[Effect of cytotoxic hypoxia on the metabolism and ultrastructure of cortical synaptosomes and mitochondria]. The study is concerned with morphochemical changes in the metabolism and ultrastructure of the mitochondria and synaptical endings from the cortex of the hemispheres in rats under the influence of cyanide (7mg/kg) following 30 min, 2 hours and 24 hours after its administration. Subfractions of the light and heavy synaptosomes, as well as in the mitochondria of the cell bodies showed changes in the activity of the enzyme systems (cytochromoxidase, K+, Na+-ATPase and Mg2+-ATPase) and disturbances of the ultrastructure of the eliminated organella. After 24 hours the metabolism normalized, which may be explained by a biochemical brain plasticity at the subcellular level under conditions of histotoxic hypoxia.


[Neuropsychological analysis of personality disorders in lesions of the frontal lobes of the brain]. The paper concerns some problems of disturbances in the most complicated forms of human behaviour and psyche in local brain lesions. A neuropsychological analysis of personality disturbances determines them as an integrative formation--a product of the work of the whole brain in social human activity. It is directed towards the distinguishing of "components" inside this formation and a study of the brain areas providing their functioning. In 63 patients with lesions of the left and right frontal lobes, as well as of deep areas of the right hemisphere, the authors studied the traits of self-evaluation (its 2 levels - cognitive: the knowledge of oneself, and emotional: feeling oneself) and emotional sphere. The data obtained indicate specific personality disorders with different localizations of brain lesions and, in particular, in lesions of the frontal lobe. Besides consolidated results given in the table, 2 cases (with pathology of the left and right frontal lobe) show principle differences in disorders of the emotional-personality sphere, related most likely to the localization of the pathological focus.


Interaction of metal ions with nucleic acids. Interaction of copper(II) with guanosine and its derivatives. Interaction of copper(II) with guanosine, 2'-deoxyguanosine, 1-methylguanosine, 7-methylguanosine and GMP was studied withe use of spectroscopic and magneto-chemical methods. The main site of copper(II) binding in guanosine is nitrogen N-7; participation of N-1 is not excluded. The involvement of carbonyl oxygen in copper binding or copper chelation to N-7 and 0-6 is rather unlikely. A crystalline complex of copper(II) with GMP [Cu(C10H12O8N5P) .(H2O)3] was obtained, and it was demonstrated that copper(II) is bound with N-7 and the phosphate group.


The cyto-histopathology of a pseudomesotheliomatous carcinoma of the lung. A cyto-histopathologic study of a pseudomesotheliomatous carcinoma of the lung has been presented. The cytologic preparations of the early morning and post-bronchoscopy sputum specimens, bronchial washings and pleural fluid contained tumor cells similar to those exfoliated from a terminal bronchiolar carcinoma, of which this neoplasm is considered a variant.


Selection of material for training cytotechnologists. Out of 450 specially selected cases (gynecological and non-gynecological material) presented to 30 students during their educational program lasting 12 months, 20 cases caused the most problems. These 20 cases, in effect "selected by the students", were again presented as "unknowns" at the end of the course. The mean percentage of error improved from 64 per cent to 26 per cent. Furthermore, we gave the ten gynecological "unknowns" to ten cytotechnologists with at least five years' experience and their diagnoses were compared with those of the students at the end of the course. The majority of the diagnoses were similar with the exception of two cases: in one case the experienced cytotechnologists overlooked the scarce adenocarcinoma cells more often. In the other case follicular cervicitis was correctly diagnosed by the trained cytotechnologists but frequently misinterpreted by the students.


Hepatoma development during long term follow-up period of liver cirrhosis. An attempt was made to elucidate the pathogenesis of hepatoma. The material comprises 20 cases which were followed up more than 3 years after diagnosed liver cirrhosis and verified by autopsy. Hepatoma was found in 10 out of these 20 cases (50%). The follow-up period of these 10 cases with hepatoma was from 3 to 9.5 years (the mean value; 5.5 years). All 10 cases were not heavy drinkers, and showed liver cirrhosis of the mixed type by autopsy. HBsAG was positive in 6 out of 8 cases by RIA method (75%), and alpha-f was also detected in 5 of 7 cases by RIA method (70%). On the contrary, only 2 out of 10 cases without hepatoma were HBsAG positive (20%). The present results indicate that HBsAG positive liver cirrhosis of the mixed type is closely related to hepatoma in our country.


Computed tomography in hepatobiliary diseases. Computed Tomography (CT) was introduced to detect lesions in 48 cases with various hepatobiliary disease. In 8 out of 11 cases with liver cell cancer, diagnosis were made by CT. A case was detected in early stage, the low density area was so small that it can be resected segmentally. In 7 out of 9 cases with metastatic liver cancer, multiple low densities were detected by C.T. Gallbladder cancers, which is known as diagnostic difficulty, were detected in five cases as low density in gallbladder area. CT has superiority to liver scintiscan, 1) CT can determine the tumor more exactly except for the diffuse type. 2) CT can be performed repeatedly without any risk and use of isotopic substances. 3) CT observes the transverse configuration of the organ, which could not be done in any conventional method.


Scan-guided fine needle aspiration biopsy in malignant hepatic disease. The method of scan-guided fine needle aspiration biopsy of the liver is described, and the diagnostic value of this combined method in the diagnosis of malignant hepatic disease is evaluated in 83 confirmed cases, showing a specificity of 100% and a sensitivity of 94%. The combined method is compared to liver scanning alone and to Menghini biopsy. Different methods for the diagnosis of malignant hepatic disease are discussed, and it is concluded that scan-guided fine needle aspiration biopsy has a diagnostic value only obtainable otherwise by a combination of liver scanning and biopsy during laparoscopy. Cytologic features in the two most common tumor types in this study, i.e., metastatic colonic adenocarcinoma and hepatocarcinoma, are presented along with a brief discussion of the specificity of the cytologic diagnosis of hepatocarcinoma.


Hepatitis B virus infection and chronic liver disease in Taiwan. Three hundred and eighty-five patients mostly with chronic liver diseases and 729 apparently healthy adults were studied for hepatitis B surface antigen (HBsAg) with reversed passive hemagglutination and antibody (anti-HBs) with passive hemagglutination. In healthy adults around 15% was HBsAg positive and in 45% was anti-HBs positive, estimating hepatitis B virus (HBV) infection in nearly two thirds of the population. The infection already occurred before adulthood. The prevalences of HBsAg were invariably over 80% in chronic hepatitis, cirrhosis and hepatocellular carcinoma (hepatoma) indicating an intimate relationship to HBV. On the contrary, the positive rates of anti-HBs in these diseases were far lower than those in healthy people and patients with other diseases, this is similar to the situation in chronic HBsAg carriers. The prevalence of HBsAg in hepatoma patients was unusually high, being 82.7% in contrast to 11.9% in patients with other malignancies. Not only hepatoma patients with cirrhosis but also those without cirrhosis were found to have high prevalence of HBsAg. The fact indicates an even more intimate relationship between hepatoma and HBV.


Cytologic evaluation of experimental type 2 herpes simplex infection in mice. The nature and frequency of cytopathologic changes in female mice genitally infected with type 2 herpes simplex virus have been investigated. The extent of virus infection in an individual mouse was assessed by a system of "plus scoring". Exfoliative cytology clearly provided a reliable evaluation of the extent of virus infection and a reliable prognostic index of mouse mortality. A composite index combining both cytologic and virologic information ('vircyt' value) was derived and shown to provide a convenient and precise prognostic index of mouse mortality.


Reduced serum 1,25-(OH)2 vitamin D3 levels in prednisone-treated adolescents with systemic lupus erythematosus. The serum levels of 1,25-(OH)2 vitamin D3 were assayed in samples from 12 adolescent patients with SLE. Subnormal levels were observed in 7 of these 12 patients. Low levels of the metabolically active polar metabolite of vitamin D3 may contribute to the development of osteopenia observed in this disease. The cumulative effects of the osteoporotic and anti vitamin D effects of long term steroid therapy in children with SLE may require the cautious administration of supplemental vitamin D.


A variant of the Klippel-Trenaunay-Weber syndrome with temporal lobe astrocytoma. An 8-year-old boy with a variant of the Klippel-Trenaunay-Weber syndrome (KTW syndrome) is described. The hemangiomatous tissue located to the right half of his trunk and extremities was hypotrophic. On the same side, on his face and gingivae the tissue appeared hypertrophic and dental abnormalities were present. Moreover, the patient suffered from psychomotor epilepsy caused by a right-sided temporal astrocytoma. The connection between the KTW syndrome and the neurocutaneous syndromes is discussed.


Prediction of adult height with various methods in Finnish children. Successive height predictions were made by several methods for a group of healthy Finnish children (30 boys and 30 girls), examined annually at ages of 7 to 17 years (1st series) and for 7 boys aged 14 to 19 years with familial delayed growth and puberty (2nd series). The methods used were those of Bayley & Pinneau (BP), Walker (W), Tanner et al. (T) and RWT, and two simple principles: the relative height method (RH) which assumes constancy of height S.D.S. throughout growth, and the index of potential height (IPH) method which assumes constancy of height S.D.S. for bone age (BA). The predictions with RH, W and IPH were inaccurate. BP, T and RWT were for the 1st series as accurate as for the basic series of the respective methods, and none was superior to the others. The BA of average Finns was delayed as compared with the standards of Greulich-Pyle Atlas. When corrections were made for this delay, the IPH method gave predictions comparable in accuracy to BP, T or RWT. In the 2nd series prediction was more accurate with the corrected IPH, BP and RWT methods than with those using BA according to TW2RUS.


Experimental mixed CNS infections in mice caused by three Ixodes ricinus transmitted Arboviruses. Approximately 12-day-old mice were infected intracerebrally with tick-borne encephalitis (TBE) virus (strain Hypr), Unkuniemi virus (strain By E50) and Tribec virus, as single virus inoculations, coinfections with two or three viruses, and sequential infections with two or three viruses at 24-hour intervals. The effect of mixed infections on mortality, morbidity and average survival time was recorded. The main findings were that: 1. Some mixed infections with TBE and UUK viruses reduced the mortality and acute morbidity significantly as compared to single infections with each virus. The average survival times were lengthened. 2. Mixed infections with TBE and Tribec did not affect the 100% mortality of TBE. 3. Mixed infections with UUK and Tribec seemed to result in a cumulative effect of the two viruses. 4. With triple co-infections (TBE + Tribec + UUK simultaneously), the mortality and acute morbidity rates were reduced significantly as compared to TBE single infections. 5. Some of the mixed infections tended to result in chronic disease among the survivors.


