Herpes simplex virus-IgM specific antibodies in Guillain-Barré syndrome and encephalitis. Herpes simplex virus (HSV) has veen associated with a variety of inflammatory neurologic disorders. Recently we studied a patient with Guillain-Barré syndrome (GBS) following acute herpes vaginalis infection. Since IgM virus-specific antibody is thought to be a reliable indicator of acute viral infection, we employed a 2-h serologic assay for serum IgM antibodies to HSV using an indirect immunofluorescent technique. This patient demonstrated high serum IgM titers to HSV type 2 during the acute phase of her neurologic syndrome. The titer dropped substantially as convalescence progressed. A search for similar elevations in HSV-IgM specific antibody was made on sera from more than 70 other GBS patients. No other significant IgM antibody titers to either HSV type 1 or type 2 were found in this GBS series and a large number of neurologic controls. However, sera from two patients with a presumptive diagnosis of acute herpes encephalitis based on clinical and cerebrospinal fluid findings were positive, showing high titers in our test. The results of this study suggest that associated acute HSV infection is uncommon in GBS and an immunofluorescent seroassay of the type reported here may be a valuable noninvasive technique enabling the clinical laboratory to rapid confirm a diagnosis of herpes encephalitis.


Fine structural changes in the mutant hamster with hind leg paralysis. Various parts of the central and peripheral nervous system of the mutant hamster with hind leg paralysis were studied in the electron microscope. A number of alterations involving the myelin sheath, the axon and certain neuronal perikarya were observed. Anterior horn cells were apparently well preserved. This condition represents an inherited form of peripheral neuropathy.


Comparative ultrastructural observations on peripheral nerve abnormalities in the late infantile, juvenile and late onset forms of metachromatic leukodystrophy. The ultrastructural findings in nerve biopsies from two cases of late onset metachromatic leukodystrophy were compared with those in cases of late infantile and juvenile onset. Hypertrophic changes and regenerating clusters were more evident in the late onset cases, in which macrophages were less frequent, presumably reflecting the chronicity of the disorder in this form. Inclusions within Schwann cells and endoneurial macrophages were similar in all four cases. Myelin figures, in which the periodicity of major dense lines was 8 nm, were present in Schwann cells associated with myelinated axons. The electron lucent zones between the major dense lines were bisected by lines of lesser electron density. These inclusions were probably related to myelin breakdown. All other inclusions displayed a periodicity of 5.8 nm and consisted of zebra bodies, vacuoles containing irregularly orientated lamellar material and stacks of flattened discs. These inclusions represented the metachromatic sulphatide deposits. Occasional inclusion bodies were observed within axons.


Giant axonal neuropathy. Involvement of peripheral nerve, myenteric plexus and extra-neuronal area. A case of giant axonal neuropathy in a 8 years old child is reported by light and electron microscopy. Clinically, this case is strikingly similar to the rare previous reports and characterized by a distal neuropathy, CNS symptoms and tightly curled hair. Giant axons were found in the sural nerve but had been absent at the onset of the illness. An increase in the number of neurofilaments was found in the axons and neurons of the myenteric plexus. The number of microfilaments was also increased in various types of cells namely Schwann and endothelial cells and fibroblasts: This suggests that the metabolic disorder, probably inborn and genetic, does not only affect the nervous system.


The role of the subependymal plate in glial tumorigenesis. We have studied the sequential morphological events of glial tumorigenesis in neonatal dogs, using high titer subgroup C Bratislava-77 Avian Sarcoma Virus, given as 0.01 ml by intraventricular inoculation. The cells of the subependymal plate are those which seem to form the gliomas; cytoplasmic alterations are evident within 24 h after inoculation and microfoci of gliomas, contiguous with the subependymal plate of the lateral ventricles, are visible within 7 days. Independent tumors are present by the 10th post-inoculation day. These studies support the hypothesis of Globus and Kuhlenbeck, which implicates the cells of the subependymal palte in glial tumorigenesis.


