Interstitial cystitis: early diagnosis, pathology, and treatment. In a retrospective review, 52 patients with interstitial cystitis have been studied. Patients with persistent lower tract irritative symptoms, repeatedly sterile urine, and negative urine cytology must be suspected of having interstitial cystitis, and a diagnosis of urethral syndrome in such patients is highly questionable until cystoscopy under anesthesia has been performed. We believe that the finding of multiple petechia-like hemorrhages (glomerulations) on the second distention of the bladder is the hallmark of interstitial cystitis, and that a reduced bladder capacity and a Hunner's ulcer represent a different (classic) stage of this disease. In all stages, the characteristic histologic finidng is submucosal edema and vasodilation. The presence of eosinophils and mast cells is variable, and even in the classic disease the muscularis often appears to be normal. Immuno fluorescent studies and laboratory tests, including the fluorescent antinuclear antibody test (FANA), have not helped us to diagnose (or investigate) interstitial cystitis. Bladder instillations with a 0.4 per cent solution of oxychlorosene sodium (Clorpactin WCS-90) have provided remarkable relief for many patients with this disease, particulary those with the classic form.


Accuracy of preoperative studies in staging nonseminomatous germ cell testicular tumors. The preoperative staging procedures used in 45 patients with surgical Stage I and Stage II nonseminomatous germ cell tumors of the testis were analyzed retrospectively. Our results indicate that gallium-67-citrate scan and supraclavicular lymph node biopsy add little information in the routine preoperative evaluation of these patients. Bipedal lymphangiography, in our experience, was no more accurate than excretory urograms in selecting patients with retroperitoneal disease and in addition provides no information regarding the status of the upper urinary tract. Thus, we suggest that physical examination, excretory urography, chest x-ray film, whole lung tomography, serum tumor markers, and liver scan provide sufficient information to proceed with surgical treatment when appropriate.


Signet ring cell carcinoma of bladder.

Signet ring cell carcinoma of bladder. The ninth reported case of primary signet ring cell carcinoma of the bladder is described. This particular tumor, whose histology was examined repeatedly during its evolution, showed an interesting change in microscopic appearance after irradiation. The emerging features of signet ring cell carcinoma of the bladder are discussed.


High density lipoproteins--correlation with cardiovascular disease in hemodialysis patients. 1) HDL levels are low in hemodialysis patients. 2) Lipid abnormalities do not correlate with the presence of CVD in hemodialysis patients. 3) Smoking may not effect blood lipid levels in hemodialysis patients. 4) Nandrolone decanoate may not play a role in CVD in hemodialysis patients. 5) Longer time on hemodialysis does not result in a decrease in triglyceride or increase in HDL levels.


Susceptibility of chicks to infectious bursal disease (IBD) following vaccination of their parents with live IBD vaccine. Vaccination of parent chickens with a commercial live infectious bursal disease (IBD) vaccine under field conditions at varying ages and by different routes resulted in variable susceptibility to the disease in their chicks. There was little correlation between the methods of vaccination and the levels of immunity in the chicks. There was some evidence that levels of transferred immunity decreased with the age of the parents. Of five flocks examined, the onset of susceptibility to IBD occurred at two days of age in two flocks and about one week of age in the other three. Four flocks were completely susceptible by the 27th day, the other at 31 days. Precipitins were demonstrated at day old in 100 per cent of chicks in three flocks and in 80 per cent in the other two. The precipitins had disappeared in all flocks by 17 days of age.


[Granular cell tumor and the phagocytozing form of Schwann cells. Electron microscopic examinations of 3 cases (author's transl)]. In granular cell tumors, the granule-containing tumor cells and their processes form rounded complexes surrounded by a common bounding membrane. In the tumor, these complexes are closely related to the peripheral nerves and are seen in the perineurium and in the endoneurium. In addition, there are mixed complexes composed both of Schwann cells and granular tumor cells: the two types of cells are in close contact with each other and are also surrounded by a common bounding membrane. Furthermore, there one contacts between granular tumor cells and axons. These observations strongly suggest the existence of a relationship between Schwann cells and the cells of granular cell tumors. A comparison between the granular tumor cells and the phagocytic forms of Schwann cells reveals striking similarities: the granular cell tumor complexes are comparable with the Büngner bands of phagocytozing Schwann cells. A relationship between granular cell tumors and the phagocytozing form of Schwann cells is therefore assumed.


[Glucuronic acid, glucuronyltransferase and estrogens in breast cancer and precancer]. The glucuronic acid level in the serum and urine, the diural excretion of estrogens and 17-KS with the urine, the activity of glucuronyltransferase are reported in 101 patients with benign and malignant tumors and in 22 healthy females. The decrease in the activity of glucurolytransferase and increase in the percentage of free (nonconjugated) estrogens in patients with malignant tumors of the mammary gland are noted, the analogous results were obtained in patients with benign tumors, but these are statistically insignificant. The decrease of the glucuronyltransferase activity is suggested to result in the development of relative hyperestrogen in normal total excretion.


[Differentiated expression of the viral genome in mammalian cells transformed by the Rous sarcoma virus]. In hybridization of 3H-DNA-product of Rous sarcoma virus with the RNA isolated from mammalian cells transformed by the virus concerned, it was found, that the virus-specific RNA, isolated from cryptovirogenic cells RVP-3, differs in nucleotide sequences from virogenic cells XC, XPO and TWERC.


[Degradation of C1q, the first subcomponent of the complement sequence, by synovial collagenase from patients with rheumatoid arthritis (author's transl)]. Human C1q is shown to be degraded by high concentrations of RA synovial collagenase (enzyme : substrate ratio 2 : 1). The collagen-like sequence of C1q is attacked by the enzyme. A possible cleavage site is described and compared with the cleavage site in collagen.


[Detection of collagenase in passive haemagglutination using collagen-coated erythrocytes (author's transl)]. Human rheumatoid arthritis (RA) collagenase and bacterial collagenase were shown to agglutinate collagen-coated erythrocytes. Native collagens of type I and type II reacted equally well, while denatured collagens showed less distinct agglutination activity. The sensitivity of the method for the detection of purified bacterial collagenase from Clostridium histolyticum is very high (100 pg). It is, however, low for human RA collagenase. The agglutination reaction is not inhibited by concentrations of native collagen causing distinct inhibition of anticollagen sera (2mg%). EDTA inhibits the agglutination completely.


[Primary lymphosarcoma of the lung (author's transl)]. The histological, histochemical and cytological changes were reported in 6 patients with primary lymphosarcoma of the lung. All cases are diffuse lymphocytic lymphosarcomas, histochemically with a similar enzymatic behaviour. Cytologically, small lymphocytes with different degrees of anaplasia were observed.


[Development of the ossification centres of the skeleton of the hand in patients with idiopathic scoliosis (author's transl)]. In 84 patients with idiopathic scoliosis, the skeletal age was estimated by the method of Greulich and Pyle. The average values were within the normal distribution curve. According to Prader, the normal values for skeletal age lie within + or -20% of the chronological age. Using his criteria, all our values are within the normal range.


[About the importance of chemical flocculation of wastewater in regard to hygienical aspects (microbiological and virological examinations in a wastewater treatment plant) (author's transl)]. In a small wastewater treatment plant corresponding samples from the intake and outtake of the chemical flocculation were chemically, microbiologically and virologically investigated and compared. It was found that both, the plate count and the number of coliforms, decreased about 90% to 95%. The phosphate content went down about 88%. The BOD5 reduction was ca. 80%, the COD reduction ca. 50%. Poliomyelitisviruses were found regularly in the intake but never in the outtake. Specially in regard to the high plate count- and virusreduction the chemical flocculation seems to be remarkable from the hygienical point of view not only for limnic but also for coastal waters.


[Motor conditioned reactions at different stages of normal human nocturnal sleep and their electrographic correlates]. Motor conditioned reaction was studied at different sleep phases in 13 subjects by EMG and mechanogram parameters compared to SGR and EEG. During paradoxical phase motor conditioned reaction appeared more often than in the slow-wave sleep, but in a reduced form. At various sleep stages the motor conditioned reaction regularly appeared at the background of the rise in the level of cortical functional state before conditioned stimulus. At all sleep stages completed motor reaction is fixed in the consciousness. However, amnesia of conditional stimulus perception and of motor reaction to it is rapidly developed, in particular in the slow-wave phase.


[Staircase phenomenon in children with progressive muscular dystrophy and dermatomyositis]. The electrical and mechanical activity of the isometric twitch of flexor carpi ulnaris muscle during two per second indirect supramaximal stimulation for 90 sec was examined in 14 children with muscular distrophy and 8 children with dermatomyositis. The muscle electrical responses show no significant changes in the amplitude of its first negative phase. The first derivative of the dinamogram shows some of the following abnormalities in 8 of the examined children with muscular distrophy and in 2 of these with dermatomyositis: 1. Prolonged and increased negative staircase; 2. Insufficient or absent positive staircase potentiation. These abnormalities of the staircase phenomenon disclose disorders of the contractile function of the examined muscle.


[Electroencephalography in children with malignant neoplasms of the internal organ and support-motor apparatus]. A neurological examination of 120 patients with malignant newgrowths of a different localization and histological structure was conducted. Neurological changes due to lesions of the central and peripheral nervous systems were revealed. With the aid of EEG studies and subsequent clinico-EEG correlations 29 patients were examined. The conclusion is made that EEG studies of malformations in children allow to detect subclinical forms of brain lesions. In most of the cases there was an inadequacy between the slightly expressed cerebral symptomatology and crude changes of the EEG. The changed EEG was especially marked in primary cancer of the liver, also with normalization of the EEG in the development of positive dynamics of the main disease. The studies conducted indicate the significance of EEG in receiving thorough characteristics of the neurological changes in malignant tumors.


[Detection of the critical period of pituitary-adrenal system development during postembryonic chicken ontogenesis]. Studies have been made on postembryonic development of the hypophyseal-adrenal system in domestic hens. Most significant functional rearrangements were observed at the 3rd week of life, when corticosteroid content of the blood plasma decreased threefold. Birds subjected to a series of cold stresses at this time, exhibited more rapid sexual maturation, more rapid reaction of the adrenals to exogenous corticotropin and higher resistance to unfavourable factors. Stress expositions in other days of the first month of life also resulted in trace phenomena, although these were less evident. It is suggested that the 3rd week after hatching is a critical period in the development of ihe hypophyseal-adrenal system in hens.


