Serum carcinoembryonic antigens in patients with carcinoma of the cervix.

Serum levels of carcinoembryonic antigen (CEA) were measured by a radioimmunoassay technique. The mean CEA level for 80 controls was 2.03 ng/ml with a standard deviation of 0.49 ng/ml. Hence, the upper limit of normal for serum CEA levels was considered to be 3.01 ng/ml, ie, two standard deviations above the mean. Serum CEA levels were measured in 86 patients with cervical squamous cell carcinoma, Stages 0 through IV. Thirty-five of the 74 patients with invasive cervical carcinoma were CEA-positive (serum levels above normal); patients with cervical dysplasia or carcinoma in situ were all CEA-negative. Study of the distribution of these patients together with the extent of their disease leads to the following conclusions: a) determination of serum CEA levels cannot serve as a test for the early diagnosis of cervical cancer or precancerous lesions; b) in patients with clinical Stage I or II cervical cancer, an elevated serum CEA level indicates a greater likelihood of parametrial invasion or lymph node metastasis; c) in patients with treated carcinoma of the cervix, continued normal levels of serum CEA affirm continued absence of the disease, whereas development of an elevated level is highly suspicious of occult residual or recurrent cancer. The authors urge periodic determinations of serum CEA levels in patients with treated cervical cancer.


Borderline microinvasive carcinoma of the cervix.

This study identifies borderline microinvasive carcinoma of the cervix as a subgroup of microinvasive carcinoma. We define borderline microinvasive carcinoma of the cervix as the infiltration of neoplastic squamous epithelial cells into the stroma where the depth of infiltration is 1 mm or less from the basement membrane of the epithelial surface immediately adjacent to the site of infiltration without capillary-like or lymphatic-like space involvement. In a 20-year review of cervical neoplasia in our institution, 29 cases of borderline microinvasion were identified. None of these 29 patients had recurrent carcinoma. Of our in situ carcinomas, 4.8% were found to be borderline lesions on review. Of our cases initially interpreted as microinvasion, 27.1% were, in fact, borderline lesions. There are better data to establish the criteria for borderline microinvasive carcinoma than there are to establish the absolute depths of invasion that would be unequivocally acceptable as "microinvasion." Borderline microinvasive carcinoma of the cervix is a lesion which is not metastatic and can be treated by nonradical methods.


Prenatally diagnosed blocked atrial premature beats.

A case of persistent severe bradycardia in labor, diagnosed as blocked atrial premature beats, is presented. Simultaneous recording of fetal heart rate (FHR) and fetal electrocardiogram (FECG) during labor established an accurate diagnosis of an innocent fetal sinus bradycardia and differentiated it from fetal distress. This method should be applied in all cases of persistent fetal dysrhythmia, in order to differentiate it from hypoxic distress, and thus enable the obstetrician to avoid unnecessary cesarean sections.


Maternal serum estrogen and progesterone concentrations preceding normal labor.

Simultaneous measurement of serum concentrations of estrone (E1), estradiol (E2), estriol (E3), and progesterone were carried out in multiple serial blood samples obtained during the last 3-10 weeks of pregnancy, labor, and the immediate postpartum period in 5 normal women. Estrogen and progesterone levels showed a small, but statistically significant diurnal variation during pregnancy. They did not change during labor; however, with the exception of E1 levels, all declined following delivery. Individual patterns preceding labor, derived from calculated moving mean values, showed no consistent decline in progesterone levels nor a surge in E1 and E2 concentrations whereas estriol levels showed a steady rise starting 14-28 days prior to the onset of labor. Whether this E3 elevation reflects fetal maturation and/or plays a role in the triggering mechanism of labor is unknow. Failure to detect changes in E1, E2, and progesterone levels in the maternal peripheral circulation does not preclude the possibility that alterations of metabolism of these hormones in the fetal or uterine compartments might be involved in the initiation of human labor.


The morphology of the earliest invasive cell in low genital tract epidermoid neoplasia.

The light and electron microscopic characteristics of the distinct eosinophilic microinvasive cell in the lower genital tract epidermoid neoplasia are described. The eosinophilic quality of the invasive cell is associated with an accumulation of contractive protein seen at the ultrastructural level. The presence of these differentiated cells near the basement membrane should be viewed with more concern as they contain the cytoplasmic machinery with which to invade.


Argon laser iridotomy in the treatment of patients with primary angle-closure or pupillary block glaucoma: a clinicopathologic study.

A "pulsed" argon laser was successful in 48 of 64 (75%) attempted laser iridotomies. Scanning and transmission electron microscopy performed on specimens taken at varying intervals following laser treatment revealed progressive scarring of iris tissue. The complications appear minimal at this time, but longer follow-up is required before it can be stated that laser and surgical peripheral iridectomies are comparable. However, the laser's simplicity and ease of administration appear to warrant its continued use at this time.


Cryopreservation of the infective larvae of the common nematodes of ruminants.

Exsheathed infective larvae (L 3) of 19 species of nematodes were tested for infectivity in either sheep or cattle after they had been frozen in 0,9% NaCl solution, stored for a relatively short time in the gas phase of liquid nitrogen and subsequently thawed. In addition, 13 of these species were tested after similar storage for up to 18 months. In sheep, Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus axei, Trichostrongylus colubriformis, Nematodirus spathiger and Oesophagostomum columbianum were viable after 2 years of cryopreservation, a mean of greater than 90% of the L 3 being alive when thawed after this period. Similar results were obtained with Chabertia ovina L 3 after 18 months and with Marshallagia marshalli, Trichostrongylus falculatus and Dictyocaulus filaria, after a short period of freezing. On the other hand, Gaigeria pachyscelis and Strongyloides papillosus survived freezing for up to 7 months but neither was viable at the end of this period, nor was exsheathed G. pachyscelis viable without freezing. Most of these infestations were established by inoculating the infective larvae into the abomasum and/or duodenum. M. marshalli, T. falculatus and C. ovina also proved infective after oral dosing. D. filaria, the only other species tested by this route, was not infective when dosed per os after thawing. The infective larvae of the bovine nematodes, Haemonchus placei, Ostertagia ostertagi, Nematodirus helvetianus, Oesophagostomum radiatum, Cooperia pectinata and Cooperia punctata survived freezing for a mean of 26 months, greater than 90% being alive on thawing, but infectivity was generally lower than with the same genera in sheep. Even when not frozen, exsheathed Bunostomum phlebotomum was non-infective. When Cooperia spp. after thawing were tested for infectivity by the oral route, more worms developed in one calf infested orally than in another infested by inoculation into the duodenum. Ova of H. contortus, M. marshalli, O. circumcincta, T. colubriformis, T. falculatus, N. spathiger, C. ovina, H. placei, O. ostertagi, Cooperia spp. and N. helvetianus were recovered from the faeces of animals infested with cryopreserved L 3. No ova of O. columbianum or O. radiatum were recovered from faeces, because differential larval counts were performed before they were patent. Nevertheless, gravid females were obtained post-mortem. Frozen L 3 of N. helvetianus were used to re-establish a pure strain in calves, 2,3 million ova being recovered from infestations with 10 670 L 3 frozen for 26 months. The infectivity of the progeny of frozen L 3 was tested with M. marshalli and C. ovina. In both instances infectivity was high and the worms which developed also produced ova, thus completing the cycle. This appears to be the first report of infective larvae of parasitic nematodes retaining their infectivity after being frozen in liquid nitrogen (gas phase) for longer than 2 years. This is also apparently the first time that M. marshalli T. colubriformis, T. falculatus, T. axei, N. spathiger, C...


Forelimb reflexes modulated by tonic neck positions in cats.

The modulation of monosynaptic forelimb reflexes by tonic neck positions was investigated in cats with the head fixed. Lateral flexion of the body in a horizontal plane markedly facilitates reflexes of the deep radial nerve (DR) in the ipsilateral forelimb, while the antagonistic ulnar nerve (ULN) reflexes are strongly inhibited. Opposite effects are seen after contralaternal body movement. Dorsiflexion of the body clearly increases DR-reflexes and exerts a reciprocal although more pronounced inhibition on ULN reflexes. Opposite effects appear after ventriflexion. The reflex modulation starts with head-body displacements of approximately 5 degrees and increases with increasing angles. Furthermore reflex modulation does not depend on the intact cerebrum and cerebellum. The comparison of forelimb and hindlimb reflexes shows a decrease of the neck influences along the spinal cord.


Effective compliance of the circulation in the upright sitting posture.

The effective compliance is defined as the relation of change in blood volume to change in central venous pressure. It was measured in 8 upright sitting male subjects and amounted to 3.3 ml/(mm Hg X kg BW). It is, therefore, by about 50% greater than the effective compliance in the supine subject which amounts to 2.3 ml/(mm Hg X kg BW). . This difference is probably due to the posture dependent blood volume distribution in the low pressure system whose "upper" and "lower" sections have nonlinear pressure-volume characteristics. Immersion to the neck reduces the effective complicance to about half the control value (1.9 ml/(mm Hg X kg BW) which probably constitutes the effective compliance of the intrathoracic circulatory compartment.


Effects of pulmonary gas embolism on circulation and respiration in the dog. V. Effect of changing breathing gas composition on pulmonary gas embolization.

It was found in previous investigations that during venous gas infusion at low rates (1--5 ml/min-1) circulatory and respiratory variables reached a constant level after about 10--15 min. The present study demonstrates that this steady state can be disturbed by changing the composition of the breathing gas mixture. Alteration from air to 21% O2 in helium rapidly increased the embolic effects up to a maximum within 1.5--2 min; in the next 5--8 min the circulatory and respiratory variables returned to their previous levels during air breathing. Reverse effects occurred when changing from 21% O2 in helium to air. Similar phenomena were seen after switching from air to pure oxygen and from 21% O2 helium to pure oxygen. However, the extent of the circulatory and respiratory changes differed depending on the composition of the respective alternating breathing gas mixtures and on the initial embolic level as determined by infusion rate and kind of infusion gas. Gas movements between intravascular bubbles and alveolar space might be responsible for these changes.


Effects of pulmonary gas emoblism on circulation and respiration in the dog. VI. Influence of body position on the effects of pulmonary gas embolism.