Giant axonal neuropathy: possibly secondary to vitamin b12 malabsorption. A giant axonal neuropathy is described in an adult with no evidence of a childhood onset of his disease and no history of exposure to toxic hydrocarbons. A causal relation to vitamin B12 malabsorption is proposed. This case suggests the need to expand the spectrum of diagnoses that must be considered when giant axons are encountered in peripheral nerve biopsy specimens.


Herpes simplex encephalitis: an autopsy case with isolation of type 1 herpes simplex virus. An adult case of herpes simplex encephalitis was studied after autopsy. Postmortem examination revealed necrotizing encephalitis associated with Cowdry type A intranuclear inclusion bodies in glial cells. Herper simplex virus type 1 was isolated from the removed brain. Herpes simplex virus antigens were detected diffusely in wide areas of the brain by immunofluorescent test and viral particles characteristic to herpes simplex virus were demonstrated by electron microscopy. There was an apparent discrepancy between severity of histological changes and distribution of virus antigen.


Bioavailability of natural estrogens in young females with secondary amenorrhea. The bioavailability of 17 beta-estradiol valerate, free 17 beta-estradiol and Premarin was studied in 24 subjects suffering from secondary amenorrhea. 17 beta-estradiol and estrone were determined by specific radioimmunoassay systems. All estrogens were administered as single oral doses. The amounts applied were 2 and 10 mg of 17 beta-estradiol valerate or equivalent amounts of the free estradiol and Premarin, respectively. No elevations of 17 beta-estradiol serum levels were recorded at the lower dosages, whereas the increases of estrone serum levels were approximately tenfold over basal levels. Similar data were recorded in a group of 3 women with normal cycles after the ingestion of 2 mg of 17 beta-estradiol valerate. All subjects responded to the higher doses of estrogens with a moderate increase of 17 beta-estradiol serum levels, but with much higher elevation of estrone levels. These data suggest a rapid conversion of 17 beta-estradiol into estrone. The biological activity of 2 mg 17 beta-estradiol valerate is discussed on grounds of a possible metabolism of estrone sulfate at the target tissues.


Effects of exogenous ACTH on the rat fetal adrenal cortex: a histochemical and electron-microscopical observation. ACTH was administered subcutaneously to rat fetus directly at the late stage of fetal development and acute reaction on the fetal adrenal cortex was observed histochemically and electron microscopically. By administration of ACTH the adrenal cortex became remarkably hyperemic and there were swollen cells in all layers, particularly in the middle and inner layers (corresponding to the zona fasciculata and reticularis in adult rat). Marked reduction of lipid, enlarged mitochondria with increased vesicular cristae and increased smooth-surfaced endoplasmic reticulum (SER) were characteristic. The alterations of mitochondria preceded the change of SER, and thereafter mitochondria showed rapid degeneration. The outer layer (corresponding to the zona glomerulosa in adult rat) also showed similar changes by ACTH to those of the other two layers. These results indicated that the fetal adrenal cortex of rats was exogenous ACTH-reactive and its reaction which was different from that of adult cortical cells, seemed to be specifically related to the development and differentiation of the cells.


Functional prenatal development of anencephalic and normal anterior pituitary glands. In human and experimental animals studied by peroxidase-labeled antibody method. In order to investigate the influence of the central nervous system on the functional differentiation of the fetal anterior pituitary gland, the pituitary gland of anencephalic and normal fetus was studied by the peroxidase-labeled antibody method for the localization of various hormones. The only abnormality of pituitary endocrine cells in anencephaly was a marked decrease of ACTH cells. In the normal development, ACTH appeared as the earliest hormone in 5 weeks. And all other hormones were seen in 13 weeks. The reason for the decrease of ACTH cells in anencephaly was speculated to be a suppression at an early developmental life. The experimental observations done in rats using MAM might support this speculation. The adrenal glands of anencephalus showed atrophy of the fetal cortex which was considered to correlate with the decrease in number of ACTH cells. Absence of the histochemical activity of alkaline phosphatase in the permanent cortex of anencephaly may indicate absence or inadequate stimulation by fetal ACTH. Further experimental studies in suppression of the central nervous system in early developmental life seemed to confirm the above speculation in functional differentiation of the fetal pituitary and adrenal glands.