[Synaptic ion currents in muscle fibers of Drosophila melanogaster]. The spontaneous excitatory junctional currents (e. j. c.'s) were recorded intracellulary using voltage clamp technique in experiments performed on the isolated cutaneo-muscle bag of larvae, early pupae stadium and adult fly Drosophila melanogaster. The fast miniature e. j. c.'s with mean amplitude 0.41 nA, rise time 1.60 ms and half-decay time 3.11 ms were most frequently observed. Besides these, slow miniature (half--decay time 7--20 ms) and fast giant (amplitude 12--15 nA) were sometimes present. It was found that the time course of fast e. j. c.'s is prolonged with hyperpolarisation and with the decrease in temperature. Some drugs which effectively modify the time course of end-plate currents at the cholinergic junctions (atropine, scopolamine, lidocaine, serotonin, QX-222 and ethanol) were tested. Except for ethanol, none of these drugs when added to the muscle bath affected either the amplitude or the time course of e. j. c.'s. The properties of e. j. c.'s in different neuro-muscular junctions of vertebrates and insects are discussed.


[Several features of the metabolism of the fast and slow muscles of Emys orbicularis tortoises]. In skeletal muscles of the tortoise E. orbicularis, studies have been made on the content of glycogen, lactic acid, on the activity of glucose-6-phosphatase and phosphorylase. Histochemical studies were made on the lipid content. Experiments were performed on fast and slow bundles from mm. iliofibularis, testo cervicalis and retractor capitis. For comparison, the same indices of carbohydrate metabolism were investigated in fast m. plantaris and slow m. soleus of rats. In rats, slow muscles exhibit aerobic metabolism, in fast muscles--anaerobic one. In tortoises, slow muscles exhibit intermediate type of metabolism. Fast muscles show an anaerobic type or metabolism which is less intensive than anaerobic metabolism in slow muscles. Significant differences in some of the indices of carbohydrate metabolism were found in muscles which perform different functions in the organism.


Release of cyclic AMP from thyroid cells in vitro. Half lobes of mouse thyroid gland were incubated in vitro with TSH. They released cyclic AMP (cAMP) into the medium in amounts depending on the concentration of TSH. The release of cAMP was greatest during the first hour of incubation then it occurred at a lower rate. With an incubation time of 45 min the medium cAMP levels ranged from 43.0 +/- 11.9 pmole per mg tissue protein for controls to 296.5 +/- 29.2 pmole per mg tissue protein with 5 mU of TSH in the medium. The tissue cAMP level reached a maximum after 15--30 min of incubation with TSH, then it gradually decreased towards control level during 4 h of incubation. With 25 min of incubation the tissue cAMP level was 28.5 +/- 8.8 pmole per mg tissue protein for controls compared to 194.3 +/- 27.0 pmole per mg tissue protein with 5 mU TSH in the incubation medium. The release of thyroxine was of the same order during the later part of the 4 h incubation period compared to the first one. The results illustrate the quantitative importance of cAMP release, and the fact that in the later part of the incubaion period the cell content of cAMP was low while the release of thyroxine remained high.


[Effect of serotonin on the viability of rats with transplanted glioblastoma multiforme]. Mongrel adult albino female rats with multiform glioblastoma transplanted to the right cerebellar hemisphere were given subcutaneous injections of 8 mg/kg of a serotonin-creatine sulphate solution beginning with the 3rd and to the 28th postoperative days. Rats with a tumor inoculated at the same periods and given injections of a physiological saline solution served as controls. The injection of serotonin leads to a significant increase in the survival of rats by 20% as compared to the survival of rats in the control group, but practically has no effect on the life span of sick animals. Consequently, serotonin either produces an antineoplastic effect in which case the animals do not contract the disease, or it has no effect on the tumor so that the animals die of the developing tumor. Study of the tryptophan content in the neoplasm and the 5-OIAA content in urine provides evidence of a disturbed serotonin synthesis and metabolism in these neoplasms.


Primary aldosteronism: inability to differentiate unilateral from bilateral adrenal lesions by various routine clinical and laboratory data and by peripheral plasma aldosterone. In 31 patients with primary aldosteronism routine clinical and laboratory data, the effect of orthostasis on plasma aldosterone (PA), plasma renin activity (PRA) and cortisol (PC), effect of fludrocortisone or high sodium intake on basal PA and night-day fluctuations of basal PA and PC with and without suppression of pituitary ACTH by dexamethasone were determined to differentiate patients with a unilateral aldosterone producing tumour (adenoma, APA, n=20; carcinoma, CA, n=1) from those with idiopathic bilateral adrenal hyperplasia (IAH, n=10). Mean systolic and diastolic blood pressure, age, serum potassium and urinary excretion of sodium and potassium were not significantly different in both groups of patients. Normokalaemic primary aldosteronism occurred both in patients with APA (n=2) and in patients with IAH (n=1). Mean basal PA and mean urinary excretion rate of aldosterone-18-glucuronide were higher though not significantly different in patients with APA or CA than in those with IAH. A substantial number of the patients with APA (n=5) and with IAH (n=3) showed urinary excretion rates of aldosterone-18-glucuronide less than 13 microgram/24 h. Mean PA and PRA significantly increased (P less than 0.025) in patients with IAH in response to posture. However, these changes also occurred at times in some patients with APA. Both fludrocortisone and high sodium intake produced a variable and no group-specific effect on basal PA. Night-day variations in PA were positively correlated with those in PC in all patients with APA (n=12) and in 5 of 8 patients with IAH. A dissociation of PA and PC, however, was only observed in patients with IAH. Finally, the effect of dexamethasone on plasma aldosterone curves was variable in both groups of patients. Our results indicate that under the described conditions analysis of routine clinical and laboratory data and of peripheral PA, PRA and PC are of limited value in differentiating patients with APA or CA from those with IAH.


Cholinergic influences on hypothalamic-pituitary-adrenocortical activity of stressed rats: an approach utilizing choline deficient diets. Male rats were placed on choline (Ch) deficient diets for 3 to 14 days, without and with Ch (normal and large doses) supplemented in the drinking water, to determine whether altering the availability of Ch would affect the cholinergic system in relation to the latter's role in modulating the hypothalamic-pituitary-adrenocortical (HPA) system of non-stressed and stressed animals. The results indicate that the basal nonstressed activity of the HPA system, as assessed by adrenal and plasma corticosterone concentrations, was not affected by placing the animals on these diets for as long as 14 days. Furthermore, the in vitro production of corticosterone by these adrenal glands, in the presence or absence of adrenocorticotrophin, was similar to those observed in animals on the regular rat diet; however, the HPA responses to auditory (100 db) stress, and to a lesser extent hypercapnic (9% CO2) stress, were impaired on the Ch deficient diet (14 days), and these responses were partially corrected by supplementing the diet with Ch in the drinking water. Thus, the data suggest that altering the dietary intake of Ch may affect cholinergic activity, which in turn affects the HPA response to stressors.


Evaluation of the endocrine functions in dystrophia myotonica. Investigation of several endocrine functions was performed in seven patients with dystrophia myotonica (DM). All patients had hyperinsulinemia. Whereas the four female patients had normal pituitary-gonadal function, all three male patients presented evidence of a primary gonadal failure. Thyroid function was normal in all patients. Four patients displayed abnormal diurnal variations of cortisol secretion. Basal prolactin levels were elevated in three patients, one of whom also had consistently elevated levels of growth hormone. The investigation adds some new evidence of neuroendocrine dysfunction at the hypothalamic level in DM.


Conduction along the articular branch of the suprascapular nerve. The maximum sensory conduction velocity was measured along the articular branch of the suprascapular nerve. The potential was evoked by stimulating in the perception area of the nerve above the glenohumeral joint and recorded by an electrode near the suprascapular nerve in the supraclavicular fossa. The maximum conduction velocity averaged 42 m/s, SD 4.6 m/s (20 normal subjects); it decreased slightly with age. When correcting for the error in distance arising from the measurement by obstetric calipers (20%), the maximum conduction velocity averaged 50 m/s. The peak-to-peak amplitude of the main component of the sensory potential was 0.8 muV, SD 0.5 muV. In one of seven patients with a pain syndrome in the shoulder secondary to a brachial plexus neuropathy the velocity and the amplitude of the sensory potential was diminished. In five other patients with pain in the region of the shoulder the conduction velocity was normal but the amplitude was diminished.


Ultrastructural sequence of myelin degradation. II. Wallerian degeneration in the rat femoral nerve. Myelin degradation in Wallerian degeneration of rat femoral nerves has been studied with the electron microscope. In the initial stages, a decrease of myelin periodicity from 115 A to 88 A was noted, followed by the transformation of the myelin structure into uniformly layered lipid inclusions. 10--14 days after nerve section, most of the inclusions found represented unstructured lipid droplets or crystals. In the later stages of degeneration, numerous pleomorphic lamellar inclusions were found, some of them resembling the structure of pi and micron-granules. Lysosomal enzyme activity was found especially in pleomorphic inclusions during the late stages of myelin degradation. Normal myelin sheaths, as well as unstructured lipid droplets and crystals, were devoid of enzyme activity. The results are compared with alterations found in Wallerian degeneration of the central nervous system.


Microtubules observed within the cistern of RER in neurons of the aged dog. Twenty-seven randomly selected dogs ranging from 1 month to 16 years of age were examined light- and electron microscopically. An intraneuronal inclusion body was found im 13 of 27 cases. In particular, 12 of 13 positive cases were elderly dogs of over 8 years of age. The inclusions showed amphophilic violet color with H.-E. stain and measured 3--42 micrometer in diameter. Histochemically, they were thought to be a glycoprotein complex. The inclusions were characterized by the electron microscopy and composed of aggregated cistern of RER closely packed with tubular structures. The individual tubules measured about 24 nm in diameter and had 11--13 subunits forming their walls. These constituents were very similar to those of microtubules. The occurrence of the inclusion bodies showed an apparent age-dependency.


Ultrastructural sequence of myelin degradation. I. Wallerian degeneration in the rat optic nerve. The ultrastructural events in myelin degradation in the rat optic nerve following transection have been studied. Myelin debris was found in cells similar to multipotential glia cells (Vaughn and Peters, 1968) as well as in astrocytes and in few oligodendrocytes. The different types of inclusions found during myelin degradation were described in their quantitative relations. Similarities to inclusions described in adrenoleukodystrophy adn multiple sclerosis are discussed. By comparison of the ultrastructural findings with histochemical and biochemical data available a hypothetical model of myelin degradation is presented. The process starts with the degradation of digestible proteins resulting in uniformly layered lipid inclusions. Lipid degradation leads to the formation of unstructured lipid droplets and crystals. During the late stages of Wallerian degeneration numerous polymorph inclusion typed can be found, probably representing poorly digestible lipids or lipoproteins.