In the present study the influence of body position on the effects of venous gas infusion was examined. The body position of anesthetized dogs ventilated artifically varied between supine, right-side-down and left-side-down position. Without venous gas infusion the change of body position hardly affected pulmonary arterial pressure (Pap) and alveolar CO2 fractional concentration (FACO2). However, during venous gas infusion a change of body position immediately elicited a rapid increase Pap and a decrease in FACO2 completed within a few seconds. Thereafter both variables gradually returned to their initial levels as before the change of body position. The extent of change in Pap and FACO2 due to alteration of body position depended on the initial embolic level (determined by the rate of infusion and the nature of the gas used) and on the change of body position.


Left ventricular active stiffness: dependency on time and inotropic state.

Left ventricular systolic stiffness was measured by rapidly changing ventricular volume (within 7 ms) of isovolumically contracting isolated rabbit hearts. Instantaneous pressure-volume relations were found to be linear with slopes that depended upon the moment during contraction at which the volume change was induced. These slopes were proportional to the total pressure developed in the ventricle just prior to the volume change. The same was found when the time course of pressure was influenced by changing the Ca++ content of the perfusate. An influence, however, also could be detected when end-diastolic volume was changed. At the same pre-release pressure a greater volume caused a decrease of active stiffness. The results indicate the possibility of an active component in ventricular systolic stiffness.


Distal site of calcium reabsorption in the rat nephron.

The site of outflux of 45Ca along the nephron  were investigated using microinfusion technique in acutely thyroparathyroidectomized (TPTX), intact and TPTX Wistar rats substituted with parathyroid hormone (PTH). In all three groups 45Ca outflux occurred along the proximal tubule, the loop of Henle and along the distal tubule. After microinfusion into late distal tubules 45Ca recovery in ipsilateral urine was essentially complete for the TPTX group but was only 83 and 65% for the intact and the PTH substituted animals. Increases in microinfusion flow rate from 2--20 nl/min into early and middle distal tubules resulted in increased urinary recovery of 45Ca for all three groups. Similarily, increases in microinfusate Ca concentration from 0.2--2.0 and 5.0 mmol/l resulted in increased fractional urinary recovery of 45Ca both in the presence and absence of PTH. When 45Ca and 3H insulin containing solutions were continuously microinfused into early distal tubules for one hour periods an anticalciuric effect of PTH could be demonstrated. It is concluded that Ca, in addition to its outflux in the proximal tubule and in the loop of Henle, is reabsorbed in the distal tubule accessible to micropuncture. PTH acts anticalciuric at this latter site.


Central thermosensitivity in conscious goats: hypothalamus and spinal cord versus residual inner body.

Experiments were performed on conscious goats to confirm the suggestion that in this species the inner body contains more thermosensitive structures than those residing in the hypothalamus and spinal cord. For this purpose goats were chronically implanted with local thermodes and intravascular heat exchangers to allow independent temperature control of the hypothalamus, spinal cord and residual inner body. With the hypothalamus and spinal cord clamped simultaneously at different levels between 32 degrees C and 40 degrees C, residual internal temperature was lowered by subtracting heat via the intravascular heat exchanger. The residual internal temperature at which shivering and increased heat production occured due to heat extraction, was directly related to the value of the combined hypothalamic and spinal cord clamp temperature. The higher hypothalamic and spinal cord clamp temperatures were, the lower residual internal temperature fell before shivering occurred and heat production rose. Plots relating residual internal temperature to hypothalamic and spinal cord temperature at different levels of heat production showed the signal input generated within the residual inner body to be of nearly the same order of magnitude as that from the hypothalamus and spinal cord.


CO2-dependent component of the neurogenic vascular tone in the cat.

Complete vascular isolation of the hindlimbs was performed in vagotomized cats under Sodium Pentobarbital anesthesia. The hindlimbs were perfused at constant flow with blood kept at a constant and physiological PO2, PCO2, and pH values by means of a specially designed pump-oxygenator system. The animals were hyperventilated with different CO2 mixtures (0%, 5%, 7% and 10% in O2) thereby changing blood gases and pH levels in the upper body but not in the hindlimb vascular bed. At body PaCO2 (mm Hg) of 13.7 +/- 1.0 (means +/- SE), 30.6 +/- 1.05, 40,4 +/- 0,9 and 58.4 +/- 2.9 the hindlimb perfusion pressure (mm Hg) was, respectively 124 +/- 7.6, 138 +/- 7.4, 156 +/- 11.9 and 187 +/- 15.1. These changes in perfusion pressure were still present after complete peripheral chemoreceptor denervation but were abolished after section of the spinal cord at the T5 level. Since hindlimb perfusion pressure fell when body PaCO2 was lowered below physiological levels it is concluded that part of the neurogenic vascular tone of the hindlimbs is maintained by a CO2 mediated stimulation of supraspinal structures.


Renal responses to angiotensin II and 1-sar-8-ala-aII in sodium replete and deplete dogs.

In order to elucidate the effects of angiotensin II on renal function, angiotensin II (AII; 1 ng/kg per min) and the AII antagonist 1-sar-8-ala-angiotensin II (AIIA; 200 ng/kg per min) were infused into the renal artery of anesthetized dogs (pentobarbital), on either a high (8 mmol/kg per day for seven days) or a low sodium intake (0.5 mmol/kg). In sodium replete dogs AII produced renal vasoconstriction with decreased RBF (-28%; P less than 0.001), but with less decrease of GFR (-14%; P less than 0.001), leading to an increase of FF (+19%, P less than 0.001), andantidiuresis (-39%, P less than 0.001); the antinatriuresis (-58%; P less than 0.001) exceeded the antidiuresis (P less than 0.001). delatRBF (-10%; P less than 0.001) was less pronounced (P less than 0.001) during AII in sodium deplete dogs, GFR remained unchanged, but FF increased to the same extent (+16%; P less than 0.05); diuresis and urinary electrolyte excretion were however not affected. AIIA did not affect RBF, GFR, FF, nor diuresis in sodium replete dogs suggesting that endogenous AII has no tonic influence on renal function in these conditions. In sodium deplete animals AIIA produced an 11% (P less than 0.001) increase of RBF, without changes of GFR; FF decreased by 12% (P less than 0.01), but diuresis, natriuresis and kaliuresis were not affected.


Nucleosome-associated proteins and phosphoproteins of differentiating Friend erythroleukemia cells.

Mononucleosomes derived from brief digestion of uninduced Friend cell nuclei with micrococcal nuclease contain a set of non-histone chromosomal proteins which are partly or altogether missing in the oligomeric nucleosomes. On the other hand, the latter contain a protein of Mr 190,000 not seen in the mononucleosomes. Longer digestion removes most of these non-histone proteins, excepting the Mr 190,000 protein. Brief digestion of nuclei from Friend cells induced by DMSO or by n-butyrate removes most of the non-histone proteins from the nucleosomes, as did the prolonged digestion of uninduced nuclei. The Mr 190,000 protein remains, while a protein of Mr 27,000 is increased. The rate of phosphorylation of histone H1 associated with mononucleosomes was 3 to 4-fold greater in cells induced with DMSO. The major phosphoprotein and most of the other phosphorylated non-histones were modified at the same rate in control and induced cells. However, a Mr 95,000 protein was less phosphorylated in the induced cells.


The presence of gastric parasites in winter-slaughtered reindeer.

The presence of gastric parasites in winter-slaughtered calves and adult animals, was investigated. The number of parasites found was low in case of the calves indicating that gastric worms are of low significance concerning the winter losses. In case of adult animals was found a higher infestation indicating that gastric nematodes maybe of importance concerning the winter losses of 1,5 years old animals, Ostertagia leptospicularis was the only found species except for one animal in which was also present a few spiculopteragia alcis. The total dominance of Ostertagia leptospicularis means a marked difference from the findings of autumn-slaughtered reindeer bulls where Ostertagia leptospicularis was not found to be such a frequent finding but in addition several other species were found. In view of that is discussed a seasonal varation, winter ostertagiosis seems not to be a problem in reindeer calves.


[Day-to-day variation in cell counts in milk (author's transl)].

The article presents results from two series of milk samples where samples from individual cows were collected at each milking over a period of two weeks. Fat content, protein content and cell count were determined for each sample. The cell counts (in thousands per ml) were transformed to logaritmic values and statistically analysed. As much as 75 to 80% of the variation (expressed as proportion of the total sums of squares) was due to differences "among cows" and about 3% due to differences "among days" during the sampling period. Samples from morning milkings had about 20% lower cell counts than samples from afternoon milkings. The standard deviation among samples from two consecutive milkings of the same cow (after removal of systematic differences between days and between morning and afternoon milkings) was computed as about 30% of the mean (i.e. coefficient of variation approximately 0.3). By combining samples from two milkings the random "error" in cell count can be reduced to about 20% of the mean. The samples exhibited a highly significant, but nummerically small, positive within-cow correlation between fat content and cell count, and between protein content and cell count, while the corresponding correlation between milk yield and cell count was slightly negative (non-significant).


Use of common plant lectins for isolation and characterization of constitutive and developmentally regulated cell surface associated glycoproteins of Dictyostelium discoideum.

Glycoproteins as a class of molecules have been implicated as serving crucial roles in cell recognition events. Using 3 common plant lectins, we have isolated and identified a number of cell surface associated glycoproteins. The appearance of at least 5 of these proteins is under developmental regulation.


Developmentally regulated lectins in cellular slime molds and embryonic chick tissues.

Several species of cellular slime mold (including D. discoideum and P. pallidum) and a number of embryonic chick tissues (including muscle, heart, brain, and liver) contain lectin activities that can be extracted and assayed as hemagglutinins. In all cases studied the lectin activities show significant changes with differentiation. The studies with cellular slime molds are more advanced; and suggest that lectins play a role in developmentally regulated cell cohesion. The function of the embryonic chick lectins in differentiation is presently under investigation.


Closed-circuit television monitoring of problematic radiotherapy patients.

The authors suggest that closed-circuit television be used to monitor patients who cannot understand or cooperate with hazardous medical treatment.


Congenital pulmonary atresia with ventricular septal defect: angiographic and surgical correlates.

Of 181 patients with severe congenital pulmonary atresia and ventricular septal defect or "type IV truncus" (an obsolete term), all but 11% had true central pulmonary arteries. These arteries were demonstrable by large serial biplane angiograms using multiple selective injections into collateral vessels, frequent photographic subtraction, and occasional pulmonary vein-wedge angiograms. These techniques are extremely important for accurate diagnosis and in planning corrective or palliative surgery, which was done in 77% of patients with pulmonary arteries.


Effects of prostaglandin E2 and DL204 IT, an inhibitor of prostaglandin degradation, on ovulation and ovum transport in the hamster.

