A synergistic interaction between aspirin, or other non-steroidal anti-inflammatory drugs, and stress which produces severe gastric mucosal damage in rats and pigs.

A synergistic interaction was observed in the development of damage to the gastric mucosa of rats following the administration of a single oral dose of 50 or 200 mg/kg body weight aspirin and exposure to brief periods of cold or restraint stress. Under the experimental conditions employed, the stressed (control) animals did not develop any visible signs of damage while the rats given only aspirin developed typical small erosions. However, the animals given aspirin and simultaneously exposed to stress developed a large number of deep ulcers and massive haemorrhage. Similar results were obtained in rats given a variety of non-steroidal anti-inflammatory drugs, but not with dextropropoxyphene -- an analgesic devoid of ulcerogenic activity. In pigs, the chronic administration of aspirin and exposure to restraint stress resulted in the formation of deep crater-like ulcers. Only small focal lesions were found in the pigs given aspirin alone and no mucosal damage was evident in the pigs exposed only to stress. It appears that the aspirin plus stress synergism may be the basis for the formation of chronic gastric ulcers in humans.


The influence of procaine and isoprenaline on the lung deflation reflex during the histamine-induced bronchial asthma attack.

The histamine-induced respiratory reflex response arising from the lung deflation (irritant) receptors was influenced by both procaine and isoprenaline, but in an essentially different manner. Procaine administered via the pulmonary circulation prevented or interrupted the asthmatic tachypnoea associated with stimulation of the lung deflation receptors. The effect was less consistently obtained when the drug was given by way of the bronchial circulation or as an aerosol. It is concluded that the lung deflation receptors in the guinea-pig are located in sites easily accessible by way of the pulmonary circulation, i.e., in the peripheral airways. Isoprenaline, irrespective of the way of administration, counteracted the asthmatic increase in bronchial resistance which underlies the stimulation of the lung deflation receptors. A respiratory response, however, characterized by increased respiratory rate, still occurred when the drug was administered either before or after histamine inhalation. The tachypnoic response to isoprenaline is probably of central origin.


[Function and morphology of isolated rat kidney following cellfree perfusion with various plasmaexpanders (author's transl)].

Isolated arteficially perfused rat kidneys prepared as described by Franke et al. (1971) were perfused for 60 min with solutions of Haemaccel, Dextran 40, Pluronic-F-108, or hydroxy-aethyl starch in a single pass system. The glomerular filtration rate (GFR) of the Haemaccel or Dextran 40 perfused organs amounted during the first 30 min to 0.58 ml X g-1 X min-1 and 0.47 ml X g-1 X min-1 respectively. Using Pluronic-F-108 or hydroxy-aethyl starch GFR rose to 0.94 ml X g-1 X min-1 and to 0.85 ml X G-1 X min-1. With Haemaccel or Dextran 40 solutions a mean tubular Na-reabsorption of 75.4 mumol X g-1 X min-1 and of 59 mumol X g-1 X min-1 respectively was determined. Employing Pluronic-F-108 or hydroxy-aethyl starch a mean sodium net transport of 92.6 mumol X g-1 X min-1 in both experimental groups was obtained. The differences described in the functional capabilities of Haemaccel or Dextran 40 and of Pluronic-F-108 or Hydroxyethyl starch perfused kidneys are in good accordance with morphological changes in the ultrastructure. The most striking morphological deviations were found in proximal tubules of those kidneys perfused with Haemaccel solutions. On the other hand after perfusion with hydroxyethyl starch only very few morphological alterations could be detected.


Fetal distress and birth scores in newborn infants.

The relation between fetal distress and the subsequent condition at birth was studied in 2791 pregnancies. Fetal distress was defined as a heart rate greater than 160 or less than 120/min between uterine contractions, with or without meconium-stained liquor. Infants of 28 to 42 weeks' gestational age were examined at 1 and 5 minutes after birth when the heart rate, respiration, and skin colour was recorded. Birth scores of 0, 1, or 2 were given respectively if respirations were absent, gasping, or regular; if the heart rate was undetectable, less than 100/min, or greater than 100/min; and if the colour was white, blue, or pink. Fetal distress was associated with low birth scores in infants at 1 and 5 minutes of age. Among those who had not suffered fetal distress a significantly greater proportion of preterm infants had low birth scores compared with term or post-term infants at 5 minutes of age. Infants did not score equally for colour, heart rate, and respiration at 1 and 5 minutes of age. Colour usually gave a birth score of 5 and heart rate was recordable when infants scored 0 for colour and respiration. The reduction in birth scores was greater in the presence of meconium-stained liquor and abnormal fetal heart rate than meconium-stained liquor alone; the latter being an early sign of fetal distress. Since fetal distress was not diagnosed by conventional methods in 93 term infants who probably suffered prenatal asphyxia, more sophisticated techniques are necessary for an accurate assessment of fetal condition during labour.


Anticerebral oedema therapy in Reye's syndrome.

Sixteen patients with Reye's syndrome were seen over a 3-year period and treated with conservative management with an overall mortality of 31%. 6 of the 16 had illness limited to stages II and III. Intensive therapy of suspected cerebral oedema, with careful monitoring of serum osmolarity, was associated with survival in 5 of 10 patients with stage IV disease. The risks of lumbar puncture in the presence of cerebral oedema (stages III-IV) are emphasized. A change in clinical status (usually a reversal to a less severe stage and an improved electroencephalogram) was seen within hours of starting anticerebral oedema therapy. Neurological sequelae (memory deficit, hemiparesis, hemiballismic movements, and delayed motor milestones) that were present in stage IV survivors at discharge were absent 12 months after discharge. Conservative supportive management emphasizing treatment of presumed cerebral oedema in severe cases of Reye's syndrome has a  mortality comparable to that occurring in exchange transfusion or peritoneal dialysis. This form of therapy should be included in controlled trials to determine which form of therapy is optimal.


Hypernatraemia as a cause of intracranial haemorrhage.

29 definite intracranial haemorrhages and 4 suspected ones occurred during a 25-month period during which 10 072 live infants were born. There were 4 subdural haemorrhages (all fatal), 4 isolated subarachnoid haemorrhages (2 fatal), and 21 intraventricular haemorrhages (all fatal--2 beyond the neonatal period). There was no evidence of a causal relation between intraventricular haemorrhage and either hypernatraemia or large sodium intakes. There were too few cases of other types of intracranial haemorrhage to draw any aetiological conclusions.


Factors predisposing to a complicated initial febrile convulsion.

131 consecutive admissions to hospital for a first febrile convulsion were studied to find which factors predisposed to a complicated fit--defined as one lasting more than 30 minutes, unilateral, or repeated within the same illness. A significant excess of complicated attacks occurred where the age of onset was less than 16 months, where both family history of convulsive disorder and perinatal abnormality were present, and, in females only, where it was suspected that neurological disorder preceded the first fit.


Lamellation of the diploe in the skulls of patients with sickle cell anaemia.

This study describes the radiological and pathological findings in a necropsy series of 70 skulls of Nigerian patients with sickle cell gene, and 70 controls matched for sex and age with no sickle cell gene. 6 (35%) of the 17 patients with sickle anaemia, or 17% of 35 patients with sickle cell gene excluding the trait, all under age 10 years, were shown to have bone trabeculae within the diploe arranged in stripes parallel to the curvature of the cranial tables on radiography. Histological examination of the skulls with curvilinear stripes showed long trabeculae of bone within the diploe similarly arranged in parallel rows but joint at variable intervals by short bridges of bone. The radiolucent areas between trabeculae corresponded to areas of marrow hyperplasia. A skull radiograph in an African child presenting with this radiological sign should raise the suspicion of sickel cell disease.


Limb infections in infancy presenting with pseudoparalysis.

Three cases of pseudoparalysis in infancy are reported in which the appearance of localized infection in the affected limb was delayed for a variable period after the onset of pseudoparalysis. Blood cultures on admission in all cases were positive, and bacteraemia due to the three organisms isolated is discussed.


Neonatal ascites from spontaneous rupture of the bladder.

Two premature infants who presented with neonatal ascites due to apparent spontaneous rupture of the bladder are described. In both children the site of bladder rupture was clearly shown, but neither at time of presentation nor at subsequent review at age 7 years and 7 months, respectively, was any other renal tract abnormality detected.


Reye's syndrome associated with acute tubular necrosis.

Two cases of Reye's syndrome, complicated by acute reversible renal failure, are presented. One case followed an influenza A virus infection.


Life tables for cystic fibrosis.

The past 5 years have seen a continuing improvement in life expectancy in cystic fibrosis.


[Limiting amino acids of chickpeas (Cicer arietinum) for chickens and pigs].

Three experiments, two with broilers and one with pig, were conducted to determine the limiting amino acids of chickpea (Cicer arietinum). In the first 15% protein diets based on autoclaved chickpea were supplemented with methionine (0.20%), either alone or combined with threonine (0.025%) with no significant effect on growth or feed convertion of chicks; however, the addition of methionine tended to improve both parameters in relation to the unsupplemented diet. In the second experiment methionine (0.20%) and/or tryptophan (0.03%) were added to 15% protein diets based on either raw or autoclaved chickpeas. Cooking improved growth and feed efficiency in relation to the raw controls (P less than .05); methionine supplementation was beneficial for both raw and autoclaved diets (P less than .01); the addition of tryptophan was favourable only for the cooked chickpeas. A third experiment was conducted with weanling pigs to study the effect of methionine supplementation to sorghum-chickpea diets with 14 and 12% protein. In both cases, the addition of the sulphur amino acid improved growth and efficiency to the levels obtained with a 15.34% protein sorghum-soybean meal control.


[Stress due to immobilization and low protein intake in rats. Biochemical changes].

Rats fed a control casein diet, when exposed to immobilization, loose more nitrogen, urea and vitamin C in urine. Animals receiving a protein deficient diet excrete less nitrogen, urea and ascorbic acid in urine than their controls. When protein deficiency and immobilization are associated, there is not an increase on the urinary excretion of those substance compared to the deficient animals.


[Stress caused by immobilization and low protein intake in rats. Morphological changes].