Effects of detergent formula chelating agents on the metabolism and toxicity of cadmium in mice. Chelating agents like NTA (nitrilotriacetic acid) STPP (sodiumtripolyphosphate, Na5P3O10) and EDTA (ethylenediaminetetraacetic acid) are used as components of detergents. An increased toxicity of some metal compounds when combined with NTA has led to decreased use of this chelating agent in relation to STPP. In the present studies short-term and long-term effects of these chelating agents on cadmium toxicity in mice were investigated. I: In the short-term study, mice subcutaneously exposed to CdCl2 (3.2 mg Cd/kg b. wt.) in combination with STPP (32 mg/kg b. wt.) demonstrated a markedly higher mortality compared to animals given CdCl2 alone. This increase in mortality was similar to the one encountered when CdCl2 (3.2 mg Cd/kg b. wt.) and NTA (32 mg/kg b. wt.) were combined. Animals exposed subcutaneously to CdCl2 + STPP or CdCl2 + NTA showed histological evidence of liver necrosis 24 hrs after exposure not seen in animals given the same dose of CdCl2 alone and also had markedly lower cadmium concentrations in the livers compared to only Cd-exposed animals. II: In the long-term study, mice were exposed orally to CdSO4 (50p.p.m Cd) alone or in combination with STPP (500 p.p.m.), NTA (500 p.p.m.) or EDTA (50 p.p.m.) by continuous administration via the drinking water for 18 months. A decreased total excretion of urine proteins was seen in all Cd-treated animals irrespectively of the combination with various chelating agents. The conclusion of the present work was the NTA and STPP given by subcutaneous injection to mice markedly increased the toxicity of cadmium but that neither NTA, STPP nor EDTA given orally altered the toxicity of cadmium during a period of long-term exposure of 18 months.


X-radiation actions on the neuromuscular transmission. The effects of high doses of X-radiation (100 kilorads) on the neuromuscular transmission of isolated sciatic nerve-sartorius muscle preparations of the frog, as evaluated by bioelectrical characteristics, were explored. Intracellular microelectrode recordings after X-irradiation showed that the resting, excitation and action potentials of nerve fibers approaching the synaptic terminal region of the motor end-plate became lessened, and also presented a slower velocity of impulse propagation, earlier than that observed in muscle cells. After forty minutes following the irradiation period, the neuromuscular transmission became blocked, although muscle fibers still responded to direct electrical stimulation. Records taken at the motor end-plate region of muscle cells, demonstrated the presence of postsynaptic miniature end-plate potentials (m.e.p.p.'s), the sequence of which fits closely into a random Poisson distribution. X-irradiation elicited an increase of the rate of m.e.p.p.'s and induced membrane changes over fine terminal nerve branches, leading into a failure to initiate and propagate action potentials. Only as time progressed, this nerve bioelectrical impairment was accompanied by a similar one in muscle cells, associated to the inability to develop contractile tension. The increase of m.e.p.p.'s frequency due to depolarization by a high K+ concentration, of presynaptic nerve membranes of control and irradiated preparations, was reversed by a high Mg+--Ca2+--free media. However, a concentration of Mg2+, which normally reduced quantal release of acetylcholine (ACh), without altering presynaptic nerve membrane potentials, failed to modify the spontaneous basal frequency of m.e.p.p.'s, both in irradiated and control preparations. The findings of the present study suggest that the presynaptic ACh synthesis, storage, and availability for ACh liberation are not early affected by X-rays, i.e. at a time when transmission from nerve to muscle had already failed. On the contrary, the most precocius membrane changes following X-irradiation, seem related to the mechanisms underlying nerve resting, excitation, and action potentials. The smallest presynaptic nerve terminal fibers close to the motor end-plate, are the most radiosensitive portion of the myoneural junction. Indeed, their bioelectric characteristics are early affected by X-rays, resulting in a failure to generate and propagate nerve impulses which lead to a blockade of neuromuscular transmission.


An improved procedure for purifying RNA tumor viruses from malignant tissue. A convenient method for purifying RNA tumor viruses is described. Viruses banded in isopycnic gradients are contaminated with membranes that can be removed by velocity sedimentation in glycerol gradients. On sodium dodecyl sulfate (SDS) gel electrophoresis, the particles purified by these procedures from mouse mammary tumor tissue show protein profiles typical of those observed with virus purified from milk.


Studies of the adrenergic reactivity in different regions of rabbit and rat oviduct. Experiments are made to study the spontaneous contractions and the contractile response to noradrenaline of muscle strips isolated in longitudinal direction from the ampulla, isthmus and horn of the oviduct. Left oviduct of rats (in oestrus and dioestrus) and rabbits (in dioestrus) was used. In both rats and rabbits, all muscle strips including the ovarium manifest spontaneous contractions with highest frequency in the ovarium and ampulla, lower in the isthmus and lowest in the horn. Noradrenaline inhibits spontaneous contractions of strips in rat oviduct and ovarium. The inhibitory effect is manifested at lower noradrenaline concentration for the horn and isthmus (maximum effective concentration 3 X 10(-7) M in dioestrus and 3 X 10(-6) M in oestrus) compared with the ampulla and the ovarium (3 X 10(-6) M in dioestrus and 3 x 10(-5) in oestrus). Noradrenaline stimulates rabbit oviduct contractions . The stimulating response is manifested at lower noradrenaline concentration (1 X 10(-8) M minimum effective concentration) for the isthmus, higher for the horn (5 X 10(-7) M) and highest for the ampulla (5 X 10(-6) M). The presence of different alpha- and beta-adrenergic reactivities in the different areas of the oviduct is discussed.


Adenosine and cyclic AMP in cerebral cortex of rats in hypoxia, status epilepticus and hypercapnia. The influence of hypercapnia, hypoxia and status epilepticus on cerebral cortex concentrations of adenosine, adenine nucleotides and cyclic AMP was studied on lightly anaesthetized (70% N2O) and artificially ventilated rats. Neither hypercapnia (arterial PCO2 about 80 and about 300 mmHg) nor hypoxia (minimal values of 19 mmHg) altered tissue concentrations of AMP, cyclic AMP or adenosine. Bicuculline-induced status epilepticus was accompanied by increased concentrations of cyclic AMP but adenosine concentration did not change. Experiments with ischemia, and those in which tissue hypoxia was exaggerated by unilateral carotid artery ligation, showed that tissue adenosine concentrations were elevated only when AMP concentration rose. It is concluded that the marked increase in cerebral blood flow which occurs in hypoxia and status epilepticus is unrelated to changes in tissue adenosine concentration and that the increase in cyclic AMP during neuronal hyperactivity is triggered by other mechanisms than adenosine accumulation.


Inhibition of acetylcholine release in guinea pig ileum by adenosine. The effect of adenosine on cholinergic neuroeffector transmission was studied in the isolated guinea pig ileum. Adenosine caused a dose-dependent and inverse frequency-dependent inhibition of contraction responses to transmural nerve stimulation. Blockade of adrenergic neurotransmission did not alter the inhibitory effect of adenosine. Adenosine also inhibited contraction responses to serotonin, angiotensin and high potassium, but not the responses to acetylcholine, histamine or direct electrical stimulation of the smooth muscle cells. Adenosine had little effect on basal outflow of acetylcholine but inhibited markedly and reversibly the release of acetylcholine induced by nerve stimulation. Acetylcholine was determined with gas chromatography-mass spectrometry. The results provide direct evidence that adenosine inhibits cholinergic neuroeffector transmission in the gut by a prejunctional action on acetylcholine release. This may be of functional importance since adenine compounds are released during stimulation of intestinal nerves.


Histiocytosis X. III. Clinical value of serial biopsies. In a retrospective review of sequential biopsies in 8 cases of histiocytosis X, 2 developed xanthomatous or fibrous lesions, 3 remained unchanged, whereas 3 developed malignant disease, one Hodgkin's disease and 2 malignant histiocytosis. A possible progression from benign, well differentiated to malignant histiocytic lesion is discussed, and the importance of achieving a microscopic diagnosis is emphasized.


Adenoid cystic carcinoma (cylindroma) in the head and neck. A clinical review of 82 cases. A review of 82 cases of adenoid cystic carcinoma in the head and neck is given. Radical surgery was carried out in 33 patients and yielded the best long-term results. Radiation therapy was given to 43 patients for inoperable tumour, local recurrence or, postoperatively, for sub-clinical disease. It proved especially valuable in obtaining remissions from local recurrence.


Malignant fibrous histiocytoma with skeletal involvement. Malignant fibrous histiocytoma of soft part is rather common but malignant fibrous histiocytoma of the bone is rarely encountered clinically. Authors present five cases of malignant fibrous histiocytoma with skeletal involvement and discuss their clinical course, x-ray findings and histological features. This tumor has marked tendency for local recurrence and metastasis. Other bone tumors such as giant cell tumor, aneurysmal bone cyst, non ossifying fibroma, osteosarcoma, fibrosarcoma of bone and metastatic cancer can be excluded by several characteristic findings observed in x-rays as well as histopathological features. All information on the patient should be carefully analysed, because it is difficult to decide whether bone involvement is primary or secondary. Four out of five cases definitely originated within the bone.


Relations between the pulvinar-lateralis posterior complex of the thalamus and the hippocampus in wakefulness and sleep in cats. Paucisynaptic connections between n. lateralis posterior (LP) and dorsal hippocampus (Hip) have been demonstrated in acute experiments. In the free moving cats, with chronic implanted electrodes on the neocortex, in LP, pulvinar (Pul), VA and VL nuclei of the thalamus and in the dorsal hippocampus (Hip), the theta waves recorded in LP, Pul and Hip were not of the same frequency and origin. In wakefulness and in slow-wave sleep, the theta waves were of 3.5-4 c/s and occurred exclusively or predominantly in Pul-LP, while in paradoxical sleep they were of 5-6 c/s, occurred' in Hip and invaded the Pul-LP. These two types of theta waves represent two distinct modalities of their organization and reflect the involvement of different mechanisms in the different phases of sleep.


Selected animal models for systematic antiatherosclerotic drug development. We have developed an integrated system for antiatherosclerosis drug development utilizing rats, SEA quail, and cynomolgus monkeys as animal models. In general, the way the system is presently functioning is that thousands of compounds per year are randomly screened for hypobeta- or hyperalphalipoproteinemic activity in rats, and hundreds of compounds per year are screened in SEA quail for antiatherosclerotic and hypocholesterolaric activity. A few selected compounds that have activity in both rats and quail are then tested for lipoprotein modifying activity in cynomolgus monkeys. Nontoxic compounds having very good lipoprotein modifying activity in the monkey will then be recommended for clinical trials in man. We do not anticipate that this battery of testing will guarantee activity in man, but are hoping that it will at least increase the probability for finding a truly effective antiatherosclerotic drug to control the human disease.


