in the cerebellum, brain stem, and spinal cord associated with von Hippel's disease, von Recklinghausen's disease and some visceral changes. (The members of this kindred died of similar disease.) Two patients, a 42-year-old man and his 14-year-old niece, showed various neurological signs involving central nervous system. Furthermore the man had some café-au-lait spots in the skin, a papillomatous tumors in the tongue and a vascular tumor in the right kidney. Both also had von Hippel's disease. Neuroradiological study and operations demonstrated multiple hemangioblastomas in the cerebellum, medulla oblongata and the spinal cord in association with abnormal enlargements of the medulla and the spinal cord which suggested coexistence of the parenchymatous tumor, probably glioma, in them. All hemangioblastomas in the cerebellum of both patients were removed. The literature of the familial multiple hemangioblastomas was reviewed and the coexistence of Lindau's disease, von Recklinghausen's disease and glioma was discussed.


[Aortic subvalvular stenosis].

Six cases of supravalvular aortic stenosis with other abnormalities are presented. Their causes, anatomical, pathological, and clinical aspects are discussed and reference is made to the excellent results of treatment.


Metabolic consequences of alcohol consumption.

The metabolic effects of alcohol are closely related to organic as well as societal aspects of alcoholism. Individual differences in the biologic sensitivity to ethanol are thought to represent important features underlying these afflictions. The results of recent biomedical research provide evidence for a biochemical individuality with respect to the enzymes involved in alcohol metabolism. Human liver alcohol dehydrogenase, the principle ethanol oxidizing enzyme in man, exists in multiple molecular forms (isoenzymes). In addition, a genetic polymorphism ('atypical' variant) is observed. Large racial differences are found for the prevalence of the variant enzyme, which is characterized by a high specific activity. Possible relationships of the individual isoenzyme pattern of alcohol dehydrogenase and of other alcohol metabolizing enzymes to the nature and extent of metabolic effects of ethanol are discussed.


Some biochemical aspects of chronic alcohol intoxication.

Pathways of ethanol transformation and its respective metabolic disorders in the cell have been considered. One should note the role of acetaldehyde in the ethanol toxic effect. Acetaldehyde produces a significant effect upon the metabolism of biogenic amines in brain tissue. Chronic alcohol intoxication at a certain stage is connected with a considerable reduction in the ratio of alcohol dehydrogenase:acetaldehyde dehydrogenase (this ratio determines the severity of clinical signs in intoxication). The inhibition of acetaldehyde dehydrogenase activity is an enzymological base of hallucinations and delirium tremens. The importance of the protective role of nutrition at chronic alcohol intoxication is shown.


5alpha-Reductase as a target enzyme for anti-prostatic drugs in organ culture.

Short-term organ culture of rat and human prostatic tissues has been utilized as a means of testing drlgs potentially useful in cancer of the prostate. Optimal conditions, particularly the concentration of T, have been established for organ culture of such tissues and the effects of various drugs on 5alpha-reductase activity (5alpha-RA) have been utilized as a means of ascertaining antiprostatic actions of the various compounds and drugs tested. Thus, it was shown that estracyt, estradiol-17beta, progesterone, and novel steroids and steroid-conjugates have definite effects on 5alpha-RA in this system.


Effect of expansion of extracellular fluid volume on the maximal reabsorptive capacity for inorganic phosphate in parathyroidectomized and intact rats.

Clearance studies were performed in order to examine the effect of expansion of extracellular fluid volume (ECFV) on the maximal reabsorptive capacity for inorganic phosphate (TmPi) in acutely parathyroidectomized (PTX) and intact rats. TmPi values were obtained in both control and volume expansion. In PTX rats, the TmPi values in control and expansion were 8.25 +/- 1.52 and 6.14 +/- 1.02 micronmol/min (mean values +/- S.D.), respectively; the TmPi/GFR values were 2.96 +/- 0.31 and 2.09 +/- 0.30 micronmol/ml, respectively. In intact rats, the TmPi values in control and expansion were 3.56 +/- 0.94 and 2.98 +/- 0.94 micronmol/min, respectively, and the TmPi/GFR values were 1.34 +/- 0.23 and 1.05 +/- 0.23 micronmol/ml, respectively. From these results it is concluded that expansion of ECFV decreases the TmPi values both in the absence and presence of parathyroid hormone.


Hyperosmolality and pancreatic blood flow.

In the cat pancreas, close intra-arterial infusions of hypertonic xylose, glucose and sucrose solutions caused a marked vasodilatation but no secretion. The magnitude of the vasodilator response correlated with the degree of induced glandular hyperosmolality but not with the substance per se. Stimulation of the vagus nerve as well as infusion of secretin and/or CCK evoked a pronounced secretion and a small to moderate increase in pancreatic blood flow, but did not significantly change the plasma osmolality in the venous effluent from the gland. Bradykinin, papaverine and isoprenaline caused large increments of pancreatic blood flow; none of these drugs evoked secretion nor did they change the venous osmolality. It is concluded that blood-bone hyperosmolality is a strong stimulus for pancreatic vasodilatation, but the functional hyperaemia of this gland is due to factors other than regional tissue hyperosmolality.


The placental transfer of lactate and bicarbonate in the guinea-pig.

In order to study the lactic acid transfer in a hemochorial placenta, the placenta of the guinea-pig was perfused in situ through the umbilical circulation with a colloidal solution containing L(+)-lactate and bicarbonate in various concentrations. It was found that the transfer rates of lactate and bicarbonate were proportional to the respective materno-fetal arterial concentration differences. When the concentration gradients for lactate and bicarbonate were opposite to each other, an exchange of lactate for bicarbonate occurred which is equivalent to a lactic acid transfer. The placental permeability for lactate was found to be 25 micronmol(h - micronmol/ml) per g of placental weight (S.E. = 2). A similar value was obtained for bicarbonate (23 micronmol/(h - micronmol/ml) per g; S.E. = 1.3). It is calculated that fetal concentrations of lactate and bicarbonate follow maternal concentration changes with a half time of 23 min.


The early phase of experimental acute renal failure. I. Intratubular pressure and obstruction.

Tubular obstruction in acute renal failure, postulated to cause the restricted excretory function, is suggested by raising intratubular pressure, to lower effective filtration pressure and diminish urine output. To examine the applicability of the obstruction hypothesis to the pathogenesis of experimental acute renal failure, proximal intratubular pressure and renal function were measured after renal insults of different origins and severity. Obstruction in acute renal failure kidneys should manifest itself as an increase in intratubular pressure for a least 12 h, for within this time period following ureteral occlusion, elevated pressures were found to reflect obstruction. The consistent existence of raised proximal intratubular pressure in acute renal failure kidneys could not be detected; ischaemic and nephrototoxic models were found in which no rise in intratubular pressure could be demonstrated. The oliguric nature of acute renal failure kidneys could not be verified; ischaemic and nephrotoxic models were found in which urine output was either normal or enhanced. Only for methaemoglobin induced renal failure were raised intratubular pressure, oliguria and casts concurrent. It is concluded that obstruction is not a consistent feature of experimental acute renal failure and that the obstruction hypothesis may be specifically applicable to only a few models, which include haeme pigment and folic acid induced renal failure.


Effect of extracellular K+ concentration on resting potential, caerulein-induced depolarization and amylase release from mouse pancreatic acinar cells.

Acinar cell membrane potentials and amylase release were measured from in vitro preparations of mouse pancreas. The effect of a 10-fold increase of the extracellular K+ concentration (to 47 mM) was studied on the resting membrane potential and amylase release as well as on the membrane depolarization and amylase release induced by the cholecystokinin-pancreozymin analogue, caerulein. In the presence of atropine (to exclude the effect of a possible release of endogenous acetylcholine), the increased K+ concentrations depolarized the cells from -45 to -20 mV without influencing the rate of the unstimulated release of amylase. Under these conditions, the depolarizing effect of caerulein was almost abolished, while the caerulein-induced amylase was not. It is concluded that caerulein-induced enzyme secretion from pancreatic acinar cells is independent of the level of the membrane potential as well as extracellular K+ concentration in the range from 4.7--47 mM.


The intensity-dependent changes of the visual evoked responses in man to patterned and blank stimulation.

The visual evoked responses (VERs) to blank and checkerboard-patterned stimuli of 6 degrees angular subtense were recorded referentially (OZ--A2) in 10 dark-adapted subjects using a range of 5.27 log units of intensity (maximum luminance = 6420 cd/m2). The mean peak latencies of the prominent positive-negative deflection of the VERs to the blank stimuli exhibit an exponential shortening with the rise of log stimulation intensity. The peak latencies of the positive-negative deflection of the VERs to the checkerboard-pattern stimulation at low and moderate intensities are by about 50 ms shorter, with the latency of the negative peak of the response to the patterned stimulation corresponding to the positive peak latency of the response to the blank stimuli. Accordingly, the VERs to both types of stimulation are of opposite polarity. With a further increase of the stimulation intensity, the latency of the negative peak of the VER to patterned stimulation gradually lengthens due to the glaring effects of the patterned stimuli. Therefore, at high stimulation intensities the VERs to both types of stimuli are of the same polarity. The mean peak-to-peak amplitudes of the VERs to both types of stimulation differ significantly at high-intensity end of the photostimulation range only, the amplitude of the VER to the patterned stimulation being higher.


[Bernard-Soulier syndrome from the clinical description (1948) to the molecular era (1977) (author's transl)].

Bernard-Soulier syndrome is a constitutional thrombopathy with  an impaired platelet adhesion to the vessel wall. Since the first description in 1948 many works had been reported, and recently a molecular abnormality of the platelet membrane was shown. Interactions between specific membrane sites and platelet functions are now proposed.


[Modification of patients positions in operation table during regional anaesthesia (author's transl)].

The comfort was improved by better positioning on the operating table in six patients undergoing extensive hand surgery with axillary plexus block. Opposite to that we could show in 16 similar cases with traditional position during surgery some pain, chills and discomfort despite optimal block technique.