The periodic immobilization of the animals receiving a control diet resulted in a smaller weight gain than in controls. The animals fed a protein deficient diet gained also less weight as compared to controls. The association of the deficiency and the stress of immobilization further decreases the weight gain, but the differences were not significant. The animals submitted to restraint or protein deficiency stress showed an increase in their heart weight in relation to body weight. This increase in more significant when immobilization and protein deficiency were associated. The degree of cardiac muscle fibers damage was also found more pronounced in this group of animals, when analysed through histochemical methods. Liver weight was not found different in the animals submitted to the experimental program. Histological examination of this organ showed fatty infiltration in the protein deficient animals. The picture was not found to be agravated when the animals were further stimulated by the restraint mechanism. Spleen weight was found to be similar in all groups. Histological study of the protein deficient group showed small lesions, that were increased when the deficiency was associated to immobilization. The relative testis weight of the restraint animals receiving the control diet was found to be similar to the animals not immobilized. The protein deficient animals have significantly smaller testis weight than the well nourished group. The histologic study showed that restraint or protein deficiency are responsible for a sexually retarded animal, but the lesions increased with the association of restraint and deficiency.


[Nutritional studies with rice bran].

The nutritional value and proximate chemical composition of five samples of rice bran taken from different varieties of rice grown in Venezuela was studied. Thiamin, niacin, riboflavin and tryptophan, lysine, methionine and cystine were analyzed. The apparent protein digestibility was between 59 an 74%, and the Protein Efficiency Ratio (PER) between 1.19 and 2.31. The supplementation with threonine increased the Protein Efficiency Ratio in 12%, but supplementation with tryptophan did not improve it neither alone nor combined with threonine. Combinations with corn and soyflour that simulate formulas for infants showed that there is a protein supplementation in these mixtures. Some combinations with corn, soy flour, and rice bran had the same P.E.R. as casein. The rice bran is an excellent source of vitamins and minerals in these combinations. The results showed that rice bran has potential value for human consumption.


Pharmacologic properties of gama-aminobutyric acid (GABA) and its derivatives. V. Anticonvulsant action of alpha-,beta-, and gama-phenyl derivatives of GABA and their lactams.

The influence of alpha, beta, and gamma-phenyl derivatives of gamma-aminobutyric acid (GABA) and their lactams on convulsions induced with pentetrazole, bemegride and strychnine, and with electric current, were studied. All the lactams exhibited anticonvulsant action, prolonged the latent period of action of the convulsants, and in some cases diminished mortality due to intoxication. Acid forms were devoid of anticonvulsant properties, and in some cases even potentiated convulsions.


Influence of fluorostigmine on some parameters of the catecholaminergic and serotoninergic systems in the mouse brain.

Fluorostigmine (DFP) injected i.p. in doses of 2-45 and 5-0 mg/kg in mice distinctly lowered levels of noradrenaline in the brain, raised levels of dopamine slightly, and very distinctly raised levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. The same dose also weakened MAO activity and diminished oxygen uptake by brain tissue. Drugs which antagonized the above-mentioned changes in the levels of biogenic amine (L-DOPA, PCPA, reserpine) or blocked receptors (phentolamine) only slightly diminished acute toxicity of DFP. On the other hand, a-methyl-p-tyrosine, d,l-tryptophane and nialamide had virtually no effect on acute toxicity.


Influence of some antidepressant drugs on the circulatory system. I. Imipramine.

Imipramine exerts various, dose-related, effects on arterial blood pressure. A distinct hypotensive effect occurs at dosses of at least 0-5 mg/kg body weight. At lower dosage, the action of the drug is biphasic. In experiments in situ with animals, imipramine diminished amplitude of the heart's contractions. Controlled respiration during experiments with imipramine reduced its toxicity. In decapitated animals the action of imipramine was the same as in animals with intact central nervous system. At all dosage levels its effect on blood pressure was biphasic. Blockade of the sympathetic, parasympathetic system and vegetative ganglia had no significant effect on the circulatory response to imipramine. Low doses of imipramine potentiated the hypertensive effect of noradrenaline, and high doses weakened it.


Influence of some antidepressant drugs on the circulatory system: II. Action of amitriptyline and nortriptyline on basic circulatory parameters.

Amitriptyline and nortriptyline in doses higher than 0.5 mg/kg exert a hypotensive action, and doses of less than 0-5 mg/kg have no characteristic effect on blood pressure. Both drugs diminished amplitude of cardiac contractions in situ in experimental animals. Low doses increased frequency and amplitude of respirations, and higher doses paralyzed respiratory function. Animals died as a result of paralysis of the respiratory center. In decapitated animals both drugs exhibited activity similar to that in animals with intact central nervous system, but their hypotensive effect was less pronounced. Blockade of the sympathetic and parasympathetic systems and of vegetative ganglia had no influence on the action of amitriptyline and nortriptyline on blood pressure. In low doses both amitriptyline and nortriptyline potentiated, and in high doses weakened the hypertensive effect of noradrenaline.


Influence of imipramine on the circulatory system in the course of endogenous depressive syndromes. II. Influence of imipramine on vascular reflexes.

In patients with endogenous depression imipramine normalizes vascular responses in vegetative tests (orthostatic test, Schellong's test, cold pressor test). The highest percentages of normal vegetative tests during treatment with imipramine were observed in patients in remission of symptoms of depression. The orthostatic tests seem to have the highest diagnostic value. In tests based on measurement of surface temperature imipramine improved function of the vascular system.


New derivatives of 2-carboxychromanone-4 as potential antiinflammatory drugs. I. Cis-and trans-beta-2,4-dihydroxybenzoylacrylic acids and their derivatives.

Proof is presented that the product of the reaction of resorcin and maleic anhydride in the presence of aluminum chloride in ethylene chloride solutions is cis-beta-2,4-dihydroxybenzoylacrylic acid (I). Cis and trans acids (I and II) were isomerized to 2-carboxy-7-hydroxychromanone-4(III). Reactions of acetylation of compounds I, II and III were studied.


Influence of disorders of adrenal function of activity and pharmacokinetics of some neurotropic drugs. I. Influence of adrenalectomy on potency and pharmacokinetics of drugs.

The influence of disorders of adrenal function on pharmacodynamics and biotransformation of selected neurotropic drugs was studied. Pharmacodynamic activity of salicylamide, morphine and hexobarbital were investigated. Pharmacokinetic parameters of salicylamide and hexobarbital were determined.


Influence of adrenal dysfunction on activity and pharmacokinetics of some neutropic drugs. II. Influence of chronic premedication with dexamethasone on pharmacodynamic activity and pharmacokinetics of drugs.

The influence of long-term administration of dexamethasone on pharmacodynamic activity and biotransformation of salicylamide and hexobarbital, including their absorption, distribution and excretion, were studied. Activities of the following enzymes were also determined: beta-glucuronidase (E.C.3.2.1.31), uridinediphosphoglucose dehydrogenase (E.C.1.1.1.22), uridinediphosphoglucuronyl transferase (E.C.2.4.1.17), uridinediphosphoglucuronic pyrophosphatase (E.C.3.6.1.9), and hexobarbital oxidase.


Experimental studies on activation of the kininogenic system after exclusion of the hepatic circulation.

Levels of kininogen and kallikrein activity were studied in the plasma of rabbits with ligated hepatic blood vessels. Ligation of hepatic veins and arteries arrested visceral circulation in the animals and produced symptoms of shock and death of the animals. Ligation of the superior mesenteric artery at the same time prevented these symptoms, creating an experimental model of exclusion of the liver. Fibrinolytic activation of the kininogenic system by intravenous injection of xanthinol nicotinate (Sadamin, Polfa) in rabbits with excluded hepatic blood circulation caused a rise in kallikrein activity and transient drop in levels of kininogen. Return to normal of kininogen levels in the animals with excluded liver indicated that the process of restoration of kininogen deficiency in the blood is a complex one, independent of direct kininogen synthesis in the liver or its release from the liver.


Influence of cystamine on activity and biotransformation of hexobarbital.

Influence of cystamine on hypnotic potency and biotransformation of hexobarbital in rats was studied. Duration of hexobarbital-induced sleep was prolonged maximally by 42% on the first day after premedication, and by 37% on the third day. After six days, differences from the control group were within the limits of experimental error. Biotransformation of hexobarbital was only slightly inhibited in rats premedicated with cystamine, confirmed by determinations of hexobarbital oxidase activity. Excretion of hexobarbital and its metabolites was delayed.


Sesquiterpene lactones. XVI. In vitro studies on cytotoxic properties of sesquiterpene lactones in tissue cultures of human and animal malignant cells.

Cytoxicity of 18 new sesquiterpene lactones and related compounds was studied by tissue culture method using human malignant KB and HeLa cells, normal RK 13 animal cells, and by the modified plate test of Miyamura. On the basis of criteria of CCNSC HIH, USA, seven compounds with ED50 activities between 0-41 and 3-5 mug/ml were qualified for further investigation in vivo. Cytotoxic activity of sesquiterpene lactones was dependent on presence of an unsaturated lactone ring, (see article). As a rule activity of germacranolids was higher than that of guaianolides.


Sesquiterpene lactones XVII. Cytostatic and pharmacological activity.

Of four lactones studied in the systems Sa-180, EAC and L-1210, two compounds: alatolide, (ALA) and eupatoriopicrin (EUPP), according to the criteria of CCNSC, showed high cytostatic activity, and ursiniolide A (URSA) "moderate" cytostatic activity against at least one type of transplantable tumor. Two compounds were selected for further confirmatory investigation: EUPP, which gave 92% inhibition of EAC and 60% increase in survival of animals bearing Leukemia L-1210; and ALA, which gave 96% inhibition of growth of EAC.


Experimental benzene poisoning.

In guinea pigs poisoned with benzene fumes, early signs of biochemical impairment of the liver parenchyma were demonstrated. Enzyme activities and serum proteins were assayed in the blood of the animals. The results indicate the need for liver function testing in workers exposed to the toxic action of benzene.


[Methodology of therapeutic trials in psychopharmacology (author's transl)].

The paper discusses the general methodologic aspects of therapeutic trials in psychopharmacology under three main headings: definition of the concepts of disease, treatment, and healing. In each case, the author discusses the main difficulties, and gives concrete examples. In conclusions, the complexity of the methodologic problems is stressed, but the author considers that the cost of using correct experimental designs is more than balanced by the safety of the statistical conclusions.


[Spontaneous recovery or successful therapy? A diagnostic and catamnestic problem (author's transl)].

The assertion often made very emphatically and predominantly by laymen that analytic psychotherapy does not help the patient is seen here as a problem still under review. The author gives due consideration to the control group, the diagnosis, the percentage of follow-up examinations in relation to the original case material, additional therapeutical components effective during psychotherapy, and to the various factors promoting spontaneous recovery.