Penetration of erythromycin stearate into maxillary sinus mucosa and secretion in chronic maxillary sinusitis. The penetration of oral erythromycin stearate (Abboticin), administered in a dosage of 500 mg three times a day, into the maxillary sinus mucosa and secretion was studied in 15 patients (22 sinuses) operated on for chronic maxillary sinusitis. The average concentration in serum was 2.3 microgram/ml, 1.2 microgram/ml in secretion, and 1.8 microgram/ml in  mucosa. These concentrations are highly effective against diplococci and most aerobic and anaerobic streptococci (MIC value 0.06 microgram/ml) but not against Haemophilus influenzae (MIC value for 80% of 2 microgram/ml).


Glomus tumor of the stomach. Light and electron microscopic study with literature review of related tumors. A gastric tumor from a 27-year-old female showed the light microscopic features of glomus tumor. Ultrastructurally there were two types of tumor cells, i.e. smooth muscle and possible pericytes. From the literature review of ultrastructure of glomus tumor, hemangiopericytomas (HPC), leiomyoblastomas and leiomyomas, the glomus tumor appeared to exist as an intermediate form between HPC and leiomyomas which were considered to be in a broad spectrum of smooth muscle tumors.


Skeletal muscle fibres and muscle enzyme activities in monozygous and dizygous twins of both sexes. Significance of the genetic component in determining the interindividual variation observed in skeletal muscle fibre composition and enzyme activities was investigated in 31 pairs of male and female monozygous (MZ) and dizygous (DZ) twins, whose ages ranged in all but one pair (11 years) from 15 to 24 years. Percent distribution of slow twitch muscle fibres and activities of Ca2+ and Ng2+ stimulated ATPases, creatine phosphokinase, myokinase, phosphorylase, lactate dehydrogenase (LDH) and distribution of its isozyme LDH-1 were all analyzed in biopsy samples taken from the vastus lateralis muscle. The data disclosed that in contrast to DZ twins the MZ twins of both sexes had an essentially identical muscle fibre composition. Calculation of the heritability estimate for this parameter gave the values of 99.5% and 92.8%, respectively for males and females. In contrast to the fibre composition presence of a significant genetic component was not observed in any of the enzyme activities studied. It was concluded that there is a predominant genetic influence on the skeletal muscle fibre composition in man, and thus also on the potential capacity of the muscles to perform work.


Adenosine in rat cerebral cortex: its determination, normal values, and correlation to AMP and cyclic AMP during shortlasting ischemia. It has recently been suggested that adenosine is a metabolic coupling factor responsible for an increased cerebral blood flow during hypoxia or increased functional activity. However, tissue adenosine concentrations have been reported to increase in situations previously shown to be unassociated with changes in tissue AMP concentrations. The present experiments were undertaken to assess cerebral cortex concentrations of adenosine under normal circumstances, and to relate changes in adenosine, AMP and cyclic AMP during shortlasting ischemia. Following freezing and extraction of tissue, adenosine was measured using high pressure liquid chromatography. In paralyzed and anaesthetized (70% N2O) rats, freezing of tissue through intact skull bone gave an adenosine concentration of 0.9 +/- 0.1 mumol-kg-1 (mean +/- S.E.M.). With freezing through the exposed dura the concentration was 3 times as high with a large scatter. When special precautions were taken to avoid tissue trauma during craniotomy, the adenosine concentration was 1.1 +/- 0.1 mumol-kg-1. It is concluded that previously reported values are erroneously high. During the first 60 s of total ischemia there was a linear correlation between increase in AMP and in adenosine concentration (as well as between adenosine and cyclic AMP concentrations). It is concluded that increases in tissue adenosine concentration only occur if AMP accumulates. However, since (relative) changes in adenosine concentrations are at least twice those of AMP, analyses of adenosine may provide sensitive measures of a change in phosphorylation state.