[Induced hypocalcaemia test using salmon calcitonin as a means for the evaluation of osteoclastic activity (author's transl)].

The authors measured the degree of hypocalcaemia (delta Ca S), hypophosphataemia and the fall in urinary hydroxyproline excretion induced by an intramuscular injection of 100 MRC U of synthetic salmon calcitonin (S.C.T.) during the 24 hours following the injection. In 15 control subjects, the fall in plasma calcium was slight ( - 2.1 +/- 0.9 mg/l) but significant. In bone diseases involving hyperosteoclastosis, the degree of hypocalcaemia was much greater: 10.6 +/- 1.1 mg/l in 24 cases of Paget's disease, - 9.0 +/- 1.6 mg/l in 5 cases of diffuse malignant disease of bone, - 8.0 +/- 1.4 mg/l in 6 cases of primary hyperparathyroidism and - 3.5 +/- 0.8 mg/l in 13 cases of algodystrophy of the limbs. In the subjects studied as a whole there was a significant linear relationship between the delta Ca S and the extent of the trabecular surfaces of osteoclastic resorption, but not between delta Ca S and total 24 hour urinary hydroxyproline excretion. The S.C.T. hypocalcaemia test would appear to be a simple means for the evaluation of osteoclastic activity within the skeleton, and thus to select those bone disorders which should respond to antiosteoclastic therapy (calcitonin, diphosphonates).


Time course of delta9-tetrahydrocannabinol inhibition of predatory aggression.

Three studies assessed the time course of inhibition of predatory aggression and changes in levels of brain serotonin following administration of delta9-THC. In Study One, six groups of six rats each were administered 1.25 mg/kg delta9-THC IV and frog-killing behavior was measured at six postinjection intervals: 30, 60, 90, 150, 210, and 270 minutes. In Study Two, four groups of six rats each were tested. Group One received a vehicle control injection and was tested immediately, i.e. zero-minutes, postinjection. The remaining groups received 1.25 mg/kg delta9-THC, and behavior was measured at 0, 15, and 30 min postinjection. In Study Three, two groups of six rats were treated with the vehicle or 1.25 mg/kg delta9-THC and sacrificed one minute postinjection. Additional drug groups were sacrificed at 30 and 210 min postinjection. Levels of 5-HT were determined in four brain sections: cortex, midbrain, medulla, and cerebellum. Significant inhibition of predatory aggression was found for groups tested at 0, 15, and 30 min postinjection. Brain levels of 5-HT in the midbrain and/or medulla were significantly increased over the same period.


Induced PKU in rats: effects of age and melatonin treatment.

Newborn rats injected on Days 1-8 of life with L-phenylalanine (2 g/kg) and p-chlorophenylalanine (80 mg/kg) displayed biochemical symptoms analogous to human phenylketonuria (PKU) and maze learning impairments. The behavioral effects were less evident in rats treated on Days 9-16 or 7-24. None of the symptoms observed were alleviated by simultaneous administration of melatonin (10 mg/kg/day).


[Formation of vitamin B6 by by the fungus Cladosporium resinae on media with n-dodecane or glucose].

Accumulation of vitamin B6 by the fungus Cladosporium resinae str. Moscow University eas investigated on media containing n-dodecane or glucose. Vitamin B6 was built up in the mycelium and the culture liquid filtrate. Under stationary condiditions of growth the maximum amount was found on the 28th day and reached 750/mkg and 925/mkg per 1 of the culture liquid on the glucose and n-dodecane containing medium, respectively.


An analysis of the effects of cocaine on the responsiveness of the isolated guinea pig vas deferens to noradrenaline and other agonists.

In the isolated guinea pig vas deferens, 10(-4) M cocaine shifts to the left (13.5-fold at the EC50 level) the concentration-effect curve and increases the maximum response to noradrenaline, whilst supersensitivity to phenylephrine, an amine with a low affinity for the neuronal uptake, was smaller (4.1-fold) and the maximum response was not increased. Cocaine did not enhance sensitivity and maximum response to acetylcholine, potassium and calcium. Supersensitivity to noradrenaline was caused by a decreased dissociation constant (Km) for the agonist-adrenoreceptor interaction without alteration of the tissue's maximum response (Rmax). pA2 and pD'2 values in the presence of cocaine were not significantly different from control which indicates that cocaine did not increase the affinity of adrenoreceptors for the sympathomimetic amines used. It is concluded that the supersensitivity of the isolated guinea pig vas deferens to noradrenaline and phenylephrine by cocaine is entirely of prejunctional origin and results from the blockade of the neuronal uptake process.


Regional distribution of barbital in the brain of mice during the development of tolerance and physical dependence.

ICR male mice each receiving a 16 mg barbital pellet implanted subcutaneously for three days developed about 40 percent tolerance to barbital and more than 50 percent tolerance to pentobarbital as measured by sleeping time. The development of physical dependence in these mice was demonstrated by an increased sensitivity to convulsions with pentylenetetrazol. The concentration of barbital rose to high levels in the subcortex and the cerebellum during the time between the implantation of the pellet and the loss of the righting reflex and distributed uniformly thereafter. After a challenge dose of the drug, higher barbital concentrations were found in these two areas as well as in the pons-medulla at 30 minutes and in all areas at the time of the loss of righting reflex, in withdrawn mice. The latter finding would indicate an increase in threshold for barbital anesthesia. The mechanisms of the higher uptake in the brain of withdrawn mice are discussed.


Immunological defects in healthy twin siblings to patients with Hodgkin's disease.

We studied the immunocompetence of 6 healthy twins, whose monozygotic or dizygotic same-sexed twin partner had died from Hodgkin's disease. Lymphocyte DNA synthesis induced by concanavalin A was markedly reduced at 3 different concentrations in all twins compared to an age-matched group of healthy controls. The lymphocyte response to pokeweed mitogen and to phytohaemagglutinin was  also impaired. PPD induced lymphocyte DNA synthesis was low in 3 twins and correlated well with their delayed skin hypersensitivity to the antigen. One twin was completely anergic to 3 different skin antigens. The mean total blood lymphocyte count did not differ from that of controls. There was no change in T or B-lymphocyte subpopulations. The presence of a functional lymphocyte deficiency in all twins strongly suggests that the immunodeficiency in Hodgkin's disease is partly caused by genetic and/or environmental factors.


A radioimmunoassay of primary bile acid conjugates in human serum.

The fasting levels of chenodeoxycholic and cholic acid conjugates in various groups of patients [25 healthy subjects, 20 patients with chronic active liver disease (CALD), 21 patients with primary biliary cirrhosis (PBC) and 5 patients with cholesterol gallstones before and after chenodeoxycholic acid therapy] were determined by using a sensitive, accurate and precise radioimmunoassay. The results obtained with this method were compared with those of a gas-chromatographic method with methylation and acetylation of the bile acids using a 2 m x 0.4 cm glass column packed with 3% of AN 600 on Anakrom Q 110-120 mesh. The results obtained with both methods are in agreement; therefore the method used can be applied for quantitative analysis. In diagnosis, the measurement of serum bile acid levels, fasting or after meals, proved to be a very sensitive method, although further correlations are necessary with standard liver function tests.


Radioimmunoassay of morphine and morphine-like substances in biological fluids and human tissues.

A radioimmunoassay is described for the determination of morphine and morphine-like substances in plasma, serum, biological fluids and tissue homogenates using an antiserum to morphine-6-hemisuccinyl-BSA and 125I-morphine as the labelled tracer. In the B/F separation with ammonium sulphate, calcium sulphate was added to make the precipitate more compact. Some parameters related to the use of this method in direct assay on plasma, serum, other biological fluids and tissue homogenates were evaluated.


Alternative pathways for proline synthesis in mammalian cells.

Proline is synthesized in animal cells by way of two alternative pathways. Both of these pathways are functional in many cell lines. The relative contribution of a pathway to total proline synthesis may be altered by a mutational event. Differences in the developmental origin of a cell line are retained as differences in the pathways of proline synthesis.


Chromosome loss is responsible for segregation at the HPRT locus in Chinese hamster cell hybrids.

The phenomenon of segregation of gene expression has been examined in intraspecific somatic cell hybrids. Specifically, segregation at the hypoxanthine guanine phosphoribosyltransferase (HPRT) locus has been studied in hybrids of Chinese hamster cell lines. The role of chromosome segregation, or other chromosomal events has been assessed by detailed comparison of karyotypes in the 6-thioguanine resistant segregants with those of the parental hybrid lines. The results clearly demonstrate that loss of an entire X chromosome is the primary event responsible for segregation at the HPRT locus, while deletion of a portion of the short arm of an X chromosome was also a frequent event. The results provide the first direct evidence for the assignment of the mapping of this locus to the distal region of the short arm. Analysis of chromosome number distributions in the hybrids and segregants suggests that in selecting chromosomal segregants one may also select for hybrid lines with reduced chromosome stability.


A new method for evaluating an increased general capillary permeability in patients.

The difference between total plasma volume determined with a substance which escapes from vascular beds in the presence of an increase of general capillary permeability and that determined with a substance which is confined to blood even in the presence of an increased capillary permeability may reflect the degree of an increase of general capillary permeability. The total plasma volume was determined by simultaneous injections of 131I-HSA and 51Cr tagged red cells. The capillary permeability was evaluated by calculating the difference (deltaTPV) between total plasma volume determined with 131I-HSA and that determined with 51Cr tagged red cell. deltaTPV in patients with systemic lupus erythematosus, idiopathic thrombocytopenic purpura, chronic active hepatitis, liver cirrhosis and subacute baterial endocarditis was larger than that of controls, averaging 204ml/m2, 178 ml/m2, 82 ml/m2, 131 ml/m2 and 179 ml/m2, respectively. The increase of deltaTPV was considered to indicate the increase of capillary permeability in these patients. A permeability increasing factor was present in serum of patients with an elevated deltaTPV. There was a significant correlation between deltaTPV and the titer of serum capillary permeability increasing factor in these patients.