The effects of 2(3-ethoxyphenyl)-5,6-dihydro-s-triazole-[5,1-a]isoquinoline (L-11204 or DL 204 IT and PGE2 on ovulation and ova transport were studied. DI 204 IT was administered in doses of 0.2-25 mg/kg s.c. on the day of estrus. A smal reduction in ovulating follicles was observed 96 hours later, but only at the 5 mg/kg dose level. At all dose levels, however, DL 204 IT caused a dose-related reduction in the number of ova in the oviducts. PGE2 at a total dose of 2 mg/animal s.c., administered in 4 divided doses over the second and third day of the cycle did not affect ovulation or ova transport. PGE2 plus DL 204 IT (5 mg/kg), however, completely blocked ovulation in all but one animal. That animal had one ovulated follicle and a single ova was recovered from its oviduct.


Stereospecific antibodies to methadone. II. Synthesis of d- and 1-methadone antigens.

Diastereomeric methadols were prepared by reduction of the methadone enantiomers. Resulting methadols, after purification and characterization by mass spectrometry, were succinylated. The hemisuccinyl derivatives were conjugated with thyroglobulin via carbodiimide condensation. The conjugates of d- and of 1-methadol hemisuccinyl-thyroglobulin were employed as the antigens for immunization of white New Zealand rabbits in order to obtain specific anti d- and anti 1-methadone antisera.


[Antiserums against carcino-embryonic antigen (CEA) can induce a specific lysis of colon carcinoma cells by normal lymphocytes].

Antibody-dependent cell-mediated cytotoxicity (ADCC) against human colon carcinoma cells grown in vitro was demonstrated with two specific rabbit anti-carcinoembryonic antigen (cea) antisera. The same antisera did not lyse the colon carcinoma cells in the presence of complement but without lymphocytes. The normal human lymphocytes in the absence of anti-CEA antiserum had a very low cytotoxic activity during the three hours 51Cr release assay used in this study. Two colon carcinoma cell lines, HT-29 and Co-115, expressing CEA on their surface as demonstrated by immunofluorescence, were significantly lysed in the ADCC test, whereas control tumor cell lines, not expressing CEA, were not affected by the anti-CEA sera and the lymphocytes. The specificity of the reaction was further demonstrated by the inhibition of antibody-dependent cell-mediated cytotoxicity after the addition of increasing amounts of purified CEA to the antiserum. The absorption of the anti-CEA antisera was controlled by radioimmunoassay. Absorption of the antisera by normal lung extracts and red cells of different blood groups did not decrease the cytotoxicity.


Preparation of sarcolemmal membrane from myocardial tissue culture monolayer by high-velocity gas dissection.

A high-velocity stream of nitrogen is used to simultaneously disrupt myocardial cells in monolayer culture and fractionate their sarcolemmal membranes. The membranes show a high degree of ultrastructural and enzymatic purity, with less than 1 percent intracellular residuum. They are produced in less than 1 second and remain as tightly adherent sheets on the surface on which the cells were grown. The cells are exposed to no agent other than nitrogen gas during the preparative procedure.


Biochemical evidence for keratinization by mouse epidermal cells in culture.

More than 70 percent of the urea-extractable proteins from mouse stratum corneum or from differentiated cells of mouse epidermis grown in culture are two proteins of molecular weight 68,000 (keratin I) and 60,000 (kerae are two proteins of molecular weight 68,000 (keratin 1) and 60,000 (keratin 2), which are present in equimolar amounts on polyacrylamide gels. These proteins are the subunits of the keratin filaments, because when isolated from stratum corneum or cells grown in culture they form native-type epidermal keratin filaments in vitro. These observations provide biochemical evidence that epidermal cells grown in culture synthesize the major differentiation products of the epidermis.


Induction of Zugunruhe by photostimulation of encephalic receptors in white-crowned sparrows.

Daily 20-hour encephalic photophases (DEPP), transmitted (hours 0 to 20) via chronically implanted light-conducting fibers to selected sites in the basal hypothalamus of male white-crowned sparrows, were superimposed on daily 8-hour (hours 0 to 8) external ambient photophases (DAPP). Initially the birds displayed motor activity only during the 8-hour DAPP. After a delay of at least 2 weeks, some of the birds became intensively active during hours 8 to 20. We postulate that this period of "nocturnal" activity is equivalent to the nocturnal Zugunruhe shown by caged individuals of many nocturnally migratory species subjected to long days; such activity is generally regarded as the expression of migratory behavior.


Long-term treatment with lithium prevents the development of dopamine receptor supersensitivity.

Long-term treatment of rats with haloperidol produced an increased sensitivity to the locomotor and stereotypic effect of apomorphine. This behavioral dopaminergic supersensitivity was accompanied by increased binding of [3H] spiroperidol in the striatum. Rats treated concurrently with lithium and haloperidol failed to develop both behavioral sensitivity to apomorphine and increased striatal dopamine receptor binding. The ability of lighium to prevent recurrent manicdepressive episodes may be related, in part, to its ability to stabilize dopaminergic receptor sensitivity.


Neuroleptic-induced "anhedonia" in rats: pimozide blocks reward quality of food.

The dopamine receptor blocker pimozide attenuated lever-pressing and running for food reward in hungry rats. In each case the characteristic behavior of pimozide-treated rats was the same as that of undrugged rats when reward was simply withheld. Drug-induced performance difficulties were ruled out by the presence of periods of normal responding in drug-treated animals. Pimozide appears to selectively blunt the rewarding impact of food and other hedonic stimuli.


Rabies: decimation of a wolf pack in artic Alaska.

In a pack of ten wolves, one wolf behaved atypically and fought with several packmates. This wolf was shot when it approached the author. Within 4 weeks at least six other members of the pack were dead. Rabies was confirmed in the wolf that was shot and in two others that had not decomposed. Most of the wolves infected with rabies had sought or remained at familiar areas in the core area of their territory, which implies that they were not contacting neighboring packs. This was confirmed with an aerial survey. Arctic foxes, experiencing a regionwide rabies epizootic, were suspected vectors.


Early maternal separation increases gastric ulcer risk in rats by producing a latent thermoregulatory disturbance.

Rat pups that are separated early from their mothers, at postnatal day 15, become hypothermic when subjected to physical restraint on postnatal day 30. Restraint of separated pups also elicits an unusually high incidence of gastric erosions, as well as insomnia and an increase in quiet wakefulness. If hypothermia during restraint is prevented, neither the erosions nor the behavioral responses occur. Rat pups separated at the customary age (postnatal day 22) do not become hypothermic during restraint, and the restraint of such pups is not associated with either gastric erosion or insomnia.


Severe thrombocytopenia after generalized herpes simplex virus-2 (HSV-2) infection.

Our patient, we believe, experienced a primary HSV-2 infection manifested by fever, malaise, and orogenital mucocutaneous lesions. With resolution of systemic manifestations, and at a time of theorized rise in HSV-2 antibody levels, he had thrombocytopenic purpura which persisted for several weeks. An immune disorder secondary to HSV-2 infection similar to that of postrubella infection is postulated. If this theory is correct, severe immune thrombocytopenic purpura is yet one more of the many observed complications of HSV infection.


The selection of wild-type revertants from methotrexate permeability mutants.

In a previous report, we described the selection and partial characterization of three distinct classes of methotrexate (Mtx)-resistant Chinese hamster ovary cells (CHO) (1). Class I cells contained a structural alteration in dihydrofolate reductase. Class II cells showed a alteration affecting the permeability of the drug. Class III cells, selected from class I cells, had an increased activity of the altered enzyme. In the work described here, the sensitivity of these lines to the diaminopyrimidines has been investigated. Class I cells are as sensitive, class II cells are 5- to 10-fold more sensitive, and class III cells are 10- to 30-fold more resistant than wild-type cells. The increased sensitivity of the class II cells provided an opportunity to select for revertants of these mutants and such phentotypic wild-type revertant cells have been selected using one diaminopyrimidine, pyrimethamine. Such cells have drug sensitivities and permeability characteristics similar to wild-type cells. A second class has been identified which has wild-type drug sensitivities to the diaminopyrimidines but Mtx class II resistance to Mtx, and drug permeabilities characteristic of Mtx-resistant class II cells.


Dominance of colchicine resistance in hybrid CHO cells.

Intraspecific hybrids of colchicine-sensitive with colchicine-resistant (CHR) Chinese hamster ovary cells were constructed, using six different colchicine-resistant clones from two independent series. In each instance, colchicine resistance was expressed in an incompletely dominant manner. Some hybrid clones were examined further for the expression of the pleiotropic CHR phenotype and for the cell surface P glycoprotein. These features of the colchicine-resistant phenotype were also expressed coordinately.


Assignment of the genes for triose phosphate isomerase to chromosome 6 and tripeptidase-1 to chromosome 10 in Mus musculus by somatic cell hybridization.

Evidence is presented for the assignment of the gene for triose phosphate isomerase to Mus musculus chromosome 6 and tripeptidase-1 to chromosome 10 by synteny testing and chromosome assignment in Chinese hamster X mouse somatic cell hybrid clones. Neither TPI nor TRIP-1 were expressed concordantly with any known isozyme markers in 45 hybrid clones (13 primary and 32 secondary). Karyotypic analysis of 21 clones showed that the expression of TPI and chromosome 6 were concordant in all cases as was expressed of TRIP-1 and chromosome 10. Both chromosomes were previously unmarked by isozymes.


Assignment of a Mus musculus gene for triosephosphate isomerase to chromosome 6 and for glyoxalase-I to chromosome 17 using somatic cell hybrids.

Chinese hamster X mouse hybrid cells segregating mouse chromosomes have been used to assign a gene for triosephosphate isomerase (TPI-1, EC 5.3.1.1, McKusick No. 19045) to mouse chromosome 6, and a gene for Glyoxalase-I (GLO-1, EC 4.4.1.5, McKusick No 13875) to mouse chromosome 17. The genes for TPI-1 and lactate dehydrogenase B are syntenic in man and probably so in the dog. It is therefore likely that they are syntenic also in the mouse. It is of interest then that there is a mouse gene, Ldr-1, on chromosome 6 that regulates the level of LDH B subunits in mouse erythrocytes. The locus for GLO-1 is closely linked to the major histocompatibility complex in man. Since the major histocompatibility complex in the mouse is present on chromosome 17, this locus and the Glo-1 locus are syntenic in the mouse as well. This finding adds to the number of autosomal gene pairs which are syntenic in both mouse and man and reinforces the belief that there is considerable conservation. of linkage groups during evolution.