[Medico-sociologic analyses of the effectiveness of psychiatric consultation (author's transl)].

Certain observations led us to test the validity of the general assumption that hysterical syndromes occur more frequently among those inpatients who are refered to us from other departments of our faculty than among the psychiatric outpatients referred by private physicians. Such an assumption was verified in both hysterical neurotics and hysterical personality structures. Moreover, phobic neurotics, and depressive as well as infantile personality structures were underrepresented among the nonpsychiatric inpatients. These findings revealed a selection in psychiatric consultation. The social environment usually reacts to hysterical syndromes by showing vivid affective rejection; infantile syndromes are usually met by complementary protective attitudes. Phobic syndromes and depressive personality structures lead to withdrawal. We are inclined to believe that certain patterns of reactions of staff within the close communication network in a ward are responsible for the above mentioned selection. As far as therapy is concerned nonpsychiatric physicians deviated from the advice given by psychiatrists only in the case of psychogenic psychosyndromes. Despite specific psychiatric advice, their therapeutic measures tended to be uniform. Apparently the non-psychiatrist does not regard psychogenic psychosyndromes as diseases due to the lack of objective consideration. In summary: It appears that the neutral patient-clinician interaction is disturbed in the case of psychogenic psychosyndromes. This fact limits the effectiveness of "indications" and "therapy" in psychiatric consultation, especially if we bear in mind that psychogenic syndromes constitute by far the most prevalent psychic disturbances.


[Two-dimensional ultrasonic diagnosis of brain tumors and subdural hematomas by electronic sector scanning (author's transl)].

Electronic sector scanning (ESS) is a new two-dimensional ultrasonic technique which provides continuous and instantaneous cross-sections of intracranial structures through the intact skull, including the ventricles and large cerebral arteries, by means of a stationary probe. 2. The efficiency of the ESS in the diagnosis of brain tumors and extracerebral hematomas in 295 neuroradiologically controlled cases out of an unselected number of patients during 1972-1974 is described. 3. Supratentorial brain tumors can be detected directly with the ESS by abnoramal reflections of the tumors as well as indirectly by displacement of intracranial reference structures, mainly the ventricular borders. In 239 cases of suspected brain tumor, 126 were neurodiologically confirmed as supratentorial brain tumors. Among these 126 brain tumors the correct localization was determined by the ESS in 86.5%. 4. The highest reliability of the ESS proved to be the direct demonstration of frontal tumors (93%), whereas space-occupying lesions near the midline could be shown only in 79%. Up to now there have been difficulties in the diagnosis of tumors situated near bony structures, e.g., calvarian meningiomas. 5. Subdural hematomas (56 patients) could be lateralized correctly in 93%. Hwever, direct demonstration of the border of the hematomas could be achieved only in 48,2%. Chronic subdural hematomas in children are easier to recognize and the border could be demonstrated in 18 out of 19 cases. 6. The clinical applicability and diagnostic values of the ESS as a nontraumatic investigation procedure are discussed in comparison to cerebral angiography, pneumoencephalography, brain scintigraphy, and CAT scan. scintigraphy, and CAT scan.


Some recent developments in psychiatric genetics.

The methods and results of some recent family, twin and adoption studies of childhood behaviour disorders, crime, alcoholism, psychopathic personality and neurosis are briefly described. The data of Slater (1938) on the parents and children of manic-depressives are reanalysed. Bipolar affective illness were more frequent in the families of bipolar than unipolar probands. There was no support for sex-linked inheritance in either group or for further genetic subdivision of the unipolar group according to age of onset or alcoholic or psychopathic family history. It is suggested that for the time being we may have to be satisfied with three broad and aetiologically overlapping clinical types of depression: bipolar, unipolar and reactive.


[The influence of an early brain damage on psychic diseases in adulthood. A study documented by the AMP-system (author's transl)].

The data of 1926 psychiatric in-patients documented by the AMP-system were evaluated with respect to the anamnestic item "early brain damage". There were 82 cases (4.26%). For each patient with an early brain damage a control-case matched for age, sex and diagnosis was selected. Patients with mental handicaps were examined seperately. For methodical reasons the demonstrated frequencies are an underestimation, and subtle differences between index- and controlgroups are not expected to be visible, but those differences which could be found, will be real. The highest frequency for "early brain damage" was found in the diagnostic group which also contained the psychic disturbances in epilepsy. Among neuroses and schizophrenia the item was found with the average-frequency of the total psychiatric population. It was under-represented among affective psychoses and involutional diseases. An early brain damage predisposed to an earlier age of first manifestation, and the psychic disease showed a more chronic course. Hypotheses concerning the uneven distribution over the diagnostic spectrum were discussed with particular emphasis on the fact that hypoxic perinatal disturbances do not lead to diffuse and unspecific consequences, but predominantly to a sensory impairment and possibly to a deficit in the aminergic system. Early brain damage was also discussed as one mode of the transmission of psychic diseases.


[Dichloroethane poisoning with myoclonic syndrome, seizures and irreversible cerebral defects (author's transl)].

A 48-year-old man, who took by mistake a sip of ointment containing dichloroethane, survived, and showed a course of two phases of toxic symptoms. After an initial narcosis and an interval with few pathological symptoms seizures, myoclonia and somnolence occurred. Irreversible final disturbances were lasting mental defects, cerebellar dysarthria, ataxia, and hydrocephalus. Concomitant diseases were acute liver dystrophy, nephropathy, and anemia. The clinical picture of dichoroethane posoning is outlines, the pathogenesis of this particular cerebral lesion described, and the therapy discussed.


[Acid-base and electrolyte correlations in blood and fluid in alcoholic delirium (author's transl)].

The gas and electrolyte homeostatic changes in arterialized capillary blood were studied in 51 patients with acute alcoholic psychosis. In 29 patients the blood and fluid data were correlated. It was established that acute alcohol delirium is mostly accompanied by alkalosis of metabolic, respiratory, or mixed origin. Irrespective of the approximate uniformity of blood and fluid changes, there is a distinctly expressed imbalance between the different parameters. After subsidence of psychotic symptoms (7-10 days after admittance) fluid acid-base fluctuations were to some extent still observable. They manifested greater resistance in comparison with blood.


[The morphology of the microcirculatory system of the visceral pleura in chronic non-specific lung diseases].

In chronic nonspecific diseases of the lungs lesions of the microcirculatory system of the visceral pleura are of generalized character. The most marked changes were observed in postcapillary and venular links of the microhemocirculation. A pronounced hypertrophy of the venular department and rearrangement of the postcapillary network were noted. The microcirculatory lymphatic system was found to be considerably developed. Along with the functioning lymphatic network there were seen emptying sclerosing lymphatic vessels. The changes in vascular terminals revealed were directly dependent upon the duration of the disease, character of expansion of the process in the lungs, degree of cardiopulmonary incompetence. Moreover, disorders of rheological properties of the blood and permeability of vessels were observed, these disorders being particularly pronounced in exacerbation of chronic pneumonia and cor pulmonale insufficiency of II-III degree. It may be assumed that changes in the microcirculation system in chronic nonspecific lung diseases may represent both an important link in the compensatory mechanisms at early stages of the disease and also a cause of deep irreversible metabolic disturbances in persisting and progressing process in the lungs.


The technique for application of measuring ruler for karyometry.

A technique for measuring sectional plane of nuclei with the help of measuring ruler is described. The ruler may be of any transparent or opaque material with contours of measuring figures plotted on it. The area of the latter corresponds to that of nuclei projection maximal for this or that class under definite magnification. The article comprises also calculations of classes of nuclei, areas of measuring figures. The process of measurement consists in confrontation of the projection of the nucleus under study with measuring figures plotted on the measuring ruler in strict sequence from a smaller figure to bigger one.


Prenatal infection with Fasciola Hepatica in calves.

The livers from 16,776 calves 1 to 3 weeks of age slaughtered at Shepparton abattoirs were examined for gross evidence of infection with Fasciola hepatica. Those livers with thickened bile ducts were examined for the presence of liver fluke by slicing. One hundred and eight F. hepatica were collected from 84 of these livers, giving a minimum prevalence rate of prenatal infection of calves of 0.5%. These results are discussed in context with reports from other countries.


The efficiency of clioxanide and rafoxanide against Fasciola hepatica in sheep by different routes of administration.

Groups of sheep were infected with 100 viable metacercariae of Fasciola hepatica. The efficiencies of clioxanide and rafoxanide were evaluated against infections aged 6 and 12 weeks, by using 3 dose rates of each compound by each of 3 routes of administration. Clioxanide, at 40 mg/kg, administered orally and intra-ruminally against 6-week-old liver fluke was 85 and 90% efficient respectively. At 80 mg/kg intra-abomasally its efficiency was 43%. Clioxanide at 20 mg/kg was 96% efficient against 12-week-old liver fluke when given orally or intra-ruminally and 82% efficient when given intra-abomasally. Because of its lower efficiency intra-abomasally, clioxanide may be unsatisfactory in a proportion of sheep, for use against immature liver fluke at a dose rate of 40 mg/kg. It may be expected to give a moderate to high efficiency against mature infections at 20 mg/kg.


59Fe utilisation and excretion in anaemia of cattle caused by Pimelea trichostachya intoxication.

Experimental chronic Pimelea poisoning, with severe anaemia, was produced in 4 calves by daily oral dose rates of Pimelea trichostachya of between 20 to 60 mg/kg body weight of whole plant. Bone marrow function was studied before and during intoxication using 59Fe to determine plasma iron clearance rates, intraerythrocytic iron incorporation rates and percentage iron uptake, and faecal blood loss was measured before and during intoxication. It was shown that bone marrow activity was neither significantly depressed nor enhanced during intoxication. There was however, evidence of a slight increase in erythrocyte maturation rate. Reticulocytosis was not observed during the development of anaemia, but did occur in 3 of the calves shortly before death.


Cattle and the paralysis tick Ixodes holocyclus.

Paralysis of domestic stock by the paralysis tick Ixodes holocyclus is chiefly a disease of young animals (especially calves) and of non-habituated stock introduced into tick-infested country in spring. The tick has a wide host range, but its principal hosts are bandicoots. The tick has one generation per year and the adult female, which causes almost all paralysis, is abundant in spring and early summer and occurs most commonly in overgrown or regrowth country where bandicoots are abundant. The distribution and behavior of the long and the short-nosed bandicoots are reviewed. The number of ticks required to induce paralysis in cattle and the protection from paralysis afforded by prior experience of the tick are discussed.