Myroridin, a new peptide antibiotic from Myrothecium SP. 285F.

Myroridin, a new basic peptide antibiotic was isolated from culture filtrate of a strain of Myrothecium, No. 285f. The present paper describes the production, isolation and characterization of this antibiotic.


Direct radioimmunoassay of progesterone in mare plasma.

A rapid and low cost radioimmunologic procedure for progesterone assay in mare plasma is proposed. Radioimmunoassay is performed directly on 10 microliter of unextracted plasma. Free progesterone is adsorbed on dextran-charcoal, then the aqueous phase is decanted and extracted by 1 ml of scintillation fluid. Counting is performed directly on this two-phase system. Results are comparable to those obtained with radioimmunoassays using extracted plasma.


Simultaneous measurement of absolute pressure values in the urethra and bladder. Experimental model for the construction of a new measuring device.

In order to improve the accuracy of bladder and urethral pressure recording, a measurement system has been tested experimentally. It is possible to measure absolute pressure values during withdrawal of the catheter only when the system is constantly perfused. The optimum relationship between catheter diameter, perfusion rate, withdrawal rate, measurement inertia and systemic resistance has been analysed.


Alloplastic spermatocele: insemination from epididymal reservoir.

Insemination with the sperm of an epididymal reservoir three days after implantation of the prosthesis led to a successful pregnancy with subsequent delivery of five healthy sucklings. Alloplastic spermatocele can function longer than four months as proved by a successful pregnancy.


Effect of caffeine on urethral pressure.

Urethral pressure profiles have been a useful adjunct in the study of continence. Caffeine, a known smooth muscle inhibitor and skeletal muscle stimulator, is shown to decrease the urethral pressure profile in anesthetized dogs. This would lead one to believe that the smooth muscle component of urethral tonus is the determining factor. Discussions follow on the mechanism of caffeine action and the possible effect of caffeinated beverages on stress incontinence.


Transurethral vesicovaginal extraction of stone: nonoperative approach for intramural ureteral calculi in women.

Herein we describe a new technique for the removal of an impacted intramural ureteral calculus in a female patient. The stone was extracted by digital manipulation with the index finger of one hand in the bladder and the index and middle fingers of the other hand in the vagina. The relative ease of performing the procedure and the absence of any immediate and long-term postoperative morbidity and complications warrant further use of this technique.


Diseases of the commercial rabbit.

Throughout its short history, the commercial rabbit industry has suffered from a poor home market due to the long national memory of the 1950s myxomatosis outbreak, the strong competition from the broiler chicken industry and of low-priced imported rabbit. In the past few years, a new market for British rabbit has opened up in Europe with a potential demand far in excess of the present production. The veterinary profession can assist in this expansion.


Diseases of aquarium fish--4: treatment.

Prevention and treatment of aquarium fish diseases is described. A variety of husbandry factors may predispose to disease development and these should always be considered. Any treatment should first be tried on a small sample of fish as toxicity does vary between species.


Effects of hormones on the aggressive behaviour and social organization of the scincid lizard, Sphenomorphus kosciuskoi.

In order to ascertain whether hormones influence social organization of lizards, caged Sphenomorphus kosciuskoi were studied both before and after treatment with testosterone, estradiol, adrenaline and thyroxine. Testosterone and estradiol increased aggressiveness in male lizards and caused shifts in dominance. Adrenaline caused a temporary increase in activity and agressiveness but no change in social structure. Thyroxine did not affect social behaviour.


[On applicabilities of polarization microscopy in diagnostic histopathology (author's transl)].

Apart from its importance in ultrastructure research polarization microscopy turns out to be a valuable additional method in the daily hitological diagnostics of pathologist. By means of some examples the applicabilities of the polarization microscopy in this field are demonstrated. After some physical bases and practical hints for the use of polarization microscopes some staining reactions leading to an optical anisotropic effect are reported. Morever, it is reffered to the demonstration and characterization of crystals in biological fluids and tisdues. In our opinion, simple polarization optics should belong to the optical equipment of each pathologist.


[Cytopathic effect of the tularemia microbe on a culture of peritoneal macrophages].

Morphological analysis of the process of interaction of tularemia microbe strains differing by virulence with macrophages demonstrated that all these strains produced a lethal effect on macrophages obtained from the animales sensitive to the infection. The macrophages obtained from the animals were but little sensitive to tularemia and were resistant to the action of the causative agent of this infection. The data obtained led to a supposition on the presence in the tularemia causative agent of a factor responsible for its lethal action on the macrophages.


[Experimental neuroses in dogs caused by an increase in the intensity of (light) stimuli conditions].

The influence of enhanced intensity of general illumination on conditioned reactions of a different degree of complexity was studied on dogs by the classical method of secretory conditioned reflexes. In most of the dogs, increase of general illumination from 30 to 300 luxes leads to more intensive secretory conditioned and unconditioned reactions, a smaller number of errors in differentiation, and stabilization of parameters of conditioned activity, which testifies to the improved general functional state of the brain. In two animals in the same conditions of the experiment, an experimental neurosis set it, not connected with the complexity of the elaborated activity. It is assumed that the neurotizing agent was the superfluous situational (photic) stimulation which presented excessive requirements to the mechanisms regulating the general functional state of the brain.


[Immunodepressive activity of the different fractions of the antilymphocyte serum obtained after separation on DEAE-Sephadex].

Three protein fractions were obtained after the separation of the antilymphocytic sera (ALS). The first and the second ones chiefly consisted of gammaglobulins, and the third fraction contained the rest serum proteins. The second fraction possessed the greatest lymphocytotoxic activity in vitro, and also immunodepressive activity in vivo; administration of this fraction to mice caused depression of antibody-producing cells in the spleen to 9.1 +/- 2.8 (90 +/- 28.9 antibody-producing cells per 1 X 10(6) cells in control). The first fraction possessed a much lesser immunodepressive activity, and the third one practically failed to depress the immune response.


[Effect of chemical action on the biological activity of staphylococcal allergen].

The authors present the results of study of chemical action on the specific properties of staphylococcus allergen showing that deamination, iodation, and formalinization was accompanied by reduction of the allergenic capacity of the preparation; as to acetylation -- it produced an insignificant reduction of the allergen activity.


Experimental preparation of deantigenized vascular heterografts and study of tolerance after transplantation.

A new technique in preparing a heterograft is presented. Deantigenized calf carotid arteries are obtained by papain digestion and formol tanning. The biochemical determinations show a pronounced reduction in total protein content after papain digestion. The formol tanning gives a good rigidity and elasticity in adapting to different blood volumes without aneurysmal dilatation. Eight dogs were grafted : two died after surgery, two were killed after 35 days and two others 60 days after transplantation, one died after 8 months and one is alive 30 months after transplantation. The good in vivo tolerability has been appreciated. There have been no haemodynamic troubles and no cell changes of rejection. An insignificant quantity of immunoglobulins G has been found in the sera of the animals with heterografts. These data draw attention on the possibility of the use, in clinical practice, of the deantigenized calf arteries.


Effects of whole body CO60 irradiation on the male genital tract of gerbil (Meriones hurrianae), hedgehod (hemiechinus auratus Collaris), and house rat (Rattus rattus Rufescens).

1. The effects of 400 and 575 rads of whole body irradiation in gerbil (Meriones hurrianae), hedgehog (Hemiechinus auratus Collaris) and house rat have been studied with a view to compare the effects of irradiation on the desert mammalian species with those of domestic ones. 2. Typical signs and symptoms of radiation sickness, transient body loss and radiation mortality in gerbils and house-rats were apparent, whereas the hedgehogs were not affected at this dose level. 3. Extensive necrosis, exfoliation of seminiferous element, intertubular edema and shrinkage of the seminiferous tubule and Leydig cell nuclei in gerbils and house-rats were conspicuous in histological preparations. Mild regressive tubular lesions were also observed in hedgehogs treated with 575R. 4. Whole body irradiation depleted the RNA, protein and sialic acid contents of the testes. High cholesterol contens in the testes of irradiated gerbil, hedgehog and house rats identified this as the site of degenerating cells and fragments. 5. Reduced androgen production was confirmed in non active Leydig cells and decreased fructose contents in the seminal vesicles of gerbil and house rats. At 575 R dose level, hedgehog was comparatively radio-resistant. But at 875 R extensive damage to the reproductive organs could be noticed.


Lactose and protein absorption from breast milk and cow's milk preparations and its influence on the intestinal flora. Investigations on two infants with an artificial anus.

Lactose and protein absorption from breast milk and a cow's milk preparation enriched up to 7% of lactose were studied in two infants with an artificial anus applied in the ascending colon region. The concentrations of protein, lactose, glucose and galactose were measured in the fistula stools. In addition, the stools were analysed microbiologically. There were relatively high concentrations of lactose and its decomposition products and low concentrations of protein and aminonitrogen in the fistula stools when breast milk was fed. When the cow's milk formula was applied, only traces of lactose but high amounts of protein were measured. The microbiological findings are in agreement with the hypothesis that the bacterial flora of the large intestine is influenced by the lactose and protein concentrations in the intestinal content which reach the large intestine.


Monozygotic twins concordant for tracheo-esophageal fistula and discordant for the VATER association.

Monozygotic female twins were concordant for tracheo-esophageal fistula (TEF); and one twin also manifested other anomalies in the VATER association, including agenesis of the female reproductive tract. Review of the literature discloses a familial tendency for recurrence of TEF and a high concordance rate in monozygotic twins, indicating a significant genetic influence for the isolated anomaly. In the case of the VATER association, the sporadic occurrence of affected individuals and discordance in twins implicates the effect of non-genetic factors.