Selenium and vitamin E in cord blood from preterm and full term infants. Selenium was determined in erythrocytes and serum, and vitamin E and beta-lipoprotein in serum from cord blood samples of 31 full term and 20 preterm infants. Venous samples from 21 mothers at birth and 15 normal adult women were also analyzed. No difference for either selenium or vitamin E was found between the preterm and full term infants. The selenium concentration in red blood cells was the same for newborn, mothers at birth, and normal adult women. The serum concentration of selenium was, however, significantly lower in the newborn, the mean level in the children being 64% of that in the mothers. The level in the mothers did not differ from that in non-pregnant women. The vitamin E concentration was found to correlate very well with the beta-lipoprotein concentration. This indicates that differences in the transport capacity account for the large difference in the serum tocopherol levels of mothers at birth and newborn.


Hepatic sarcoma associated with hepatoma. An autopsy case with simultaneous occurrence of hepatoma and spindle cell sarcoma in the liver was presented. These tumors arose in the left and right lobes and showed no continuity. The sarcoma metastasized in hilar lymph node of the liver and in the cervical and lumbar vertebrae, but no metastasis of the hepatoma was found except in the opposite lobe of the liver. Literature on such combinations was briefly reviewed.


Hepatocellular carcinoma and myocardial sarcoidosis.--An autopsy case. An autopsy case of a 65-year-old male who died of hepatocellular carcinoma superimposed on liver cirrhosis complicated with systemic sarcoidosis is presented. No organ metastasis of hepatocellular carcinoma was found except for a minute tumor embolus in the left upper lobe of the lung. Involved organs by sarcoidosis were the lymph nodes, lungs, heart, liver and spleen, but its presence was not noticed before death. Its cardiac involvement coincide with his clinical symptom of exertional dyspnea and the ECG finding of A-V block.


Comparison of small hepatitis B surface antigen particles and human serum low density lipoprotein molecules by electron microscopy. The small spherical particles associated with hepatitis B surface antigen (HBsAg) could be distinguished from the low density lipoprotein (LDL) molecules in human serum by examination of coded, negatively stained preparations. The HBsAg associated particles showed a more marked contrast against the background than LDL. Addition of specific antiserum to LDL caused a significantly reduced mean diameter of LDL molecules. An insignificant reduction in size of HBsAg particles was found by corresponding treatment. It is suggested that the antibody molecules protect LDL molecules protect LDL molecules against artificial flattening during preparation.


beta-Adrenoceptor stimulation of the human urinary bladder in vivo. The effect of beta-adrenorecptor stimulation on the volume of the urinary bladder in 16 neurologically normal humans without symptoms of micturition disturbances was investigated. Terbutaline, a selective beta2-adrenoceptor stimulating agent, was tested in 9 persons and isoprenaline, a general beta-adrenoceptor stimulating agent, was tested in 7 persons. After terbutaline the maximum increase in the bladder volume was 10% and on an average aroung 5%. After isoprenaline the maximum increase in the bladder volume was 15% and on an average around 5%. Terbutaline as well as isoprenaline administration resulted in tachycardia and an increased pulse pressure. The tachycardia was somewhat more marked after isoprenaline. In conclusion, only a small increase in the volume of the urinary bladder was noted after beta-adrenoceptor stimulation in neurologically normal humans without symptoms of micturition disturbances, in contrast to effects achieved in some patients with urgency. Terbutaline seems to have less cardiac effects compared to isoprenaline and is therefore to be preferred when beta-adrenoceptor stimulation is required in patients with urgency.


Differences in postsynaptic alpha-adrenoceptor populations between isolated cat urethra and various other isolated tissues. This study was undertaken with the aim of determining whether the postsynaptic alpha-adrenergic receptor population of the cat urethra differed from that of other isolated tissues (rabbit aorta and rat vas deferens) and if so the possibility of selectively affect these receptors. For this purpose the substances 2-methylammonio-1-(spiro[cyclopentane-1,1'-indene]-3'-yl)ethanol (KABI 2023), noradrenaline (NA) and dopamine (DA) were used. KABI 2023 and NA acted as full agonists on all three tissues investigated. DA was a full agonist on the vas deferens but was almost inactive on urethra. The contractile response of urethra to KABI 2023 was of an alpha-adrenergic nature, as it could be blocked with phentolamine. Compared with NA, KABI 2023 showed a 10 times higher selectivity for the receptors of urethra than for those of aorta. Affinity constants (log KB) for phentolamine and haloperidol with use of the various agonists were estimated. The affinity of phentolamine was found to be significantly different when using NA and KABI 2023 as agonists on the urethra but not on the aorta. Corresponding findings were obtained with haloperidol. On the vas deferens a greater difference in log KB values than that on the urethra was found. On the basis of the results, it is suggested that the population of postsynaptic alpha-adrenoceptors in the urethra (cat) differs from that in the aorta (rabbit). On the vas deferens a heterogenicity of postsynaptic receptors seem to exist which makes the interpretation of the results more difficult on this organ. In the presence of phentolamine and haloperidol the maximum responses to NA were potentiated on the aorta and vas deferens, but not on the urethra. Investigations to evaluate this difference are now in progress.


Cholinergic mechanisms in the rat detrusor muscle. The motor response of the urinary bladder to nerve stimulation is resistant to atropine, and it has been proposed that the nerves are non-cholinergic, but are possibly purinergic. In this review evidence is presented suggesting a cholinergic transmission in the rat detrusor muscle, part of the receptors being inaccessible to atropine. The rat bladder receives postganglionic cholinergic fibres not only from the pelvic but also from the hypogastric nerves, some fibres passing outside the pelvic ganglia and some relaying distal to them. There is a functional overlap between the right and the left pelvic nerve, but the contractile response to stimulation of the hypogastric nerves is added to the pelvic nerve response with no functional overlap or antagonism.


The effects of anticholinergics on the urinary bladder mechanism. A summary is given of the physiological conditions concerned with collection and expulsion of urine from the bladder. The role of afferent and efferent nerve activity from and to the urinary bladder and urethra is discussed. When studying the effects of anticholinergics on the urinary bladder in animals an in situ model described here seems to be the most valid for conditions in man. This method involves recording of the intravesical pressure in conscious rabbits stimultaneously with a bladder infusion. An assessment is made of the evidence for a purinergic transmission in the urinary bladder.


Methodological aspects on drug receptor binding analysis. Although drug receptors occur in relatively low concentrations, they can be visualized by the use of appropriate radioindicators. In most cases the procedure is rapid and can reach a high degree of accuracy. Specificity of the interaction is studied by competition analysis. The necessity of using several radioindicators to define a receptor population is emphasized. It may be possible to define isorecptors and drugs with selectivity for one isoreceptor.


Metabolism of zearalenone in rat liver.

Metabolism of zearalenone in rat liver. The metabolism of zearalenone in rat liver has been investigated. The studies were performed mainly with liver homogenate, though isolated microsomes and hepatocytes have also been used. Zearalenone was metabolized along two principal pathways, conjugation with glucuronic acid, which was the main route and reduction to an isomer of zearalenol. In no case, however, could all zearalenone metabolized be accounted for as conjugated zearalenone and free and conjugated zearalenol. Therefore another, so far unknown metabolite cannot be excluded. Reduction to zearalenol could be increased three times by the addition of NADH (or NADPH) and is probably catalyzed by a hydroxysteroid dehydrogenase. Some 25-50 per cent of the zearalenol could be conjugated, depending on the incubation conditions. The capacity of hepatocytes to eliminate zearalenone was estimated to be about 100 microgram per gram of liver in one hour. With a liver homogenate the highest value obtained was 82 microgram.


Beta-adrenoceptor stimulation and cyclic AMP levels in bovine tracheal muscle of old and young animals. The relationship between cyclic AMP levels and mechanical activity after exposure to isoprenaline was studied in tracheal smooth muscle. It was found that the basal cyclic AMP content decreased with age. The relaxing effects of isoprenaline, theophylline and papaverine were tested on muscles contracted by histamine, acetylcholine or carbacholine. Isoprenaline completely relaxed histamine contracted tracheas, but not those contracted by acetylcholine or carbacholine. Theophylline and papaverine completely relaxed the tracheas irrespective of whether the contracting agent was histamine, acetylcholine or carbacholine. Isoprenaline increased the cyclic AMP content of bovine trachea; this effect was stronger in muscles with spontaneous tension than in histamine contracted muscles. In muscles contracted by carbachol, isoprenaline increased the cyclic AMP level after 5 min. The correlations between the changes in the cyclic AMP levels and the tension in tracheal smooth muscle support the hypothesis that this nucleotide plays a role in the relaxation process.


Effect of lowering of the temperature on the tissue levels of cAMP, cGMP, PGE and PGF2 alpha in spontaneously beating rat atria preparation. Tissue levels of cAMP, cGMP, PGE, and PGF2 alpha were measured in spontaneously beating rat atria preparation at 20C and 37C. At 20C the formation of cAMP increased in correlation with the markedly increased amplitude and reduced frequency. The other biochemical parameters were not significantly affected by the low temperature.


Activity of acid hydrolases in skeletal muscle of untrained, trained and detrained mice of different ages. The activities of p-nitrophenylphosphatase, beta-glucuronidase and beta-N-acetylglucosaminidase from crude skeletal muscle homogenates of 4 and 7 months old mice were assayed after short-term intensive and long-term moderate training and after terminated training. In the older untrained mice the activity of the hydrolases was higher than in the younger mice. The level increased with training and this increase was far more pronounced in the older animals. Cessation of training for 7 and 21 days decreased this activity in the older animals but it was again increased 42 days later and close to the level observed in the trained mice. In young mice 3 days' terminated training increased the activity of the acid hydrolases above the level of the trained animals but after additional 4 and 11 days' terminated training the activity decreased to slightly below that of the trained mice. The changes were most prominent in the activity of beta-glucuronidase and to a lesser extent in that of beta-N-acetylglucosaminidase while p-nitrophenylphosphatase activity was almost unaffected by training or terminated training. The effects of terminated training can be intepreted as representing altered catabolic processes in the turn-over of tissue components of skeletal muscle.