Wimmera rye grass toxicity in Western Australia.

Outbreaks of Wimmera rye grass toxicity in the south-west of Western Australia, and the associated distribution of Wimmera rye grass parasitised by Anguina sp and Corynebacterium sp were investigated. Between 1970 and 1974, 58 outbreaks occurred on 26 farms in sheep and cattle grazing pasture, cereal crop, stubble, screenings, or hay containing parasitised Wimmera rye grass. Morbidity rates up to 77% were observed. Clinical signs were characterised by staggering, collapse, periods of convulsions and other nervous signs, often followed by death. A pale, friable liver and haemorrhages in different organs were the most constant gross autopsy findings, but no specific histopathological changes were observed. Symptomatic treatment of affected animals and agronomic control measures attempted by farmers were unsuccessful in controlling the disease.


[Quantitative morphology of the coronary arteries in the second and third decades of life (author's transl)].

1. In 8 cases in the second decade and 10 cases in the third decade without coronary sclerosis and 5 cases with early sclerosis quantitative measurements were made on graded sections of the coronary arteries which were fixed in toto by compression. The surfaces of the lumen, intima and media were determined planimetrically and the thickness of the intima and media and the radius of the lumen of the three main branches of the coronary arteries were determined micrometrically. A post-mortem coronary angiogram was made of each heart and the connective tissue content of the right and left heart was determined planimetrically. 2. Higher values are found in the absolute measurements of surface and thickness of each cross-section in the third decade than in the second. In both age groups the anterior descending ramus is predominant in all criteria. About the end of the second decade the intima attains the thickness of the media and shows the greatest variability of all parameters, especially in the second decade. In both decades the media plays an equally important role in growth as the intima. In the anterior descending ramus the intima has a higher percentage growth rate than in the right coronary artery and in the left ramus circumflexus. In the third decade it has reached a mean thickness of 122 mu in the initial part of the anterior descending ramus and a mean surface area of 1.18 mm2. In the same area the mean thickness of the media also in the third decade, would be 124 mu, and the mean surface area of the media 1.64 mm2. 3. The indices of coronary sclerosis and coronary insufficiency were determined by the method of Freudenberg, Knieriem, Möller and Janzen (1974). Using the mean values for the second and third decades and calculating the regression in the fourth to seventh decades, we found as upper normal limits a coronary sclerosis index of I = 0.3 for hearts without coronary sclerosis, for the coronary sclerosis index II = 0.6, for the coronary insufficiency index I = 0.3, for the coronary insufficiency index II = 0.6 and for the coronary insufficiency index III = 1.0.


[Experimental visualization of the ventricular conduction system of the heart intra vitam (author's transl)].

The in-vivo tolerability of an in vitro in cow, calf and sheep hearts developed method for radiologic visualization of the left ventricular conduction system is tested in four animal experiments. The clinical in-vivo tolerability could be demonstrated on principle; however, it is to accent that hypertonic X-ray contrast dyes may be the cause of morphological changes in the micro- and ultrastructures of the specialised musculature of unknown dignity.


Scanning and transmission EM of rat kidney following low dose mercuric chloride administration.

The development of necrosis and the subsequent regeneration of the proximal tubular epithelium located in the cortex and the outer medulla of the rat kidney following subcutaneous injection of 2 mg of mercuric chloride per kilogram of body weight was observed utilizing light micromicroscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The cortical proximal tubules were largely free of injury. In the medullary proximal tubules, the residual, undamaged cells underwent a change in phenotype appearance involving loss of the microvillus border, a decrease in cell height, and an increase in cytoplasmic ribosomes. These cells phagocytosed luminal debris. With time the cell height gradually increased, specialized organelles returned, and the luminal microvilli progressed from short, sparse profiles, to tufts of longer microvilli and finally the brush border was completely reformed. Some kidneys contained calcified tubules which regenerated more slowly than damaged but uncalcified tubules. Similarly, the medullary segments of the proximal tubules regenerated more slowly than the juxtamedullary region. Clusters of epithelial cells were occasionally seen growing into the tubular lumina during regeneration. Marked intersitial leukocyte infiltrations were observed.


[The exogenous and genetic components of some vessel wall characteristics in the pig (author's transl)].

Insufficiencies of the circulatory system and increasing transport losses in pigs as well as analogies with respect to atherosclerosis of men and swine were the motives for a broad statistical investigation of important characteristics of the circulatory system in a big population of female German landrace pigs, fattened as progeny groups under identical conditions in a testing station and slaughtered at 100 kg weight. As the most essential results, highly significant seasonal and genetical influences on several traits are to be mentioned, and some meaningful correlations between them: Plasma cholesterol, ceruloplasmin and hematocrit showed markedly lower levels in the summer and increased values in the cold season; the thickness of the intima (aorta and arteria pulmonalis) was quite distinctly greatest in the spring, this phenomenon being almost exactly paralleled by augmented amounts of copper and iron in the aortic wall. Increased heart weights were again found in the cold, decreased ones in the warm seasons. On average, bigger hearts and vessels were accompanied by higher elastin contents of the aorta, but these contents stood in very significant negative correlation to the ash content and the amounts of certain mineral components (Ca, Mg and P) of the vessel wall, especially to the ash percentage of the elastic fibers. This indicates that calcifying and mineralizing processes in the wall obviously take place at the cost of the elastic components. The estimation of heritabilities in half and full sibs revealed with h2 = 60% high henetic influences on the elastin content of the aorta and equally so on the ash percentage of elastic fibers. Future investigations must correlate these findings with direct measurements of biomechanical and rheological properties of the vessels.


[The determinants of intramyocardial pressure (author's transl)].

In 20 open-chest dogs intramyocardial pressure was measured simultaneously in two regions: a) in the normal myocardium (IMPsp) b) in a controlled perfused area of the myocardium, supplied by a cannulated coronary artery (IMPp). The preparation permitted the study of the influence of contractility, ventricular pressure and coronary blood flow on IMP. 1. A 47% change in coronary flow with a 26% change in coronary perfusion pressure results in changes of systolic and diastolic IMPp of 14% and 29% respectively. These effects can be explained by variations of intramural fluid content and, hence, of diastolic fiber length. 2. Changes of systolic ventricular pressure (mean 27%) by preload variations result in a mean change of systolic IMPsp of 19% and of systolic IMPp of 11%. 3. Changes of systolic ventricular pressure (mean 33%) by afterload variations augment IMPsp by 30% and IMPp by 13%. 4. The increases of IMPsp and IMPp induced by instantaneous changes of afterload are equal. The most important determinants of IMP are myocardial contractility, coronary perfusion and intraventricular pressure. The influence of coronary perfusion and ventricular pressure on IMP is of the same order of magnitude.


Goblet cells, enterochromaffin cells, superficial gastric-type epithelium and antral-type glands in the gallbladder.

From a material derived from routine investigations, 40 gallbladder specimens were selected in which metaplastic cells had been observed. All the cholecystectomies were performed for gallstones. Of the patients 6 were male and 34 female. The mean age was 51.2 years. 36 specimens revealed goblet cells, enterochromaffin cells were found in 22, antral-type (pseudopyloric) glands in 23 and islands of gastric surface epithelium in 15 specimens. Histochemical methods to visualize sulphated, non-sulphated acid and neutral mucins were used. Ordinary gallbladder epithelium showed a predominance of sulphated mucosubstance. Sporadic goblet cells usually occurred in so-called goblet cell areas which, if small, were located in the tops of folds and only when larger also in the deeper parts of folds. As the goblet cell area enlarged, the relative proportion of sulphated mucin diminished and correspondingly non-sulphated acid mucin increased, while neutral mucin was noted both in the goblet cells and in the intervening columnar cells. In 20 specimens there were enterochromaffin cells in the goblet cell areas while only 2 specimens revealed enterochromaffin cells outside the goblet cell area. The glands outside the neck region of the gallbladder resembled gastric antral glands in their general architecture and in the appearance of individual cells. A part from frequent enterochromaffin cells (in 12 specimens) the glands are composed of mucous cells. The glandular cells contained sulphated mucin, non-sulphated acid and neutral mucin chiefly in the peripheral parts of glandular cells. In the gallbladders there were numerous abnormalities in some areas: heavy mucous secretion, goblet cells, enterochromaffin cells and superficial gastric-type epithelial spots were seen chiefly in the upper parts of folds, while proliferation of antral-type glands occurred in the basal parts. It is probable that some common pathological factors are responsible for the frequent simultaneous appearance of different types of metaplasia.


Effect of carotid sinus nerve stimulation on coronary blood flow in myocardial ischaemia: role of the collateral vessels.

The carotid sinus nerves of dogs were electrically stimulated to reveal reflex effects exerted on the coronary blood flow both in normal and ischaemic states. Myocardia ischaemia was produced by occlusion of the left anterior descending (LAD) coronary artery. In 10 experiments the coronary sinus outflow was measured as an index of the overall coronary flow; in 30 cases the local myocardial blood flow was registered by means of the heat clearance technique. In the overall coronary flow carotid sinus nerve stimulation (CSNS) elicited coronary dilatation. After acute LAD occlusion this effect was slightly potentiated. A similar but significantly greater potentiation was observed in the local reflex vascular dilatation recorded with the aid of the thermal probes immediately after LAD occlusion when the myocardial area explored was supplied exclusively by collateral channels. 24-48 hours and 5-64 days after the coronary ligation the effect of the CSNS on the local blood flow was tested in the developing and the regenerative phases of the myocardial infarction. In both phases an enhanced reflex dilatation was found in the collateral-dependent ischaemic areas as compared to the myocardial areas supplied by the normal vessels. The results suggest that reflexly induced intrinsic redistribution of the myocardial blood flow is one of the mechanisms responsible for the therapeutical effects of the CSNS.


Electron microscopic study on permeability of coronary artery wall of normotensive rabbits using horseradish peroxidase as a tracer.

In order to study the pathways in the coronary artery vessel wall horseradish peroxidase (HRP) was used as a tracer. HRP was injected directly in the left ventricle of rabbit hearts. 30 seconds after intracardial injection of HRP in normotensive rabbits, peroxidase reaction products could be located in random areas of the coronary arterial system and could then be observed in all three layers of the coronary walls at these locations. HRP reaches the subendothelial space of the coronary arteries along two pathways: through intercellular junctions and by plasmalemmal vesicles. Through the fenestations of the internal elastic lamina HRP reaches the media and can be detected between the media smooth muscle cells. The influence of the methodology on the results is discussed.