A male MZ twin pair, concordant for transsexualism, discordant for schizophrenia.

A pair of male monozygous twins of gynandromorphic habitus but normal male body hair and genitalia, who appear concordant for transsexualism and explosive personality disorder but discordant for schizophrenia, is presented. No evidence of specific family dynamic factors, imitative learning or folie a deux was found in the twins' history. A constitutional aetiology of their transsexualism and one twin's schizophrenia is suggested. The relationship between transsexualism and schizophrenia is briefly reviewed. No evidence can be found that the modal transsexual is suffering from a schizophrenic disorder, florid or attenuated. A more subtle relationship is possible of transsexualism occurring as a schizophrenic spectrum disorder. This twin pair appears to illustrate such a relationship.


Bone changes during prednisone treatment.

To evaluate changes inbone composition during treatment with corticosteroids, the bone mineral content (BMC, measured by photon absorptiometry) and the degree of bone mineralization (measured as the bone phosphorus/hydroxyproline ratio) were determined in 18 patients during prednisone treatment for haematological and connective tissue diseases. The prednisone dose ranged from 12 to 51 mg/day (mean 27). The BMC decreased significantly (mean 2.5%) during the studied 12 weeks of treatment, but the change did not correlate significantly to the prednisone dose. The degree of bone mineralization remained unchanged, indicating equal losses of mineral and of collagen in bone during prednisone treatment. The changes correspond to a rapidly developing oesteoporotic state.


Effects of beta-adrenergic blockade on diurnal variability of blood pressure and plasma noradrenaline levels.

The effect of propranolol on diurnal variability of BP and plasma noradrenaline levels was assessed in 15 patients with uncomplicated essential hypertension. While total variability and average noradrenaline level remained unaltered, the pressor range (difference between basal and maximum BP readings) was reduced in most patients. An inverse relationship was observed between changes in pressor range and noradrenaline.


Genetic studies in outpatients: plasma cholesterol in family and twin studies.

Quantitative genetic studies have much potential in partitioning the causes of variation of quantitative traits such as risk factors for atherosclerosis. Only if specific causes of variation are identified can specific therapy be developed to modify risks. There have been extensive family studies of plasma cholesterol which reveal that the level of plasma cholesterol is correlated in family members. However, except for the relatively rare familial hypercholesterolemia the evidence is not convincing that correlations of relatives are due to genetic rather than environmental factors. Early twin studies were interpreted as supporting the hypothesis that levels of plasma cholesterol were strongly influenced by genetic factors. However a recent large study of twins cast doubt upon this hypothesis by finding no significant genetic variance of plasma cholesterol after correcting for differences in total variance of monozygotic and dizygotic twins.


The effects of chronic ethanol consumption on goniomitosis in the rat.

Male rats, provided with dissimilar diets with regard to thiamine (deficient, normal and superfluous) received either water or alcohol (7-20%: w/v) as the only supply of liquid for 4-7 months. Mitotic acitivity was very low in the spermatogonia of many of the individuals especially those belonging to the alcohol groups. The frequency of cells with visible chromosomal defects was invariably quite low. It seems that combining abnormal thiamine supply with alcoholism does not lead to a drastic increase in the frequency of chromosomal aberrations.


Labeling of rat brain synaptosomal phosphatidyl serine in the after state of acute alcoholic intoxication and in the withdrawal state.

The synaptosomal phosphatidyl serine labeling by 14-C-serine after elimination of a single dose of 6 g EtOH/kg b.w. and after a prolonged ethanol period (8-11 g EtOH/kg b.w. for 8 days) was studied in vivo. In both experimental groups the 14-C-labeling of the phosphatidyl serine is decreased as compared with the controls. There is a great deal of evidence which implicates that phosphatidyl serine plays a major role in neural excitation providing ion exchanges sites which control the sodium current, known to be sensitive to ethanol. These ethanol induced changes in phosphatidyl serine labeling may be reflected functionally in the impulse conduction and increased sensitivity in the withdrawal state. These changes are suggested to be consequences of the primary membrane fluidity increasing properties of ethanol.


Common mechanism for the adaptive increase in hepatic ethanol and acetaldehyde metabolism due to chronic pretreatment with ethanol.

Perfused livers from ethanol pretreated rats utilized ethanol and acetaldehyde at higher rates than appropriate controls. This adaptive increase in hepatic ethanol and acetaldehyde uptake was associated with a marked (greater than 60%) increase in hepatic oxygen uptake. Ethanol uptake in both ethanol-treated and control livers was similarly sensitive to inhibition by 4-methylpyrazole, rotenone, and antimycin A. The adaptive increase in ethanol uptake was apparently specifically abolished by ouabain, an inhibitor of the sodium-plus potassium-activated ATPase. The data are consistent with the hypothesis that chronic treatment with ethanol increases ATPase activity. The ADP produced from these initiating events enters the mitochondrial space and stimulates electron transport and oxygen uptake. As a consequence of these events, a greater rate of NADH reoxidation occurs, resulting in a greater rate of production of NAD+ which stimulates ethanol oxidation via alcohol dehydrogenase and acetaldehyde oxidation via aldehyde dehydrogenase(s).


Metabolism of alcohol at high concentrations: role and biochemical nature of the hepatic microsomal ethanol oxidizing system.

At intermediate and higher alcohol concentrations, ethanol metabolism proceeds via alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system (MEOS), whereas catalase plays no significant role. Following prolonged ethanol consumption, an enhancement of both MEOS activity as well as the rates of ethanol metabolism occurs; the latter persisted despite inhibition of ADH by pyrazole and catalase by sodium axide, suggesting the involvement of MEOS in the adaptive increase. MEOS exhibits characteristics similar to those of other microsomal drug metabolizing enzymes and can be differentiated and isolated from both ADH and catalase activities. Reconstitution of MEOS activity was achieved with partially purified cytochrome P-450 and NADPH-cytochrome c reductase in the presence of synthetic phospholipid.


Gonadal function in chronic alcoholic men.

Alcoholism affects nine million individuals in the United States according to United States Government estimates. As many as 80% of hard-core alcoholic men show evidences of feminization including impotence, testicular atrophy, sterility, gynecomastia and changes in bodily hair. The causes of feminization of male alcoholics have remained obscure until recently. Largely as a result of advances in the techniques of measurement of sex hormones, it has become possible to begin to examine the pathogenesis of feminization. The results of initial studies suggest that alcoholics become feminized through the secondary effects of alcohol-induced liver disease, and also through primary effects of alcohol on the endocrine system. It can be shown that liver disease permits the peripheral escape of steroid precursors and their conversion to estrogenic substances. These substances are then inadequately cleared by the liver. In addition, however, alcohol alters testicular steroidogenesis and testosteronogenesis. Hypothalamic-pituitary function also is diminished in chronic alcoholics, and this change contributes to the syndrome of feminization.


Adaptative changes in Ca++-membrane interactions following chronic ethanol exposure.

The data reported here together with recent reports from other investigations suggest that ethanol may act selectively to alter Ca++ metabolism in nerve cells. Changes in calcium content and binding after acute and chronic exposure to ethanol suggest that nerve cells may adapt to ethanol exposure through increasing endogenous calcium content on the synaptic membranes. Since calcium plays an integral role in neurotransmitter metabolism, it may be suggested that adaptation to ethanol may occur via such Ca++ dependent processes as altered membrane transport capabilities and excitation-secretion coupling mechanisms. Future research in these areas would hopefully be directed toward the role of Ca++ in neurotransmitter release and subsequent activation of cyclic nucleotide metabolism.


Selective breeding of rats for differences in reactivity to alcohol: an approach to an animal model of alcoholism. III. Some physical and behavioral measures.

The results of selective breeding for differential impairment of motor activity after alcohol injection is shown for the first 13 generations of the LA and MA rat strains. In F13 rats, the mean decrement of activity after 1.5 g ethanol per kg i/p. is 90% for MA rats and 42% for LA rats, the strain difference significant at a "p" of 1.8 x 10(-11). Blood alcohol levels, body weight, litter size, organ weights and induction of taste aversion to alcohol and lithium chloride are described for these strains in various of the generations. Although strain differences are apparent on some of these measures, none are of a degree or kind which offers more than a speculative explanation of the large difference between the strains in their central nervous system sensitivity to alcohol.


Chemistry of the crosslinking of collagen during tanning.

The materials commonly used for crosslinking collagen as part of the process of converting animal hides into leather fall into three main groups: mineral tannages, aldehyde tannages, and "vegetable" tannages. The most important mineral crosslinking agents are hydrated basic chromium III sulfate complexes. These compounds form extended polynuclear coordination complexes containing hydroxol, oxo, and sulfato bridges into which ionized carboxyl groups on collagen enter readily as coordinating ligands accomplishing crosslinking. On pH adjustment and partial drying, highly stable complexes are formed with oxo bridges predominating and protein amide groups entering the coordination complex. The aldehyde tannages proceed through aldehyde condensation reactions with collagen amino groups to give alpha-hydroxyamines which can condense with other collagen amine groups to effect crosslinking. The vegetable type tanning agents, whether natural plant extracts or synthesized, are complex, high molecular weight polyhydroxy compounds that do not rely on crosslinking as such to be effective. Their effectiveness appears to depend on other properties. This and additional information concerning these commerical tannages are reviewed.


Cross-linking of amino acids by formaldehyde. Preparation and 13C NMR spectra of model compounds.

Model cross-linked systems have been prepared by reacting amino acids or alkylamines with formaldehyde and various amino acid model compounds such as 2,4-dimethylphenol (tyrosine), 3-methylindole (tryptophan) and alkylamides (glutamine, asparagine. 13C NMR spectra of the products show the resonances of the formaldehyde-derived methylene carbons in the region 45-60 ppm. Interferences occur from resonances of the alpha-amino acid methine carbons. From the data for these products and other model compounds it has been possible to predict the shifts of the residual methylene carbons in a variety of cross-linked systems. This NMR technique shows promise as a rapid non-degradative method for identification of cross-linking sites.