The intestinal phosphate transport under condition of experimental hypercalcemia. The analysis of the serum calcium and phosphate level changes in intact Vitamin D--dosed animals showed the increasing serum calcium values without any concomitant change in serum phosphate concentration. The observed discrepancy of intestinal phosphate transport in vitro and in vivo studies together with the effect of Vitamin D towards normalizing serum phosphate level in TPTX Vitamin D--dosed animals suggest the presence of Vitamin D as some phosphate regulatory factor. The participation of the possible role of 25 OH D3 in the observed phenomenon is under current investigations. In PTH supressed hypercalcemic conditions we did not reproduce, with the usage of 1alpha--OH D3, the regulatory effect of 1,25 (OH) 2D3 described by Garabedian et al. /1/.


Benign multilocal cystic nephroma.

Benign multilocal cystic nephroma. Three cases of multilocular cystic nephroma are described. This entity differs from congenital multicystic kidney and adult polycystic disease in that it involves only a segment of one kidney. While the excretory urogram, nephrotomogram, and arteriogram show the lesion to be primarily avascular, the two cases studied by ultrasound were predominantly solid. This finding is felt to relate to the small size of the cysts as well as the presence of some solid primitive components. Because it is difficult to differentiate this lesion from an avascular renal carcinoma, surgical biopsy should be considered to help avoid a needless nephrectomy.


Detection of B-lymphocyte (B-cell)-associated antigens on human leukemic lymphocytes. Masking of membrane antigens. An indirect immunofluorescent technic has been used for rabbit antisera (anti-EP) that demonstrated complement-dependent cytotoxicity against human leukemic lymphocytes but not against normal blood lymphocytes. With the immunofluorescent technic, the antisera were found to react with 2--23% of normal blood lymphocytes. Simultaneous staining of normal cells with anti-EP and for surface immunoglobulins (SIg) on bone-marrow-derived B-cells showed that the proportions of stained cells were similar to percentages of cells stained by anti-EP alone or for SIg alone. The percentage of anti-EP reactive cells also approximated the percentages of cells reactive to a known antiserum to human B-cell associated, or Ia-like, antigens. The anti-EP reacted with lymphoblastoid cells from two B-cell lines lacking the Epstein-Barr viral genome. The antigens detected by anti-EP probably are B-cell-associated. The anti-EP intensely stained neoplastic cells of acute or chronic lymphocytic leukemia and lymphosarcoma-cell leukemia. Cells from two patients with chronic lymphocytic leukemia and from two patients with acute lymphocytic leukemia showed increased intensity of anti-EP staining and/or increased proportions of stained cells following overnight incubation in culture medium, compared with the preincubation samples. This observation suggests the presence of a "blocking component(s)" on cell surfaces, which interfered with anti-EP reactivity. After overnight incubation, the component might have been removed from the antigenic sites on cell surfaces. Further studies of leukemia lymphocytes using anti-EP for the cell-bound "blocking component" may reveal important pathogenetic mechanisms.


Inhibition by propranolol of bile acid- and PGE1-stimulated camp and intestinal secretion. Three colonic and three ileal loops were prepared in six rabbits pretreated with propranolol (PR) 4 mg./kg. I.V. and in five untreated rabbits. In random order, 1 ml. of either deoxycholic acid (DCA) 6 mM., prostaglandin E1 (PGE1) 20 microgram./ml., or saline was placed in each colonic loop and 1 ml. of either cholera enterotoxin (CE) 10 microgram./ml., PGE1 20 microgram./ml., or saline was placed in each ileal loop. In untreated animals, DCA and PGE1 in the colon and CE and PGE1 in the ileum stimulated (P less than 0.01) adenylate cyclase (AC) and net secretion. In the colon, PR abolished DCA-stimulation of AC and net secretion and decreased PGE1-stimulated AC (P less than 0.01) and net secretion. In conclusion, at the doses and times studied, colonic-AC and net secretion stimulated by PGE1 or DCA was distinguished from small bowel-AC and net secretion stimulated by PGE1 or CE.


Cystosarcoma phyllodes metastatic to the pancreas. A case is presented of cystosarcoma phyllodes of the breast metastatic to the pancreas. Solitary metastasis to the pancreas has not been reported. The lesion was excised in toto with a good result. Clinical and pathological features of cystosarcoma phyllodes are discussed.


Focal nodular hyperplasia of the liver and oral contraceptives. The increased incidence of liver tumors in women of childbearing age who have been using oral contraceptives for many years suggests an environmental causation. The causative agent may be the steroidal oral contraceptives. Two lesions are recognized: focal nodular hyperplasia and hepatic adenoma. This paper concentrates on focal nodular hyperplasia, with two cases added to the four previously described cases. It is postulated that the estrogen component causes vascular lesions characterized by myointimal hyperplasia and thrombosis, leading to infarct, necrosis, and subsequent nodular hepatic regeneration. The clinical feature highlighted is the long history of gastrointestinal disturbance associated with negative gastrointestinal investigation with the possible exception of cholelithiasis. It is suggested that gray-scale ultrasonography is an effective screening method that also aids in a definitive diagnosis. As these tumors are often incidental findings it is emphasized that the liver should always be inspected at laparoscopy. Ultimately, diagnosis by biopsy or excision is essential as it may well be possible to treat cases of focal nodular hyperplasia of the liver conservatively, once oral contraceptives have been discontinued.


Cytomegalovirus in juvenile iridocyclitis. We cultured cytomegalovirus from lens material aspirated from the eye of a 4-year-old boy who had a severe bilateral iridocyclitis and secondary cataracts. There were neither systemic manifestations of congenital disease nor chorioretinitis.


Corneal donor material selection.

Corneal donor material selection. Histologic study of eyes used as donor material for corneal transplant revealed one instance of massive leukemic infiltration with leukemic keratic precipitates on the fellow eye. In another eye, microabscesses composed of acute and chronic inflammatory cells containing Crytococcus neoformans were present. In a third patient metastatic anaplastic cells were present in the choroid. We think donor eyes are absolutely unacceptable if death was caused by any chronic neurologic disorder, unless clearly secondary to trauma. Eyes from patients with septecimia, hepatitis, jaundice and any evidence of any active viral infection, syphilis, and positive serology are also unacceptable. Extreme caution should be used in selecting eyes of patients with ocular or systemic malignancy, long-term diseases, particularly if immunosuppressive agents were used, where a history of eye disease exists, including corneal disease or dystrophy, iritis, absolute glaucoma or acute glaucoma, and eyes with a history of previous intraocular surgery.


Acyclic antimetabolite therapy of experimental herpes simplex keratitis. In a masked controlled study we compared 3% acycloguanosine, 0.5% idoxuridine, and 3% vidarabine ointments in therapy of experimental herpes simplex virus keratitis in rabbits. The results of the acycloguanosine group were significantly better than the control groups and both other treatment groups, while producing none of the toxic side effects of increasing iritis, conjunctivitis or stromal keratitis, with continued drug application.


Serum angiotensin converting enzyme activity and the capacity to develop hypertention-associated arterial disease. Studies during the induction phase of one-kidney perinephritis hypertension in rabbits. Serum angiotensin converting enzyme (ACE) activity and plasma renin activity (PRA) were studied during the development of the widespread necrotic arterial disease that occurs in the induction phase of one-kidney perinephritis hypertension. Control serum ACE activity was significantly higher in rabbits developing many arterial lesions than it was in rabbits developing relatively few arterial lesions. Serum ACE decreased 7 days after the production of unilateral perinephritis in all rabbits. Following contralateral nephrectomy, serum ACE decreased further in rabbits devloping many arterial lesions but returned toward control values in rabbits developing relatively few arterial lesions. Significant inverse correlations were demonstrated for the total number of arterial lesions that developed relative to a) the decrease in serum ACE activity 7 days after the production of unilateral perinephritis, b) the lowest or the average serum ACE activity during the period of development of the arterial lesions after contralateral nephrectomy, and c) the change in serum ACE activity during the period of development of the arterial lesions. Chronic treatment with SQ 20,881, a synthetic nonapeptide inhibitor of ACE activity, during the period of development of the hypertension and the arterial lesions significantly reduced the serum ACE activity and the hypertension but did not change interrelationships between serum ACE activity and the number of arterial lesions that developed. PRA significantly decreased after the production of perinephritis and decreased somewhat further during the induction period of the hypertension after contralateral nephrectomy. No relationships were demonstrated between PRA, or changes in PRA, and the development of arterial lesions. The increase in blood pressure during the incubation period of the hypertension did not correlate with the number of arterial lesions that developed. These finding indicate that serum ACE activity reflects importantly on the capacity to develop necrotic arterial lesions during the induction phase of one-kidney perinephritis hypertention and on functional events relating to their pathogenesis.


Pulmonary ultrastructure of the late aspects of human paraquat poisoning. The pulmonary ultrastructure of the late aspects of a case of human paraquat poisoning is investigated and compared with normal human pulmonary ultrastructure. Alveoli in the paraquat patient are numerically reduced in comparison to the control. They are filled with edematous proteinaceous plasma-like fluid containing erythrocytes, macrophages, leukocytes, fibroblast-like cells, platelets, and fibrin. These alveoli are lined by granular pneumocytes. Interstitial areas in the paraquat patient are greatly expanded and there are no alveolar septums. Interstitial areas contain proteinaceous plasma-like material, collagen, fibrin, platelets, mature fibroblasts, plasma cells, many leukocytes, numerous erythrocytes, and capillaries. Capillary permeability seems to be enhanced in the paraquat patient either by vesicles forming transendothelial channels or pores or by disruption of endothelial cells.


Seasonal pattern in the rate of growth in height of children living in Guatemala. Monthly increments of height for a sample of 164 Guatemala City school children are analyzed for the presence of a seasonal pattern in rates of growth. It is found that pre and post adolescent children follow a seasonal pattern of growth but adolescent children do not. It is suggested that the results are due to an effect of seasonal changes in ultraviolet light availability and the synthesis of vitamin D3 as mediated by the level of maturation of each child.