Relative atherogenicity of different plasma lipoproteins. Originally, data from the Framingham study appeared to show that serum lipoprotein fractions were no better in predicting coronary heart disease than the total serum cholesterol. More recently, the concentration of high density lipoprotein has been shown to exhibit a strong negative correlation with coronary heart disease, especially in the older age groups in which total serum cholesterol shows little or no correlation with clinical events. Biochemical mechanisms that might clarify the role of high density lipoprotein in atherogenesis are forthcoming. Another aspect of the lipoprotein-atherogenesis question pertains to the possible role of chylomicrons. Animal experiments show that cholesterol feeding is frequently accompanied by an increase in beta-migrating, very low density lipoproteins which appear to be chylomicron remnants. The atherogenic effect of serum low- and very low-density lipoproteins, including chylomicron remnants, appears to depend more on their contribution to the total cholesterol concentration than to their origin in liver versus intestines.


Results of a five-year study of the curative effect of double stranded ribonucleic acid in viral dermatoses and eye diseases. Double stranded RNA obtained from non-permissive E. coli cells infected with f2-phage was tested in 5 hospitals in viral dermtoses such as herpes simplex recidivans, herpes zoster, male genikeratonconjunctivitis herpetica and conjunctivitis lignosa. The results of clinical tests indicate that the preparation of phage double stranded RNA applied topically is harmless for man and has, in the majority of cases, a beneficial effect in the disease. This conclusion was based on the judgment of physicians, opinion of patients expressed in a questionnaire, and, results of a double-blind experiment.


Production of interferon in human cell cultures by a new, potent viral inducer. A new discovered double-stranded RNA inducer of interferon, bluetongue virus (BTV), stimulates the production of large amounts of interferon in animals as well as in many types of mammalian cell cultures, including human leukocytes, and continuous cell lines. The exceptional pH lability of BTV and its lack of pathogenicity for man further recommend its use as an interferon inducer. Among several human cell lines tested, the most efficient producer of interferon was a continuous cell line designated HT-1376, derived from a bladder carcinoma. With infectious BTV as the inducer, the HT-1376 line produced more interferon per cell than did leukocytes; interferon yields ranged from 10,000 to 60,000 units per ml of crude, unconcentrated supernatant fluid. Noninfectious BTV, inactivated by ultraviolet irradiation, was as effective as infectious virions. The interferon produced in HT-1376 cells has physicochemical and antigenic properties resembling those of fibroblast interferon produced in diploid cells.


Membrane alterations following interferon treatment. Interferon treatment appears to induce a number of changes in the plasma membrane of uninfected cells. Interferon treatment altered the surface exposure of gangliosides of both Ly and KB cell membranes. The differences were found in the amount and pattern of incorporation of tritium after galactose oxidase treatment. In AKR,C- (AKR-2B) mouse cells, not only was there an apparent increase in the number of intramembranous particles in response to treatment with interferon but also the kinetics of the increase followed that of the establishment of the antiviral activity. The buoyant density of plasma membrane was also found to be significantly increased in interferon-treated cells. Moloney murine leukemia virus produced in interferon-treated mouse thymus and bone marrow cells had a high particle to infectivity ration. This virus contained a prominent glycoprotein with a molecular weight of about 85,000. This large glycoprotein was only a very minor component of Moloney leukemia virus produced in control TB cells and might be an uncleaved precursor to gp 69-71.


Oat cell carcinoma manifesting as a bronchocele. Three cases of oat cell carcinoma appearing as a bronchocele on the chest radiograph are described. A bronchocele as the major radiologic manifestation of oat cell carcinoma has not been emphasized previously. Such a bronchocele may be filled with neoplastic cells rather than only inspissated mucus. Needle aspiration biopsy was definitive in two of the cases when conventional diagnostic methods failed.


Antrochoanal polyps.

Antrochoanal polyps. The antrochoanal polyp, a benign solitary polypoid lesion, usually arises in a maxillary sinus, opacifying and enlarging the sinus cavity without bone destruction. It passes through the ostium of the sinus into the choana, and from there into the posterior nasopharynx. The soft tissue mass does not erode or destroy contiguous soft tissue or bony structures. In this sequence of events, its radiologic findings are characteristic. Five case reports are presented, and the differential diagnosis is discussed.


Hepatocellular carcinoma: clinical and angiographic findings and predictability for surgical resection. Demographic, clinical, and angiographic data were reviewed for 63 consecutive patients with hepatocellular carcinoma. Angiography remains the critical examination in determining extent of disease and potential surgical cure. Angiographic findings were correlated with surgical or autopsy findings for 26 of the patients. The absence of venous invasion and lack of involvement of at least one hepatic segment favor resectability. Selective hepatic injections and oblique views accurately answered these questions in more than 80% of our patients. Pitfalls to angiographic accuracy include vascular invasion by very small tumor masses, hypovascular or diffuse hepatocellular carcinomas, metastatic disease, and involvement of the left lobe.


Comparison of a sodium chloride aerosol filter test method to silica-dust and silica-mist filter test methods. A LASL-developed sodium chloride aerosol filter penetration test has been compared to the silica-dust and silica-mist tests used by NIOSH for respirator approval testing. Filter discs were made from two types of resin impregnated electrostatic felt filter materials and tested at LASL for resistance to air flow and sodium chloride aerosol penetration. Sets of these filters were sent to four respirator manufacturing companies, where silica-dust and silica-mist penetration tests were performed. One set of filters was sent to NIOSH Division of Physical Sciences and Engineering in Cincinnati where sodium chloride aerosol penetration tests were performed by NIOSH personnel.


Two and three dimensional display of myocardial ischemic "border zone" in dogs. It is intuitively apparent that the ultimate fate of reversibly damaged, peri-ischemic "border zone" tissue should relate to individual patient survival. The purpose of this study was: (1) to describe a technique of assessing the adequacy of epicardial and myocardial oxygenation, and (2) to examine the extent and character of the peri-ischemic "border zone" in the dog after coronary arterial ligation. A diagonal branch of the left anterior descending coronary artery was ligated in four anesthetized open chest, neurohormonally intact dogs. The same diagonal coronary artery was ligated in six isolated perfused canine heart preparations in which coronary partial pressures of oxygen and carbon dioxide, pH, blood flow and temperature were fixed. The ischemic zones were rapidly frozen and reduced nicotinamide adenine dinucleotide (NADH) fluorescence photographs were taken of the epicardium and at 0.5 mm depths into the myocardium. The distinction between perfused and ischemic myocardium is not apparent with the naked eye or natural light photography. Epicardial and myocardial oxidation-reduction status is well seen with NADH fluorophotography. In both the intact and perfused heart preparations the NADH-fluorescent (ischemic) border is jagged along all edges. Islands of perfused nonfluorescent tissue appear within the ischemic border. The transition between NADH-fluorescent ischemic cells and adjacent non-fluorescent tissue is less than 0.1 mm. The ischemic border is narrow. The distance between homogeneously NADH-fluorescent tissue and homogeneously nonfluorescent tissue (across the zone of island normoxia or microheterogeneity) may be as wide as 6 to 8 mm.


The influence of dietary mackerel oil on the condition of organs and on blood lipid composition in the young growing pig. A feeding experiment was carried out in which piglets were fed to a diet enriched with either mackerel oil or olive oil. The oil consumption amounted to about 100 g per animal per day. The aim of this experiment was to study the effect of feeding high amounts of fish oil rich in polyunsaturated and long-chain monoenoic acids in order to determine if any morbid changes occurred in the animals as a result of this addition. The piglets fed olive oil served as controls. After 4 weeks, blood hemoglobin, plasma glucose, and serum triglycerides were significantly lower in the mackerel oil group as compared with the control group. There was no difference in serum cholesterol and serum lipid composition. Very low density lipoproteins were lower in the mackerel oil group. The fatty acid composition of blood serum, heart muscle, and liver showed considerable differences, omega3 acids being higher and both omega6 and omega9 acids being lower in the mackerel oil group than in the control group. Some increase in the amount of triglycerides in the heart muscle was observed in the mackerel oil group. Some characteristics of "yellow fat disease" developed in the mackerel oil group. This type of vitamin E deficiency seems to be the result of the considerable amount of omega3 fatty acids present in the mackerel oil. No clinical symptoms due to ingestion of long-chain monoenoic acids were observed.


Malignant mixed tumor of the salivary-gland type, primary in the prostate. A previously undescribed malignant mixed tumor arising in the prostate of a 72-year-old man is herein presented. Clinically, it was manifested by slowly progressing urinary frequency and urgency, as well as by intense pain. The total serum acid phosphatase value and the prostatic fraction were within normal limits. Six months after prostatectomy the patient died, with local recurrence and roentgenologic evidence of a single pulmonary metastasis. Both light-microscopic and electron-microscopic examination showed features similar to those of a malignant mixed tumor of the salivary gland. These findings suggest that this tumor originated in seromucinous ectopic glands. The important factor in its recognition is that it is not hormone-dependent.


Hypoglycorrhachia and coxsackie B3 meningoencephalitis. The case of a 3-week-old infant with Coxsackie B3 meningoencephalitis is discussed. Hypoglycorrhachia and neutrophils in the cerebrospinal fluid characterized the first ten days of her illness. Coxsackie B3 should be added to the list of enteroviruses that can cause hypoglycorrhachia during infections of the central nervous system in children.


Sinking pre-beta lipoprotein and coronary heart disease in Japanese-American men in Hawaii. A "sinking" pre-beta lipoprotein was sought in a probability sample of 1854, 50--72-year-old men of Japanese ancestry in Honolulu by ultracentrifugation of plasma and electrophoresis of the bottom fraction (density greater than 1.006) in agarose. A definite electrophoretic band was found in 5.6% of the men and a trace band was found in 4.6% of them. The frequency of such a band increased with age and decreased with adiposity. The relative risk for coronary heart disease, based on prevalence cases was found to be 1.7 in men with a definite band, and 1.4 in those with a trace band, when compared to men without. This association could not be explained by the higher low density lipoprotein levels in men with trace or definite bands. These data are consistent with previous reports suggesting that the Lp antigen (for which a sinking pre-beta lipoprotein is probably an insensitive marker) is associated with coronary disease.