Sensory irritation to formaldehyde and acrolein during single and repeated exposures in mice.

Mice were exposed to various concentrations of formaldehyde or acrolein. Concentration-response relationships were developed by measuring per cent decrease in respiratory rate, indicating upper respiratory tract sensory irritation. Relationships are presented between the concentration associated with a 50% respiratory decrease and TLVs. A summary of other animal inhalation studies is presented. The basis for the acrolein and formaldehyde TLVs are reviewed. Mice exposed for 4 days showed increasing sensitivity daily for both compounds. A re-evaluation of the TLVs is suggested.


Preimplantation development, fate of the zona pellucida, and observations on the glycogen-rich oviduct of the little bulldog bat, Noctilio albiventris.

The reproductive biology of Noctilio albiventris was investigated histologically in 112 females collected at the start of their synchronized breeding season during two different sampling years in the Cauca Valley of Colombia. Both ovaries were functional, but the animals were generally observed to be monovular. Embryonic development in the oviduct was found to proceed to blastocyst formation and loss of the zona pellucida. In 22 animals the discarded zona had been left behind in the oviduct upon passage of the embryo into the uterus and was still undissolved at the time of amniogenesis, the latest stage examined. The zonae which had passed into the uterus with the embryos often exhibited signs of dissolution. Most of the early blastocyts were morphologically distinctive, lacking a typical inner cell mass and being instead largely bilaminar. Degenerating ova from previous ovulations were found in the oviducts of two pregnant bats, suggesting that Noctilio may be another species in which the embryo stimulates its own escape from the oviduct. During tubal passage of the embryo the secretory cells of the oviductal ampulla and isthmus exhibited a transient engorgement with glycogen, particularly on the side ipsilateral to the new corpus luteum.


Elastic tissue in the limiting membrane of the human seminiferous tubule.

The structure and distribution of elastic tissue were studied in the limiting membrane of the seminiferous tubule from normal human testis. The elastic and elastic-related fibers (oxytalan and elaunin) were recognized by their tinctorial and ultrastructural characteristics. The connective structures of the limiting membrane, including the fibrotubules and the amorphous material of the elastic system, were studied after tannic acid-glutaraldehyde fixation. Fibrotubules (oxytalan fibers) were observed in almost all intercellular spaces of the limiting membrane, closely related to the contractile cells; the elaunin fibers (patches of amorphous material surrounded by bundles of fibrotubules) were evident in the outermost layers. The function of this system of elastic tissue and myoid cells is discussed, considering the permeability membrane and the role of the myoid cells in the elastogenesis and contractility of the seminiferous tubule.


Placental pathology compared with clinical outcome: a retrospective blind review.

The usefulness of the microscopic examination of the placenta, associated membranes, and umbilical cord was tested in a retrospective clinical review. Fifty-nine patients with inflammation were matched by sex, race, and gestation with 59 patients without inflammation. Blind review of the clinical course of these infants revealed five cases of culture-positive septicemia, 28 cases of probable sepsis, 39 cases of possible sepsis, and 46 normal infants. The clinical categorization was significantly correlated with the microscopic appearance of the placenta, membranes, and cord. Triple vessel vasculitis in the umbilical cord vessels and chorionic microabscesses were significantly related to the incidence of proven, probable, and possible clinical sepsis. The microscopic examination of the umbilical cord and placenta provides a useful, but not infallible, tool in the evaluation of sepsis in the newly born infant.


Cytologic features of Harding-Passey melanoma following different regimes of colchicine treatment.

Ultrastructural observations were undertaken on Harding-Passey melanomas in control tumors and in tumors treated with different regimens of colchicine. The treated tumor was made up of pleomorphic cells containing tubulovesicular mitochondria, ribosomes, and rough endoplasmic reticulum. Tumor-bearing mice in Experiment A received a single regimen of colchicine, 0.5 mg/kg/day of 7 days. The treated tumor was subsequently passed through five transplantations in mice. Tumor-bearing mice in Experiment B received colchicine treatment of 0.5 mg/kg/day for 7 days followed by passage through five transplantations. In addition, the mice carrying the tumor received the same colchicine treatment during the second and fourth transplantations. Colchicine treatment resulted in tumor cells of Experiments A and B developing microfilaments, margination of melanin granules, and junctional complexes, considered to be evidence of altered morphologic differentiation in melanocytes. The effects persisted for 10 weeks throughout the five transplantations. The features were more striking in Experiment B animals receiving intermittent therapy.


High sensitivity of cultured cardiac muscle cells to autonomic agents.

We have established conditions under which cultured embryonic myocardial cells are highly sensitive to the autonomic agents norepinephrine and acetylcholine and have determined that the most important factors affecting this sensitivity involve the application protocol. Using cells 3-5 days in culture, isolated from ventricles of 13-day chick embryos, the ED50 for noerpinephrine was 800 pM and that for acetylcholine was 370 pM. These cells were more than 2 orders of magnitude more sensitive than 13-day embryonic hearts freshly isolated, but not dispersed. Intracellular recording of the membrane actions of norepinephrine and acetylcholine on these cultured cells showed changes in pacemaker slope similar to those seen in freshly isolated hearts. These data demonstrate that preparation of ventricular muscle as isolated cells in culture does not necessarily result in the loss of sensitivity to autonomic agents. On the contrary, the isolated cells show the highest sensitivity to norepinephrine and acetylcholine that has been reported for the myocardium.


Bioelectrical and contractile behavior of rabbit mesotubarium superius: estrogen withdrawal.

The mesotubarium superius of the female rabbit is a thin, plane sheet of smooth muscle responding to the in vivo endocrine states of ovulation, estrous, castration, pregnancy, and replacement estrogen therapy of the castrate in a manner similar to that of the uterus. Both isometric tension and microelectrode recorded transmembrane potentials were measured in vitro to make these comparisons. In addition, confirmation of the "estrogen-withdrawal" theory of activation was obtained when it was noted that about 12 h after an abrupt withdrawal of estrogen there is an increase in contractile activity coinciding with an increase in subthreshold activity and a slight (about 5 mV) decline in the average resting potential compared to the control estrous level. It is concluded that the mesotubarium superius is an excellent tissue for reproductive smooth muscle studies, where a geometrically simple model is useful.


Energetics of Na+-dependent sugar transport by isolated intestinal cells: evidence for a major role for membrane potentials.

Intestinal epithelial cells isolated from 6-wk-old chickens maintain the capability for Na+-dependent concentrative accumulation of 3-O-methylglucose (3-OMG). Cells depleted of ATP exhibit a transient accumulation of 3-OMG in response to imposed Na+ gradients ([Na+]o greater than [Na+]i) or when transmembrane ion diffusion potentials (cell interior negative) are established. Phlorizin or lack of extracellular Na+ prevents formation of sugar gradients in every case. A nonconcentrative, non-Na+-dependent sugar transport system is also operative in these cells. The latter system is inhibited to various degrees by phloretin, theophylline, cytochalasin B, and a variety of flavonones and flavones, including apigenin. These agents also act to inhibit efflux of sugar from the cell via this pathway. The concentrative system normally operates against a "leak" of sugar through the nonconcentrative carrier. If the passive system is made inoperative by any of the agents named above, a significant enhancement of steady-state sugar gradients maintained by the cells is observed. With cytochalasin B, gradients as large as 30-fold are established. The energy inherent in cellular Na+ gradients cannot account for sugar gradients of this magnitude unless both chemical electrical driving forces are considered. When the passive leak is maximmally inhibited, more than half of the total energy required must be derived from the membrane potential.


Early sexual experience and prostitution.

The authors compared several aspects of early sexual experience found in two earlier studies of prostitutes with results of research on "normal" women. The prostitutes had in common many negative experiences not found or found less often in other populations of young women. These include incestuous and/or coerced sex, lack parental guidance, intercouse at a young age, and few or no meaningful relationships with males. These women had discovered that sex could lead to a kind of status, even though that status is negatively labeled by the wider culture. In a society that values women on the basis of their sexuality, a woman who views herself as "debased" may see prostitution as a viable alternative--perhaps the only alternative.


Attack and defensive behaviour in the albino rat.

Attack of dominant colony males of an albino rat (Rattus norvegicus) strain, on introduced strangers, produced a non-random distribution of bites, with ventral trunk virtually never bitten. Also, vibrissae-contact of attacker and defender interfered with bites to the defender's head and upper back. The specific agonistic reactions of attacking and defending rats appeared to involve strategies based on these limitation on attack: defenders utilized 'boxing' and lying 'on-the-back' behaviour, which interposed ventral trunk and vibrissae between attacker and defender. In turn, the 'lateral display' permitted attackers to circumvent the defender's behaviour. Limitations on attack therefore appeared to underlie the specific agonistic behaviour of both attacking and defending rats.


The influence of females upon aggression in domesticated male rats (Rattus norvegicus).

The aggression of adult male Long-Evans rats (Rattus norvegicus), toward males of the same strain, was tested before and after a 1-week period of cohabitation with a pair of intact females, ovariectomized females, or intact males, comparable to the females in size. Only cohabitation with intact females increased the aggression of resident males against unfamiliary male intruders. Female enhancement of aggression does not appear to be caused by sexual frustration of males, or a function of dominance-subordinance relations, per se. Increased aggression may be mediated by elevated testosterone production associated with mating.


Agonistic display and spacing in the black-headed gull, Larus ridibundus.

Black-headed gulls nesting on islands in a marsh habitat had a higher breeding success than those nesting on the periphery of the colony. Island birds maintained close inter-nest distances whereas peripheral nests were spaced further apart as predation of eggs increased. These changes in spacing corresponded with changes in the response distances of agonistic displays. There was no change during incubation for island birds but peripheral birds displayed to intruders at much greater distances than during pair formation. Island birds were more likely to attack and display more frequently to intruders than peripheral birds. However, in one season the peripheral birds were more aggressive during pair formation because of an increase in intrusions by unpaired females.