An evaluation of the miles method of ageing using the Tepe Hissar dental sample. The Miles system of ageing, based upon analysis of the rate of molar wear, was evaluated using the available dental sample from Tepe Hissar, Iran. The independently estimated ages for the mandibles and maxillae of the same individuals were found to be highly correlated (r = 0.87, p less than 0.001). Ages of a subsample of the dentitions were compared with skeletal ages for the same individuals estimated from pubic symphyseal faces and found to be significantly correlated (r = 0.82, p less than 0.005) with no significant differences in the mean ages. Although a complete evaluation of the Miles method would require its testing on a controlled population, the available dental sample from Tepe Hissar provided evidence of the reliability and validity of the Miles method of ageing archeological populations on the basis of dental wear. Due to selective retention of burial remains, the available skeletal sample from Tepe Hissar I-III is not representative of the human populations of the site and can not be used to generate meaningful demographic statistics.


Experimental amebiasis. III. A rapid in vitro assay for virulence of Entamoeba histolytica. A rapid and simple assay for cytopathogenicity of axenically cultivated Entamoeba histolytica has been developed employing baby hamster kidney (BHK) or mouse 3T3 cells conventionally tissue cultured. Three of the twelve amebal strains tested produced total destruction of the BHK cell monolayer in 2--3 hours, and these three strains are the three most virulent strains for the newborn hamster liver. Two additional strains were of moderate cytopathogenicity in vitro and of moderate virulence in vivo. Seven strains were of low cytopathogenicity and virulence. Within these three major groupings, however, the cytopathogenicity ranking was not entirely reproducible. The general correspondence of cytopathogenicity in vitro and virulence in vivo and the possibility of obtaining data within a few hours suggest such an assay may prove a useful tool in amebiasis research.


Hepatic amebiasis in spider monkeys.

Hepatic amebiasis in spider monkeys. In the past, investigators have been able to produce hepatic amebiasis in laboratory animals only by direct introduction of parasites into the liver or its vasculature, or by other artificial manipulations. A natural model of human visceral amebiasis has been lacking. We document an extensive outbreak of amebic dystentery which took place in a colony of spider monkeys; severe hepatic abscesses occurred in many animals. The spider monkey is highly susceptible to infection with Entamoeba histolytica and could provide a valuable model for the study of the pathogenesis of invasive amebiasis.


The presence of liver auto-antibodies induced by Entamoeba histolytica in the sera from both naturally infected humans and immunized rabbits. Auto-antibodies against normal human liver have been detected in the sera of humans with highly positive indirect hemagglutination (IHA) amebiasis titers and with clinically-proven amebic liver abscess. Sera of amebiasis patients and rabbits immunized with killed Entamoeba histolytica were tested for anti-amebic antibodies by the IHA test and for auto-antibodies by the complement fixation test, using the antigens prepared from extracts of human liver and rabbit liver. A direct correlation was found to exist between high anti-Entamoeba antibody titers and the presence of anti-liver antibody in the serum. It is proposed that, in addition to direct parasite damage to host tissue, immunological damage could result from the attachment of circulating antigen to the cell surfaces of host tissues such as the liver.


Granular cell tumor of the optic nerve.

Granular cell tumor of the optic nerve. A case of a combined neurofibroma-granular cell tumor is presented. The tumor had developed in the left middle cranial fossa after an intracranial trigeminal nerve operation 23 years before. It had displaced and infiltrated the temporal lobe and expanded probably via the fissura orbitalis into the orbit. The thickened optic nerve revealed a marked widening of the subdural fissure by typical granular cells. The cufflike tumor cell aggregation in the subdural fissure had compressed the optic fascicle, thereby inducing a demyelinisation and axonal degeneration. A reactive gliosis in the optic fascicle masks the typical pattern of the optic nerve atrophy. The gangliocytes of the third retinal neuron are atrophic and replaced by reactively proliferated fibrillary astrocytes. A short review of the literature and theories concerning histogenesis of the granular cell tumor (neurogenic or mesoderma) is given. An intermediary type of neurofibromatous and granular cells which we found motivates us to agree with a mesodermal origin.


Anaesthesia for carinal resection.

Anaesthesia for carinal resection. A case of adenocystic carcinoma (cylindroma) of the trachea is reported. Ventilation was successfully maintained for long periods by use of the venturi technique during resection of the carina, and during a later operation for relief of tracheal stenosis.


A histochemical study of the microvasculature in the left and right cardiac ventricles of the dog. Subepicardial and subendocardial arteries and arterioles in both the left and right normal canine ventricle were examined histochemically to determine their metabolic profiles. Aerobic metabolic capacity was assessed by determining the reactivities of the enzymes cytochrome oxidase, succinate dehydrogenase and NAD-isocitrate dehydrogenase. Glucose-6-phosphate dehydrogenase was examined to assess activity of the hexose-monophosphate-shunt. The substrate glycogen was determined as an evaluation of anaerobic metabolic capacity, while the amounts of deoxyribonucleic and ribonucleic acid were assessed as an indication of protein synthesis. Results of the present investigation indicate that despite known hemodynamic differences, the metabolic profile of the coronary vasculature is similar in all regions of ventricular myocardium. Reactivities of the enzymes succinate and NAD-isocitrate dehydrogenase and cytochrome oxidase are greater in smooth muscle of arterioles than in arteries. This suggests that arteriolar smooth muscle has a higher capacity for aerobic metabolism than does arterial smooth muscle. The greater reactivity of glycogen in arterial, than in arteriolar smooth muscle, suggests that arterial muscle is more adapted for anaerobic metabolism. Deoxyribonucleic and ribonucleic acids demonstrate a low reactivity in both arteries and arterioles from all regions of ventricular myocardium which conforms to the opinion that under normal conditions, coronary vasculature is quite stable with little cell proliferation. Glucose-6-phosphate dehydrogenase shows little reactivity in all myocardial vessels with implies a low capacity for nucleic acid and protein synthesis.


Genetics of a low-density lipoprotein allotype in a cattle. The paper describes a cattle serum antigen (LdlA1) located on a low-density lipoprotein and detected by single radial diffusion. The specificity is inherited in a simple Mendelian manner and the gene controlling its synthesis is inherited independently from the one controlling the synthesis of the alpha 2 macroglobulin McA1 antigen.


Intranasal tumor of the ethmoid olfactory mucosa in sheep. Intranasal tumors (papillary adenomas or adenocarcinomas) of the ethmoid olfactory mucosa of sheep were investigated by light and electron microscopy. The fine structure of the tumor cells was characterized by the presence of numerous secretory granules. Viral particles, which were morphologically similar to a visna-maedi virus, were detected in all tumor tissues and in 3 of 4 cultures examined. The particles (about 97 nm) had an eccentrically located electron-dense core and numerous spikes on their surfaces. The RNA-dependent DNA polymerase activities in the tumor cells or the cultured cell from the tumor were greater than those in the normal intranasal tissues or the cultured cells from the choroid plexus. Viral particles similar to herpesvirus were also detected in 1 culture.


Independence of gonadotropin and adrenal androgen secretion. Five groups of 5 normal adult males have been studied. Group 1 received clomiphene, group 2 received exogenous FSH and group 3 testosterone. These three groups received drugs to stimulate LH and FSH, increase levels of FSH or suppress LH and FSH respectively. Circulating levels of testosterone (T), estrone (E1) and 17-hydroxyprogesterone (17-OHP) were altered while serum concentrations of androstenedione (A), dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DS) and urinary 17-ketosteroids (17-KS) were not. The other two groups of 5 adult males had adrenal androgen levels suppressed or stimulated while receiving dexamethasone or ACTH. Serum 17 OHP, A, DHA and DS levels and urinary 17 KS were affected while gonadotropins were unaltered. Hence, no relationship has been demonstrated between circulating levels of adrenal androgens and gonadotropins.


Preadsorption of boar semen with kaolin: increased efficiency of foot-and-mouth disease virus detection. The boar semen-associated cytotoxic factor(s), but not the antiviral activity, were removed by adsorption with kaolin. Although foot-and-mouth disease virus was efficiently removed from medium by kaolin or kieselguhr, the virus was not removed from semen-virus mixtures. Because the cytotoxicity induced by boar semen apparently altered the ability of tissue culture cells to support virus replication, preadsorption with kaolin increased the probability of detecting this virus in semen samples.


Common membrane neoantigens on bovine papilloma virus-induced fibroma cells from cattle and horses. Cultured cells from bovine papilloma virus (BPV)-induced fibroblastic tumors and normal dermis of cattle, horses, and hamsters were examined for cell membrane or internal neoantigens, using the indirect immunofluorescence technique. Sera from cattle and horses bearing BPV-induced fibromas cross reacted with cell membranes of tumor, but not with normal dermal cells of both species. The reaction could be blocked with homologous, but not heterologous, serum of these 2 species. Immunofluorescence was not detected with sera from hamsters bearing BPV-induced sarcomas if incubated with bovine, equine, or hamster cells. Internal neoantigens were not found in any of the acetone-fixed tumor cells, using sera from the 3 species. Both tumor and normal cells were all found free of BPV antigen, using direct immunofluorescence.


Cytomegalovirus infection in dialysis patients and personnel. In a 12-month prospective study of cytomegalovirus infection on an acute hemodialysis unit, 10 of 80 patients (13%) and none of 26 staff developed active cytomegalovirus infection. Seven infections were coincidental with renal allograft rejection; three occurred 3 to 6 weeks after the transfusion of multiple units of conventional blood into seronegative patients. No person-to-person transmission was documented. In contrast to the effects of transfusing conventional blood, all 21 patients who entered dialysis without detectable cytomegalovirus antibody and received 2 to 10 U of frozen deglycerolyzed erythrocytes (total of 157 U) remained seronegative. Transmission of cytomegalovirus infection with transfusion with conventional blood is probably secondary to passage of leukocyte-borne virus that is lost during the freezing and deglycerolization procedure. Frozen erythrocytes prepared by cytoagglomeration procedures appear to be free of viable leukocytes and appear to carry a minimal risk of transmitting cytomegalovirus infection.


Steroid hormone action: recent advances. Pn entering the cell, steroid hormones are bound to specific cytoplasmic receptors. The hormone-receptor complexes are then translocated to the nucleus, in an "activated" form, whereupon they are bound to the target cell genome. The target cell responds by increased RNA synthesis with the transcription of specific mRNAs. The mRNAs are exported to the cytoplasm where protein synthesis takes place. Recent advances in steroid hormone action involve the purification of specific steroid hormone receptors and the preparation of specific antisera, the elucidation of the subunit structure of the progesterone receptor, the purification of a hormone-inducible mRNA and the synthesis of its DNA complement, the purification and amplification of the synthetic and natural gene for this RNA and the identification of intragenic spacers, and most recently the identification of specific precursors to the hormone-induced mRNA. We discuss here the medical significance of some of these advances.