In vitro liver clearance of tritiated estradiol-17beta in the female rat after retrochiasmatic transection and ovariectomy.

It was reported in a previous study that serum estradiol-17beta (E2) was elevated in rats after retrochiasmatic transection (FC). Serum E2 was also higher in estradiol cypionate treated, ovariectomized (OVX) rats that had been subjected to FC than in those that had not. This suggested that increased secretion of E2 was not the only factor responsible for elevated serum E2 after FC. To ascertain the contribution of decreased metabolism of E2 to this response, liver tissue slices were incubated with 3H-estradiol-17beta, and the rates of 3H uptake and conversion to water-soluble conjugates were measured. The rate of uptake of 3H by the tissue was not indicative of the rate of conjugate formation. Livers of rats with high serum E2 exhibited lower rates of 3H uptake than those of rats with low serum E2. Even so, the formation of 3H conjugates was greater in liver of rats with high serum E2. As hypothesized, livers of rats with FC formed conjugates at a significantly lower rate than those of similarly treated rats without FC. Thus, FC of an intact rat leads to an increase in serum E2 by increasing the secretion of E2, and apparently also by decreasing the rate of E2 metabolism by the liver.


Progesterone in the uterus. X. Dependence of the in vitro progesterone metabolism on progesterone binding in rat uterus.

The effect of estrogen pretreatment was stud-ed on the in vitro metabolism and binding of progesterone in uteri of ovariectomized rats in order to prove the dependence of the metabolism of progesterone on its binding. For this purpose, the extent of progesterone binding was varied in uterine tissue by different estrogen treatment of the rats and compared with the metabolism under the same conditions. The protein content determined in 100 mg tissue was used as parameter indicating the success of the pretreatment. Estrogen exposure of the rats for 30 or 45 hrs. caused a rise of protein amount in uterine tissue which was accompanied by an increase of binding sites of progesterone binding components. The binding sites were determined by charcoal adsorption technique and SCATCHARD-analysis. Under nearly the same success of estrogen pretreatment, the increase of the portein amount and with it the rise of binding sites reduced the amount of progesterone metabolites in uterine tissue. The metabolites were  determined by quantitative TLC-analysis of the recovered compounds from uterine segments after incubation with radioactive progesterone. Additionally, an enlarged metabolic rate could be observed after saturation of binding components. It is concluded from the results of these experiments that progesterone binding components are factors limiting the enzymatic conversion of progesterone in rat uterus.


Failure of breast cancer cells in long-term culture to aromatize androstenedione.

The ability of breast cancer cells in long-term tissue culture to aromatize androstenedione to estrone and estradiol was examined. (3H) androstenedione (1.1 x 10(-7)M) was incubated with 9 cell lines of human breast cancer and one line derived from a dimethylbenz(a)anthracene induced rat mammary tumor. No conversion to estrone or estradiol was detected. The findings are discussed in light of previous studies showing aromatization of androgens in breast cancer tissues.


California goats with a disease resembling enzootic ataxia or swayback.

In a retrospective study typical signs and lesions of enzootic ataxia or swayback were found in 16 young dairy goats from eight widely scattered herds in California. In addition to the constant appearance of chromatolytic neurons in brainstem and spinal cord, and myelin deficiency in certain tracts of the cord, cerebellar hypoplasia was found frequently. Liver copper was subnormal in six of nine kids tested. The disease is viewed as a developmental defect in which failure of neuronal perikaryon metabolism leads to distal axonopathy with secondary demyelination.


[The content and types of sulfhydryl groups in muscle creatine kinase detected by their accessibility to different reagents].

Using three independent methods tte amperometric titration, Boyer's method and the method of Ellman it is shown that rabbit muscle creatine kinase contains 11-12 SH-groups, 3-6 of which are easily oxidized by atmospheric oxygen to form S-S-bonds. It is found that creatine kinase has four types of SH-groups distinguished by their accessibility to different SH-reagents. The first type related to the enzymatic activity is detected by the Ellman method (2 SH-groups), the first and the second ones taken together--by the Boyer method (4 SH-groups), the first, second and third ones--by the method of amperometric titration (6 SH-groups), all the 4 types together--when detecting SH-groups after protein denaturation--by any of the above methods (8-12 SH-groups).


[The effect of Solcoseryl on in-vitro cultured cells].

Explants of peripherical nervous system (PNS), skin and ventriculus cordis from chick embryo were cultivated in Maximow chambers and the effect of Solcoseryl, Fa. Solco Basel AG, on some morphological parameters was tested. 1. The growth of tissue cultures is influenced by Solcoseryl in relation to concentration and time of application. The index of area in cultures of PNS and cor increased within the first days. By long time application up to 6 days in vitro the index of area decreased and the index was the same than in controls. Explants of skin showed no essential stimulation of growth. 2. The number of cells per unit of culture in the outgrowth of PNS, cor and skin was different influenced. The density of cells in cultures of PNS and skin decreased (signif. difference). In explants of heart we could not observe a difference between the inside and outside of the outgrowth. An influence of Solcoseryl on the degree of migration is discussed. 3. The area of cell nuclei from heartcells was observed. The area decreased under the influence of Solcoseryl. The difference is significant. 4. The mitotic index of heart cells increased by application of Solcoseryl within the first 2 and 3 days in vitro. 5. The number of nucleoli per nucleus of heart cells under experimental conditions increased significant. It is discussed, Solcoseryl influenced in vitro metabolic processes in suitable systems; stimulation of cell proliferation and migration and rns-synthesis was observed within the first days of cultivation. In-vitro-systems are important objects and they are suitable for tests of pharmaca in vitro.


The role of formaldehyde in the formation of haemodialysis-associated anti-N-like antibodies.

In the sera of 68 (20.9%) of 325 haemodialysis patients, a specific cold agglutinin, cross-reacting with anti-N, was detected. Each patient showing this anti-N-like antibody used a formaldehyde-sterilized dialyser. By contrast, the antibody was not found in any of the 73 patients using a non-formaldehyde-sterilized dialyser. The results of transfusion experiments indicate an in vivo haemolytic activity of the antibody. In vitro, formaldehyde pretreatment of erythrocytes increased the agglutinability of the cells by the anti-N-like antibody. This effect could be prevented when the MN receptor of the red cells was exposed to neuraminidase. Trace quantities of formaldehyde inevitably enter the patient during dialysis when a formaldehyde-sterilized dialyser is used. It is postulated that this in vivo formaldehyde exposure might interact with the MN receptor of the red cells, rendering it immunogenic, and thus induce the formation of the haemodialysis-associated anti-N-like antibody.


[Histochemical behavior of acetylcholinesterase in the diaphragm and that of unspecific esterase in the hypothalamus, testes and liver of rats in relation to organophosphates].

The enzyme behaviour of acetylcholinesterase in diaphragm and that of unspecific esterase in liver, testes and hypothalamus were investigated in view of various organophosphates on total-preparation and cryostat section of 10 male wistar rats. It had pointed out that the blockade was dependent upon the concentration as well as the acid possessing P = O-binding proved to be appropriate for in vitro experiment. The most intense blockade of unspecific esterase was reached in tanycytependym of the third ventricle. The acetylcholinesterase in the motor endplate of diaphragm was less influenced. From these findings follows that a direct conclusion for in vivo toxicity can not be drawn from in vitro results. The significance of the chemical structure of the substance utilized was discussed concerning its inhibitory effect.


[Characteristics of the central nervous system metabolism reaction to stress in acute alcoholic intoxication].

In a state of acute alcohol intoxication metabolic response on the stress of the central nervous system was distinctly altered in rats (formation and binding of ammonia in brain and medulla spinalis). The following effects were observed: deamidation of brain proteins was impaired, the intensity of ammonia formation was decreased, content of urea decreased and dynamics of gamma aminobutyric acid, dicarbonic amino acids and their amides was altered.


[Reversible mental disturbances in craniocerebral injuries (author's transl)].

The necessity of an exact documentation of mental disorders after cranio-cerebral injuries in their temporal development is stressed. There is a quantitative relation between functional psychosis and the underlying cerebral process. Close observation of the course enables the surgeon to diagnose intracerebral complications early.


[Prognostic value of neurologic findings in the newborn infant for the obstetrician].

Prognostic value of neurologic findings of the neonate. 1. Severe cerebral symptoms of the neonate persisting during some days leads in follow-up of the survivors in 20 to 30% to severe cerebral disorders like cerebral palsy, epilepsy, physical and mental handicap, behaviour disorders. 2. Moderate cerebral disorders during neonatal period are followed by severe cerebral handicaps only in about 10%. 3. Mild cerebral symptoms of the neonate, which are abating during 24 hours, most not will be followed of severe mental disorders. - On the strength of this statistical statement exactly recorded neurological findings of the newborn could be used as an evaluation of the performance of an obstetric department.


[Newer antimycotics. IV. Aryl-hydrazones of mesoxalic-acid-seminitril-hydrazid (author's transl)].

The author produced a number of aryl-hydrazones of mesoxalic-acid-seminitril-hydrazide and their N2-acyl-derivatives, farther the halogeno-substituted phenyl-hydrazones of mesoxalic-acid-seminitril-hydrazones, and investigated their fungistatic efficiency in vitro. From the author's results it can be concluded, that 2-, 3- and 4-chloro-phenyl-hydrazones of mesoxalic-acid-siminitril-hydrazide exert a strong fungistatic effect on Trichophyton- and Epidermophyton-species, but they are inactive on other fungi-strains. Their N2-acyl-derivatives, farther with aldehydes and ketones formed derivatives of the previous compounds exert any fungistatic effect neither on Trichophyton- and Epidermophyton-species, nor on other fungi-strains. From this it can be concluded, that the fungistatic activity of the investigated compounds is strong structur-specific.


[Newer antimycotics. V. 3-aryl-azo-indoles (author's transl)].

The author produced a number of 3-aryl-azo-indoles, and investigated their fungistatic efficiency in vitro. He proved, that the 3-(tolyl-azo)- and 3-(bhloro-phenyl-azo)-indoles exert a strong fungistatic effect on Trichophyton- and Epidermophyton-species, but they are inactive on other fungi-strains. Their fungistatic efficiency is considerable independent of the position of their methyl- or chloro-substituents.


[Effect of the extreme factors of antarctic regions on the composition of serum in polar explorers].