Renal angiomyolipoma in a case of tuberous sclerosis, an electron microscopy study.

Electron microscopic study of bilateral renal angiomyolipoma in a case of tuberous sclerosis showed two cell types: smooth muscle cells and fibroblasts. There were no tubular or glomerular elements within the tumor mass. To our knowledge this study represents the first ultrastructural demonstration of smooth muscle cells occurring in the renal lesions of this complex.


[Myocardial electrolytes in "cardioplegic" myocardosis (author's transl)].

Changes of the mineral concentrations of the heart muscle can point at disturbances of myocardial metabolism. Disturbances of heart muscle with functional loss and without coronary or inflammatory heart disease are called myocardosis, especially cardioplegic myocardosis after open-heart surgery with extracorporal bypass. 30 dogs were examined in three groups varying the method of induced cardiac arrest: 1. ischemic cardiac arrest by clamping the ascending aorta, 2. functional cardiac arrest by electrically induced fibrillation and 3. ischemic cardiac arrest and in addition injection of a Mg-aspartate-procain-solution. Sodium, potassium, magnesium, calcium, copper and zinc were analyzed by atomic absorption spectrophotometry. Specimens from the left and right ventricular wall were examined before and after extracorporal circulation. After a recovery period for one hour the dogs were killed and specimens from the right and left ventricular wall and from the basis and apex of the interventricular septum were taken and reduced to ashes with mineral acids. In all animals changes of the mineral content were most marked after the recovery period. In all forms of cardiac arrest mineral metabolism showed monotone reactions: water content increased, potassium and magnesium decreased. Variations of mineral concentrations were more expressed in the right ventricular wall than in the left. Animals with cardiac arrest by electrically induced fibrillation indicated the smallest deviations from the basic values. The comparison of the values of dogs with sufficient circulation at the end of the experiments and those dogs with medicamentally or mechanically supported circulation at this time showed a more increased water content and simultaneously a decrease of all cations in the group with supported circulation. The decrease of the osmolality of the cations seems to be the metabolic answer to the increased cardioplegic damage of heart muscle.


Purkinje fibre glycogen. A morphologic and biochemical study of glycogen particles isolated from the cow conducting system.

Glycogen from the cow conducting system was extracted by crude and mild methods. For comparison similar extractions were also performed on cow ordinary ventricular tissue. Glycogen particles from the conducting system, isolated by a mild method, were characterized by a low molecular weight (3-5 X 10(6)) and small dimensions (average diameter about 30 nm). 3.5-7% protein was firmly bound to the glycogen. The glycogen, based on spectrophotometric analysis, appeared to be in a native state. Glycogen as a polysaccharide-protein complex can thus be obtained from the cow conducting system and is proposed to be useful for analysis of the structure and function of glycogen in the conducting system.


Acetyl-coenzyme A hydrolase, an artifact? The conversion of acetyl-coenzyme A into acetate by the combined action of carnitine acetyltransferase and acetylcarnitine hydrolase.

1. The nature of the acetyl-CoA hydrolase (EC 3.1.2.1) reaction in rat and sheep liver homogenates was investigated. 2. The activity determined in an incubated system was 5.10 and 3.28nmol/min per mg of protein for rat and sheep liver homogenate respectively. This activity was not affected by the addition of l-carnitine, but was decreased by the addition of d-carnitine. 3. No acetyl-CoA hydrolase activity could be detected in rat or sheep liver homogenates first treated with Sephadex G-25. This treatment decreased the carnitine concentrations of the homogenates to about one-twentieth. Subsequent addition of l-carnitine, but not d-carnitine, restored the apparent acetyl-CoA hydrolase activity. 4. Sephadex treatment did not affect acetyl-carnitine hydrolase activity of the homogenates, which was 5.8 and 8.1nmol/min per mg of protein respectively for rat and sheep liver. 5. Direct spectrophotometric assay of acetyl-CoA hydrolase, based on the reaction of CoA released with 5,5'-dithiobis-(2-nitrobenzoic acid), clearly demonstrated that after Sephadex treatment no activity could be measured. 6. Carnitine acetyltransferase (EC 2.3.1.7) activity measured in the same assay system in response to added l-carnitine was very low in normal rat liver homogenates, owing to the apparent high acetyl-CoA hydrolase activity, but was increased markedly after Sephadex treatment. The V(max.) for this enzyme in rat liver homogenates was increased from 3.4 to 14.8nmol/min per mg of protein whereas the K(m) for l-carnitine was decreased from 936 to 32mum after Sephadex treatment. 7. Acetyl-CoA hydrolase activity could be demonstrated in disrupted rat liver mitochondria but not in separated outer or inner mitochondrial membrane fractions. Activity could be demonstrated after recombination of outer and inner mitochondrial membrane fractions. The outer mitochondrial membrane fraction showed acetylcarnitine hydrolase activity and the inner mitochondrial membrane fraction showed carnitine acetyltransferase activity. 8. The results presented here demonstrate that acetyl-CoA hydrolase activity in rat and sheep liver is an artifact and the activity is due to the combined activity of carnitine acetyltransferase and acetylcarnitine hydrolase.


The transfer of mannose to dolichol diphosphate oligosaccharides in pig liver endoplasmic reticulum.

The transfer, catalysed by pig liver microsomal preparations, of mannose, from GDP-mannose, to lipid-linked oligosaccharides and the properties of the products are described. Solubility, hydrolytic and chromatographic data suggest that they are dolichol diphosphate derivatives. The presence of two N-acetyl groups in at least part of the heterogenous oligosaccharide portion was tentatively deduced. Reduction with borohydride of the oligosaccharide showed that the newly added mannose residues were not at its reducing end. Periodate oxidation suggested that 60% of these were at the non-reducing terminus and that 40% were positioned internally. T.l.c. showed the presence of seven oligosaccharide fractions with chromatographic mobilities corresponding to glucose oligomers with 7-13 residues. The molar proportions of the oligosaccharide fractions in the mixture were determined by borotritiide reduction and the number of mannose residues added to each oligosaccharide fraction during the incubation was calculated. Two of the oligosaccharide fractions had received on average one, or slightly more than one, mannose residue per chain during the incubation; four of the other fractions were each shown to be a mixture, 20-25% of which had received one mannose residue during the incubation and 75-80% of which had not been mannosylated during the incubation. This supported other evidence for the presence of endogenous lipid-linked oligosaccharides in the microsomal preparation which had been formed before the incubation in vitro. Evidence for the possibility of two pools of dolichol monophosphate mannose, one being more closely associated with mannosyl transfer to dolichol diphosphate oligosaccharides than the other, is also discussed.


4-aminobutyrate in mammalian putrescine catabolism.

The effects of inhibitors of diamine oxidase (EC 1.4.3.6), monoamine oxidase (EC 1.4.3.4) and 4-aminobutyrate aminotransferase (EC 2.6.1.19) on the catabolism of putrescine in mice in vivo were studied. Diamine oxidase inhibitors and carboxymethoxylamine (amino-oxyacetate) markedly inhibit the metabolism of [(14)C]putrescine to (14)CO(2), but affect different enzymes. Aminoguanidine specifically inhibits the mitochondrial and non-mitochondrial diamine oxidases, whereas carboxymethoxylamine specifically inhibits 4-aminobutyrate transamination by the mitochondrial pathway. Hydrazine inhibits at both sites, and results in increased concentrations of 4-aminobutyrate in brain and liver. Pretreatment of mice with carboxymethoxylamine and [(14)C]putrescine leads to the urinary excretion of amino[(14)C]butyrate. Carboxymethoxylamine does not affect the non-mitochondrial pathway of putrescine catabolism, as the product of oxidative deamination of putrescine in the extramitochondrial compartment is not further oxidized but is excreted in the urine as derivatives of 4-aminobutyraldehyde. Another catabolic pathway of putrescine involves monoamine oxidase, and the monoamine oxidase inhibitor, pargyline, decreases the metabolism of [(14)C]putrescine to (14)CO(2)in vivo. Catabolism of putrescine to CO(2)in vivo occurs along different pathways, both of which have 4-aminobutyrate as a common intermediate, in contrast with the non-mitochondrial catabolism of putrescine, which terminates in the excretion of 4-aminobutyraldehyde derivatives. The significance of the different pathways is discussed.


Polyphasic changes in incorporation of precursors into ribonucleic acid of oestradiol-stimulated mammary gland.

1. At 3 weeks after ovariectomy, mammary glands (5th pair) of adult Swiss mice show (i) no significant decrease in weight, (ii) 20% of the original rate of incorporation of [(3)H]-uridine into RNA (after a 30min pulse), and (iii) 90% of the original rate of incorporation of l-[(3)H]leucine into protein (after a 15min pulse). 2. A single injection of oestradiol-17beta into these ovariectomized mice produces, during the next 17h, a series of discrete bursts of increased incorporation of [(3)H]uridine into mammary-gland RNA; the bursts, which are variable in height, reach peaks at approx. 1, 9, 12 and 16h after hormone administration; an increase is already detected at 15min, the earliest time-point investigated; each burst lasts for approx. 2h. There is no significant stimulation of [(3)H]uridine incorporation into RNA of liver and quadriceps femoris muscle. 3. Nuclear incorporation of [(3)H]UTP into RNA of mammary gland in vitro is linear with time for up to 20min at 15 degrees C; it requires CTP, GTP and ATP and is inhibited by actinomycin D. Also, the incorporation is strongly inhibited by alpha-amanitin in high salt concentrations but only weakly in low salt concentrations, a result indicating that RNA polymerase II activity predominates in high salt, whereas RNA polymerase I activity predominates in low salt concentrations. Injection of oestradiol-17beta in vivo followed by measurement of nuclear RNA synthesis in vitro shows a definite increase in both RNA polymerase activities 30min after oestradiol-17beta injection, the earliest time-point investigated, a higher increase at 1h, a decline at 4h, and again a large increase at 12h. These results in general agree with the changes in precursor incorporation into RNA measured directly in the animal and suggest that changes in [(3)H]uridine uptake into RNA are not precursor-pool-dependent.


The kinetics of incorporation in vivo of (14C)acetate and (14C)carbon dioxide into the fatty acids of glycerolipids in developing leaves.