Plasma high-density lipoproteins and ischemic heart disease: studies in a large kindred with familial hypercholesterolemia. The expression of ischemic heart disease was studied in a large kindred with familial hypercholesterolemia. Tendon xanthomas, multiple generation transmission, and the appearance of bimodality in the distributions of total and low-density lipoprotein cholesterol were found. The segregation ratio was 0.9 in females and 0.43 in males, a difference first apparent during adolescence. The upper quartile of total and low-density lipoprotein cholesterol contained all but two cases of ischemic disease, whereas the lower quartile of high-density lipoprotein cholesterol contained one half of the cases. The ratio of high- to low-density lipoprotein cholesterol (range, 0.06 to 1.6) was less than or equal to 0.20 in each patient with ischemic disease. The association of a low level of high-density lipoprotein cholesterol with ischemic disease persisted after adjustment for differences in other lipids and lipoproteins. A low level of high-density lipoprotein cholesterol, as well as a high level of low-density lipoprotein cholesterol, may influence the development of ischemic heart disease in this disorder.


[Coronavirus and "astrovirus" observed in stools of children with gastroenteritis (author's transl)]. In a year's survey (December 1976-November 1977) of 190 children admitted to hospital with acute gastroenteritis, an "aetiological" agent was found in stools by electron microscopy in 41% of cases. Rotavirus were found in 34% of patients. We also found Coronavirus-like particles and Astrovirus-like particles in 25 and 5 stools, respectively. Improvements are awaited to demonstrate the responsibility of these virus in gastroenteritis.


Coinfection with a rhabdovirus: vesicular stomatitis virus of Indiana and New-Jersey serotypes. Coinfection of cells with vesicular stomatitis virus (VSV) of Indiana and New-Jersey serotypes were performed. Thermosensitive mutants (ts) of VSV Indiana and the wild type strain (+) of New-Jersey were used. Harvests and titrations were made at permissive(PT) and nonpermissive (NPT) temperatures. It was shown that the harvest was mainly composed of one parental-like infectious particles. The dominance of one serotype over the other was shown to be a function of the relative multiplicity of the two viruses; the presence of a thermosensitive lesion imparts a disadvantage to the corresponding serotype. Non parental-like particles were also detected. As expected, these particles were detected only in two conditions. 1) Harvest performed at NPT and titrations allowed at PT.- Most of the infectious particles (i.e. twin particles) resistant to anti-Nj serum developped a plaque (i.e. mixed-plaque)containing virions of both serotypes: Indiana (ts) and New-Jersey (+). After sonication or EDTA treatment of the harvest, prior to titrations, no more mixed-plaques were formed. Examination of the harvest by electron microscopy showed that 7-17 % of the particles formed aggregates; therefore, it is likely that the twin-particles are in fact aggregates. 2) Harvest performed at PT and titrations allowed at NPT.-It has been shown that 1 % of the wild type infectious particles was resistant to anti-Nj serum even though being of Nj genotype. It was inactivated by a mixture of anti-Nj and anti-In sera and therfore behave as pseudotypes. But since twin particles, when plated at Nt, would give rise to an homogenous progeny from New-Jersey (+), they could be confused with pseudotypes. Under those conditions there is no absolute evidence that phenotypic mixing really occurs between VSV of Indiana and New-Jersey serotypes.


Stimulation of poly(adenosine diphosphate ribose) synthase activity of Xenopus germinal vesicle by progesterone. A practical procedure for the isolation of massive numbers of GV from oocytes of Xenopus laevis at various stages of oogenesis was developed. The method is simple, rapid, and easy to perform. The isolated GV possess high activity of poly(ADP-ribose) synthase. Incubation of class-A oocytes (stages V and VI) with progesterone resulted in a stimulation of the poly(ADP-ribose) synthase activity in the GV. The stimulation of enzymatic activity occurred prior to GVBD. This stimulatory effect of progesterone on enzymatic activity was blocked by cycloheximide and actinomycin D, suggesting that induction is dependent on protein and RNA synthesis. Progesterone, however, was unable to cause disintegration of GV or to stimulate poly(ADP-ribose) synthase activity of class-B oocytes (stages III and IV). This finding suggests that the oocytes must progress to a certain stage of differentiation before progesterone can induce GVBD or stimulate poly(ADP-ribose) synthase activity.


Discussion paper: induction by progesterone and a "maturation-promoting factor" of soluble proteins in Xenopus laevis oocytes in vitro. In vitro incubation of isolated X. laevis oocytes with progesterone induces the specific labeling of proteins during maturation. They are detected as several discrete peaks with a double-labeling technique that involves the injection of [3H] leucine into hormone-treated and [14C] leucine into control cells. The peaks are separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Identical proteins are obtained with two other steroids that provoke maturation and with p-chloromercuribenzoate. The same progesterone-induced proteins are observed even if oocytes have been treated with actinomycin D or ethidium bromide or have been enucleated. Cycloheximide suppresses the labeling of proteins that are induced by progesterone, if administered either at the time of radioactive amino acid exposure or after prelabeling the oocytes to determine whether the hormone-induced peaks are due to compartmental changes of the proteins. A cytoplasmic fraction, obtained from maturing oocytes before GVBD, promotes maturation when injected into resting oocytes and therefore contains an MPF. After this injection, GVBD occurs earlier than during incubation with progesterone and is accompanied by the formation of the same proteins and of MPF, both suppressed by cycloheximide. The possibility that MPF is an induced protein is then discussed. It has been also found that there is a decrease in membrane permeability, as evidenced by decreased leucine uptake into proteins of oocytes incubated in radioactive amino acids and exposed to progesterone. The same decrease occurs after injection of MPF-containing cytoplasm into oocytes.


Glomus jugulare and vagale.

Glomus jugulare and vagale. The therapeutic results in 72 patients with glomus jugulare and nine with glomus vagale have indicated a surgical cure rate of 80% in the former and 100% in the latter. Radiotherapy demonstrated a 65% tumor response rate and a 25% cure rate histologically and clinically. Embolization with Gelfoam beads in seven patients resulted in diminished tumor size and arterial circulation from the external carotid system. However, in all cases the tumor persisted. Embolization diminished intraoperative bleeding. Nevertheless, the use of embolization as a palliative modality demonstrated significant symptomatic relief in aged, debilitated patients and in all patients with large inoperable glomus jugulare tumors.


Juvenile nasopharyngeal angiofibroma.

Juvenile nasopharyngeal angiofibroma. The diagnosis of angiofibroma can be suspected in most cases by clinical examination, supplemented by routine x-rays and tomograms and is confirmed by angiography. Adjunctive therapy including embolization, estrogens, cryotherapy and arterial ligation is discussed. Surgical resection is the preferred treatment. Radiotherapy as the primary treatment modality is contraindicated except in select cases.


[Recent data on the group of melanotropic and lipotropic pituitary hormones (MSH-LPH) and on the brain morphinomimetic peptides (endorphins)]. It was admitted that human beta-MSH was responsible for the hyper-pigmentation observed in some syndromes associated with ACTH hypersecretion. beta-LPH was a pituitary polypeptide, containing the entire sequence of beta-MSH in its fragment 37-58, and the physiological role of which remained unknown. alpha-MSH and CLIP (Corticotrophin-like Intermediary Peptide) were thought to be specific of certain species possessing a distinct pituitary pars intermedia. Recent data give new insight upon some of these conceptions. beta-MSH seems not to exist in man; it is almost established now that plasma "Immunoreactive beta-MSH" (IR-beta-MSH) is in fact beta- and/or gamma-LPH. In chronic renal failure plasma IR-beta-MSH is elevated because of a decreased plasma disappearance rate, whereas ACTH is normal. Good evidence suggests that both LPH and ACTH are synthesized in the same pituitary cell within a common polypeptidic precursor. Endogenous peptides with morphinomimetic activity (Endorphins) have been isolated from brain and hypophysis; they are all made up of different fractions of beta-LPH-C-terminal fragment 61-91; It is likely that they represent a new class of brain neurotransmitters involved in some functions of the central nervous system, structural similarities suggest that beta-LPH may be the biosynthetic precursor of Endorphins, however such a hypothesis remains to be clearly demonstrated.


The EEG spike: signal of information transmission? Enhanced neuronal excitability or coherence, leading to a rapid-bursting mode of unit discharge or to synchronous polarization, underlies the electroencephalographic spike. The propensity for EEG spike activity to occur in relation to events that require absolute command of neural circuitry suggests that the EEG spike represents a mode of discharge of underlying neural elements which is employed for communication of imperative messages. Normal when confined to certain axial nuclei of the brain during sleep or during photic or sexual excitation, compensatory in response to deafferentation or hypoxia, this powerful transmission mode must have certain advantages to have persisted throughout evolutionary history.


A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release. A new myasthenic syndrome is described in a patient whose symptoms began soon after birth and included generalized weakness increased by exertion, easy fatigability, hyporeflexia, and refractoriness to anticholinesterase drugs. Electromyography showed a decremental response at all frequencies of stimulation and a repetitive response to single nerve stimulation. Miniature end-plate potentials (mepps) were of normal amplitude but of decreased frequency. The mepp duration and half-decay time were prolonged, and prostigmine was without any addtitional effect. The quantum content of the end-plate potential was decreased due to a reduced store of quanta immediately available for release, but the probability of release was normal. Quantitative electron microscopy demonstrated a 3-fold to 4-fold decrease of nerve terminal size and reduced postsynaptic membrane density. The postsynaptic folds showed focal degeneration, and many were distended by labyrinthine membranous networks that communicated with the synaptic space. Degenerating nuclei were found in the junctional sarcoplasm. The ultrastructural localization of the acetylcholine receptor protein was normal. Acetylcholinesterase (AChE) was absent from the motor end-plates by histochemical and electron cytochemical criteria. Biochemical studies indicated total absence of the end-plate-specific 16 S species of AChE and marked decrease in total muscle AChE. A congenital defect in the molecular assembly of AChE or in its attachment to the postsynaptic membrane might represent the basic abnormality and condition the morphological and physiological alterations.