Extreme conditions of the Antarctic continent caused adaptive changes in the protein composition of human blood, expressed in the increased level of blood globulin fraction. The detected reduction in the Beta1A-gloubulins in the blood indicated a reduction of the infection immunity level. An increase of blood transferrin content of polar explorers served as a response of the organism to the influence of hypoxic hypoxia.


[Specific immunologic reaction in autoantibody-producing cells].

Experiments were conducted on albino mongrel female mice. The capacity of the plasma obtained in 30 minutes from the animals vaccinated uith the microbial antigens of the animals to cause temporary activation of the autoimmune reaction in the recipients, in passive transfer, was revealed. The capacity of spleen cells, forming autohemolysins, to produce antibodies to sheep red blood cells after the immunization with this antigen was demonstrated by means of Cunningham and Pilarsky's method.


[Effect of thiamine on the formation of immune response in toxic lesions of the liver].

The authors studied the influence of various doses of thiamine on the formation of immune response in the animals with toxic affection of the liver. As revealed, thiamine in a dose of 400 microgram per kg of body weight inhibited the formation of the immune response in healthy rats, but failed to influence this process in the animals with toxic affection of the liver. Thiamine in a dose of 100 microgram per 100 g of body weight stimulated the formation of the immune response in healthy rats and in those poisoned with carbon tetrachloride. The simulating effect of thiamine was more pronounced in poisoned than in healthy rats. The blood serum of rats poisoned with carbon tetrachloride enhanced the immunostimulating action of thiamine.


[Use of the indirect hemagglutination test for the study of ornithosis. Report 2. Preparation and approbation of the dry ornithosis erythrocyte diagnostic agent].

An original preparation--dry ornithosis erythrocytic diagnostic agent for the indirect hemagglutination test was prepared on the basis of formalinized tannin-treated sheep red blood cells and group-specific phospholipid antigen of the causative agent of ornithosis. This diagnostic agent retained its specific activity for 18 months (observation period). The use of this preparation considerably facilitated the method of performance of this test, this offering a possibility of its wide application in practice. A sufficiently high sensitivity and specificity of the indirect hemagglutination test with the suggested diagnostic agent, in comparison with the complement fixation test was demonstrated.


[Spatial distribution of correlative associations in the electrical activity of schizophrenic patients].

The paper deals with the space distribution of correlational contacts of electric activity in 5 areas of the cortical brain in producing non-signal photo stimula and in conditional trace reflexes with a preliminary verbal instruction. Such studies were convened in schizophrenic patients and in normals. The author assessed the general and regional coefficient of cross-correlations in certain time periods prior to and following production of photo signals. More distinct differences between normals and schizophrenic patients (especially with juvenile malignant schizophrenia) were seen after an instruction and conditional signals. In patients the signal activity was not accompanied by a formation of a system of functional contacts which may be seen in normals, and which possibly may be the basis in the functioning of a conditional reflex.


Histone and non-histone proteins from rabbit mammary gland at late pregnancy and early lactation.

The content of non-histone protein in epithelial cell chromatin from rabbit mammary gland increased during late pregnancy and early lactation up to 30%, while the histone content remained unchanged. No qualitative changes, as judged by polyacrylamide-gel electrophoresis, were found during accumulation of non-histone proteins at the onset of lactation. The chromatin isolated at lactation, assayed either by polylysine or Toluidine Blue binding, contained slightly more available DNA-phosphate than the chromatin isolated at pregnancy.


An electroimmuno-assay of the pregnancy-specific beta1-glycoprotein (SP1) in normal and pathological pregnancies, and its clinical value compared to human chorionic somato-mammotropin (HCS).

A 95% reference interval for the pregnancy-specific beta1-glycoprotein (SP1) was established on the basis of 299 samples from 254 normal pregnant women by electroimmuno-assay (rocket immunoelectrophoresis). A positive correlation was found between SP1 and the human chorionic somato-mammotropin (HCS). The SP1 concentration in maternal blood was halved about 30 hours after separation of the placenta at delivery. Thus emergency analyses would be of little value in detecting acute placentae failure. 172 determinations of SP1 in maternal sera were carried out on 56 pregnant women with various types of pathological pregnancies. To assess the clinical value of SP1 a comparison with HCS (HPL) was made. It was concluded that SP1 could possibly be a valuable parameter for monitoring and discovering pathological pregnancies. Larger investigations, however, must be performed to decide whether SP1 determinations will provide more extensive information than other laboratory analyses presently used.


Post-transfusion purpura treated with plasma exchange by haemonetics cell separator. A case report.

A case of post-transfusion purpura in a 61-year-old, multiparous female with a platelet alloantibody (anti-Zwa) in her serum is reported. The patient was successfully treated with plasma exchange by means of a Haemonetics 30 cell separator and corticosteroids. Compared with other therapeutic measures, plasma exchange seems to shorten the duration of thrombocytopenia. Major surgery was possible in our patient within ten days of development of the syndrome.


The preparation of phospholipids by phospholipase D.

The transfer of the phosphatidyl residue from egg phosphatidylcholine to primary alkanols catalyzed by phospholipase D was systematically investigated. It was demonstrated that 1) the chain length of the alkanols is of critical importance, e.g. transphosphatidylation does not occur to alkanols or alkandiols with more than six carbon atoms; 2) double or triple bonds in the acceptor molecule do not influence the transfer reaction; 3) fluorine is tolerated in the acceptor molecule, but the transfer rate decreases with increasing atomic weight from chlorine to iodine. Synthetic phosphatidylcholines with large variations in the apolar part of the molecule, the phosphorylcholines of 1.2-diacyl-sn-glycerol, Acyl-propandiol-(1.3) and 1.2-cyclopentadecylmethylidene-glycerol, have been successfully used in the transfer reaction. Transesterification is an attractive route for the synthesis of phospholipids differing in the polar part of the molecule.


Endothelial cells in the glaucomato-cyclitic crisis.

In 21 patients with unilateral glaucomatocyclitic crisis (Posner-Schlossman syndrome) the central corneal endothelium was photographed with a clinical specular microscope. In each patient the endothelial cell density was determined in both the affected and the contralateral healthy eye. In patients who had had several attacks of P-S the endothelial cell density was lower in the affected eye than in the healthy eye (16 cases). 4 patients seen after the first attack and 1 of 3 patients after the second attack had the same cell density in both eyes. Thus, loss of endothelial cells seems to be due mainly to the recurrent attacks of elevated pressure. The role of the inflammatory changes occurring in eyes with the P-S syndrome, especially keratic precipitates, is discussed.


Release of oxytocin and substance P-like peptides from the rat posterior pituitary lobe incubated in situ after infusion of hypertonic solution into the third cerebral ventricle.

Release of oxytocin and Substance P-like peptides from the rat posterior pituitary lobe incubated in situ after infusion of hypertonic solution into the third cerebral ventricle. Acta Physiol. Pol., 1978, 29 (1): 9-16. The experiments were carried out on male rats. Under general urethane and chloralose anaesthesia the ventral surface of the hypothalamus and the pituitary gland were exposed by a transpharyngeal approach and the anterior pituitary lobe was entirely removed. The posterior lobe with the remaining neural and partially vascular connections with the hypothalamus was incubated in situ. Oxytocin and Substance P-like peptides were assayed biologically in six 20-min samples of the fluid outflow from the posterior pituitary lobe incubated in situ. At the beginning of collection of the fourth sample a hypertonic solution was infused into the third ventricle through a micropipette. This infusion increased significantly the release of oxytocin and insignificantly that of Substance P-like pepides from the posterior pituitary lobe into the incubation fluid.


Effect of ethanol on glucose and water absorption in hamster jejunum in vivo. Methodological problems: anesthesia, nonabsorbable markers, and osmotic effect.

We studied the effect of ethanol on glucose and water absorption in vivo. In preliminary experiments, using sodium amytal anesthesia, we found that control animals, whose jejunal segment was perfused without ethanol, required more anesthetic agent than those perfused with ethanol. Thus, to allow for unbiased comparison of the absorption data between the two groups of animals, all absorption studies were carried out on conscious restrained hamsters. We found that ethanol did not influence the permeability of the jejunum to polyethylene glycol (PEG) and meglumine diatrizoate. In addition, ethanol did not influence the time required for the onset of steady-state absorption. Using both the gravimetric and the electrical methods, we were unable to show any measurable osmotic pressure exerted by ethanol (150-1050 mM) on the hamster jejunum. In the absorption studies we found that perfusion of the hamster jejunum with five increasing concentration of ethanol (450-1050 mM) appeared to cause a concentration-dependent depression in steady-state glucose transport. Water transport was depressed only when 4.8% (1050 mM) ethanol was perfused.


Effect of ethanol on the morphology of hamster jejunum.

In order to study the morphological effects of exposure of the jejunum to low ethanol concentrations, we perfused hamster jejunum with 2.1-4.8% ethanol. Following 45 min exposure, many of the villi developed fluid-filled blisters. To compare these findings to the effect of an inert solute at similar concentrations, we perfused hamster jejuna with mannitol. This caused necrosis of the villus tips but no blister formation. Therefore the blisters were the result of the action of ethanol. The rat jejunum was less resistant to ethanol than that of the hamster. We suggest that the initial insult of the freely permeant ethanol is deep to the epithelium, resulting in accumulation of edema under the epithelium.


On the statistical validity of standards used in profile monitoring of health care.

In current methods of profile monitoring, standards of acceptability (cut-offs) are set either by consulting panels of experts, or by selecting an arbitrary point (e.g., the 75th percentile) on the profile (statistical distribution). However, experts have only vague ideas of what outcome rates ought to be, while profile statistics stem from samples for which unknown percentages of cases have received acceptable care. Poorly chosen standards could cause profile monitoring to be ineffective, inefficient, or unnecessarily disruptive. A new method proposes to set standards by using statistics for which the percentage of adequate care has been predetermined by examining  the process of care. Plans to circumvent the pitfalls involved are described, as are two approaches to estimating the degree of process adequacy from routinely produced outcome rates.


Erythropoietic response of hypertransfused neonatal rats suckled by anemic mothers.