The adrenocortical response to angiotensin II infusion in anephric and non-nephrectomized patients on regular hemodialysis. In the present study 8 anephric and 4 non-nephrectomized patients were stimulated with angiotensin II (A-II). In 5 of the anephric patients, an increased plasma aldosterone concentration (PAC) in response to ACTH stimulation had previously been demonstrated. After A-II stimulation, all 8 anephric patients responded with a significant rise in PAC although the increase was less pronounced than in 4 non-nephrectomized patients. In both groups of patients the increase in PAC was correlated to the increase in diastolic and systolic BP and to the A-II dose. Furthermore, in the non-nephrectomized patients, the plasma renin activity showed a significant decline, which was inversely correlated to the increase in PAC. When all 12 patients, regardless of the difference in remaining renin-angiotensin system, were considered as one population, the variable basal levels of PAC correlated significantly to the increase in PAC during A-II and ACTH stimulation. It is concluded that the adrenals of anephric man respond to A-II with an increase in PAC and that the reason for a lower response appears to be the lack of the renin-angiotensin system.


On the functional significance of sleep. Some aspects of the functional significance of sleep are considered. These involve studies on (i) the dynamics of electrical activity in the neo- and archi-paleocortical structures of the brain in the sleep-wakefulness cycle, (ii) the effect of selective deprivation of different sleep phases on the sleep-wakefulness cycle, (iii) effect of stimulating synchronizing and desynchronizing systems on the sleep-wakefulness cycle, and (iv) the dynamics of emotional tension in the sleep-wakefulness cycle. Analysis of our findings and their comparison with those reported in the literature support a hypothesis that every phase in the sleep-wakefulness cycle operates in two directions; it withdraws the factors formed in the previous phase which are potentially aimed at disturbing brain homeostasis; and, at the same time, it forms new antihomeostatic factors, withdrawal of which requires the triggering and work of a subsequent phase. The triggering links of the systems regulating each phase are very sensitive to the factors formed in the preceding phase. Therefore, in normal conditions the anti-homeostatic factors fail to attain a critical level of disturbance of homeostasis of the brain, since the threshold for their activation is far lower than the critical level of homeostatic disturbance. Activation of the triggering links of the paradoxical phase and wakefulness seems to be mediated through the same anti-homeostatic factors formed in the orthodox phase. However, the threshold for activation of the paradoxical phase is lower than that of wakefulness. As a consequence, the orthodox phase readily passes into the paradoxical. The latter, effectively reducing the antihomeostatic factors formed in the orthodox phase, prevents the onset of undue awakening that would have been undesirable because there would have been insufficient time for inactivation of the anti-homeostatic factors formed during wakefulness.


Supratentorial recurrences of gliomas. Morphological studies in relation to time intervals with oligodendrogliomas. On the basis of a three stage grading system we report 23 stage one recurrent oligodendrogliomas (O 1), and 29 stage two recurrent oligodendrogliomas (O 2). In the O 1 group after the first interval 15 became O 2 and 2 became glioblastomas. Twenty tumours of the O 2 group after the first interval were not changed, three became oligodendroglioma-astrocytomas stage 2, and six became glioblastomas. The time relation for the recurrent phase in the primary O 1 group is calculated as 42 months, and in the primary O 2 group as 22 months, but this is without significance. For the development of malignancy, especially for the change to glioblastoma, a prominent participation by transformed local astrocytes seems to be essential. Postoperative irradiation most probably does not favour malignant change. A prolongation of the expectation of life by radiotherapy is not noticed.


Lymphocytic infiltration in long-survival glioblastomas: possible host's resistance. A series of 200 patients operated on at the Rome University Neurosurgical Clinic for primary glioblastoma is analyzed. Eight of these patients (4%) survived for over four years. The histological preparations showed more or less heavy perivascular lymphocytic infiltration in six of these cases. Since such infiltrations in malignant tumours of other organs are recognized as having an immune function, expressing the host's resistance to his tumour, the longer survival of the cases considered may well denote an immune defensive mechanism.