[Automated measurement of elastase activity and elastase inhibitory capacity of serum].

A technic of autoanalysis of the elastase activity and the capacity of elastase inhibition of the serum is described. This estimation depends on the hydrolysis by elastase of N-ter-butoxycarbonyl-L-nitrophenyl ester with liberates p.nitrophenol the colour of which is read at 405 nm. The means of this sample estimation are reported in a few cases of respiratory, dermatological and pancreatic disease.


Angiosarcoma of the breast.

Two surviving patients treated for angiosarcoma of the breast are presented, along with a summary of the previous 44 reported cases. Because of early vascular metastasis and indistinct tumor margins, early excision with very wide margins, including total mastectomy, surrounding muscle and bone, is necessary.


[Pseudo-angiosarcomatosis (kaposi) and arterio-venous fistulae (author's transl)].

In a few cases, arterio-venous fistulae of the lower limbs lead to cutaneous symptoms of the toes, feet or legs exactly similar to Kaposi's disease; the fairly precocious occurrence, the unilateral localisation, the existence of clinical and radiological arterial symptoms and usually, but not always, particular histological features allow this discrimination. Seen in both sex, male prevailing, between 12 and 50, it can simulate Kaposi's disease even on histological grounds; the diagnosis may, then, be difficult inasmuch as vascular symptoms may clinically lack. The development may be very different from one case to another so that there is no standard treatment between "wait and see" and more or less extensive amputation.


[Experimental method for the quantitative assesment of the pain reaction occuring to the injection  of drug preparations].

The procedure for estimation of painfulness of injection solutions is based on registration of changes in the mobility of albino mice after administration of the solution under the aponeurosis of the anterior pad. The method was tested in the experiments with formaldehyde solutions of various concentrations and a number of drugs used in medical practice. The method provided definition of a clear dependence between the concentration of the irritating substance and the stregth of the animal response. Correlation between the drug painfulness in clinical use and supression level of the animal motor reaction was found.


Increasing breast feeding in a community.

A second survey of infant feeding practice was carried out by questionnaire among patients discharged from one maternity ward at the John Radcliffe Hospital, Oxford, in the winter 1974/75. In comparison with the first survey in the winter of 1972/73, significantly more mothers went home breast feeding (52% compared with 37%); these mothers breast fed their babies for a significantly longer period (43% at 5 months compared with 23%), and introduced mixed feeds significantly later (17% at 2 months compared with 64%). Information was also collected on the difficulties the mothers had experienced with breast feeding. The changing patterns in infant feeding practice in Oxford may relate to changes in advice given by health visitors and community health personnel.


Inhibition of 3H-Angiotensin II binding to zona glomerulosa cells by several analogs.

Inhibition of 3H-angiotensin II (Ang II) binding to zona glomerulosa cells prepared from male rabbit adrenals, was determined by addition of approximately equimolar (10(-8)) concentrations of unlabelled peptide analogs. The unlabelled octapeptide inhibited binding by 20%, while the heptapeptide analog [des-Asp1, Ile8] Ang II inhibited by 51%. Octapeptide analogs with sarcosine substituted in position one all inhibited more than 50% of the bound ligand ([Sar1, Ala8] Ang II, 55%; [Sar1, Thr8] Ang II, 58%; [Sar1, Ile8] Ang II, 68%, and [Sar1] Ang II, 62%). Addition of other octapeptide analogs ([Ile8] Ang II, [Ala(betathi)] Ang II, [MeAla1, Ile8] Ang II, and [Me2Gly1] Ang II) inhibited 30-40% of the labelled hormone. [Ser(OAc)]n - [Asp1, Ile5] Ang II at two different concentrations inhibited less than 10%. Increasing concentrations (10(-9)M-10(-7)M) of the analogs produced increased inhibition of angiotensin binding to zona glomerulosa cells. These results seem to correlate well with reports that show sarcosine substituted analogs to be the best antagonists of angiotensin-induced aldosterone biosynthesis or release.


Enhanced ocular penetration of the methyl ester of (+/-) alpha-methyl-para-tyrosine after lontophoresis.

A comparative study of ocular penetration of the methyl ester of (+/-) alpha-methyl-para-tyrosine after the intraperitoneal route of administration versus that after the more localized subconjunctival and iontophoretic routes has been undertaken. Levels of alpha-methyl-para-tyrosine in the aqueous humor of rabbits were measured both 2 and 6 hr affter drug administration. Changes in norepinephrine levels in iris and ciliary processes at these time points were also determined. The results indicated that the highest concentrations of the drug in aqueous were reached 2 hr after iontophoresis (40 mg/ml, positive pole, 3 mamp for 5 min), at which time norepinephrine tissue levels were reduced by 20%. While norepinephrine levels 2 hr after the intraperitoneal route (100 mg/kg) remained unchanged, those after subconjunctival injection (5 mg in 0.3 ml saline) were slightly but significantly elevated. By 6 hr after alpha-methyl-para-tyrosine administration by each route, only small amounts of the drug were detected in aqueous humar. Norepinephrine levels in iris and ciliary processes after iontophoresis, however, were still depleted by 20%. Norepinephrine stores after the intraperitoneal route likewise were reduced by 20%, while those after subconjunctival injection did not differ from control. These results suggest that iontophoresis, in addition to confining the site of drug action, actually enhances ocular penetration.


The effects of ethanol and pentobarbital on the naloxone precipitated escape response in morphine dependent mice.

Morphine dependence in mice is produced in a two day test. The effects of (1) ethanol, (2) pyrazole, (3) ethanol with pyrazole, and (4) pentobarbital are observed and recorded on the naloxone precipitated escape response in morphine dependent mice. Ethanol suppresses the escape response in doses of 2.0 and 3.0 g/kg which produce mean blood ethanol concentrations of 1.88 and 3.28 mg/ml, respectively. When a pyrazole regimen is employed with morphine dependent mice, ethanol reduces or abolishes the naloxone precipitated escape response at doses of 1.0, 2.0 and 3.0 mg/kg. The corresponding mean blood ethanol concentrations are 1.14, 2,82 and 3.74 mg/ml, respectively. When pentobarbital (20 and 30 mg/kg) is given to morphine dependent mice, jumping bevarior is prevented following naloxone injection. Since narcotic antagonists such as naloxone may be employed in studying the phenomenon of physical dependence on ethanol based on the hypothesis of a relationship between endogenous opiates and ethanol dependence, it is essential to verify that blood ethanol concentrations are low enough so that ethanol will not interfere with the effects of naloxone in ethanol dependent animals.


The pharmacology of N-substituted azidomorphines.

N-allylnorazidomorphine (NAM), N-allyl-14-hydroxynorazidomorphine (NOAM), N-cyclopropylmethylnorazidomorphine (CAM) and N-cyclopropylmethyl-14-hydroxynorazidomorphine (COAM) were synthetized and their pharmacological effect in comparison to naloxone and naltrexone were analyzed. While naloxone and naltrexone are pure antagonists at all points, the N-substituted norazidomorphines were found to be more potent antagonists than naloxone in some of the tests and extremely potent pure agonists in others. Using CAM for routine work we differentiated between opiate A-receptors which are stimulated and opiate B-receptors which are antagonized by CAM. Opiate A-receptors were found to be involved in the behavioral disturbances (inhibition of conditioned avoidance responses, characteristic EEG changes, elimination of slow wave and paradoxical sleep, etc.) caused by the opiates. The guinea-pig ileum and mouse vas deferens are the suitable isolated organs for testing A-receptors. Opiate B-receptors are responsible for the analgesic, antitussive, cataleptic, respiratory depressant and hypotensive effects of the opiates. The isolated nictitating membrane of the cat is an appropriate model for testing the B-receptors. The hypothesis is proposed that A-receptors relate to cholinergic and B-receptors to adrenergic mechanisms; the N-substituted norazidomorphines are tools for the analysis of the two kinds of opiate receptors.


Effects of tricyclic compounds and other drugs having a membrane stabilizing action on analgesia, tolerance to and dependence on morphine.

Several drugs affecting nerve cell excitability, by opposing ion movements in membranes, were tested in mice rendered tolerant to or dependent on morphine. The purpose of the study was to investigate whether these drugs share the ability to attenuate morphine tolerance and dependence exhibited by tricyclic antidepressants. Tolerance to morphine was decreased by the administration of imipramine, doxepin, promethazine, propranolol, lidocaine and quinidine. Chlorpromazine and carbamazepine were ineffective. The intensity of the abstinence syndrome provoked by naloxone was decreased by chlorpromazine, imipramine, doxepin, lidocaine, quinidine and propranolol. Diphenyl. hydantion and carbamazepine had no effect. The results are discussed in relation with the blockade of ion conductance and their interference with the release of neurotransmitters produced by the drugs assayed.


Effect of maternal methadone addiction on offspring in rats.

Female rats were addicted to methadone via small dosages in their drinking water. The addicted animals were impregnated, and continued to receive the drug during pregnancy and lactation. Offspring were examined at birth and at age 21 days. Compared to controls whose mothers did not receive the drug, pups of addicted mothers at birth had significantly lower weight, brain weight and brain protein; litter size, brain DNA and brain acetylcholinesterase activity were not significantly different between the two groups. At age 21, pups of addicted mothers had significantly lower brain protein and brain acetylcholinesterase than did controls; body weight and brain DNA were not significantly different.


[Contribution to the experimental hemophilus infection (Haemophilus parahaemolyticus, Haemophilus parasuis) in SPF piglets. 2. Comparative pathology and histology].