Twelve-day-old hypertransfused neonatal rats nursed for four days by a twice-bled mother exhibited higher 48-hour RBC-59Fe incorporation than control neonates nursed by a normal mother. Erythroprotein (Ep) in plasma of 12-day-old hypertransfused neonates suckled for four days to twice-bled mothers was initially equivalent to approximately 0.5 IU/day. This calculation was based on the observation that reticulocytosis induced in these animals was similar to that produced in neonates of the same age injected intraperitoneally with 0.5 IU Ep for four days while nursing from normal mothers. The reticulocyte maturation curve was shifted to the left in 12-day-old hypertransfused neonates suckled by anemic mothers, and in 12-day-old normal neonates rendered anemic by bleeding, while nursing from normal mothers. This left-shift of the reticulocyte maturation curve was also evident in 12-day-old hypertransfused neonates injected with Ep. Decreases in relative percentages of nucleated RBC was evident in spleens of 12-day-old neonates nursed by anemia mothers and spleens of 12-day-olds injected with Ep. Significant reduction in nucleated RBC were noted in both spleen and marrow of 12-day-old anemic neonates. These results suggest: (1) Ep, present in increased amounts in the anemic mother, is transmitted through milk to nursing neonates thereby stimulating erythropoiesis in these animals; (2) Ep may not stimulate stem cell differentiation towards the e4ythroid compartment but rather acts on already differentiated erythroid cells by influencing their rate of maturation.


Acute changes in plasma testosterone levels and their relation to measures of sexual behaviour in the male house mouse (Mus musculus).

There is an increasing amount of evidence, from several mammalian species, that plasma testosterone levels increase acutely when the male is exposed to sexual stimuli. Work reported here investigates whether such responses occur in male mice, and whether their incidence is related to measures of sexual behaviour. Close proximity of oestrous female mice was found to result in increased plasma testosterone levels in some strains within 15 min. Immediately after a sexual behaviour test, plasma testosterone levels were higher in males showing sexual responses. There were correlations between testosterone levels and mount latency, but none with ejaculation latency. Testosterone levels were greatest at the initiation of mounting responses, and declined during copulation, although not significantly.


[Dehydration under one month of age. A review of 132 cases. Epidemiological, clinical and Bacteriological aspects (author's transl)].

132 cases of dehydration in children under one month of age with a hight proportion of hypertonic dehydration, relating usually to a hyperconcentrated diet, are analyzed, taking into consideration ecological, epidemiological, clinical, biochemical and bacteriological aspects. Decrease in maternal lactation and social hygienic situation were principal factors. Hyperthermia and diarrhoea, were the initial symptoms requiring medical attention, in hypertonic dehydration, being of little importance the neurological manifestations of considerabble incidence and serious posterior repercussion. Important metabolic alterations and the small proportion of positive cultures in feces are evident, relating to those of other authors.


[Hypophenylalaninemia in dietary treatment of phenylketonuria (author's transl)].

One case of hypophenylalaninemia during the dietary low phenylalanine treatment is presented. The general problem of dietary treatment from early ages is reviewed. The appearance of this iatrogenic disease despite adequate supply of this essential aminoacid is stressed. Authors recommend follow-up of these patients in a regional reference center with adecuate technology.


Interferon synthesis in human diploid cells pretreated with insulin.

Interferon production by Newcastle disease virus in human diploid (WI-38) cells was greatly reduced in the absence of serum. Pretreatment of the serum-free cells with insulin in excess of 1.2 IU/ml for 2 h before induction considerably increased the amount of interferon produced. No enhancement of interferon production was seen when the cells were exposed to insulin 2 h after induction or later. The insulin's effect persisted for at least 6 h after its removal, but not for 24 h. A possible mechanism of insulin action is discussed.


Psoriasis in an unselected series of twins.

The relative importance of genetic factors in the origin, age at onset, clinical type, course, and severity of psoriasis was evaluated on the basis of an unbiased sample of twins, ie, the Danish Twin Register, which covers the total population of twins born in Denmark. All verified and probable cases of psoriasis in twins, born 1891 through 1920, were ascertained. Results are presented of an examination of all members of index pairs in which both partners were alive on a certain date. Fourteen monozygotic and 22 dizygotic, like-sexed pairs were found to include at least one partner with unquestionable psoriasis. Zygosity determination was mainly based on extensive serological examinations. The analyses show that the manifestation of psoriasis depends almost exclusively on the presence of the specific genotype. The age at onset, clinical type, course, and severity are also mainly determined by the genetic constitution. Association with certain HLA antigens of the B series has been confirmed, but the fact that many of the twins (including several of the concordant monozygotic pairs) possess neither of these antigens shows the corresponding genes to be important, but not decisive, elements in the predisposition. We conclude that psoriasis is a genetically determined disorder that may, to a limited extent, be modified by environmental influences.


[Macrolid resistance in Staphylococcus aureus strains from chicken synovitis and dermatitis in industrial production].

In outbreaks of synovitis and dermatitis in chicken caused by Staphylococcus (Staph.) aureus we observed erythromycin-resistant strains. These strains belong to the host-specific variety gallinae of Staph. aureus or can not be alloted to one of the known host-specific varieties. The macrolide-resistance-determinant is not carried by a plasmid, presumably it is located on the chromosome. The strains show constitutively cross-resistance to erythromycin, thurimycin, linomycinc and pristinamycin (M-L-S-phenotype). An ecological investigation in a chicken farm has shown that there is no distribution of Staph. aureus-strains from chicken to workers and no occurence of macrolide-resistance in Staph. aureus-strains from the workers.


[Attempts at control of parturition in swine with dexamethasone. 1. Effect of various treatment dates in late pregnancy on onset of labor, litter and rearing performance of the sows].

Studies were conducted with 66 gilts with synchronised ovulation, all kept in five separate experimental groups (I-V). Each of the animals received 75 mg Dexamethason (DXMS) per die over three consecutive days of pregnancy. Treatment of Groups I through V was started in this order on the 101st, 103rd, 105th, 107th or 109th days of pregnancy. The average intervals that elapsed between the last DXMS injection and onset of parturition were, in the same order, 174, 167, 133, 94 or 74 hours. Births were concentrated on two consecutive days in Group V. DXMS had no significant effect on the average duration and course of parturitions. The lowest average litter and piglet birth weights were recorded from those DXMS groups with shortest pregnancy. No significant mean differences in piglet weight were any longer established between the groups on the tenth day of age.


[Pathohistological studies on so-called subclinical mastitis].

Three different localisations of each one of 118 udder quarters were histologically tested. All the 118 quarters had been clinically unchanged for not less than three months before slaughter, and the milk obtained from them had been without any major change over at least six weeks. Sixty-two quarters that had produced positive response to the highspeed mastitis test just before slaughter exhibited 45 inflammatory changes (72 per cent), most of them in terms of proliferative lobular mastitis or exudative alveolitis. One of such changes was recorded from 20 in 47 quarters (21 per cent) which had reacted negatively to the highspeed mastitis test. Comparison with the clinical history of the udders showed that 47 per cent of the established changes could be interpreted as sequels of previous clinical disorder in udder condition, while the greater part of all findings was based on completely negative udder histories.


[Fixed fibrous subaortic stenosis. Postoperative evaluation].

Fibrous sub-aortic stenosis in 19 patients surgically treated is discussed. The clinical, radiologic, EKG and cardiac catheterization data in the pre and post-operative evaluations are reviewed. There were no surgical deaths in this series. In 14 cases post-operative cardiac catheterization was carried out, in 11 patients a significant decrease in the gradient was found. In 4 cases pharmacological testing was done during catheterization before and after surgery, without significant change in gradients.


[The digestibility of milk substitutes with various soybean products in young calves].

Digestibility trials were performed to study the suitability of mixtures made up of treated soybean and whey powder for replacing skim milk powder. Three different milk replacers were used, the replacers T-18/II and T-18/III containing Plyllac preparations manufactured by different technologies. When using the T-18 preparation with 18% fat content it was found that the protein source may contain 25% Plyllac preparation and 11% sweet whey powder. In two cases, at the age of 5 and 7 weeks, the digestibility of the crude protein in the T-18/II preparation was found to deteriorate significantly. For this reason, the authors suggest this milk replacer to be used from the 5th week of life. Trials were performed with 3 milk replacers (lactine preparations) containing Plyllac preparations of different manufacturing technology (35%), treated soybean (10%) and sweet whey powder (10%). It was found that the use of Plyllac preparations, i.e. of treated soybean in larger amounts causes the nutrient digestibility, mainly that of crude protein, to be significantly lower at the age of 3 and 5 weeks than that at the age of 7 to 9 weeks. No significant differences were found in the digestibility of the various Plyllac preparations manufactured by different technologies. The milk replacer lactine is recommended for use from the 5th week of life on.


[Effect of milk substitutes with various soy bean products on the N metabolism in calves].

N-balance trials on young calves aged 3, 5, 7, 9 and 11 weeks, respectively, revealed that a mixture of soybean and whey powder accounting for 39.5% of the total protein amount can be fed without any disadvantage. Feeding this mixture gave N-balance results differing only slightly in the groups aged 7, 9 and 11 weeks. The milk replacer with a higher proportion of soybean and whey powder revealed a more unfavourable N-balance. This allows to conclude that milk replacers containing soybean preparations can be successfully applied to young calves from 5 weeks on, no disadvantages being likely as to N-balance and live weight gain.


[The effect of types of rations on a straw basis on fermentation and volatile fatty acid production in the rumen of lactating cows. 2. Ruminal fermentation and milk yield criteria after use of a high-fiber straw pellet batch as a basic ration component].

Lactating Black-Pied (DSR) cows were used to study, over a period of 100 days, the influence of different basal ration types (experimental group - straw pellets; control group - dried forage + fodder root crops) on fermentation response and daily production rate of volatile fatty acids (VFA) as well as on some criteria of milk yield. Whilst only slight differences were found between the experimental groups in the molar proportions of VFA, the straw pellet-concentrate ration resulted in a lower VFA production as compared to the conventional ration. The control group's VFA production relativated to energy intake, was found to be of the same level (4.1, 4.3 and 3.9 Mol/1 kilo energetic feed equivalents/cattle) after 30, 60 and 100 days of feeding, respectively. The corresponding values in the experimental group declined from 3.3 to 2.3 and 1.9 Mol/1 kilo EF/cattle when feeding a high-fibre straw-pellet batch as basal ration component. The VFA production rates rather diverging between both groups were not found to have a uniform effect on the milk synthesis processes. Both the daily and the first 100-day milk yields did not differ between the groups but within the range of statistical error. Statistically secured positive correlations were found to exist between concentration and production of VFA which, however, depend on the basal ration type and revealed a relatively wide deviation.


Methylphenidate in 6-hydroxydopamine-treated developing rat pups. Effects on activity and maze performance.