Na-K pump and Na-K-ATPase: disparity of their temperature sensitivity. As previously observed in red blood cells, ouabain-sensitive K influx of kidney cells grown in culture for 3 days was much less inhibited by cooling that Na-K-ATPase of the same cells. (At 5 degrees C K influx was 9.7% of that at 38 degrees C, Na-K-ATPase, 1--2%.) Resealed ghosts of erythrocytes of ground squirrels were made containing 24Na and ATP, and the Na efflux and ATP hydrolysis were measured simultaneously. Under these conditions there was no difference in the reduction of activity with cooling, and the amount of reduction was close to that of active K transport in intact cells. The high sensitivity to temperature, characteristic of broken membranes, could not be induced in intact cells or resealed ghosts by eliminating either the Na/K gradient or the ATP gradient nor by chelation of cellular and extracellular Ca. It could not be eliminated in broken membranes by protection with ATP or Mg. Structural reorganization of membrane during lysis may cause the increase in temperature sensitivity of Na-K-ATPase.


Evaluation of oxidative phosphorylation in hearts from euthyroid, hypothyroid, and hyperthyroid rats. The energy relationships between cytosolic and mitochondrial metabolism were studied in the hearts from euthyroid, hypothyroid, and hyperthyroid rats. Isolated mitochondria showed high respiratory control ratios and impermeability to exogenous NADH. Hypo- and hyperthyroidism, respectively, resulted in lower and higher contents of both cytochromes per mitochondrion and mitochondrial protein per gram of wet weight of heart without changes in the ratio of cytochrome c to cytochrome aa3. In isolated perfused heart, the hyperthyroid state led to an increase in work rate and thereby an elevation of Vo2, which resulted in an increase oxidation-reduction turnover number for the cytochromes. An agreement was found between [ATP]/[ADP][Pi] of cytosolic free adenine nucleotides and the value calculated from a mathematical model of mitochondrial respiration. This implies that mitochondrial respiration is controlled at the cytochrome oxidase reaction and that oxidative phosphorylation in intact tissue is tightly coupled irrespective of thyroid state. It is concluded that thyroid hormone causes an increase in the mitochondrial mass, mitochondrial cytochrome content, and respiratory rate, and consequently expands the capacity of oxidative metabolism without an uncoupling effect on oxidative phosphorylation.


Insulin release, cGMP, cAMP, and membrane potential in acetylcholine-stimulated islets. Acetylcholine potentiated the glucose-induced insulin release from microdissected mouse islets of Langerhans but had no effect on basal insulin release. Significant potentiation was obtained with 0.1 micron acetylcholine in the presence of 10 micron eserine and with 1 micron or more acetylcholine in the absence of a choline esterase inhibitor. Carbamylcholine, too, potentiated insulin release. Potentiation was blocked by methylatropine, whereas methylatropine alone had no effect on insulin release. Acetylcholine or carbamylcholine (5-500 micron) had no obvious effect on cyclic GMP or cyclic AMP in the islets. In the presence of 11.1 mM D-glucose, the membrane potential of beta-cells oscillated slowly between a polarized silent state of -50 to -55 mV and a depolarized active state of -33 to -39 mV, at which a fast spike activity occurred. Acetylcholine made the potential stay at the plateau and induced a continuous spike activity pattern. Atropine inhibited the electrical effects of acetylcholine but not those of glucose alone. It is suggested that cholinergic potentiation of insulin release is mediated by changes of transmembrane ionic fluxes, probably without the intervention of cyclic GMP or cyclic AMP.


Hyperlipidemia and myocardial infarction among 118 patients with polycythemia vera. Hyperlipidemia was reported among 46 of 118 polycythemia vera patients as compared to a control group of 115 healthy subjects in whom hyperlipidemia was reported in 20. Among the 46 hyperlipidemic patients with polycythemia vera 14 had a myocardial infarction, while among the other 72 nonhyperlipidemic polycythemia vera patients myocardial infarction occurred amont 17. Since repeated phlebotomies may induce hyperlipidemia, this form of treatment of polycythemia vera may be potentially dangerous in already hyperlipidemic polycythemia vera patients.


Principles of nephron differentiation.

Principles of nephron differentiation. Differentiation of cell function should be studied in homogeneous cell populations. The differentiating mammalian kidney is a thoroughly heterogeneous organ. Consequently, the single epithelial segment was studied in situ and, particularly, by in vitro analysis of physical, chemical, and ultrastructural phenomena in perfused and nonperfused dissected nephrons. The changes of hydraulic permeability in the proximal nephron appear to be important in utilizing extracellular forces for absorption, since cellular transport is restricted by low basolateral membrane area and by ion pump sites (Na+-K+-ATPase). Salt transport in the diluting segment, by contrast, changes at constant osmotic permeability and at increasing ion concentration gradients across the epithelium. Extracellular volume and osmotic homeostasis in the neonate testify to the competence of organ function, although cell structure and function differentiate. In the future, interactions between nephron cell functions will be studied by altering the natural sequence of phenomena during differentiation.


Effect of ouabain and colloid osmotic pressure on renal tubule cell volume. Proximal renal tubule cell volume increases in ouabain but cell swelling is limited by the tubule basement membrane (TBM) and the colloid osmotic pressure from the bath protein. We compared the effect of ouabain, external protein concentration, and TBM on cell volume of proximal convoluted (PCT), proximal straight (PST), and cortical collecting tubules (CCT). We blocked active solute transport with ouabain and evaluated cell size by measuring the outer diameter of nonperfused tubules. Proximal tubules in ouabain swelled 35-40% in isoncotic medium and 20-25% further in hyponcotic medium (0.3 g/100 ml albumin), but PCT swelled faster than PST. The CCT swelled minimally in similar mediums, indicating pronounced heterogeneity in the response of cortical nephron segments to ouabain. In the presence of ouabain, all tubules swelled extensively when we removed the TBM with collagenase. In the hyponcotic medium fluid flux across the peritubular membrane was 0.081, 0.049, and 0.030 nl/min per mm tubule length for PCT, PST, and CCT, respectively. The rates of fluid flux in PCT and PST were proportional to estimates of the respective basolateral surface areas. We suggest that differences in swelling rates between proximal segments reflect variations in surface area rather than intrinsic peritubular membrane permeability to solute and water.


Nycthemeral rhythm in adrenal responsiveness to ACTH. Adrenal adenosine 3',5'-cyclic monophosphate (cAMP) and corticosterone responses to exogenous ACTH were found to be about 2.5 times greater in the evening (at lights off) than in the morning (at lights on) in rats. The rhythm in adrenal responsiveness to ACTH was found to persist in rats treated with dexamethasone 15 and 3 h before exogenous ACTH (in the presumed absence of a rhythm in endogenous ACTH). Treatment with p-chlorophenylalanine did not affect the daily rise in circulating ACTH levels but did abolish the rhythm in adrenal responsiveness to ACTH. The magnitude of the rhythm in adrenal responsiveness to ACTH is greater than the magnitude of the rhythm in ACTH. Because the rhythms are dissociable, we conclude that in vivo measurements of adrenal corticosteroid levels do not necessarily reflect ACTH levels.


Agonist-induced secretions and potassium release from rat submandibular gland slices. Secretory activity induced by stimulation of alpha-adrenergic, beta-adrenergic, and muscarinic cholingeric receptors and by dibutyryl cAMP and 8-bromo cGMP has been investigated in rat submandibular tissue slices. Isoproterenol produced a sialic acid secretion from the acinar cells that was inhibited by propranolol, but not by phenoxybenzamine or atropine. Dibutyryl cAMP produced a sialic acid secretion from the acinar cells that was not inhibited by propranolol, phenoxybenzamine, or atropine. Both norepinephrine and acetylcholine produced significant secretion of sialic acid but at a reduced efficacy. Norepinephrine stimulated both peptide hydrolase secretion from the granular duct cells and a release of K+ from the acinar cells. Both actions were inhibited by phenoxybenzamine, but not by propranolol or atropine. Acetylcholine stimulated a minimal secretion of peptide hydrolase from the granular duct cells and a significant release of K+ from the acinar cells. The norepinephrine- and acetylcholine-stimulated release of K+ was increased after the addition of 1 mM ouabain. High concentrations of 8-bromo cGMP induced a K+ efflux that was not inhibited by phenoxybenzamine or atropine. Vacuolation of the acinar cells was correlated with K+ release.


Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini. Isolated pancreatic acini were prepared by a new method from mouse and rat pancreases by digestion with purified collagenase and chymotrypsin followed by mechanical shearing. Acini were structurally similar to those of the intact pancreas, having a normal luminal structure but with the basal acinar cell membranes exposed to the incubation medium. Amylase release in response to both cholinergic analogues and the cholecystokinin analogues caerulein and pentagastrin was comparable to that of the intact pancreas, but was much greater than previously reported for isolated acinar cells. Cholinergic-stimulated release was inhibited by atropine with a Ki value of 1.4 nM which is comparable to other muscarinic receptors. All agonists tested, when added at supramaximal concentrations, produced a submaximal release of amylase even though ATP levels and the release of slowly exchanging 45Ca2+ were normal or increased. Acini releasing amylase submaximally after being exposed to supramaximal concentrations of carbachol failed to respond to a maximal amount of caerulein or to the Ca2+ ionophore A23187. It is concluded that the decreased response (desensitization) is a postreceptor phenomenon and possibly mediated by Ca2+ itself.


Inducibility of the hepatic drug-metabolizing capacity of mice infected with Schistosoma mansoni. The activities of some hepatic microsomal drug metabolizing enzymes, which are markedly depressed in mice infected with Schistosoma mansoni, can be increased by treatment with phenobarbital or 3-methylcholanthrene. Administration of these compounds to infected mice increased the capacity of the liver to metabolize drugs up to the maximum level inducible in non-infected animals. However, the increased hepatic microsomal mass, reflected in glucose 6-phosphatase activities and cytochrome b5 levels, observed in schistosome-infected mice, was not increased further by the same treatment. The changes in the activities of several drug metabolizing enzymes in vitro were confirmed in vivo by determination of hexobarbital-induced sleeping time and zoxazolamine-induced paralysis duration.


Serum 5'-nucleotide phosphodiesterase as a predictor of hepatic metastases in gastrointestinal cancer. Isoenzyme V of 5'-nucleotide phosphodiesterase (5'-NPD-V) is present in the peripheral sera of patients with hepatic metastases. A total of 122 patients underwent prospective serologic analysis followed by operation for primary tumors of the gastrointestinal tract and careful evaluation of the liver. A positive 5'-NPD-V assay was found in fifty-nine of sixty patients with liver metastases. A negative 5'-NPD-V assay was found in forty-three of sixty-two patients with no evidence of hepatic metastases. The accuracy of the test was 84 per cent, and the predictive value was 75 per cent. Serum 5'-NPD-V was abnormal significantly more frequently in patients with metastatic liver disease than were liver scans or carcinoembryonic antigen (CEA), alpha fetoprotein, serum glutamic oxalacetic transaminase (SGOT), and total serum bilirubin or serum alkaline phosphatase levels.