The pathologico-anatomic and even more the histological pattern of experimental Haemophilus parahaemolyticus pleuropneumonia in specific-pathogen-free piglets was found to be characteristic in the peracute, acute, and subacute-chronic stages of the disease. It is an infection which can be morphologically differentiated from other forms of pneumonia in swine primarily by three factors, localisation of the changes, inflammation, and a typical cell response. Changes following experimental Haemophilus parasuis infection were found to occur irregularly on serous skins and, in continuation, in the lung and joints. These were not characteristic and failed to exhibit morphological peculiarities.


[The effect of Suisynchron on the glucose tolerance and the plasma insulin in bitches].

Suisynchron, a derivative of bisthio-urea commonly used for oestric synchronisation, was applied to nine female Alsatians over 21 days. All animals received intravenous glucose injections before ten, and 21 days from the beginning of treatment as well as 21, and 84 days after the end of treatment. The glucose-stimulated plasma insulin levels were significantly reduced during Suisynchron treatment and 21 days after the end of treatment. Both glucose tolerance and response of free fatty acids remained unaffected. This phenomenon might be attributable to a stimulated hepatic insulin degradation, to a biguanid-like effect on "peripheral" glucose turnover, or to an inhibited secretion of hormonal insulin antagonists of the anterior lobe of the pituitary gland. However, the long persistence of the Suisynchron action after interruption of treatment, could not be explained by any of these effects.


[Attempts at biotechnical induction of puberty in female young pigs. 1. Estrus and ovulation induction with Suigonan (Vemie) or FSH plus HCG mixtures in animals at the age of approximately 200 days].

64 prepuberal gilts in 4 groups were treated with 400 PMS + 200 HCG (Suigonan - Vemie) (I), 100 FSH + 100 HCG) (II), 200 FSH + 200 HCG (III) ("international units") or served as untreated controls (IV). One halve of the groups laparotomized at the 12th day p.i. had ovulated 100, 25, 75 and 12,5% resp., the other halve slaughtered at the 36th day p.i. had ovulated to 83, 43, 88 and 50% resp. Sexual cycle was registered in 50, 29, 43 and 12.5% of the animals. Zystic ovaries (greater than or equal to 11 mm) developed only in a few cases in I and III.


[Attempts at biotechnical induction of puberty in young female pigs. 2. Effects of various time intervals between one puberty induction with PMS and HCG to the following estrus synchronization on estrus and ovulation in animals about 190 days old].

A biological engineering approach to induce puberty in 125 young female fattening pigs aged 190 days was undertaken on the basis of a mixture of 500 IU PMS (Prolosanserum, Dessau) with 250 IU HCG (Gonabion, Dresden). The injections were made subcutaneously. Pronounced oestrus symptoms were recorded from the external genital organs of 80% of the probands up to ten days after injection, associated with toleration in 52.8% of them. Toleration usually started on the fourth to sixth days after injection. Cycles began to develop in 57.1% up to the next oestrus period. Animals with -/x weight increase per die of 400 g exhibited lower responses. Results in terms of heat and ovulation were lower along with shorter intervals, when oestric synchronisation was undertaken 53, 32, and 17 days after the induction of puberty (20 days Suisynchron, Bernburg; 750 IU PMS).


[Studies on the success of insemination after various insemination dates in biotechnical puberty induction of young sows].

Different frequencies and periods of insemination were checked with the view to optimising puberty induction to young sows, for which purpose 500 IU PMS/250 IU HCG were injected to 571 animals in seven experiments. Insemination was carried out by deadline, since follicle stimulation was exhibited by almost all animals following the above treatment, while only some of them displayed tolerance. Advantage was taken of the induced oestrus, since its ovulation rates were higher than those associated with subsequent heat cycles, and because a synchronised second oestrus was recordable only from some of those animals which exhibited follicle stimulation in response to puberty induction. The most favourable results in terms of pregnancy and number of embryoes, against the background of the great variability in ovulation onset, were obtained, if insemination was applied 72, 96, and 120 hours after gonadotrophin treatment. From among the variants with two inseminations, good results were obtained from those 96 and 120 hours after PMS/HCG treatment.


Oestradiol and progesterone: soluble receptor levels and metabolism in the uterus of the ovariectomized ewe.

Ovariectomized ewes received injections designed to mimic to some extent oestradiol and progesterone secretion during early pregnancy (maintenance progesterone), during oestrus (oestrous oestradiol) and during the luteal phase of the previous cycle (priming progesterone). The animals were killed at times equivalent to 1, 4 or 7 days after oestrus in those animals which had received oestrous oestradiol. The level of soluble oestradiol and progesterone receptors in whole uterus, and [3H]oestradiol and [3H]progesterone metabolism by uterus minces were measured. Oestradiol receptor level was highest on day 1 in those animals receiving oestrous oestradiol with no significant effect at any stage of the inclusion or omission of priming or maintenance progesterone. Progesterone receptor level was also high on day 1 in those animals receiving oestrous oestradiol with high levels maintained to day 4. Again, inclusion of priming or maintenance progesterone was without effect. In animals not receiving oestrous oestradiol the level of both receptors was uniformly low. Metabolism of [3H]oestradiol was low and not affected by treatment. [3H]Progesterone metabolism, although more variable, was also low and not affected by treatment.


Preweaning mortality in the pig. The prevalence of various causes of preweaning mortality and the importance of some contributory factors.

The relative importance of the various causes of preweaning mortality in the pig was determined from the results of autopsy and laboratory examinations on 718 animals. Conditions associated with parturition accounted for 25.1% of the losses, while physical factors (33.0%), starvation (12.8%) and septicaemia (10.9%) were the most common causes of death in piglets which were born alive. In contrast enteric diseases, viral infections, genetic conditions and various miscellaneous diseases played a relatively minor part. Some biological factors affected the prevalence of the various causes of death. Most losses from physical factors, starvation and septicaemia occurred during the first 4 days of life, while other infectious conditions were more common in older piglets. Large litters at birth had significantly more deaths associated with parturition and due to physical factors and starvation. Increased losses from physical factors occurred in the litters of gilts and sows of parity 5. The size of the enterprise and the use of farrowing crates combined to influence the extent of losses due to physical factors. A significantly higher mortality occurred in the large piggery in which crates were not used. The large units also had fewer deaths resulting from starvation.


Effect of chronic ethanol ingestion on the small intestinal ultrastructure in rats.

Rats maintained for a period of 16 weeks on a supplemented solid semisynthetic diet and ethanol corresponding to 35% of the total caloric intake developed ultrastructural changes in the small intestine as compared to pair-fed controls. The enterocytes from jejunal and ileal villi of the alcoholic animals exhibited conspicuous alterations of mitochondria and smooth and rough endoplasmic reticulum. The mitochondrial changes were characterized by enlargement, swelling, decreased matrical density, ruptured cristae, and occasional myelin figures. The smooth endoplasmic reticulum was dilated and apparently proliferated in a few epithelial cells. The rough endoplasmic reticulum appeared scarce with fewer ribosomes attached to the cisternae. These findings are postulated to provide further evidence that the chronic consumption of ethanol exerts a direct causative role in the pathogenesis of small intestinal damage in rats. Furthermore it can be especulated that these changes could be responsible, at least in part, for the functional abnormalities commonly found in chronic alcoholism.


The radiological investigation of intramedullary spinal tumours.

The place of the various radiological techniques in the diagnosis of spinal cord tumours is described. With appropriate regard to the clinical picture, the choice of selective angiography. Metrizamide or Myodil myelography, and possible cyst puncture and endomyelogram, may be made with accuracy. Air myelography is less useful and less frequently employed. With these radiological aids, accurate localisation of tumour nodules for biopsy or excision is usually possible, and the necessity for long exploratory laminectomies avoided.


Recurrent postpartum uterine inversion.

A patient with recurrent postpartum uterine inversion is presented and discussed.


Mechanism of the prenyl-transfer reaction. Studies with (E)- and (Z)-3-trifluoromethyl-2-buten-1-yl pyrophosphate.

The prenyl-transfer reaction catalyzed by porcine farnesyl pyrophosphate synthetase has been studied using (E)- and (Z)-3-trifluoromethyl-2-buten-1-yl pyrophosphates as substrates and inhibitors. The rate of condensation between isopentenyl pyrophosphate (IPP) and the allylic fluoro analogues is drastically depressed relative to the normal catalytic rate observed with dimethylallyl pyrophosphate (DMAPP) or geranyl pyrophosphate (GPP). A similar depression is found in the rates of solvolysis for methanesulfonate derivatives of the fluoro analogues in aqueous actone under typical SN1 reaction conditions. Prolonged incubation of [14C] IPP and (E)- or (Z)-CF3-DMAPP with the enzyme, followed by treatment with alkaline phosphatase, gave a product that comigrated with geranylgeraniol on a polystyrene column. Both fluoro analogues showed mixed linear inhibition patterns with DMAPP or GPP as the variable substrate. We interpret these results in terms of an ionization-condensation-elimination mechanism for the prenyl-transfer reaction.


Nature of DNA synthesized in the presence of ATP in isolated nuclei.

Optimal DNA synthesis in isolated Ehrlich ascites tumor cell nuclei depends upon the presence of ATP. The increased synthesis in the presence of ATP is shown to be due primarily to increased synthesis per active site rather than initiation of synthesis at different sites. The size of the short pieces observed in the presence of ATP is larger than the corresponding pieces observed in the absence of ATP.


Effect of ATP analogs of DNA synthesis in isolated nuclei.

Optimal synthesis of DNA in Ehrlich ascites cell nuclei is shown to be dependent upon the presence of both ATP and ADP. ATP can be replaced only by dATP. An ATP regenerating system is less effective than ATP alone or ATP in combination with ADP. ATP does not stimulate DNA synthesis primarily by maintenance of deoxyribonucleotide triphosphate levels. When the inhibition of DNA synthesis by high ATP levels is taken into account, the ATP analogs adenosine 5'-(alpha,beta-methylene)triphosphate, adenosine 5'-(beta, gamma-methylene)-triphosphate, and adenosine 5'-(beta, gamma-imino)triphosphate can neither substitute for ATP nor inhibit the ATP stimulation of DNA synthesis. Adenosine 5'-(3-thio)triphosphate, however, is a competitive inhibitor of DNA synthesis.