1. The patterns of incorporation of (14)C into glycerolipid fatty acids of developing maize leaf lamina from supplied [1-(14)C]acetate and from (14)CO(2) during steady-state photosynthesis were similar. Oleate of phosphatidylcholine and palmitate of phosphatidylglycerol attained linear rates of labelling more rapidly than did other fatty acids, particularly the linoleate and linolenate of monogalactosyl diacylglycerol. 2. After the transfer of lamina from labelled to unlabelled acetate, there was a decrease in labelled oleate and linoleate of phosphatidylcholine and a concomitant increase in the amount of radioactivity in the linoleate and linolenate of monogalactosyl diacylglycerol. 3. The rapidly labelled phospholipids, phosphatidylcholine and phosphatidylglycerol, were shown by differential and sucrose-density-gradient centrifugation to be associated with different organelles, the former being mainly in a low-density membrane fraction, probably microsomal, and the latter mainly in chloroplasts. 4. During a 48h period after supplying spinach leaves with [(14)C]acetate, radioactivity was lost from the oleate of phosphatidylcholine present in fractions sedimented at 12000g and 105000g, and accumulated in the linolenate of monogalactosyl diacylglycerol of the chloroplast. 5. It is proposed that the phosphatidylcholine of some non-plastid membranes is intimately involved in the process of oleate desaturation and that this lipid serves as a donor of unsaturated C(18) fatty acids to other lipids, principally monogalactosyl diacylglycerol, of the chloroplasts.


Folate metabolism in the rat liver during regeneration after partial hepatectomy.

1. Folate metabolism was studied during the early phases of liver regeneration after partial hepatectomy in rats accustomed to eating during the first 8h of a daily 12h dark period. 2. The content of 5-CH(3)-H(4)folate was drastically decreased during the first hours of regeneration. 3. The total HCO-H(4)folate coenzymes showed a constant decrease during the first 3 days of regeneration, and a continuous interconversion between 5-HCO-H(4)folate and 10-HCO-H(4)folate. 4. 10-HCO-H(4)folate synthetase, serine hydroxymethyl-transferase and 5,10-CH(2)-H(4)folate dehydrogenase activities were relatively low during the first hours after the operation, and increased only several hours later. 5. The increase in enzyme activities showed a stepwise pattern, apparently due to an interaction between the regeneration process and the controlled feeding schedules.


Reconstitution of pig lymphocyte plasma membranes from solubilized components, with particular reference to membrane-associated immunoglobulins.

Plasma membranes of lymphocytes obtained from pig mesenteric lymph nodes were reconstituted after solubilization with bile salts. The proportion by weight of immunoglobulin in the reconstituted membrane was no greater than about 5-10% of that in the original membrane. Possible reasons for the low reincorporation of immunoglobulin are discussed.


Biosynthesis and hydrolysis of cholesteryl esters by rat skin subcellular fractions. Regulation by prostaglandins.

The properties and subcellular distribution of the enzymes involved with the synthesis and hydrolysis of cholesteryl esters were investigated in skin of normal and essential fatty acid-deficient rats. Most of the activity of the cholesterol-esterifying enzyme(s) is associated with the 12000g and 105000g particulate fractions. The dependence of the enzyme reaction on ATP and CoA suggests that the esterification of cholesterol by rat skin is mediated by a fatty acyl-CoA-cholesterol acyltransferase (EC 2.3.1.-). On the other hand, most of the activity of the cholesteryl ester hydrolase (EC 3.1.1.13) is localized in the 105000g supernatant fraction. Although the activity of the cholesterol-esterifying enzyme(s) was elevated in skin preparations from essential fatty acid-deficient rats, the activity of the hydrolase was significantly decreased. These observations may explain in part the elevated concentrations of sterol esters in the skin of these animals. Prostaglandin E(2) at low concentrations exerted marked inhibitory effect on the activity of the cholesterol-esterifying enzyme(s), whereas no effect was observed on the activity of the hydrolase at similar concentrations. However, at high concentrations prostaglandin E(2) exerted moderate stimulatory effect on the activity of the hydrolase. These results suggest a possible physiological role of this substance in regulating the production of sterol esters in this tissue.


Studies on the glycosylation of hydroxylysine residues during collagen biosynthesis and the subcellular localization of collagen galactosyltransferase and collagen glucosyltransferase in tendon and cartilage cells.

1. The glycosylation of hydroxylysine during the biosynthesis of procollagen by embryonic chick tendon and cartilage cells was examined. When free and membrane-bound ribosomes isolated from cells labelled for 4min with [(14)C]lysine were assayed for hydroxy[(14)C]lysine and hydroxy[(14)C]lysine glycosides, it was found that hydroxylation took place only on membrane-bound ribosomes and that some synthesis of galactosylhydroxy[(14)C]lysine and glucosylgalactosylhydroxy[(14)C]lysine had occurred on the nascent peptides. 2. Assays of subcellular fractions isolated from tendon and cartilage cells labelled for 2h with [(14)C]lysine demonstrated that the glycosylation of procollagen polypeptides began in the rough endoplasmic reticulum. (14)C-labelled polypeptides present in the smooth endoplasmic reticulum and Golgi fractions were glycosylated to extents almost identical with the respective secreted procollagens. 3. Assays specific for collagen galactosyltransferase and collagen glucosyltransferase are described, using as substrate chemically treated bovine anterior-lens-capsule collagen. 4. When homogenates were assayed for the collagen glycosyltransferase activities, addition of Triton X-100 (0.01%, w/v) was found to stimulate enzyme activities by up to 45%, suggesting that the enzymes were probably membrane-bound. 5. Assays of subcellular fractions obtained by differential centrifugation for collagen galactosyltransferase activity indicated the specific activity to be highest in the microsomal fractions. Similar results were obtained for collagen glucosyltransferase activity. 6. When submicrosomal fractions obtained by discontinuous-sucrose-density-gradient-centrifugation procedures were assayed for these enzymic activities, the collagen galactosyltransferase was found to be distributed in the approximate ratio 7:3 between rough and smooth endoplasmic reticulum of both cell types. Similar determinations of collagen glucosyltransferase indicated a distribution in the approximate ratio 3:2 between rough and smooth microsomal fractions. 7. Assays of subcellular fractions for the plasma-membrane marker 5'-nucleotidase revealed a distribution markedly different from the distributions obtained for the collagen glycosyltransferase. 8. The studies described here demonstrate that glycosylation occurs early in the intracellular processing of procollagen polypeptides rather than at the plasma membrane, as was previously suggested.


Mode of formulation of cholesta-5,7-dien-3beta-ol from Cholest-5-en-3beta-ol by Larvae of Calliphora erythrocephala.

1. The conversion of cholest-5-en-3beta-ol (cholesterol) into cholesta-5,7-dien-3beta-ol by axenic Calliphora erythrocephala larvae was demonstrated. 2. The transformation is probably direct (Delta(5)-->Delta(5,7)) and does not involve a Delta(0) intermediate (Delta(5)-->Delta(0)-->Delta(7)--> Delta(5,7)). 3. Delta(7)-bond formation involves the stereospecific elimination of the 7beta hydrogen atom. 4. The relative amounts of free and esterified sterols were determined in larvae grown on cholesterol as sole sterol source and on 5alpha-cholestan-3beta-ol supplemented with minimal amounts of cholesterol. 5. The significance of the results is assessed in relation to the probable role of cholesta-5,7-dien-3beta-ol as an intermediate in the biosynthesis of ecdysones.


Evidence for the coupling of biosynthesis and secretion of serum albumin in the rat. The effect of colchicine on albumin production.

1. By using isotopic-dilution techniques it was found that colchicine causes a slight increase in the proalbumin content of liver, from 0.63+/-0.06 to 0.83+/-0.10mg/g of liver, but has no effect on albumin content (0.50+/-0.05mg/g of liver). All the proalbumin and 67% of the albumin is found in vesicles from which they are liberated by detergents. 2. Colchicine inhibits secretion of albumin, decreases the rate of conversion of proalbumin into albumin and decreases the rate of incorporation of l-[1-(14)C]leucine into proalbumin. 3. Balance studies in vivo show that all the (14)C appearing in serum albumin can be accounted for by the flow of (14)C through the proalbumin, in the presence or absence of colchicine. 4. When cycloheximide is given to the rats, 2min after [(14)C]leucine, further synthesis of protein stops. The label in proalbumin disappears and the proalbumin content of the liver falls, so as to account for the albumin appearing in the plasma. This occurs both in the presence and in the absence of colchicine. By contrast, there is little change in liver albumin. Studies with isolated perfused livers are in agreement with the above. Lumicolchicine has no effect on any of these systems at doses at which colchicine exerts its action. 5. These results suggest that biosynthesis and conversion of proalbumin into albumin, and secretion of serum albumin are controlled at each step.


The microbial metabolism of C1 compounds. The electron-transport chain of Pseudomonas am1.

Pseudomonas AM1, Hyphomicrobium X and Pseudomonas MS all contain cytochrome a/a(3) and a b-type cytochrome able to react with CO. Pseudomonas AM1 and Hyphomicrobium X also have a CO-binding cytochrome c. The purified cytochrome c (redox potential 0.26V) of Pseudomonas AM1 was not susceptible to oxidation by molecular oxygen. CO reacted slowly with the reduced form giving a CO difference spectrum with a peak at 412nm and troughs at 420nm and 550nm. Similar results were obtained with the cytochrome c of Hyphomicrobium (aerobically grown or anaerobically grown with nitrate) and with that of Pseudomonas extorquens. The results given in the present paper are incompatible with an oxygenase or oxidase function for the soluble cytochrome c of methylotrophs. Studies with whole cells of Pseudomonas AM1 and a cytochrome c-deficient mutant have demonstrated that cytochrome b (redox potential 0.009V) is the first cytochrome in the electron-transport chain for oxidation of all substrates except methanol (and ethanol) whose oxidation does not involve this cytochrome. All substrates are usually oxidized by way of cytochrome c and cytochrome oxidase (cytochrome a/a(3)), but there is an alternative route for the reduction of cytochrome a/a(3) in the mutant lacking cytochrome c. Results of experiments on cyanide inhibition of respiration and cytochrome oxidation support the suggestion that the susceptibility of cytochrome b to oxidation by molecular oxygen (reflected in its ability to react with CO) is probably irrelevant to the normal physiology of Pseudomonas AM1.


A difference in the incorporation of 14C into hippurate glycine from DL-(2-14C)-glutamate and DL-(5-14C)glutamate in guinea pigs.