Electron microscopy of retinal tapetum (Caiman crocodilus). The distribution and ultrastructure of the retinal tapetum lucidum in Caiman crocodilus is described. In the light adapted eye the tapetum is recognized in the superior half of the fundus. It consists of guanine containing crystalline platelets which are spread almost over the entire retinal pigment epithelial cells which can be divided into different layers: 1. The basal surface facing the choriocapillary vessels is differentiated into numerous densely packed true microfolds which are commonly described as "basal infoldings". 2. A remarkable high content of mitochondria as well as a great number of lipid droplet-like spherical bodies is observed. 3. In the nuclear zone a Golgi apparatus and all stages of phagocytosis are found. 4. Within the level of intercellular junctions, crystalline platelets are arranged mainly perpendicularly to the long axis of the neighbouring receptor cells, whereas 5. platelets in large pigment epithelial cell processes extending from the apical cell surface between the photoreceptors are oriented parallel to the receptor axis. 6. Heavy pigmentation of the apical tips of pigment cell processes by melanosomes is observed, but only within the lower half of the fundus. The functional significance of the tapetum of Caiman crocodilus is discussed.


Ultrastructural studies of extraocular muscles in ocular motility disorders. II. Morphological analysis of 38 biopsies. Thirty eight extraocular muscle biopsies obtained from thirty patients (1 normal and 29 affected with various kinds of ocular motility disorders such as strabismus, Duane's syndrome, paralysis), were studied by electron microscopy. Except for the control biopsy considered as normal, they showed: atrophy, disorganization of myofilaments, double Z-disks, rods, curving arrays of myofibrils, concentrically disposed electron-dense sarcotubules, clusters of mitochondria with numerous modifications of their cristae, and subsarcolemmal inclusions, such as dense bodies, laminated bodies, lipofuscin granules and lipid droplets. In addition, subsarcolemmal granulo-fibrillar aggregates, characterized by periodic granulated foci spaced at about 120 nm intervals, were seen in all the biopsies, even in that of the control case. The authors stress the pecularity of the granulo-fibrillar aggregates which, up to now, have never been described in skeletal muscles and the function of which in the extraocular muscles fibers is impossible to define. They point out the difficulty in determining if the motility disturbances may be related to the various changes observed in extraocular muscles of squinting eyes.


Investigations on the turnover of adrenocortical mitochondria. XII. Studies on the mechanism of the ACTH-induced elongation of the half-life of rat zona fasciculata mitochondria. The half-life of rat adrenocortical mitochondria was determined by high resolution autoradiography and liquid scintillation spectroscopy as previously described (Mazzocchi et al., '76). The results obtained by the two approaches were in good agreement. In the normal rats the half-life of adrenocortical mitochondria averaged 11 days. ACTH significantly increased mitochondrial half-life to about 16 days, and chloramphenicol significantly decreased this parameter in both untreated and ACTH-administered rats to about seven days. It is suggested that the ACTH-induced maintenance and slowing down of the degradation rate of adrenocortical mitochondria requires continuous mitochondrial DNA-dependent protein synthesis.


Scanning and transmission electron microscopic study of equine infectious anemia virus. Scanning and transmission electron microscopy were used to study in detail the morphogenesis and replication of equine infectious anemia virus (EIAV) in cultured, persistently infected equine fetal kidney fibroblasts. The EIAV was shown by thin-section electron microscopy to resemble morphologically more closely the members of the genus Lenti-virus in the family Retroviridae than other genera. Scanning electron microscopy demonstrated budding virus on only about 5% of the equine fetal kidney fibroblasts; however, the entire surface of these cells was involved in viral replication. Except where virus budding was observed, EIAV-infected cells were smooth and free of the topographic surface alterations characteristic of cells transformed by type C retroviruses. The morphologic relationship of EIAV and pathologic manifestations of EIAV infection to those of other Retroviridae are discussed.


[EEC syndrome: ectrodactyly, ectodermal dysplasia and cleft lip-palate (author's transl)]. Authors present a new and complete from of EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip-palate), analysing its' clinical, genetic and therapeutic aspects. Syndrome malformations involving mainly mesenchymal tissue and with diverse clinical expression suggest a heterogenetic heredity. Participation of environmental and unknown factors is not excluded.


A correction to the TW2 RUS-based tables for predicting adult height. An error in the table for predicting the adult height of girls from RUS bone age, height and age, is identified and corrected.


Genetic polymorphism of human phosphoglycolate phosphatase (PGP). 1. A method has been devised for the detection after starch-gel electrophoresis of phosphoglycolate phosphatase (PGP) isozymes. 2. PGP isozymes can be detected in all human tissues including red cells, lymphocytes and cultured fibroblasts. The highest activities occur in skeletal muscle and cardiac muscle. 3. PGP is a relatively specific phosphatase which shows enhanced activity in the presence of mercaptoethanol at a neutral pH.4. Six different commonly occurring electrophoretic types of PGP have been identified. Family studies indicate that they are determined by three alleles at an autosomal locus (PGP). 5. The gene frequencies of PGP1, PGP2 and PGP3 in a random sample of Europeans were 0.826, 0.129 and 0.045 respectively. 6. The three-banded isozyme patterns seen in heterozygotes suggest that PGP is a dimeric enzyme.


[Ultrastructural localization of the oxydasic activity in Toxoplasma gondii (author's transl)]. Toxoplasma belonging on the RH strain were studied under a transmission electron microscope. The activities looked for were: peroxidase, cytochrome oxydase and acid phosphatase. An oxydasic cytochrome respiratory activity was seen. It is localised on the crests and on the peripheral membrane of the mitochondria of Toxoplasma gondii. In the given experimental conditions, no such activity appeared in the other intracytoplasmic organels of the parasite, nor in the vacuoles of the host-cells containing living toxoplasma but the organels of those host-cells presented an oxydasic activity.


Fibrous histiocytoma of the trachea.

Fibrous histiocytoma of the trachea. Intratracheal tumors are rare in children. A case is reported of a two-year-old female child with a fibrous histiocytoma of the trachea which caused severe respiratory obstruction and persistent right middle lobe pneumonia. Fibrous histiocytomas are basically benign tumors of histiocytes and have been mistaken for other tumors such as fibroma, sclerosing hemangioma, neurilemoma, fibromatosis, hemangiopericytoma, fibrosarcoma, and some primitive sarcomas. Fibrous histiocytomas have not been reported in the trachea or bronchi. The patient was treated with endoscopic removal of the tumor, and has remained free of disease to this date.


The syndrome of diabetic amyotrophy.

The syndrome of diabetic amyotrophy. Changes in the electromyograms and motor nerve conduction velocities in 12 patients with diabetic amyotrophy suggested mild distal and moderate proximal neuropathy in the lower limbs. Histological and histochemical findings in the vastus medialis muscles were consistent with denervation. Electron microscopical examination of the vastus medialis muscles in 6 patients revealed myofibrillar degeneration. One patient had abnormal mitochondria and tubular aggregates. The basement membranes of the intramuscular capillaries were thickened in all but 1 patient. Histochemical staining of the myoneural junctions showed changes consistent with degeneration and regeneration. We conclude that diabetic amyotrophy is a distinct clinical entity and is secondary to metabolic derangement rather than  diabetic microangiopathy.


Glucocorticoid effects on the edrophonium responsiveness of normal and degenerating mammalian motor nerve terminals. An intensive short-term triamcinolone regimen in cats preserves the prejunctional actions of edrophonium in degenerating motor nerves. These edrophonium actions include the induction of a stimulus-dependent afterdischarge and the initiation of fasciculations. The relationship between fasciculations and stimulus-dependent afterdischarge is discussed. The glucocorticoid preservation of these edrophonium effects is like that previously reported for the preservation of posttetanic facilitation in motor nerves equally compromised. The results therefore show that glucocorticoid and facilitatory drug actions synergize to increase facilitation in degenerating but still functional motor nerves. This drug synergy is comparable to that which occurs in normal motor nerves. This interaction may provide a basis for effectively combining glucocorticoid and facilitatory drugs in the treatment of myasthenia gravis.


Attenuated dynamic responses of primary endings of muscle spindles: a basis for depressed tendon responses in acrylamide neuropathy. Depressed or lost tendon reflexes commonly observed in patients with peripheral neuropathies may result partly from attenuation of the dynamic discharge from the primary endings of muscle spindles. This possibility was investigated in cats with an experimental neuropathy induced with acrylamide (30 mg/kg/day intramuscularly). Achilles tendon reflexes and the dynamic discharge from primary muscle spindles were evaluated after five or ten injections of acrylamide. After five injections the animals were moderately impaired neurologically, the Achilles tendon reflex was difficult to elicit in 2 of 5 animals, and the dynamic responses of primary endings of soleus muscle spindles to stretch were depressed. Following ten injections of acrylamide the cats were severely impaired neurologically; tendon responses were either absent or difficult to elicit, and the dynamic responses of their muscle spindles to stretch were reduced by 50% (p less than 0.01). Additionally, the spindels responded to stretch with only 20 to 30% the normal number of afferent impulses. These data suggest that lost tendon responses in acrylamide neuropathy result in part from inadequate activation of motoneurons by spindle afferent discharge.


Evaluation of virucidal compounds for inactivation of rhinovirus on hands. Antimicrobial liquids and foams were applied to the hands to determine their virucidal activity against rhinoviruses. Dilute solutions (1%) of iodine in ethyl alcohol or in water were most effective in causing inactivation of rhinovirus when applied immediately after viral contamination. Iodine also had a residual virucidal activity which persisted on the hands for up to 1 h. Less effective inactivation of rhinovirus was observed with foams containing 0.23% hexachlorophene and 58% ethyl alcohol and another containing 0.2% benzalkonium chloride and 50% ethyl alcohol. Ethyl alcohol alone or in a mixture with benzyl alcohol was the least effective preparation tested.


Effect of treatment with 5-ethyl-2'-deoxyuridine on herpes simplex virus encephalitis in normal and immunosuppressed mice. 5-Ethyl-2'-deoxyuridine (5-ethyl-dUrd), an analog of thymidine, was evaluated for its capacity to inhibit herpes simplex virus (HSV) replication in vitro and in vivo. The 50% effective dose concentration of 5-ethyl-dUrd for HSV types 1 and 2 (HSV-1 and -2) cultured in Vero cells was 6 and 9 mug/ml, respectively. Levels of 5-ethyl-dUrd 14-fold in excess of the 50% effective dose for HSV-1 did not inhibit the formation of confluent monolayers by Vero cells, suggesting that the compound was not cytotoxic or inhibitory for mammalian cells. In vivo studies showed that 5-ethyl-dUrd was effective in significantly reducing mortality when administered to young adult mice after subcutaneous infection with HSV-2. Intraperitoneal and intravenous inoculation of drug (250 mg/kg per day) resulted in a 50% survivor rate at 15 days. Comparative studies with adenine arabinoside at 250 mg/kg per day gave a 40% survivor rate. Intramuscular injection of 5-ethyl-dUrd at a concentration as high as 2,000 mg/kg per day for 10 days was well tolerated by uninfected animals, and HSV-2-infected mice treated at this dosage had a 100% survival rate. Treatment with 5-ethyl-dUrd at a concentration of 500 mg/kg per day significantly increased the mean survival times of HSV-1- and HSV-2-infected mice immunosuppressed by irradiation; however, the fatal course of the infection was not altered. Assay for virus in tissues showed that 5-ethyl-dUrd treatment delayed progression of the infection into the central nervous system, indicating suppression of virus replication in the tissues.