Giant axonal neuropathy: a childhood disorder of microfilaments. A sural nerve biopsy was performed on an 8-year-old boy with a chronic, slowly progressive polyneuropathy. Light and electron microscopy as well as teased nerve-fiber preparations demonstrated numerous giant axons filled with closely packed neurofilaments. Both myelinated and unmyelinated fibers were involved. Segmental demyelination, remyelination, and onion-bulb formation by multiple Schwann cell processes were observed, suggesting recurrent Schwann cell dysfunction. Abundant aggregates of cytoplasmic microfilaments occurred in Schwann cells, endothelial cells, perineurial cells, endoneurial fibroblasts, and endomysial fibroblasts. These findings support the proposal that giant axonal neuropathy is a generalized disorder of cytoplasmic microfilaments and that segmental demyelination occurs concomitantly with axonal and Schwann cell disease. The pathogenesis of this rare disorder is discussed with reference to experimental toxic neuropathies.


Subacute measles encephalitis complicating Hodgkin's disease in an adult. A progressive neurological illness characterized by myoclonus, motor and sensory deficits, and lethargy occurred in a patient with Hodgkin's disease and was fatal within two months. A focal inclusion cell encephalitis was demonstrated by immunohistological means to be due to measles virus. Measles encephalitis must be considered a potential opportunistic agent in the immune-compromised host.


Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: use of virus-containing cells in the urine to assess response to therapy. Two patients with biopsy-proved progressive multifocal leukoencephalopathy (PML) were treated with near-maximal doses of adenine arabinoside (Ara-A), 18.6 and 20 mg per kilogram of body weight per day for 14 days. In both patients, clinical progression of the disease was correlated with an increase in the size of low-density lesions seen by computerized tomography. One of the patients was observed to excrete abnormal epithelial cells into the urine. These cells contained papovaviruslike particles, and JC virus was cultured from the urine sediment. The relative number of these abnormal cells declined during Ara-A treatment. Both patients died shortly after the conclusion of therapy without a change in the progression of the central nervous system disease. Systemic administration of Ara-A did not offer significant clinical benefit in the treatment of these 2 advanced cases of PML.


Botulism: electrophysiological studies.

Botulism: electrophysiological studies. In a patient with botulism type B, electrophysiological studies showed: (1) a pattern in the repetitive nerve stimulation test resembling that found in the Eaton-Lambert syndrome but without any significant increment at high rates of stimulation or posttetanic exhaustion phenomenon; (2) a prominent response to guanidine hydrochloride; (3) a short mean duration of motor unit potentials that reversed with recovery; (4) a mild, prolonged latency and low amplitude of the H-reflex; (5) mild peripheral nerve dysfunction; and (6) a long-lasting persistence of abnormalities beyond the time of clinical recovery. The literature reports two types of responses in the repetitive nerve stimulation test in botulism: in the severe form one obtains a low-amplitude muscle potential, a decremental response at low rates of stimulation, and an insignificant incremental response at high rates of stimulation; in the mild form a normal amplitude of muscle potential occurs together with a normal response to low rates of stimulation and a significant incremental response at high rates of stimulation.


Huntington's chorea: selective depletion of activity of angiotensin coverting enzyme in the corpus striatum. The activity of angiotensin converting enzyme, which transforms the relatively inactive decapeptide angiotensin I to the active octapeptide angiotensin II by removal of an L-histidyl-L-leucine residue, has been assayed in numerous region of the calf brain and of the brains of humans with Huntington's chorea and controls. In calf brain there are pronounced regional variations in enzyme activity, with highest activity in the globus pallidus and area postrema. In human brain, enzyme activity is highest in the corpus striatum, with similar levels in the caudate, putamen, and globus pallidus. Converting enzyme activity is reduced by 83 to 92% in the globus pallidus in Huntington's chorea. The caudate and putamen of choreic patients display 62 to 69% reductions in enzyme activity. Converting enzyme activity in two cerebral cortical regions from choreic brains is not significantly different from control.


Sequential cerebral biochemical and physiological events in controlled hypoxemia. Effects of controlled hypoxemia on cerebral functional activity were studied in rats using cyclic adenosine monophosphate (cAMP) and aminergic neurotransmitters in the brain tissue as special references. Evidence is presented that: (1) mild hypoxemic stress (PaO2 60 to 40 torr) may activate cerebral glycolysis with no evidence of anaerobic metabolism but that further reduction of PaO2 impairs cellular respiration, as evidenced by accumulation of glycolytic products; (2) glycogenolysis in the brain tissue, leakage of potassium ions from the brain cell, increase in brain water, and suppression of neural functional activity occur concomitant with accumulation of cAMP and prior to the fall of adenosine triphosphate; (3) the diminution of cerebral high-energy phosphates during hypoxia is associated with and may be caused by hypoxemia-induced neuroglycopenia and occurs at PaO2 15 torr; (4) induced hypoxemia per se does not affect the level or aminergic neurotransmitter substances in brain tissue.


delta-Aminolevulinic acid: influences on synaptic GABA receptor binding may explain CNS symptoms of porphyria. Symptoms of acute porphyria have been attributed to effects of delta-aminolevulinic acid (ALA). We report that ALA selectively competes for the binding of tritiated gamma-aminobutyric acid ([3H]GABA) associated with synaptic GABA receptors in central nervous system membranes. Concentrations of ALA that inhibit GABA receptor binding are consistent with levels of ALA thought to exist in the central nervous system of porphyric patients. Some of the symptoms of acute porphyria resemble those elicited by muscimol, a potent GABA agonist drug. Barbiturates, which exacerbate porphyric symptoms, are potent facilitators of the synaptic actions of GABA. The results suggest that some symptoms of acute porphyria might be attributable to a mimicking by ALA of GABA at its central nervous system receptor sites.


The cerebrospinal fluid in visna, a slow viral disease of sheep. The temporal development of the CSF abnormalities was examined in visna, a chronic neurological disease caused by a persistent viral infection of sheep. Two types of changes were observed. During the first 30 to 40 days there was an intense mononuclear pleocytosis associated with high protein and proportionately elevated IgG. Later, there was a persistent slight pleocytosis associated with mildly elevated protein which had an increased proportion of IgG and antivisna antibody. These later cellular and protein changes are similar to those found in a number of chronic neurological diseases of man.


Mixed intracranial sarcomas: rare forms and a new association with previous radiation therapy. The first two instances of mixed sarcoma-glioblastoma with a history of therapeutic irradiation to the head are reported, both occurring within one year of radiation therapy (for pituitary adenoma and residual meningioma). Two novel variants of mixed sarcomas of brain with extreme tumor metaplasia (fibromyxoosteochondrosarcoma and fibrochondroosteosarcoma-glioblastoma multiforme) are documented, and some of the problems concerning the origin of brain tumors with mixed population are discussed.


[Antiviral action of carminomycin and some of its derivatives]. Carminomycin was shown to inhibit the development of both the DNA-containing variolovaccine virus and the RNA-containing grippe virus in chick embryos. Comparison of the effects of rubomycin, carminomycin, 14-oxy-carminomycin and carminomycin complex with bovine serum albumin in experiments with chick embryos showed that the inhibitory effect of carminomycin and its derivatives on the development of the grippe virus was much higher than that of rubomycin. The carminomycin derivatives proved to be much more active in this respect than the initial antibiotic. Carminomycin and its derivatives had a therapeutic effect on mice with experimental grippe pneumonia also on their oral use.


Antiviral activity of intranasally applied human leukocyte interferon. Previous studies in our laboratory have demonstrated that the development of antiviral activity of human leukocyte interferon (IF) in nasal epithelial cells is time and concentration dependent and that the loss of intranasally applied human leukocyte IF is rapid. The present studies compared the activity of IF applied intranasally either by nasal drops or by a saturated cotton pledget. Adult volunteers had IF applied to an area of nasal mucosa (2 by 2 cm(2)) either by repeated nose drops or by a saturated cotton pledget that was applied to the nasal mucosa and left in place for 1 h. Nasal epithelial cells scraped from the area of application, as well as the control, untreated side of the same volunteers, were challenged with vesicular stomatitis virus. No significant reduction in mean virus yield was found in volunteers who received 80,000 U by nose drops. Significant reduction (P < 0.025) in mean virus yield was found in cells obtained 4 h after 80,000, 50,000, or 20,000 U was applied by cotton pledget or in volunteers pretreated with oral antihistamines prior to receiving 80,000 U by nose drops. These experiments indicate that nasal epithelial cells can be made antiviral in vivo by application of human leukocyte IF. However, practical usefulness of human leukocyte IF for prophylaxis against respiratory viral infections may depend on the method of local application.


Generation of superoxide anions and hydrogen peroxide from beta-lapachone in bacteria. beta-Lapachone markedly increased the generation of superoxide anions and hydrogen peroxide by subcellular membranes of Bacillus subtilis and Bacillus stearothermophilus. Peroxide generation by beta-lapachone was parallel to the inhibition of growth in both microorganisms.


Artifactual depression of serum glutamic oxaloacetic transaminase by metronidazole. Eighteen patients developed abnormally low serum glutamic oxaloacetic transaminase values during metronidazole therapy. Metronidazole absorbs at 340 nm, simulating reduced nicotinamide adenine dinucleotide, which is the final colorimetric product of the serum glutamic oxaloacetic transaminase assay.


Progressive nodular histiocytoma.

Progressive nodular histiocytoma. Extensive evaluation of the condition of a 9-year-old girl with a previously undescribed proliferative histocytic syndrome showed normal serum and tissue lipid values, which rule out the known lipid storage diseases. Clinically and histologically the case is inconsistent with any of the recognized xanthomatoses or histiocytic abnormalities.


Malignant neoplasms of the paranasal sinuses involving the skin. Malignant neoplasms of the mucosa and minor salivary glands of the paranasal sinuses may involve the skin by direct extension. When a tumor appears on the overlying skin, these sinuses should be considered as a possible site of origin. Adenoid cystic carcinoma of the paranasal sinuses arise from minor salivary glands. They can infiltrate overlying skin and easily be confused with a primary cutaneous adenoid cystic carcinoma. Malignant melanomas of the paranasal sinuses are clinically very aggressive. They are often amelanotic, and this may lead to an incorrect histopathologic diagnosis. Hence, physical and radiological examination of the nose, mouth, and paranasal sinuses should be performed whenever a tumor appears in the overlying skin that does not have a clear cutaneous origin or whenever the primary site of a metastatic malignant melanoma is unknown.