The specific radioactivity of urinary hippurate glycine was determined after injecting guinea pigs with benzoate and either dl-[2-(14)C]glutamate or dl-[5-(14)C]glutamate. The isotope dilution factor for the formation of [(14)C]glycine was significantly greater (30%) with C-2 labelled glutamate. With either form of labelled glutamate the hippurate glycine was largely carboxyl-group labelled. The observations suggest a route for the incorporation of glutamate carbon into glycine that involves C-5 but not C-2. A hypothesis for glycine biosynthesis from l-glutamate is advanced, consistent with these findings, that includes conversion of l-glutamate to 4-hydroxy-2-oxoglutarate, the scission of the latter to glyoxylate and pyruvate, and the formation of glycine by transamination.


Enzymic iodination of eukaryotic ribosomal subunits. Characterization and analysis by two-dimensional gel electrophoresis.

1. Conditions are described for the enzymic iodination of ribosomal subunits from rat liver. The reaction is relatively insensitive to broad changes in the concentration of KCl, allowing subunits to be studied under conditions which minimize their dimerization. 2. Mixtures of extracted ribosomal proteins were iodinated with (125)I, the proteins separated by two-dimensional gel electrophoresis and the radioactivity in each protein was determined. Thus 19 out of 23 of the proteins of the small subunit and 25 out of 33 of the proteins of the large subunit were labelled. Iodination should therefore be a suitable method for studying the topography of the ribosomal proteins of rat liver. 3. When the intact 40S subunit (rather than the extracted mixture of proteins) was iodinated, 18 of the 19 proteins were still labelled. However five of these were labelled less strongly than before. When the intact 60S subunit was iodinated, 17 of the 25 proteins were still labelled, although six of these were labelled less strongly. 4. These results show that in rat liver most of the ribosomal proteins of both subunits are at least partially at the surface of the particles. They are also consistent with the idea that the proportion of the ribosomal proteins in the interior of the particle may be greater for the 60S subunit than for the 40S subunit.


Inhibition of fatty acid synthesis and stimulation of glycogen breakdown by vasopressin in the perfused mouse liver.

1. Vasopressin (anti-diuretic hormone, [8-arginine]vasopressin) inhibited the synthesis de novo of fatty acids (measured with (3)H(2)O and U-(14)C-labelled lactate or U-(14)C-labelled glucose) and stimulated glycogen breakdown in the perfused liver of fed mice. 2. The concentration dependence of these effects (range 200-1000muunits/ml, i.e. 0.5-2.5ng/ml) resembled that for the action on glycogen breakdown which was previously reported for rat liver. 3. The appearance of newly synthesized fatty acids in both phospholipids and triglycerides was inhibited by vasopressin, whereas synthesis of cholesterol was less affected. 4. Inhibition of hepatic lipogenesis by vasopressin is the most potent short-term hormonal action on this process yet reported. Aspects of the effect are discussed, including the lack of a role for cyclic AMP, and a possible link with vasopressin action on glycogen metabolism.


The activity of phosphoenolpyruvate carboxykinase in rat tissues. Assay techniques and effects of dietary and hormonal changes.

1. Phosphoenolpyruvate carboxykinase was assayed by three methods: (i) incorporation of H(14)CO(3) (-) into oxaloacetate: (ii) conversion of oxaloacetate into phosphoenolpyruvate, subsequently assayed enzymically; and (iii) transfer of (32)P from [gamma-(32)P]GTP to oxaloacetate. 2. Enzyme activity is increased in liver and epididymal adipose tissue in alloxan-diabetes and starvation, and in kidney in starved, acidotic and steroid-treated animals. 3. The ratios of the ;back' to the ;forward' reactions in liver, kidney and epididymal adipose tissue are different and characteristic of each tissue; they differ markedly from values reported for the purified mitochondrial enzyme. 4. The ratio of the ;back' to ;forward' reaction in any one tissue is constant in adrenalectomized, diabetic, acidotic and steroid-treated animals. 5. In starved animals, the ratio is increased in liver and kidney, but decreased in epididymal adipose tissue. 6. Administration of l-tryptophan results in an acute (1h) increase in activity measured in the ;forward' direction alone in liver and epididymal adipose tissue, but not in kidney.


The measurement of protein turnover by density labelling.

A method for measuring the rate of protein degradation in plant tissue is described. The method uses density labelling to avoid difficulties associated with compartmentation and recycling of amino acids. Although the technique cannot be readily adapted to measure the rate of degradation of single proteins, it avoids difficulties of interpretation due to enzyme activation or inactivation. Values for the half-life of Lemna minor protein obtained by this method are compared with values obtained by a number of other methods. To obtain satisfactory results it was necessary to improve the method of isopycnic centrifugation in CsCl gradients. A considerable improvement was achieved by using KBr gradients, and the advantages of using KBr rather than CsCl for the separation of density-labelled protein are discussed.


The calculation of errors and the choice of sampling times in the determination of irreversible disposal rates in vivo by isotope experiments.

In well-known methods of estimating rates of irreversible disposal (utilization) in vivo the rates are calculated from the areas to infinity under specific radioactivity-time (S-t) or quantity-of-label-time (q-t) curves obtained by measurements on samples of plasma after intravenous injection of labelled substrate. The errors in the calculated rates are mostly those of the estimates of the areas. These errors are of two kinds: random, caused by the variances of the values of S or q, and systematic, caused by differences between the curves used to interpolate between these values and the true curves. A rigorous method is given for calculating the random errors from the variances of the values of S or q, and is applied to choosing the best times to sample the plasma from small animals from which few plasma samples can be taken. A procedure for estimating systematic errors is also given. Programs in BASIC language to carry out the calculations are deposited as Supplementary Publication SUP 50058 (5 pages) at the British Library (Lending Division), Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms given in Biochem. J. (1975) 145, 5.


Changes in lectin-induced deoxyribonucleic acid synthesis in cultures of chick-embryo fibroblasts at various stages of development.

Concanavalin A and Robinia pseudoacacia lectin decreased [(3)H]thymidine incorporation into acid-insoluble material of fibroblasts cultured from 6-10-day chick embryos. In contrast, these lectins stimulated [(3)H]thymidine incorporation in cells from 16-day embryos. These effects are due to neither [(3)H]thymidine permeability modification nor toxicity of the lectins. The specificity of lectin action was proved by blocking experiments with alpha-methyl mannopyranoside and with anti-(Robinia lectin) serum.


Acute effects of carbon monoxide on the metabolism of perfused rat liver.

1. Perfusion of livers with whole blood containing carboxyhaemoglobin decreased hepatic O(2) consumption and triglyceride secretion and raised free fatty acid oxidation. 2. Perfusion with [(14)C]carboxyhaemoglobin indicated that there was negligible hepatic uptake of (14)CO. 3. The observations appear to be due to a decrease in O(2) consumption rather than to specific effects of carboxyhaemoglobin.


Treatment of immature mice with gonadotrophins. The influence of mouse age on the response of ovarian alkaline phosphatase activities to gonadotrophins.

Treatment of mice aged 23-25 days with chorionic gonadotrophin induced large amounts of an ovarian alkaline phosphatase activity (phosphatase Ib) kinetically distinct from that of untreated ovaries (phosphatase I). The activities of alkaline phosphatase I and Ib varied with age in untreated mice. Phosphatase Ib appeared when serum luteinizing hormone concentrations increased (days 4-10 and days 35-45), and disappeared when concentrations were low (days 11-35). Injection of human chorionic gonadotrophin induced progressively larger amounts of phosphatase Ib activity between day 19 and day 29. However, gonadotrophin treatment failed to induce this activity on days 10-18 and 30-35. Nevertheless, during the latter period, human chorionic gonadotrophin induced especially large increases in uterine weight. Treatment at different ages with sheep luteinizing hormone plus human pituitary follicle-stimulating hormone induced a pattern of response identical with that induced by human chorionic gonadotrophin, although sheep luteinizing hormone alone was ineffective before 35 days. In contrast, human luteinizing hormone induced a response in the absence of exogenous follicle-stimulating hormone.


[Pemphigus induced by D-penicillamine in rheumatoid arthritis. Study of 5 cases and systematic study of anti-intercellular substance antibodies of the skin in the course of treatment].

The authors present 5 cases of pemphigus induced by D-penicillamine in a series of 180 cases of rheumatoid arthritis treated with this medication. In addition, anti-epidermal intercellular substance antibodies were sought in 40 asymptomatic patients. No antibodies were found in this group. The notion of induced pemphigus seems well established, as is the value of testing for antibodies in the surveillance of D-penicillamine treatment.


[Surgical treatment of cancer of the thyroid (author's transl)].

The authors report their experience with cancer of the thyroid. Using statistical data from 760 operated cases and present day concept, they consider the difficulties of the diagnosis, the stage of evolution and the treatment in the form of a collaboration between surgery, clinic and nuclear medicine.


Increase in type A virus particles induced in BALB/c mouse epidermis during chemical carcinogenesis.

Electron microscopic observations of normal BALB/c mouse epidermis revealed the presence of isolated intracisternal A particles. Hyperplasia, papilloma and carcinoma formation induced by topical application of the carcinogenic polycyclic hydrocarbons benz(a)pyrene (B(a)P) and 3-methylcholanthrene (MC) is accompanied by an increase in the mumber of A particles. Topical application of a non-carcinogenic irritant alpha-pinene (alpha P) failed to provide comparable changes. Examination of the nuclei indicated occasional electron dense granules in the nucleoplasm which became more common throughout the progression of carcinogenesis.


Extracorporeal immunoadsorption of circulating specific serum factors in cancer patients.

Circulating serum factors have been said to abrogate the effects of immune response in cancer, i.e. "blocking" and "antigenic inhibition". The aim of this investigation was to isolate such specific factors in a purified and native state. F(ab)2 fragments isolated from hypernephroma were insolubilized on the surfaces of an extracorporeal perfusion chamber which was inserted into the circulation by means of an arterio-venous shunt. As a result, 3 proteins not present in normal serum were isolated and eluted for further study. In immunoelectrophoresis the 3 proteins were specifically precipitated by heterolgous (rabbit) antihypernephroma serum but not by anti-serum directed against normal serum components. Moreover C9 components, C3 activator and C3 were isolated in the chamber, the latter complement factor in large concentrations. This further sustained that specific antigen-antibody reactions had occurred in the chamber. One of the 2 patients studied were perfused for 60 h and 40 min. During this period 450 litres of blood were brought into intimate contact with the immunoadsorbent. Proteins in amounts sufficient for immunochemical analysis were isolated within 3 h.