In order to better devine the relationship between brain catecholaminergic mechanisms and the clinical syndrome of minimal brain dysfunction, we have developed an experimental model that has many of the features of the disorder seen in children. This model is effected by the preferential depletion of brain dopamine in 5-day-old rat pups following the intracisternal administration of 6-hydroxydopamine, and in the present investigation, we have examined the effects of methylphenidate hydrochloride (0.25 to 2.0 mg/kg) on activity levels and cognitive performance in normal and 6-hydroxydopamine treated animals. Methylphenidate therapy resulted in a significant increase in activity levels of normal rat pups 12 and 19 days of age; in contrast, methylphenidate administered to 6-hydroxydopamine-treated animals did not increase activity at 12 days of age and significantly reduced activity at 19 and 26 days. Methylphenidate had no effect on T-maze performance in normals, but significantly improved performance in 6-hydroxydopamine-treated animals. Our results suggest that the "paradoxical" response to methylphenidate found in 6-hydroxydopamine-treated rat pups may be the result of central denervation supersensitivity.


The effects on chicks of dietary fibre from different sources: a growth factor in wheat bran.

1. Groups of chicks were given a low-residue diet with or without supplements of dietary fibre in the form of wheat bran, wheat straw or bagasse. Growth and food conversion efficiency (g weight gained/g food eaten; FCE) during the first 4 weeks of life were measured. 2. In every one of seven experiments supplementation of the diet with 100 g wheat bran/kg resulted in improved growth, and in three experiments FCE was also increased. 3. Supplementation with coarsely-milled wheat straw to provide an amount of unavailable carbohydrate equivalent to that in the bran diet resulted in poorer growth; finely-milled wheat straw had little effect on growth. 4. The growth-promoting effect of bran was destroyed by sterilization with heat or gamma-radiation. 5. In some experiments weights, lengths and volumes of small intestines were measured. Differences in intestinal dimensions between birds given the diet with and without fibre were not consistent, nor were they correlated with growth rate or FCE. 6. Histometric observations on small intestines from a few birds indicated that those given coarse wheat straw had longer vili and thicker muscularis layers, and the caecal tonsils had a greater area of lymphoid tissue and more follicles.


Interaction of vitamin K dependent proteins with membranes.

The membrane-binding characteristics of six vitamin K dependent plasma proteins, which have homologous amino acid sequences, were compared. All of these proteins display calcium-dependent membrane binding and the identified equilibria for protein-membrane binding are qualitatively the same for all proteins. Quantitative characteristics of these protein-membrane interactions allow organization into distinct subgroups. Protein C and factor VII form a subgroup which has extemely low affinity for bilayer membranes; prothrombin, factor X, and protein S form the tightest complexes with membranes and factor IX displays intermediate affinity. In the presence of manganese (which substitutes for calcium in a cation-dependent protein transition), calcium titration of protein-membrane binding shows the same calcium dependence for all proteins except prothrombin which requires lower calcium. These protein-membrane binding characteristics agree very well with the relatedness of these proteins based on their partial amino-terminal sequences.


A kinetic analysis of D-xylose transport in Rhodotorula glutinis.

The kinetics of D-xylose transport were studied in Rhodotorula glutinis. Analysis of the saturation isotherm revealed the presence of at least two carriers for D-xylose in the Rhodotorula plasma membrane. These two carriers exhibited Km values differing by more than an order of magnitude. The low-Km carrier was repressed in rapidly growing cells and derepressed by starvation of the cells. Several hexoses were observed to inhibit D-xylose transport. In the studies reported here, the inhibitions produced by D-galactose and 2-deoxy-D-glucose were examined in some detail in order to define the interactions of these sugars with the D-xylose carriers. 2-Deoxy-D-glucose competitively inhibited both of the D-xylose carriers. In contrast, only the low-Km carrier was competitively inhibited by D-galactose.


Dispersion of mammalian sperm chromatin during fertilization: an in vitro study.

When "denuded spermatozoa" (spermatozoa stripped of the greater part of their acrosomes and resembling in may respects spermatozoa after acrosomal reaction) of the bull are incubated with 0.1 M 2-mercaptoethanol (pH 8), sperm chromatin is degraded extensively by a protease in the sperm head. The morphological pattern of sperm nuclear dispersion upon in vitro incubation is similar to that observed in the newly fertilized egg. Following disintegration of the outer layers of the sperm nucleus, chromatin dispersion commences from the periphery of the posterior half and proceeds to the anterior end and to the core of the head. Less basic N- and C-terminal portions of bull sperm histone molecules are digested quickly. The central, very arginine-rich portions of the molecules degrade gradually, yielding an heterogeneous series of arginine-rich peptides (molecular weight, 400-1500). Evidence suggests that the protease which is responsible for the degradation of sperm chromatin is a small fraction of acrosin. This fraction of acrosin appears to be arranged along the nuclear surface and to become associated with sperm chromatin during structural changes of the nuclear surface. A similar proteolysis of rabbit, hamster and guinea pig sperm chromatin has also been observed. The resulting pattern of dissolution of the sperm nucleus is proposed as a model of some of the steps involved in male pronucleus formation from the sperm head after fertilization. Histones H2a, H2b, H3, and H4 associated with DNA are relatively resistant to acrosin.


Ribosomal DNA in spores of Physarum polycephalum.

DNA was isolated from plasmodia, spores and newly hatched amoebae of the slime mould Physarum polycephalum. The DNA preparations were fractionated in CsCl gradients and each fraction hybridised to combined 19 S + 26 S rRNA. In all three DNA preparations hybridisation was found to be limited to satellite DNA (rho = 1.714 g/cm3) and at saturation was found to reach a level of 0.16--0.18 % of total DNA. The main band of nuclear DNA (rho = 1.702 g/cm3) did not hybridise appreciably. Further experiments using analytical CsCl gradients revealed that the ratio of satellite to main band DNA was similar in all three preparations. It is concluded that the genes for ribosomal RNA are equally reiterated in spores, hatching amoebae and in plasmodia. They appear to be similarly organised in all stages of the life cycle examined so far.


Polysome activity in relation to growth and protein starvation in brains and hearts of cultured early chick embryos.

In previous studies, brains but not hearts of intact early chick embryos were found to be sensitive to protein starvation. In this study, the in vitro protein synthetic activity of polysomes isolated from brains was found to be greater than those isolated from hearts. Starvation reduced the protein synthetic activity of polysomes in vitro but the extent of the reduction was approximately the same for both brains and hearts. A reduction in the amount of ribosomes as polysomes may have contributed to the lower synthetic activity of polysomes from tissues of starved embryos but not to the differences in synthetic activities between brains and hearts. In addition, neither the stability of isolated polysomes nor ribosome-associated ribonuclease activity appeared responsible for the differences observed in polysome synthetic activities. In direct relationship to the differential sensitivity of brains and hearts to starvation observed in the intact embryo, ribosomes isolated from brains of both growing and starved embryos were more readily degraded during in vitro incubation than those from hearts.


Protein-associated DNA breaks in cells treated with adriamycin or ellipticine.

The effect of intercalating agents on mammalian DNA in vivo was examined by the technique of alkaline elution. Adriamycin and ellipticine were found to produce large numbers of single-strand breaks. These breaks appeared to be intimately associated with protein to the extent that enzymatic deproteinization of the DNA was necessary to reveal the breaks. The frequency of breaks and cross-links increased with concentration and time of exposure to the drugs. These data suggest that DNA single-strand scission may be a feature common to intercalators. The association with a cellular protein is previously undescribed and suggests possible mechanisms for the strand scission.


Repair of lesions induced by bruneomycin in DNA of isolated mitochondria from the mature eggs of the teleost fish Misgurnus fossilis.

Addition of a radiomimetic antibiotic bruneomycin (Streptonigrin) to isolated mitochondria from mature quiescent oocytes of the teleost fish loach Misgurnus fossilis leads to the induction of unscheduled synthesis of mitochondrial DNA. Most of the newly synthesized DNA has the sedimentation properties of open circles and up to 15% of the label is present in the fraction of the covalently closed-circular molecules. The size of the newly synthesized DNA stretches determined from the bouyant shift of DNA labeled with 5-bromouracil and [3H]dAMP and sonicated to fragments of different molecular weight, was found to be equal to about 1000 nucleotides for the labeled covalently closed circles and to about 2000 nucleotides for the labeled open-circular DNA. Experiments with the centrifugation of non-sheared and sonicated 5-bromouracil and [3H]dAMP-labeled mitochondrial DNA (mtDNA) in alkaline CsCl density gradients provided evidence of a covalent linkage between newly-synthesized stretches and the parental DNA strands. It is concluded from these data that the unscheduled mtDNA synthesis induced by bruneomycin does at least in part represent mtDNA repair synthesis.


The influence of rRNA and tRNA on the translation of avian globin mRNA in cell-free systems of protein synthesis.

Cell-free synthesis of globin chains in the presence of globin mRNA in an Ehrlich ascites-cell-free system is further stimulated by addition of 18- and 28-S rRNA but not of 4-S tRNA and 5-S rRNA. This stimulation can not be observed in the wheat germ cell-free system. When 125I-labelled globin mRNA was incubated in the two systems we have found after 60 min a 75% decrease of trichloroacetic acid precipitable polynucleotides in the ascites but only a 20% decrease in the wheat germ system. The RNAase action on mRNA can be reduced by the addition of 18- and 28-S rRNA but not by 5-S rRNA and 4-S tRNA. We suggest that the stimulating effect of the two rRNA species in the ascites cell-free system is due to a higher activity of a specific RNAase in this system and a competitive protection of mRNA from RNAase action.


Developmental transitions between chromatin-bound and soluble RNA polymerase subspecies in the soybean hypocotyl.

RNA polymerase enzymes isolated from soybean hypocotyl tissue during successive developmental stages  (2-8 days old) have been fractionated by  Sephadex column isoelectric focusing. Both the enzymes bound to chromatin and those enzymes free in the soluble phase were investigated during development with respect to their distribution within these two pools. All observed activites were classified according to their alpha-amanitin sensitivity and isoelectric points. Two Class I subspecies (Ia, Ib) and two Class III subspecies (IIIa, IIIb) were continually present bound to chromatin throughout the developmental sequences except the IIb form which was absent at the latest stage. However, a great multiplicity (9 total) of Class II activities (totally inhibited by alpha-amanitin) were observed to be bound to chromatin at the 2nd day stage. These forms were first released from the chromatin complex and recovered in a soluble pool (4th day stage). Subsequent hypocotyl development was accompanied by the gradual disappearance of these Class II subspecies from this pool (6th day) until only two soluble species and one chromatin-bound Class II activity remained (8th day). These observations indicate that the early development of this tissue is accompanied by a dramatic alteration in the conplexity of chromatin-bound RNA polymerase subspecies. Such events may in part determine the domain of RNA secies synthesized at successive developmental stages.