[The lymphocyte transformation test in patients with recurrent herpes simplex diseases (author's transl)]. The in vivo stimulation of lymphocytes was used to assess cell mediated immunity to herpes simplex virus (hsv) in patients with recurrent skin eruptions caused by this virus. 1. Phytohaemagglutinine stimulation of lymphocytes was normal in all examined patients. There was no difference in the PHA-stimulation of a control group. 2. Specific lymphocytes stimulation by hsv-antigen may be regarded as a sensitive parameter for a previous hsv-infection. 3. In 6 patients with severe infections of hsv type I or II and more than 10 recurrences per year we found a lower stimulation than in patients with occasionally (up to 10 times a year) skin eruptions. 4. An antigen used as vaccine, Lupidon H, ten times more concentrated (100,000 EID/ml) than the commercially available antigen is able to stimulate lymphocytes in vitro.


Presence of two typical DNA-binding nonhistone proteins in psoriatic scales contrary to normal human dermis, epidermis and horny layer. The composition of DNA-binding proteins (DBP) was shown to be tissue-specific and to vary at different stages of gene expression. As the accelerated epidermopoesis in psoriasis indicates changed gene activities, DBP of psoriatic scales were compared with those of normal human epidermis, dermis and horny layer. Each skin fraction is characterized by its own DBP pattern, indicating different cell species. 1. The DBP of normal human epidermis shows only a small accordance with the DBP of human dermis and implies their difference in origin, function and cell types. 2. Psoriatic scale DBP and epidermal DPB contain more corresponding proteins which can be deduced from the scale's origin from epidermis. However, the composition of all proteins differs to a great extent. This either occurred during parakeratotic keratinization or reflects differences of normal to psoriatic epidermis. Imposing for psoriatic scale DBP are two protein bands with molecular weights of 84,000 and 90,000 daltons. Evidently both are not present in the DBP of other skin layers. 3. The horny layer contains a very small amount of DBP which might represent DNases to a major part. The small DBP content in horny layer confirms the previous supposition of psoriatic scales, to be mostly derived from the preserved nuclei of the parakeratotic scale layer.


A longitudinal study of in vitro tests for lymphocyte function in rheumatoid arthritis. In vitro tests of lymphocyte function have been performed in 61 patients with ;classical' or ;definite' rheumatoid arthritis. In vitro lymphocyte function was assessed by lymphocyte transformation responses to phytohaemagglutinin (PHA), Pokeweed mitogen (PWM), Candida antigen, and herpes simplex type I (HSV1). Follow up data were available after 6 months of treatment in 32 of these patients. Spontaneous lymphocyte transformation was assessed in all patients. Results obtained in patients with rheumatoid arthiritis were compared to those seen in a normal control population. Disease activity of patients with rheumatoid arthritis was assessed using standard clinical methods. Lymphocytes from patients with rheumatoid arthritis showed a similar degree of spontaneous transformation to that seen in normal subjects. In contrast, lymphocytes from patients with rheumatoid arthritis responded less well to PHA and Candida and HSV1 antigens when compared to normal patients. In patients with rheumatoid arthritis the response to PWM was markedly enhanced compared to normals. Clinical improvement was noted in 19 of the 32 patients seen at follow up, all of whom had received gold or penicillamine therapy. The abnormal responses of PHA and PWM seen before treatment became normal in those patients who improved clinically. The responses to Candida and HSV1 antigens not only returned to normal following treatment but were increased above those seen in normal controls. A statistically significant association was seen between clinical improvement and improvement of in vitro tests of lymphocyte function.


Lactic acidosis in oat cell carcinoma with extensive hepatic metastases. Lactic acidosis has been described in patients with leukemia and lymphoma, but its occurrence in other malignant diseases is not documented. We treated two patients with oat cell carcinoma of the lung and extensive liver metastases in whom lactic acidosis developed. Tumor-induced hepatic dysfunction appeared to be a major factor in the pathogenesis of the lactic acidosis observed in these patients.


Superoxide dismutase and hydrogen peroxide formation in Campylobacter sputorum subspecies bubulus. Cell-free extracts of Campylobacter sputorum subspecies bubulus contained superoxide dismutase. The enzyme was located in the cytoplasmic fraction and insensitive to cyanide. After centrifuging a cell-free extract at 144000 x g for 1.5 h the total activity in the supernatant fraction was threefold higher than in the crude cell-free extract. The pellet fraction thus obtained was shown to have a lowering effect on superoxide dismutase activities from different sources in the assay method used here. C. sputorum responded to a raised oxygen tension in the culture by an increase in the superoxide dismutase activity. The ability to produce superoxide anion radicals (O2-.) during oxidation of formate and lactate was demonstrated. Furthermore C. sputorum was found to produce H2O2 while oxidizing formate. In experiments in which the reduction of cytochrome c by formate was followed, step-wise kinetics were observed. One of the steady states then obtained was attributed to the oxidizing action of H2O2, because it was abolished by the addition of catalase and lengthened by H2O2 added in addition to H2O2 formed as a product of formate oxidation. An overall reaction for formate oxidation by C. sputorum is discussed.


Fumarate reductase of Clostridium formicoaceticum. A peripheral membrane protein. When Clostridium formicoaceticum was grown on fumarate or L-malate crude cell extracts contained a high fumarate reductase activity. Using reduced methyl viologen as electron donor the specific activity amounted to 2-3.5 U per mg of protein. Reduced benzyl viologen, FMNH2 and NADH could also serve as electron donors but the specific activities were much lower. The NADH-dependent activity was strictly membrane-bound and rather labile. Its specific activity did not exceed 0.08 U per mg of particle protein. Fumarate reductase activity was also found in cells of C. formicoaceticum grown on fructose, gluconate, glutamate and some other substrates. The methyl viologen-dependent fumarate reductase activity could almost completely be measured with intact cells whereas only about 25% of the cytoplasmic acetate kinase activity was detected with cell suspensions. The preparation of spheroplasts from cells of C. formicoaceticum in 20 mM HEPES-KOH buffer containing 0.6 M sucrose and 1 mM dithioerythritol resulted in the specific release of 88% of the fumarate reductase activity into the spheroplast medium. Only small amounts of the cytoplasmic proteins malic enzyme and acetate kinase were released during this procedure. There results indicate a peripheral location of the fumarate reductase of C. formicoaceticum on the membrane.


Effect of guanosine 5'-diphosphate 3'-diphosphate and related nucleoside polyphosphates on induction of tryptophanase and beta-galactosidase in permeabilized cells of Escherichia coli. Exogenous addition of guanosine and adenosine 5'-(mono, di and tri) phosphate 3'-diphosphates (pppGpp, ppGpp, pGpp, pppApp, ppApp and pApp) stimulated the synthesis of tryptophanase and beta-galactosidase in permeabilized cells of Escherichia coli. From the results obtained with ppGpp and pppApp, this effect appeared to be at a transcriptional level and depended greatly on the growth condition; the largest effect was observed in cells under shiftdown or grown on poor enrgy source. ppGpp and pppApp, unlike cyclic AMP, did not act to overcome the inhibition of enzyme induction by glucose, but in combination with cyclic AMP caused a synergistic stimulation effect. In the shiftdown cells, ppGpp and pppApp gave 30% or more stimulation effect on tryptophanase induction while cyclic AMP did not stimulate induction. There was therefore a pronounced difference between cyclic AMP and ppGpp or pppApp in stimulatory function.


Fine structure of the dome in Peyer's patches of mice. The dome area of Peyer's patches in adult mice was studied by electron microscopy. The cellular constituents of the area are lymphocytes, plasma cells, macrophages and reticular cells. Macrophages are filled with numerous lysosomal bodies containing dead lymphocytes or plasma cells. The epithelium covering the dome is infiltrated with numerous lymphocytes, a few plasma cells and macrophages. These wandering cells first are found intercellularly but later appear to penetrate into the epithelial cell cytoplasm just beneath the cell apex. The epithelial cells containing the wandering cells in the supranuclear portion protrude into the intestinal lumen, and their microvilli are short and scanty. The epithelial cells covering the dome often have inclusion bodies containing dead wandering cells. Such modification of the epithelial cells may be related to the presence of underlying follicles. The results suggest that the dome including the covering epithelium is a site in which antigens from the intestinal lumen might come in direct contact with lymphocytes or other wandering cells.


Corticotropin stimulation of hypertensive rats with and without arteriosclerosis. Male and female, nonarteriosclerotic (virgin) and arteriosclerotic (breeder), Sprague-Dawley rats were subjected to the hypertension-producing regimen of uninephrectomy, 1% saline drinking water, and desoxycorticosterone (Percorten) pivalate. Just before autopsy, some of the animals were given a single injection of corticotropin. The acute challenge of corticotropin caused a definite increase in free fatty acids, systolic blood pressure, creatine phosphokinase, glucose, and corticosterone. The two weeks of desoxycorticosterone and 1% saline-induced hypertension caused myocarditis and hyalinization of the coronary arteries of the nonarteriosclerotic (virgin) rats and definite exacerbation of the preexisting arteriosclerosis in breeder rats, severe myocarditis, and polyarteritis nodosa. All of the treated animals manifested lipid depletion of the zona glomerulosa indicative of reduced biosynthesis and secretion of endogenous mineralocorticoids due to the exogenous desoxycorticosterone and saline treatment.


Nephroblastomatosis and multiple bilateral nephroblastomata. Histologic, therapeutic, and theoretical aspects. A hemihypertrophic girl had multiple sequential bilateral Wilms' tumors over a period of five years. Diagnostic biopsy and resected specimens showed also the presence of nephroblastomatosis, presumably the substrate from which these multiple tumors arose. The patient died of complications of chemotherapy and dialysis after bilateral nephrectomy, but also had residual tumor. The relationships between nephroblastomatosis, Wilms' tumor, bilateral Wilms' tumor, and teratogenic disorders are discussed, and the therapeutic implications of the nephroblastomatosis/nephroblastoma complex are considered.


Intranuclear inclusions of the human vas deferens. Intranuclear inclusions in epithelial cells of the human vas deferens have not been well characterized or widely recognized. We studied their prevalence in an adult male population by light microscopy and characterized them using the techniques of histochemistry, electron microscopy, and electron microprobe analysis. They occurred in all cases studied, consisted of electron dense globules, contained neutral mucosubstances, and occasionally were single membrane bound. Epithelial intranuclear inclusions routinely occur in the vas deferens of sexually mature males, do not disappear with advancing age, and should not be interpreted as a pathologic finding.


Varicella and acute cerebellar ataxia.

Varicella and acute cerebellar ataxia. In two cases of varicella-associated cerebellar ataxia, varicella-zoster antigens in CSF cells were shown by an indirect immunofluorescent technique. Direct viral invasion in CNS disease complicating varicella plays an important part in pathogenesis and rules out a single immune-mediated mechanism.