Characterization of a bacteriocinogenic plasmid in Clostridium perfringens CW55. A bacteriocinogenic strain of Clostridium perfringens was exposed to various curing agents known to accelerate the elimination of extrachromosomal DNA, and 20 independently derived mutants that had lost both the ability to produce bacteriocin and their immunity to it were isolated and characterized. All of the mutants were missing at least two specific plasmid bands seen in the agarose gel plasmid profile of the parent strain. Evidence that the two missing bands represented the open circular and closed circular forms of the same plasmid was obtained by X-ray nicking and restriction endonuclease digestion. The data indicated that bacteriocin production and immunity are controlled by a single plasmid, pCW4, with a molecular weight of 5.6 x 10(6) in this strain. Attempts to transfer the bacteriocinogenic plasmid were unsuccessful.


Contribution of trigeminal and facial reflexes to the localization of Vth, VIIth, and VIIIth cranial nerve dysfunction. After a review of electrophysiological studies in 1,500 cases concerning different types of lesions of the trigeminal nerve, the acousticofacial complex, and the brain stem, one can conclude that beside the intensive clinical examination which most often allows a precise topographic diagnosis, study of trigeminofacial and facial reflexes appears to be an essential diagnostic method to determine the topography of the lesions. On the other hand, this study can sometimes contribute to the prognostic evaluation as well as the choice of the approach in some lesions concerning the acousticofacial complex.


Sensitization of Clostridium perfringens spores to heat by gamma radiation. Spores of Clostridium perfringens, type A, were given separate or sequential treatments of gamma radiation (0 to 0.7 Mrad) and/or high temperature (93 to 103 degrees C). Prior heating, sufficient to inactivate 40 to 99% of the viable spores, had no effect on the subsequent radiation inactivation rate. Prior irradiation had a sensitizing effect on subsequently heated spores. The degree of sensitization to heat, as measured by thermal inactivation rate, increased with increased radiation pretreatment dose.


Viral pollution of surface waters due to chlorinated primary effluents. The role of chlorinated primary effluents in viral pollution of the Ottawa River (Ontario) was assessed by examining 282 field samples of wastewaters from two different sewage treatment plants over a 2-year period. The talc-Celite technique was used for sample concentration, and BS-C-1 cells were employed for virus detection. Viruses were detected in 80% (75/94) of raw sewage, 72% (68/94) of primary effluent, and 56% (53/94) of chlorinated effluent samples. Both raw sewage and primary effluent samples contained about 100 viral infective units (VIU) per 100 ml. Chlorination produced a 10- to 50-fold reduction in VIU and gave nearly 2.7 VIU/100 ml of chlorinated primary effluent. With a combined daily chlorinated primary effluent output of approximately 3.7 x 10(8) liters, these two plants were discharging 1.0 x 10(10) VIU per day. Because the river has a mean annual flow of 8.0 x 10(10) liters per day, these two sources alone produced a virus loading of 1.0 VIU/8 liters of the river water. This river also receives at least 9.0 x 10(7) liters of raw sewage per day and undetermined but substantial amounts of storm waters and agricultural wastes. It is used for recreation and acts as a source of potable water for some 6.0 x 10(5) people. In view of the potential of water for disease transmission, discharge of such wastes into the water environment needs to be minimized.


Potential sources of error during virus thermal inactivation. A review of virus thermal inactivation data published in the literature demonstrated variations in reported virus resistance. Examination of the methods used indicated that numerous studies were made by heat processing virus suspensions in test tubes. Duplication of some of the methods using milk suspensions of poliovirus 1 showed virus persistence after heating as a result of uneven temperature distribution inside the test tubes. Unless the containers (preferably sealed ampoules or capillary tubes) are completely submerged in the water bath and agitated vigorously, apparent virus persistence may be encountered.


Comparative sensitivity of various cell culture systems for isolation of viruses from wastewater and fecal samples. In efforts to define the most sensitive cell culture systems for recovery of viruses from wastewaters, 181 samples were inoculated in parallel into tube cultures of various cell types and were plaqued in bottle and petri dish cultures of three types of monkey kidney cells. Polioviruses were recovered most frequently in the RD line of human rhabdomyosarcoma cells, group A coxsackieviruses in RD and human fetal diploid kidney (HFDK) cells, group B coxsackieviruses in the BGM line of African green monkey kidney cells, echoviruses in RD and primary rhesus monkey kidney (RhMK) cells, and reoviruses in RhMK cells. BGM cells were unsatisfactory for recovery of viruses other than polioviruses and group B coxsackieviruses, and a line of fetal rhesus monkey kidney (MFK) was not a satisfactory substitute for primary RhMK. With RhMK cells, comparable numbers of virus isolations were made in tube cultures and in plaque assays conducted in bottle cultures, but with BGM and MFK cells, fewer isolations were made by plaquing than by inoculation of tube cultures. In comparative plaque assays on fecal samples under three different overlays in bottle and plate cultures of RhMK, BGM, and MFK cells, it was found that plaquing in the most sensitive system, RhMK, was less efficient for virus recovery than was inoculation of tube cultures of RhMK or HFDK cells. Overall, plaque assays performed in petri dishes in a CO(2) incubator yielded fewer virus isolates than did parallel plaque assays performed in closed bottle cultures. Other limitations of plaque assays for recovery of human enteric viruses are discussed.


Effects of an artificial diet on growth of patients with cystic fibrosis. The effects of an artificial diet on growth were examined in a controlled trial on 43 patients with cystic fibrosis. 28 patients received the diet for 12 months. Comparison was made between their growth before, during, and after dietary treatment. Growth changes were also assessed in 15 other patients who received a conventional diet. Artificial dietary treatment led to some improvement in height, weight, subscapular skinfold thickness, and a disproportionate advance of bone age for the group as a whole. Only 10 (36%) patients had a 'clinically' significant improvement in height, weight, or both--i.e. more than 0.5 standard deviation score. Greatest improvements were in young and mildly affected patients. It is proposed that the future use of such an unpleasant and expensive diet should be restricted to a few selected cases, rather than given as routine treatment.


Slow growth of an untreated Wilms's tumour in the adolescent. Retrospective radiological documentation of a growing Wilms's tumour in rare. Considered to be a relatively rapidly growing tumour, we present a case where there was adequate radiological evidence of a Wilms's tumour 4 years before the clinical metastatic presentation.


Congenital nephrogenic diabetes insipidus in a baby girl. A 6-week-old girl with fever, hypernatraemia, dehydration, and polyuria failed to concentrate urine in response to exogenous vasopressin administration. There was no family history of nephrogenic diabetes insipidus. When she was 15 months old, the infusion of vasopressin did not produce an increase in urinary cyclic-AMP.


Acute toxicity of hydrogen cyanide to freshwater fishes. Acute toxicity of hydrogen cyanide was determined at various temperatures from 4 degrees to 30 degrees C and oxygen concentrations of 3.36 to 9.26 mg/L on different life history stages of five species of fish: fathead minnow, Pimephales promelas Refinesque; bluegill, Lepomis macrochirus Rafinesque; yellow perch, Perca flavescens (Mitchill); brook trout, Salvelinus fontinalis (Mitchill); and rainbow trout, Salmo gairdneri Richardson. Median lethal threshold concentrations and 96-hr LC50's were established by flow-through type biassays. Acute toxicity varied from 57 microgram/L for juvenile rainbow trout to 191 microgram/L for field stocks of juvenile fathead minnows. Juvenile fish were more sensitive at lower temperatures and at oxygen levels below 5 mg/L. For most species juveniles were most sensitive and eggs more resistant.


Localization  of occult insulin secreting tumors of the pancreas. Percutaneous transhepatic portal venography (PTP) and selective portal blood sample collection for immunoreactive insulin (IRI) analyses was done in four patients who had clinical evidence of the presence of an insulin secreting tumor, but selective arteriogrphy of the pancreas did not visualize any insulinomas. In all patients the clinical diagnosis was confirmed and the localization of the tumors could be calculated with the aid of the PTP and the IRI values detected in different parts of the portal trees. Because no tumor was found at the operation in two patients, despite careful exploration of the pancreas, blind distal pancreatectomy was performed to the point suggested with the help of the investigations, and insulinomas were found close to the resection lines. In the two other patients the proposed localization of the tumor preoperatively was confirmed. There have been no postoperative hypoglycemic symptoms.


Microanalytical RPC-5 columns for rapid chromatography of aminoacyl-tRNAs. A microanalytical reversed-phase chromatographic system for the separation of aminoacyl-tRNA's on microbore (0.3cm X 25cm) columns is described. Chromatography of lysyl-tRNA from polyoma virus transformed mouse fibroblasts revealed at least seven identifiable isoacceptors. The system has the advantages of speed, sensitivity and excellent resolution of isoaccepting tRNA's.


A novel method for the isolation and study of a magnetotactic bacterium. The magnetococcus, a magnetotactic bacterium, has been grown in a complex simulated natural environment. Sufficiently pure samples of cells were obtained magnetically making axenic cultures unnecessary for many purposes. The magnetococcus is a Gram-negative coccus, 1.6 micron in diameter and readily distinguished by highly refractile inclusions and its magnetotactic behavior. This organism is actively motile by means of two bundles of flagella. Electron dense ferromagnetic inclusions were localized between the flagellar bundles. Collections of magnetococci were morphologically homogeneous and negligibly contaminated by extraneous bacteria. DNA extracted from pooled collections of cells was homogeneous by analytical CsC1 centrifugation. The guanine-cytosine content was 61.7%. Total iron by percent cellular dry weight was 3.8%. Comparisons with a previously described magnetotactic marine coccus were made.