Extracellular matrix metabolism by chondrocytes. III. Modulation of proteoglycan synthesis by extracellular levels of proteoglycan in cartilage cells in culture.

Proteoglycan biosynthesis by cultured chondrocytes was shown to be depressed by extracellular concentrations of proteoglycan and partially degraded proteoglycan. This reduction in proteoglycan synthesis was reversible on removal of the added proteoglycan. Benzyl-beta-D-xyloside, an exogenous acceptor of glycosaminoglycan synthesis, was used and it was shown that proteoglycan was inhibiting glycosaminoglycan synthesis. Proteoglycan had no effect on the overall protein synthesis by the cultured cells. It was concluded that the exogenous proteoglycan was inhibiting proteoglycan synthesis at the level of initiation or elongation of the glycosaminoglycan chains.


Inhibitory effects of tunicamycin on procollagen biosynthesis and secretion.

Chick embryo cells were briefly exposed to the antibiotic, tunicamycin. Pre-exposed cells, compared to control cultures, showed a severe, progressive inhibition of the incorporation of glucosamine and mannose into total cellular macromolecules. Inhibition of the incorporation of glycine, leucine and proline was also progressive but not as marked as for the carbohydrates. Cellular secretion of all macromolecules was severely impaired. while comparison of the procollagens showed no difference in their subunit size or in their degree of glycosylation; the intracellular content of procollagen polypeptides was similar for both types of cells. In vitro studies showed that tunicamycin selectively inhibited glucosamine, but not mannose, incorporation into macromolecules. The composite results indicate that tunicamycin effectively inhibits protein synthesis, protein glycosylation and protein secretion in chick embryo cells.


Suppression of pimozide-induced prolactin secretion by piridoxine (vitamin B6).

I.V. administration of 300 mg. Pyridoxine caused an acute fall in prolactin (PRL) plasma levels in six normal subjects. Like levodopa, pyridoxine suppressed the increase in PRL secretion induced by treatment with pimozide, a specific dopamine receptor blocking agent. These findings further support the hypothesis that vitamin B6 stimulates dopaminergic activity at hypothalamic and/or hypophyseal level.


Platelet-bound complement (C3) in immune thrombocytopenia.

The fixation of complement to the circulating platelet in immune thrombocytopenia was detected by measurement of one of the complement components, C3, on the surface of platelets from patients with idiopathic thrombocytopenic purpura (ITP) and systemic lupus erythematosus (SLE) using the anti-C3 consumption assay. The surface IgG was determined simultaneously using the previously described anti-IgG consumption assay. Washed platelets from normal controls had 3.5 fg (10(-15) g) of C3, or about 11,000 molecules, per platelet, an amount comparable to the IgG (4.1 FG, or 15,000 molecules, per platelet). For most patients with ITP both C3 and IgG were increased on the platelet surface, although for 5 of 16 patients only IgG was increased. Two patients with SLE and thrombocytopenia had an increase in both C3 and Ig, six patients with SLE who were not thrombocytopenic had normal amounts of membrane-bound C3 and IgG. In 5 patients, 3 with ITP and 2 with collagen vascular disease, both surface immunoproteins decreased with successful treatment of the thrombocytopenia.


Paget's disease. Radiological changes occurring in untreated patients and those on therapy with salmon calcitonin during two years' observation.

Radiological observations over two years were made in 23 patients with Paget's disease. Radiological criteria for progression and regression of disease are defined. Fourteen of the patients were treated with salmon calcitonin. Of these treated patients four showed regression of the disease and only two showed progression, both in the skull vault. Of the remaining nine untreated patients none showed regression but two showed progression. The radiological findings confirm that calcitonin will prevent the extension and sometimes induce healing of Paget's disease in long bones but that the skull appears to respond differently. Radiological changes were slow to occur and yearly or two yearly follow up is sufficient.


The effects of Ca2+ antagonists on Ca2+ accumulation by subcellular fractions of rat myometrium.

Several agents which antagonize or interact with Ca2+ in the excitation-contraction coupling of smooth muscle have been tested for their effects on Ca2+ accumulation by subcellular fractions of the rat uterus. Na+, but not K+, reduced the amount of Ca2+ that could be accumulated by the plasma membrane fraction (PM) and the endoplasmic reticular fraction (ER). Sr2+ considerably reduced Ca2+ accumulation by PM, ER, and the mitochondrial fraction; Ba2+ had a similar effect but was not as potent as Sr2+. La3+ at concentrations up to 10 mM was unable to block Ca2+ accumulation by PM and ER completely. The pharmacological agents D600, verapamil, and chlorpromazine all inhibited Ca+ accumulation at dose levels much higher than those required to inhibit contractility, and were ineffective at lower doses. The action of Ca2+ antagonists is seen to be complex, involving interactions at different sites and on different processes. For a fuller understanding of their mechanisms of action further studies upon passive binding and on the release of Ca2+ from subcellular sites are required.


Variability in development of tolerance to repeated injections of low doses of dl-amphetamine in rats.

Male albino rats received injections of saline for 5 days before and 5 days after a series of 10 daily injections of dl-amphetamine, 1 or 5 mg/kg, sc. Core temperatures were measured every 30 min for 4 h after each injection and feeding activity (on a CRF operant schedule) every 30 min throughout. After amphetamine at either 0800 or 2000 h, a dose-related hyperthermia, stereotypic behavior, and an initial inhibition of feeding occurred. This anorexia decreased over the 4-h post injection period only in the evening-injected rats receiving 5 mg/kg. Mean body weights of all groups continued to increase during amphetamine administration. Mean 24-h food intake tended to remain below that in the control period and the hyperthermic response did not change significantly in any group. Initially on withdrawal from amphetamine all groups showed 'rebound' feeding. Taken with earlier reports, these results suggest that tolerance development to amphetamine-induced anorexia, hyperthermia, and stereotypic behavior occurs at different rates and is dependent upon frequency, route, dose, time, the amphetamine used, and whether the diet was restricted.


[Chemical composition and degradation of the cells walls of a wild-type and of a white mutant of the mushroom Drechslera sorokiniana].

The cell walls of the fungus Drechslera sorokiniana and an albino mutant have been studied to determine if disappearance of pigment also involves an important modification of the chemical structure. The albino mutant has lost, besides the pigment, pentose, xylose, and part of galactose and mannose. The protein contents as well as those of hexosamine and chitin are not modified. After treatments of the walls with 2 M NaOH-0.5 M H2SO4 and with ethylenediamine identical compounds are isolated from the two walls; however, cell walls of the mutant are more easily and more extensively degraded than those of the wild type. This difference in resistance is not only due to the presence of pigment but also to a different architectural structure of the two cell walls.


Effects of 17beta-estradiol and progesterone on growth and morphology of human endometrial carcinoma cells in vitro.

The effects of 17beta-estradiol and progesterone on the rate of growth and the morphological changes of human endometrial adenocarcinoma cells were studied in in vitro culture. 17beta-Estradiol enhanced their growth and produced no cellular morphological changes at low concentrations of less than 1 microgram/ml, whereas it suppressed their growth and produced such cellular changes as enlargement of nuclei, karyorrhexis, and karyolysis at high concentrations of more than 5 microgram/ml. On the other hand, progesterone did not affect the cells at less than 1 microgram/ml, but it suppressed their growth and induced differentiation at more than 5 microgram/ml. Specific morphological changes produced by progesterone were characterized by multinucleation, multinucleolation, prominent Golgi apparatus, occurrence of vacuoles, and papillary-like arrangement of cells. These features suggested that progesterone acted directly on the endometrial carcinoma cells and induced their histological differentiation. These changes could not be detected by the adminstration of 17beta-estradiol.


Improved growth of in vitro colonies in human acute leukemia with the feeding culture method.

Bone marrow cells freshly aspirated from the 10 consecutive untreated adult patients with acute nonlymphocytic leukemia were cultured by 2 different methods: the conventional agar culture method for myeloid colony formation and its modification by daily feeding with culture medium. In 5 patients, colonies grew in much higher numbers (4.7-to 330-fold) with feeding than without. Three patients grew colonies only with feeding. Two of these 3 patients required L-ascorbic acid in the fed medium for colony growth. Colonies did not grow from the remaining 2 patients by any method. In 7 patients the number of colonies grown with feeding were much higher, up to 170 times higher, than were those from normal control marrows, which grew the same number of colonies regardless of feeding or L-ascorbic acid. Peroxidase and Wright's stains indicated the myeloid differentiation of the cells in the leukemic marrow colonies. The leukemic origin of the colonies was proven by chromosomal analysis. The wide range of linearity between the number of cells plated and the number of colonies grown permits quantitative assay of colony-forming leukemic cells. This assay should be valuable for studies of chemotherapy, growth regulation, and differentiation of leukemic cells.


Comparative epidemiology of tobacco-related cancers.

In a retrospective study, interviews were obtained with 3,716 patients with histologically proven cancer of the lung (Kreyberg types I and II), mouth, larynx, esophagus, or bladder and with over 18,000 controls. For each of these cancers, the relative risk of both male and female present smokers increased with the quantity smoked and the duration of the habit. The strongest increase occurred for cancer of the lung and larynx, and the least increase occurred for cancer of the esophagus and bladder. For exsmokers the risk decreased with years of cessation. The risk for mouth cancer of pipe and cigar smokers who inhaled much less than cigarette smokers was less than that of the latter and increased with the quantity smoked. The risk of mouth, larynx, and esophagus cancer among smokers increased with the quantity of alcohol consumed. Greater smoking habits and lesser cessation rates were noted among lower socioeconomic groups, suggesting that these groups will bear an ever increasing proportion of the burden of tobacco-related cancer.