Differences in the effects of manganese and magnesium on initiation and elongation in the RNA polymerase I reaction.

The effects of magnesium and manganese in the initiation and elongation steps of the RNA polymerase I reaction in RNA synthesis were studied. For RNA chain initiation manganese was found to be a better effector than magnesium. For RNA chain elongation either manganese or magnesium acted as an effector, but a high concentration of manganese was inhibitory.


Purification and characterization of a low molecular weight 1,4-beta-glucan glucanohydrolase from the cellulolytic fungus Trichoderma viride QM 9414.

A low molecular weight 1,4-beta-glucan glucanohydrolase (endoglucanase) (1,4-(1,3;1,4)-beta-D-glucan 4-glucanohydrolase, EC 3.2.1.4) has been isolated from culture filtrates of the fungus Trichoderma viride QM 9414 by a two-step procedure of gel filtration and ion-exchange chromatography. The isolated enzyme appeared homogeneous upon polyacrylamide gel electrophoresis at pH 2.9, isoelectric focusing in a polyacrylamide gel slab, sedimentation equilibrium analysis and chromatography of the reduced and alkylated enzyme on a column of Sepharose 6B in 6 M guanidine - HCl. A molecular weight was calculated at approx. 20 000 and the isoelectric point was determined at pH 7.52. The purified enzyme was not a carbohydrate-containing protein.


The hydrolysis of esters of N-hippurylglycine and N-pivaloylglycine by carboxypeptidase A.

The kinetics of the hydrolysis of five esters of N-hippurylglycine (C6H5CONHCH2CONHCH2CO2CRR1CO2H (2 approximately) and seven esters of N-pivaloylglycine ((CH3)3CCONHCH2CRR1CO2H (3 approximately)) by bovine pancreatic carboxypeptidase A (Peptidyl-L-amino-acidhydrolase, EC 3.4.12.2) have been studied at pH 7.5, 25 degrees C and ionic strength 0.5. All N-hippurylglycine esters (2: R=H, R1=H, C2H5, 4-ClC6H4, C6H5CH2) display Michaelis-Menten kinetics up to at least 0.1 M substrate. The N-pivaloylglycine esters display either Michaelis-Menten kinetics (3 approximately: R=H, R1=H, C2H5 C6H5), substrate activation (3 approximately: R=H, R1=4-ClC6H4; R=R1=CH3) or substrate inhibition (3 approximately: R=H, R1=(CH3)2CHCH2, C6H5CH2). Kinetic parameters have been evaluated for each ester and compared with those for the corresponding hippuric acid esters (1 approximately). The enzymic specificity is shown to be identical for the alcohol moieties of the esters 1 approximately, 2 approximately and 3 approximately and unrelated to the occurrence of substrate activation or inhibition phenomena. These latter phenomena are shown to be characteristic of the enzymic hydrolysis of N-acyl amino acid esters but unimportant for N-acyl dipeptide ester substrates.


Thyroidal control of heaptic release and metabolism of vitamin A.

The inverse relationship that exists between thyroxine and the vitamin A level of plasma has been examined in chicken. Thyroxine treatment leads to a decrease in the level of vitamin A carrier proteins, retinol-binding protein and prealbumin-2 in plasma and liver. There is an accumulation of vitamin A in the liver, with a greater proportion of vitamin A alcohol being present compared to that of control birds. In thyroxine treatment there is enhanced plasma turnover of retinol-binding protein and prealbumin-2, while their rates of synthesis are marginally increased. Amino acid supplementation partially counteracts effects of thyroxine treatment. Amino acid supplementation of thyroxine-treated birds does not alter the plasma turnover rates of retinol-binding protein and prealbumin-2 but increases substantially their rates of synthesis. The release of vitamin A into circulation is interfered with in hyperthyroidism due to inadequate availability of retinol-binding protein being caused by enhanced plasma turnover rate not compensated for by synthesis.


Increased susceptibility to the epileptic effects of alcohol withdrawal following periodic electroconvulsive shocks.

There was a progressive intensification (kindling) of the motor seizure pattern when electroconvulsive shocks (ECSs) were administered to rats at 3-day intervals, but not when the inter-ECS interval was 1 hr. Similarly, the incidence of convulsive symptoms elicited by subsequent alcohol exposure and withdrawal was a function of the number of antecedent ECSs administered at 3-day, but not at 1-hr, intervals. Significant ECS-produced intensification of the alcohol withdrawal syndrome persisted for 3 weeks following ten periodic ECSs and occurred even when the motor seizures elicited by the antecedent ECSs were pharmacologically suppressed.


Is antidiuretic hormone elevated in psychosis? A pilot study.

Plasma antidiuretic hormone (ADH) measured by radioimmunoassay was higher in acutely psychotic subjects than in acutely anxious nonpsychotic subjects or normal subjects. ADH was not elevated in acutely anxious nonpsychotic subjects. ADH was positively correlated with degree of psychosis. Normal osmolar and volume regulatory mechanisms did not seem responsible for the ADH elevations in the psychotic subjects. Because ADH is both produced in the hypothalamus and can be accurately measured in blood, this substance may prove particularly valuable in the study of psychiatric disorders.


Dose-effect studies on estrogen induced mammary cancers in mice.

Castrated male (C3H X RIII) F1 mice were treated with graded doses of estradiol-17-beta and estrone in a life-span experiment. Estradiol-17-beta incorporated into paraffin pellets was implanted under the skin for continuous resorption. These pellets contained 1 microgram, 2.5 microgram, 5 microgram, 10 microgram or 100 microgram of hormone. Estron was given orally, mixed with the food at 3 daily dosages: 0.06 microgram, 0.6 microgram and 6 microgram. Although the smallest dosages of both hormones induced vaginal estrus in castrated females, they did not produce mammary tumors. The mammary tumor incidence reached progressively almost 100% in response to the increase of the hormonal dosages. The absence of effect of low doses of estrogen in mice is compared with the absence of an excess of breast cancers among women using oral contraceptives.


Sodium retention in chronic liver disease: lack of a natriuretic factor?

An acute volume expansion in water diuresis has been induced in 8 patients with liver cirrhosis and in 8 normal subjects, taken as controls. A two hour postinfusion urine sample has been utilized to obtain the urine fraction with natriuretic activity. This activity was assayed in 16 rats. Our results confirm a significantly lower natriuretic activity of cirrhotic urine fractions than those of controls.


[Hypothalamic self-stimulation during the abstinence syndrome in morphine-dependent rats].

Rats with lateral hypothalamic self-stimulation were treated chronically with morphine (30 injections in the course of 15 days) in doses increasing stepwise  from 20 to 120 mg/kg per injection. Morphine facilitated self-stimulation from the 9th injection. Both short-term abstinence (16-18 hours) and cessation of the narcotic resulted in inhibition of the response. Full suppression of self-stimulation occurred under the administration of nalorphine, morphine antagonist, in a dose of 5 mg/kg.


[Suppressive effect of autologous thymocytes abolished by prednisolone].

The authors studied the effect of autothymocytes on the hemolysin-producing cells formation in different lymphoid organs of young rabbits. Intravenous injection of thymocytes proved to suppress the formation of antibody-producing cells in the spleen of animals. Prednisolone treatment of thymocytes before their injection cancelled the suppressive effect of autologous thymocytes.


[Immunologic reactivity of the body and the adrenal cortex function in the early period after administration of a carcinogen].

The level of immunological reactivity and the functional state of the adrenal cortex were studied simultaneously in BALB/c mice 7 days after a single injection of various doses of methylcholanthrene. There existed a definite correlation between the immunodepression induced by various doses of methylcholanthrene determined according to the amount of plaque-forming cells in the experimental mouse spleen and free and combined 11-corticosteroids content in the blood plasma after 7 days of the carcinogen injection. This evidence suggests that the adrenal cortex hormones play a definite role in the pathogenesis of immunodepression induced by chemical carcinogenesis.


[Immunologic specificity of local inhibitory intercellular interactions].

The authors previously reported local intercellular interactions suppressing the increase of the antibody-forming cell (AFC) count in the suspension of the spleen cells of nonimmunized mice and sharply elevating with increase in density of the cultivated suspensions. This work showed that preliminary immunization of mice with an antigen eliminated or sharply reduced the accretion inhibition of the AFC cells against the given antigen, but failed to influence the accretion inhibition of cells producing antibodies against another antigen, and the proliferation inhibition of the dividing bulk cells in the culture.


[Effect of inhibitors of RNA and protein synthesis on the course of mitosis in a synchronized culture of Chinese hamster cells].

The synthesis period of various types of RNA and proteins during the interphase related to the immediate after synchronization mitosis was investigated on teh synchronized culture of Chinese hamster cells with inhibitors. Analysis of MI and forms of mitosis pathology indicated the proteins functionally related to the cell division to be mainly synthesized during the second half of the interphase. The most important action of pyromycin during this time is the induction of C-mitosis on account of suppression of proteins synthesis responsible for the spiralization of chromosomes during the prophase. Inhibition of the r RNA transcription at any stage influence the cytotomy and reconstruction of daughter nuclei, this being accompanied by the delay of the cell exit from the mitosis. In difference from pyromycin, a high dose of AMD as an inhibitor of the whole cell RNA synthesis was most effective during the first half of the interphase. It is suggested that during this period at least three kinds of RNA are synthesized which are functionally related to the immediate mitosis in a different way: RNA for genome reduplication, RNA for the tubulin synthesis, and RNA which is the division spindle component.


The neuroanatomical search for sexual dimorphism.

In the rat preoptic area, there is a region of neuropil which shows anatomical differences between males and females. Destruction of this area does not prevent ovulation. Destruction of the suprachiasmatic nuclei prevents spontaneous cyclic ovulation in female rats, but ovulation can be induced by mating in such animals. The rats with suprachiasmatic lesions also showed major disturbances in the normal diurnal timing of many bodily functions. The ovulatory disturbance caused by suprachiasmatic lesions may be due to a defect in the normal timing mechanism for the facilitatory action of progesterone on LH secretion.