Are prophylactic antiparkinson drugs necessary? A controlled study of procyclidine withdrawal. Of 55 aftercare patients receiving long-term treatment with antipsychotic and antiparkinson (AP) drugs, 37 were switched to being given placebo, and 18 remained on a regimen of procyclidine hydrochloride. The dose of antipsychotic was kept constant. After three weeks extrapyramidal side effects (EPS) developed in 54% of those patients receiving placebo and in none of those receiving procyclidine (P less than .002): Twenty-seven percent of the placebo group had EPS without akinesia, and in the same percentage akinesia developed (P = .003). We believe the risk-benefit ratio favors the routine use of AP drugs for prophylaxis and maintenance so as to avoid misdiagnosing as psychopathology, unspontaneity due to akinesia, and to reduce unreliable pill-taking due to EPS.


Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Buprenorphine was evaluated for its abuse potential and utility in treating narcotic addiction. The drug was morphine-like but was 25 to 50 times more potent than morphine and was longer-acting. Little if any physical dependence of clinical significance was produced by buprenorphine. The effects of morphine to 120-mg doses were blocked by buprenorphine, a blockade that persisted for 29 1/2 hours. In man, buprenorphine has less intrinsic activity than morphine, and as such, as a low abuse potential. Moreover, the drug has potential for treating narcotic addiction since it is acceptable to addicts, is long-acting, produces a low level of physical dependence such that patients may be easily detoxified, is less toxic than drugs used for maintenance therapy, and blocks the effects of narcotics.


Effects of a dopamine agonist piribedil in depressed patients: relationship of pretreatment homovanillic acid to antidepressant response. Piribedil, a compound that stimulates dopamine receptors in a relatively specific fashion, was administered to 11 hospitalized depressed patients. The dopamine agonist significantly decreased rapid eye movement (REM) sleep and percent REM sleep and increased REM latency. Piribedil decreased the probenecid-induced accumulation of the dopamine metabolite homovanillic acid (HVA) in CSF. A range of mild to moderate antidepressant effects was noted; one patient worsened and one developed recurrent manic episodes. The degree of improvement in depression was negatively correlated with pretreatment values of HVA in CSF (r = -.66, P less than .05). These data suggest that the heterogeneity of clinical response may be related to biological differences in depressed patients and that those with low initial dopaminergic function respond best to increased dopamine receptor stimulation.


[Some physical properties of the virus of larynxpapillomatosis in human beings (author's transl)]. Cell culture propagated virus of larynxpapillomatosis of men was purified and concentrated. Ultracentrifugation revealed an approximately 130 S- and a circa 214 S-component. 37 nm and 49 nm particles were found by electron microscope technique, the latter showing a bouyant density in CsCl of 1,34 g/ml. These first experiments demonstrate a close resemblance between this virus and polyomaviruses.


Ultrastructure of the myocardial fibroma. The ultrastructure of a myocardial tumor, referred to by a variety of names, which most currently is myocardial fibroma, has been studied. Although the tumor cells did not have the structure associated with protein synthesizing cells or active fibroblasts, there was evidence that they were participating in formation of the abundant stroma rich in collagen and elastic fibers in varying stages of maturity. The morphology of the stromal elements was similar to that in the surrounding myocardium and that described in the "normal" heart but differed from the elastica described in fibroelastosis.


Iron and the liver: subcellular distribution of iron and decreased microsomal cytochrome P-450 in livers of iron-loaded rats. To understand better the intracellular iron distribution and metabolic consequences of chronic hepatic iron overload, rats were given large doses of iron dextran or ferric citrate intraperitoneally. They accumulated large quantities of iron within Kupffer cells and hepatocytes. The relative subcellular iron distributions were similar in controls and iron-loaded rats, despite a ten- to 20-fold difference in hepatic iron concentration. Electron microscopy of whole liver and subcellular particulate fractions suggested that iron was present in highest concentration in lysosomes, which were rendered more labile by its presence. Nevertheless, quantitative iron determinations on all subcellular fractions, obtained by two preparative methods, showed that most of the iron was present in the "soluble" fraction. The amount of iron in the "microsomal" fraction varied, depending on the techniques used for preparation of this fraction. Cytochrome P-450 and total heme concentrations were decreased 40% to 50% in microsomes isolated from iron-loaded livers.


Hepatoma in familial cholestatic cirrhosis of childhood: its occurrence in twin brothers. Obstructive jaundice, pruritus, and malabsorption developed in twin brothers in infancy. Early liver biopsy specimens showed intracellular and canalicular cholestasis with normal bile ducts. By the age of 3 years, both had cirrhosis and portal hypertension. Each died during the teen years from hepatocellular carcinoma. These brothers represent the tenth reported family with familial cholestatic cirrhosis, and they are the first patients with this syndrome in whom hepatoma developed.


Adenomatous hyperplasia of the liver.

Adenomatous hyperplasia of the liver. An unusual case of adenomatous hyperplasia of the liver arose spontaneously in an 82-year-old woman. Massive fatal ascites developed during an eight-week period in the absence of cirrhosis. No drug, chemical, or hormone could be identified as the causative agent. Estrogens may play a role as possible promoters in the growth of hepatic tumors. Identifying liver tumors in women that are not associated with oral contraceptive use is valuable.


[The malignant fibrous histiocytoma of bone (author's transl)]. The primary malignant fibrous histiocytoma of bone (Stout) is a rare and autonomous sarcoma of the bone which has to be separated from the osseous sarcoma and the osseous fibrosarcoma. The malignant histiocytoma is morphologically characterized by the storiform pattern of interlacing spindle cell bundles and functionally by the phagocytosis of lipids, glycogen, hemosiderin and hematoidin. Contrary to the osteosarcomas, the main age of osseous histiocytomas are the fifth and sixth decade. Location of predilection are the metaphyses of the long tubular bones. The X-rays show moth-eaten spongiolysis, endosteal erosion and perforation of the cortex. Early metastases in the lungs are frequent. The primary treatment is a surgical one. Case record of a typical malignant osseous histiocytoma from the proximal metaphysis of the left femur with metastases in the lung of a female child, aged 14 years.


Synthesis of coreless, probably defective virus particles in cell cultures infected with rotaviruses. PK-15 cells infected with pig and lamb rotavirus strains which were not adapted to serial growth in cell cultures were examined by electron microscopy. A major difference between virus morphogenesis in the initial passage in PK-15 cells and in intestinal epithelial cells was the generation of large numbers of coreless virus particles in PK-15 cells. The numbers of coreless particles increased with increasing multiplicity of infection. Infectious virus was synthesized in PK-15 cells, but a variable decrease in infectivity titre occurred between 12 and 24 hours after infection. It is suggested that synthesis of defective interfering particles or an inhibitory substance such as interferon might account for this decrease.


Permeability changes of plasma and lysosomal membranes in HeLa cells infected with rabbit poxvirus. Infection of HeLa-cell monolayer cultures with rabbit poxvirus induces a marked decrease in cell-associated protein and in the activities of lactate dehydrogenase, acid phosphatase, and beta-glucuronidase. This effect begins to occur around 10 hours post-infection (p.i.) and is accompanied by a concomitant rise of these enzyme activities in the culture medium. Only few cells detach from infected monolayers and these cannot account for protein release. Virion release can be inhibited at 4 degrees C, whereas protein release cannot and it seems therefore that these events do not happen by a common mechanism. Moreover, penetration studies with [14C]-sucrose indicate that protein release reflects a true increase in plasma membrane permeability. Using the Gomori stain for acid phosphatase, a release of the enzyme into the cytoplasm around 8 hours p.i. can be confirmed rendering a causative role of lysosomal hydrolases in the pathogenesis of the observed plasma membrane permeability changes possible but not proving it.


Antigenic content of an in vitro cellular immunity reactive cell surface extract of Raji cells. Antigenic content of a Raji cell surface extract (TS) was studied by sequential abosrption of rabbit antiserum to this extract with different cells. Anti-TS was first allowed to react exhaustively with human blood cells followed by HeLa cells and human diploid fibroblasts. The residual reactivity was studied by stepwise absorption with an EBV-negative B lymphoblastoid cell line, BJAB, and then with B1--19, a clone derived from EBV transformed BJAB cells. These processes delineated three kinds of reactivities in anti-TS having specificities for antigens on B blasts, EBV-determined cell surface antigen(s) and antigens that are exclusive to Raji cells, respectively. These results are compatible with the heterogeneous protein content of TS and with the results of our earlier in vitro cell-mediated immunity studies using a similar preparation of Raji cell TS.


A study of Epstein Barr virus receptor activity in cell free extracts of human lymphoblastoid cells. Epstein Barr Virus (EBV) receptor activity in cell free extracts is operationally defined as one which causes a reduction in the effective concentration of the early antigen inducing particles of an EBV preparation when the latter is preincubated with the extract before infection. Such activity was detected in the surface extract of Raji cells and to a lesser extent in that of BJAB cells, both of which are B lymphoblastoid cells that are susceptible to infection with EBV. Receptor activity was not detected in similar extracts of P3HR-1 cells and human diploid fibroblasts neither of which are known to be susceptible to EBV infection. Receptor activity in the Raji cell extract was found to be associated with membranous structures. This may have rendered the activity resistant to treatment with trypsin and sonication. The activity was however abrogated if the extract was exposed to neutral detergent. Binding of receptor activity was observed when Raji cell extract was chromatographed on a column of immobilized EBV. Subsequent electrophoretic analysis showed however that this procedure did not result in an appreciable purification of the receptor activity. Neutral detergent treated extract was similarly chromatographed. The resulting eluates did not contain detectable receptor activity but were less heterogeneous in protein content as compared with that of the original extract. It is not certain at present if these EBV binding proteins are involved in the receptor activity of the extract.


Photoinactivation of the encephalomyocarditis virus. Encephalomyocarditis virus was photoinactivated by a dilution of 1:30,000 neutral red and 70 minutes exposure to light. A dye inactivation of the EMC virus is possible without destruction of its antigenicity. The EMC virus vaccine induced a good immunity response in mice; we did not find any infectious virus.


Rapid detection of IgG and IgM antibodies for cytomegalovirus by the enzyme linked immunosorbent assay (ELISA). A simple solid phase enzyme immunoassay for the detection of immunoglobulin G and M to cytomegalovirus (CMV) is described. Using this test IgM antibodies to CMV were detected in 0.7 per cent of newborns and regularly after CMV infection in transplant patients, furthermore in these latter patients IgM production was prolonged for several months. For the determination of IgG the enzyme immunoassay was more sensitive than the complement fixation test (CF) and the antibody titres were 4 to 8 fold higher. Since the ELISA test is rapid, specific and unexpensive it can become an acceptable routine diagnostic procedure.