Increase in the gastrointestinal absorption and in tissue storage of cyclophosphamide in L-1210 leukaemic mice at an advanced stage of the disease.

BDF1 mice were inoculated with 10(6) leukaemic cells and, together with control mice, were given a single oral dose of cyclophosphamide-14C of 100 mg/kg body weight. In the leukaemic mice we observed an increased 14C concentration in the plasma, bone marrow, liver, lungs, spleen, kidney and particularly fat where the level was 2-4 times higher than in control mice. Conversely, during the same period, significantly less 14C was detected in the stomach and small intestine of the leukaemic mice. These results were obtained 6 days after tumour transplantation (median survival time 7.7 days) whereas no differences were observed when the studies were carried out 4 days after tumour transplantation. These findings indicate an increase in the gastrointestinal absorption and in the tissue storage fo cyclophosphamide in L-1210 leukaemic mice at an advanced stage of the disease.


Exogenous ochronosis and pigmented colloid milium from hydroquinone bleaching creams.

An outbreak of ochronosis and colloid milium is described after the use of strong hydroquinone bleaching creams. These phenomena developed only after a few years, and took place when the melanocytes had overcome the bleaching influence. Sun-exposure and thorough inunction of the cream were required for the more advanced changes. Analogous changes have been seen when the skin is exposed to certain crude fuels in individuals working in the sun, and phenolic components in the fuels are suspected. The study presented here covers the clinical, histological, histochemical, electron microscopical and pathogenetic features as seen in thirty-five cases of hydroquinone damage to the dermis in South Africa.


Ultrastructural study of elaunin fibres in the secretory coil of human eccrine sweat glands.

The basement membrane of the secretory coil of human eccrine sweat glands was studied by light and electron microscopy. With classical staining methods for the elastic system, elaunin ring fibres were observed in the basement membrane of the secretory coil. The ultrastructural study showed that  elaunin fibres are formed by bundles of fibrotubules 10-12 nm in diameter surrounding aggregates of amorphous material. These fibres differ from elastic fibres which are thicker and have an amorphous material more homogeneous and abundant.


The fine structure of the elastic tendons in the human arrector pili muscle.

The elastic tendons by which the arrector pili muscle is inserted into the hair follicle were studied by light and electron microscopy. From the follicle to the muscle it was observed that these tendons are formed successively by oxytalan, elaunin and elastic fibres. In close contact with the smooth muscle cells, elaunin and elastic fibres were observed. The fibres penetrate the spaces between the muscle cells and are clamped by them. An explanation is advanced about the significance of this arrangement in the recovery after muscle contraction.


The influence of age and sex on skin thickness, skin collagen and density.

Forearm skin collagen, dermal thickness and collagen density were measured in a large number of normal subjects as a standard reference for future studies. Skin collagen decreased with age and was less in the females at all ages. There is a direct relationship between skin collagen and dermal thickness but variations in collagen density in disease limit the use of dermal thickness as a guide to changes in its collagen content.


Palmar ridge appearances in normal newborn infants and ridge appearance in relation to eccrine sweating.

Epidermal ridge appearances over the palm in twenty normal newborn infants are described. No clear-cut relationship between ridge appearance and sweating was found although cross ridge flattening was always associated with a negative o-phthaliadehyde sweat test.


Epidermal transit times.

Radio-isotope disappearance curves and autoradiography (labelled DNA precursors and labelled amino acids) have been used to estimate the minimum transit times for four regions of epidermis in mice. The post-mitotic maturation time in the basal layer has been estimated and the results interpreted in relation to proliferation rates and epidermal organisation.


Arterial thrombosis in scleroderma.

Clinical and pathological observations are presented on five patients with scleroderma who developed thrombosis of a major vessel. Three died following intestinal infarction or limb gangrene and two had digit or extremity amputation. Severe intimal thickening of major arteries with thrombus formation was noted but no significant abnormality was found in the clotting activity of the blood. Histochemical studies in three cases suggested a reduction of fibrinolytic activity at the site of thrombosis in the diseased vessels. These studies support the view that the vascular system is profoundly altered in scleroderma and may play an important role in some manifestations of the disease.


Angioma serpiginosum--familial incidence.

In this paper we present the first record of familial incidence in angioma serpiginosum observed in two families. The clinical and histological features are described.


Hypertrichosis due to diazoxide.

Two cases of hypertrichosis due to diazoxide are described. The mechanism is unknown bu may be due either to increased cutaneous perfusion or to increased levels of cyclic AMP.


Epidemiology and family characteristics of severely-abused children.

Severe child abuse in north-east Wiltshire was studied retrospectively during the period 1965-71, and prospectively for 18 months from January 1972, after a period of consultative activity with those actively involved to increase awareness of the phenomenon. Severe abuse was strictly defined. A rate of 1 per thousand children under four years old was obtained, together with a death rate of 0-1 per thousand. The families of the retrospective series of abused children were studied in detail and identifying characteristics of large family size, youthfulness, low social-class, instability, and gross psychiatric, medical, and social pathology described. The implications of the ascertainment and death rates are discussed in relation to data from some other studies, and the need emphasized for detailed studies of the apparent clustering of disorder in the families, using linked record systems.


Priorities in biomedical research. Indices of burden.

The relative burden of different diseases is a legitimate component in the consideration of priorities for biomedical research. Simple prevalence statistics do not directly reflect the different burdens on services imposed by diseases of comparable prevalence. This paper sets out for each 54 categories of disease five indices of the burden on services, based respectively on inpatient days, outpatient referrals, consultations in family practice, sickness benefit, and loss of expectation of life. There is considerable variation in the rank-order of categories of disease, in their contribution to the five burdens; but for each burden the number of categories accounting for 50% of the total burden is not large, ranging from 3 to 9 out of the possible 54.


Asthma in schoolchildren. Demographic associations and peak expiratory flow rates compared in children with bronchitis.

The frequency of asthma in 10 971 school-children between the ages of 5 and 14 years was reported by their parents to be 3-8%. Of these, 20-7% were said to have had bronchitis, 5-9% pneumonia, and 4-7% eczema. Asthma was reported more commonly in boys than girls and was greatest in children of social classes I and II. One-third of the children were reported to have their first attack before the age of 2 years. Few (18%) first attacks started after the age of 5 years. There was no evidence that bronchitis predisposed to the later development of asthma, or vice versa. Within each age-sex group children with a history of asthma had lower peak expiratory flow rates than children who gave no such history. These diffences in PEFR were greater than for children with a history of bronchitis.


Acceptability of the cytopipette in screening for cervical cancer.

A randomized controlled trial was carried out in which the acceptability of screening for cervical carcinoma in situ by a postal 'do-it-yourself' method--the cytopipette--was compared with that of an invitation to attend a clinic or see a general practitioner for the conventional cervical scrape examination. In parallel with this, a sociological study of women who had been invited by both methods was undertaken in which information was obtained from responders and non-responders on attitudes to health care. The results show that, while the pipette was used by a greater proportion of women overall than the scrape examination, its acceptance by women most at risk of the disease is still not high. It is concluded that, taking into account the relative merits of the two methods as screening tests, as well as their acceptability and cost, the postal pipette may be useful in some circumstances, such as areas where clinical resources are limited, and as a second approach to women who have not taken up the offer of a scrape examination.


Regional variations in the development of illness in Finland.

The aim of the present study is to investigate the incidence of morbidity leading to incapacity for work in the working age population of Finland, and to examine critically the development of such illness and variations between different population groups. An attempt is made to analyse to what extent regional differences in illness development are connected with the communal structure of an area and the provision and use of medical services. The material is based on data from the sickness insurance and national penisons, and mortality statistics. The variables used as those defined by Kalimo (1967; 1968) to describe the various features of community structure and the supply of medical services, and data from the insurance and hospital service statistics to measure the use of medical services. The results indicate considerable variation in the course of illnesses between population groups, as expressed as the incidence rates for the various phases of illness or as development probabilities. Illness development proved to be more unfavourable in men than in women. Large regional differences were found, with the course of illnesses appearing to be much more unfavourable in the eastern and northern parts of Finland than in the south and south west. This seems to be closely connected with poorer socioeconomic development and lower urbanization in an area. A clear correlation was found between illness development and the supply and use of medical services in ambulatory care. Illness development was particularly unfavourable in areas where the supply and use of ambulatory medical services, especially doctors' services, were poor. No corresponding correlation was found with the supply and use of hospital services. Development of sickness proved to be connected with a neglect of illnesses at an early phase and delay in seeking medical care. The result is confirmed by variations between population groups in the numbers of sickness benefits awarded. It was confirmed that morbidity resulting in incapacity for work is closely associated with local socioeconomic development.


Primary schoolboys: image of self and smoker.

The way primary schoolboys see themselves and also see young smokers, may have implications for health education. In this paper a comparison is made between the self-images of 229 primary schoolboys and their images of a young person who smokes. The two images were very different, both for smokers and non-smokers, although the difference for smokers was smaller. It appears that children of this age who smoke do not see themselves as 'smokers', and may not relate the health education they receive on this subject to themselves.


The influence of the birth of a malformed child on the mother's further reproduction.

Births which occurred in Birmingham in 1964-70 were assembled into fraternities by computer linkage. By calculating the frequency with which one birth was followed by another and the interval between births the reproductive behavior of mothers after the birth of a malformed child was compared with that of all mothers, taking account of differences in maternal age, parity, and period of observation. It was found that malformations which resulted in stillbirth or early death were more frequently followed by another birth and that the interval to the following birth was shorter than usual. In this respect malformations did not differ in their effect from other causes of stillbirth and infant death. The birth of children were severe malformations who survived, however, acted as a slight deterrent to further reproduction. The malformation rate among children born after a malformation was double the usual rate; the recurrence rate was particularly high for neural tube defects, 5% of subsequent children being affected. In spite of this parents of children with central nervous system malformations were not deterred from further reproduction unless the affected child survived.


A nuclear magnetic resonance study of the metal binding sites in bacitracin.

Carbon-13 nuclear magnetic resonance spectroscopy has been used to identify sites in bacitracin which bind Cu2+ and Mn2+. Results are presented which implicate the free carboxyl groups of the aspartic and glutamic acid residues and the imidazole ring of the histidine residue as metal complexation sites between pH 6 and 8. Evidence is presented which also indicates that the thiazoline ring of bacitracin binds Mn2+. Bacitracin does not bind Cu2+ or Mn2+ at pH values of 2.5 or less.