[Pulmonary microcarcinoids and their biological significance]. The results of the analysis of 41 observations of bronchial microcarcinoids ("tumorlets") established the regularities of the sex and age distribution of the patients, localizations of the tumours, the patterns of the background processes, histoarchitectonic and cytological variants of tumour foci, different variants of histogenesis as well as the capacity for invasive growth and the occurrence of argirophilic granules in the cytoplasm of tumour cells.


[Functional morphology of the heart conduction system in acute myocardial infarct]. The results of histochemical, histoenzymological, and fluorescence microscopy studies of the conductive tissue of the heart in acute myocardial infarction in 30 fatal cases are presented. Focal decrease in redox and hydrolytic enzymes, monoaminoxidase, and cholinesterase in elementa of the conduction system as well as changes in the pattern of fluorescence of the specific muscle cells were found. The intensity of metabolic lesions was more pronounced at early stages of myocardial infarction in those cases where the conducting pathways were proximal to the foci of necrosis.


Isolation of rotavirus from foals with diarrhoea. A rotavirus, morphologically similar to other known rotaviruses, was demonstrated in the faeces of 5 foals with diarrhoea on two properties. Four of these 5 samples produced specific intracytoplasmic fluorescence in cell culture when reacted with calf rotavirus antiserum conjugate. Sixteen affected foals from both properties were depressed, did not suckle and became recumbent. Most had a watery diarrhoea which lasted for 3 days and resulted in some dehydration and loss of body condition. Sick foals were separated from their mothers following the onset of diarrhoea and given fluid therapy and antibiotics, but despite these measures 4 of 12 affected foals on one property died. Acute and convalescent sera were collected from 6 foals, and in each case a rise in the titres of complement fixing and neutralising antibodies was demonstrated. Faecal filtrates containing foal rotaviruses were fed to gnotobiotic piglets and the effects compared with those of other rotaviruses. Viral isolates from both properties produced an asymptomatic infection in piglets. This contrasts with the other rotaviruses isolated in Australia that have been shown to cause diarrhoea in gnotobiotic piglets.


The subcellular location, maturation and response to increased plasma glucagon of ruthenium red-insensitive calcium-ion transport in rat liver. 1. The subcellular distribution and maturation of Ruthenium Red-insensitive Ca(2+) transport activity were determined in livers of rats ranging in age from 3 days pre-term to 10 weeks of adult life and compared with those of glucose 6-phosphatase, 5'-nucleotidase and Ruthenium Red-sensitive Ca(2+) transport. Initial rates of Ruthenium Red-insensitive Ca(2+) transport were highest in those fractions enriched in glucose 6-phosphatase, i.e. the microsomal fraction; this fraction was devoid of Ruthenium Red-sensitive Ca(2+) transport activity. Although the heaviest fraction (nuclear) contained significant amounts of 5'-nucleotidase activity it was devoid of Ruthenium Red-insensitive Ca(2+) transport activity. 2. Foetal rat liver contain minimal amounts of Ruthenium Red-insensitive Ca(2+) transport activity, glucose 6-phosphatase and 5'-nucleotidase activities. These begin to be expressed concomitantly soon after birth; Ruthenium Red-insensitive Ca(2+) transport is maximal by 3 to 4 days and remains so for up to at least 10 weeks of adult life. Glucose 6-phosphatase also reaches a peak at 3-4 days, but then rapidly decreases to approach adult values. Maximal activity of 5'-nucleotidase in the microsomal and nuclear fractions is seen about 4-6 days after birth; this enzyme activity remains increased for up to about 10 days and then falls, but not as rapidly as glucose 6-phosphatase. It is tentatively suggested that the bulk of the Ruthenium Red-insensitive Ca(2+) transport is attributable to the system derived from the endoplasmic reticulum. 3. Administration of glucagon to adult rats enhances by 2-3-fold the initial rate of Ruthenium Red-insensitive Ca(2+) transport in the intermediate but not the microsomal fraction. The hormone-induced effect is fully suppressed by co-administration of puromycin, is dose-dependent with half-maximal response at approx. 1mug of glucagon/100g body wt. and time-dependent exhibiting a half-maximal response about 1h after administration of the hormone. 4. Ruthenium Red-insensitive Ca(2+) transport in the post-mitochondrial fraction of foetal liver also responds to the administration in situ of glucagon. The response, which also is prevented by co-administration of puromycin, is maximal in those foetuses nearing term. The suggestion is made that these effects of the hormone on Ruthenium Red-insensitive Ca(2+) transport are an integral part of the physiological network in the liver cell.


The adenylate cyclase-activating activity of cholera toxin is not associated with a nicotinamide--adenine dinucleotide glycohydrolase activity. The NAD+ glycohydrolase activity of cholera-toxin samples can be separated from their adenylate cyclase-activating activity by polyacrylamide-gel electrophoresis and is inhibited by sodium dodecyl sulphate (which does not inhibit the action of toxin on cells), but not by antibodies to pure toxin. It is therefore probably not a true property of the toxin.


Dibutyryladenosine 3':5'-cyclic monophosphate-mediated changes in rat cells involve macromolecular alterations in vinblastine-precipitable proteins. ts-NT3-KR rat cell cultures show the loss of three components in the molecular-weight region 200,000--250,000 when exposed to dibutyryl cyclic AMP, under conditions of both restriction and expression of the transformed phenotype. Vinblastine is able to precipitate preferentially from control cultures the species that are decreased by exposure to the cyclic nucleotide. Serum-starved cultures exposed to dibutyryl cyclic AMP reveal differences in their vinblastine precipitates, depending on whether the expression of the transformation phenotype is restricted or not.


A simple assay for adenylate cyclase in intact cells by affinity elution chromatography. A method using the principle of affinity elution chromatography is described for the assay of adenylate cyclase in intact human platelets. By incubating platelet-rich plasma in the presence of radioactively labelled adenine, the ATP pool of the cells was prelabelled. Formation of labelled cyclic AMP from ATP was determined by extracting the platelets with HC1O4. After removal of the latter as KC1O4, the extract containing cyclic AMP and other adenine nucleotides was adsorbed in a NN-diethyl-N-2-hydroxypropylamino (QAE)-cellulose column. The column was washed, and subsequently cyclic AMP was specifically eluted with a cyclic AMP-dependent protein kinase and the radioactivity of the eluate was determined.


The interaction between mitochondrial NADH-ubiquinone oxidoreductase and ubiquinol-cytochrome c oxidoreductase. Evidence for stoicheiometric association. 1. The NADH-ubiquinone oxidoreductase complex (Complex I) and the ubiquinol-cytochrome c oxidoreductase complex (Complex III) combine in a 1:1 molar ratio to give NADH-cytochrome c oxidoreductase (Complex I-Complex III). 2. Experiments on the inhibition of the NADH-cytochrome c oxidoreductase activity of mixtures of Complexes I and III by rotenone and antimycin indicate that electron transfer between a unit of Complex I-Complex III and extra molecules of Complexes I or III does not contribute to the overall rate of cytochrome c reduction. 3. The reduction by NADH of the cytochrome b of mixtures of Complexes I and III is biphasic. The extents of the fast and slow phases of reduction are determined by the proportion of the total Complex III specifically associated with Complex I. 4. Activation-energy measurements suggest that the structural features of the Complex I-Complex III unit promote oxidoreduction of endogenous ubiquinone-10.


The interaction between mitochondrial NADH-ubiquinone oxidoreductase and ubiquinol-cytochrome c oxidoreductase. Restoration of ubiquinone-pool behaviour. 1. In the inner mitochondrial membrane, dehydrogenases and cytochromes appear to act independently of each other, and electron transport has been proposed to occur through a mobile pool of ubiquinone-10 molecules [Kröger & Klingenberg (1973) Eur. J. Biochem. 34, 358--368]. 2. Such behaviour can be restored to the interaction between purified Complex I and Complex III by addition of phospholipid and ubiquinone-10 to a concentrated mixture of the Complexes before dilution. 3. A model is proposed for the interaction of Complex I with Complex III in the natural membrane that emphasizes relative mobility of the Complexes rather than ubiquinone-10. Electron transfer occurs only through stoicheiometric Complex I-Complex III units, which, however, are formed and re-formed at rates higher than the rate of electron transfer.


Prostaglandin receptors on human platelets. Structure-activity relationships of stimulatory prostaglandins. 1. Synthetic analogues of prostaglandins E2 or F2a (monocyclic bisenoic prostaglandins), like the endogenous prostaglandin endoperoxides (prostaglandins G2 and H2) from platelets, and like synthetic analogues of prostaglandin H2 (bicyclic bisenoic prostaglandins), can induce aggregation of human platelets, although prostaglandins E2 and F2a themselves are inactive. 2. All the prostanoid compounds that induce platelet aggregation release 5-hydroxytryptamine from platelet dense bodies, but do not release beta-N-acetylglucosaminidase from lysosomal granules. Arachidonic acid evokes a similar response. 3. All endoperoxide analogues tested (bicyclic compounds) were powerful platelet stimulants, and all active compounds (whether mono- or bi-cyclid) apparently acted via the same receptor as the endogenous prostaglandin endoperoxides. 4. The nature and stereospecificity of substituents at positions 11 and 15 (or 16) on prostaglandin E2 are critical determinants for platelet-stimulating activity: deoxy substitution at position 11 plus methylation at position 15 (or 16) produces a potent stimulant, particularly if the groups around C-15 are in the S configuration. 5. The effects of these structural modifications are apparently due to, at least in part, a change in side-chain conformation.


Subcellular structure of bovine thyroid gland. The localization of the peroxidase activity in bovine thyroid. 1. After differential pelleting of bovine thyroid tissue the highest relative specific activities for plasma membrane markers are found in the L fraction whereas those for peroxidase activities (p-phenylenediamine, guaiacol and 3,3'-diaminobenizidine tetrachloride peroxidases) are found in the M fraction. 2. When M + L fractions were subjected to buoyant-density equilibration in a HS zonal rotor all peroxidases show different profiles. The guaiacol peroxidase activity always follows the distribution of glucose 6-phosphatase. 3. When a Sb fraction is subjected to Sepharose 2B chromatography three major peaks are obtained. The first, eluted at the void volume, consists of membranous material and contains most of the guaiacol peroxidase activity. Most of the protein (probably thyroglobulin) is eluted with the second peak. Solubilized enzymes are recovered in the third peak. 4. p-Phenylenediamine peroxidase activity penetrates into the gel on polyacrylamidegel electrophoresis, whereas guaiacol peroxidase activity remains at the sample zone. 5. DEAE-Sephadex A-50 chromatography resolves the peroxidase activities into two peaks, displaying different relative amounts of the different enzymic activities in each peak. 6. The peroxidase activities may be due to the presence of different proteins. A localization of guaiacol peroxidase in rough-endoplasmic-reticulum membranes (or in membranes related to them) seems very likely.