Multiple hepatic tumors and peliosis hepatis in Fanconi's anemia treated with androgens. We report the case of a 13-year-old boy who was known to have Fanconi's anemia for five years. For treatment of this condition he was given androgens and corticosteroids. Two months before his death, severe varicella developed complicated by pneumonia, jaundice, and prolonged fever; all of which resolved during a five-week hospitalization. Three weeks later he died of Clostridium septicum sepsis caused by necrotizing enterocolitis. At autopsy he was found to have multiple hepatocellular neoplasms. A striking feature of the neoplasms was cholestasis. The liver also showed peliosis hepatis. The association of the use of certain androgenic steroids with hepatic neoplasms histologically resembling hepatocarcinomas, but characterized by lack of metastases and apparent reversibility, suggests the desirability of a new nomenclature for these hepatocellular lesions.


Granular cell myoblastoma of the gallbladder. A case of granular cell myoblastoma of the gallbladder in a 39-year old Japanese female is presented. Granular cell myoblastomas arising in the biliary tract are a rare occurrence. This tumor has not yet been reported in the gallbladder.


Amebic granuloma--an experimental study. The etiopathogenesis of granuloma formation in amebiasis is not known. An experimental study was carried out in 48 guinea pigs arranged into four groups, to assess the role of hypersensitivity in formation of amebic granuloma. Repeated intracecal inoculations of saline in Group I and mixed amebic and bacterial suspension in other groups were made. Animals in Group III were sensitized by amebic antigen and in Group IV by bacterial antigen before inoculations. Lesions produced in the amebic hypersensitive group of animals were notably different from those in other groups. A higher frequency of cecal ulceration and a significantly severe grade of cecal damage was seen in these animals. Extensive pericecal adhesions and marked thickening of the wall produced nodular lesions. Granulomas were formed with dense chronic inflammatory cell infiltration including fibroblasts.


Antibodies to Epstein-Barr virus capsid antigen and early antigen in nasopharyngeal carcinoma and comparison groups. Antibodies to Epstein-Barr virus capsid antigen (anti-VCA) and early antigen (anti-EA) were measured in 263 patients with nasopharyngeal carcinoma (NPC), 624 age- and sex-matched neighborhood controls, 570 family members of NPC patients and 830 family members of neighborhood controls in Taiwan. The distribution of antibody titers was significantly different between NPC patients and the other three groups. More than 55% and 45% of NPC patients had titers of greater than or equal to 1:640 and greater than or equal to 1:80 for anti-VCA and anti-EA, respectively, while less than 6.7% and 2.5% of the other three groups had such high titers. The geometric means of anti-VCA and anti-EA titers were 1:352 and 1:45, respectively, in NPC patients compared to less than 1:77 and 1:12, respectively, in the comparison groups. Anti-VCA and anti-EA titers were significantly correlated. The association of EBV with NPC is discussed.


Atypical herpesvirus hominis type 2 infection in uremic patients receiving immunosuppressive therapy. In four uremic patients (three renal transplant recipients and one with idiopathic thrombocytopenia), painful, initially vesicular lesions developed in the anogenital region while they were receiving immunosuppressive drug therapy. These lesions enlarged, coalesced and ulcerated, presenting a puzzling diagnostic problem. Initial misdiagnoses often resulted in inappropriate antimicrobial therapy. Routine cultures, histologic sections and Tzanck preparations were seldom helpful. The correct diagnosis of herpesvirus hominis (HVH) infection was established within 18 to 48 hours by viral culture of swab or biopsy material. Subsequent identification of isolates as HVH type 2 was confirmed by neutralization kinetics, infectivity titers and ability to plaque in chick embryo cells. Various therapeutic regimens were ineffective. Clinical improvement best correlated with decrease in dosage of immunosuppressive agents.


Cytomegalovirus retinitis in adults. A manifestation of disseminated viral infection. Retinitis caused by cytomegalovirus (CMV) infection is unusual in adults. Sixteen of the 17 cases reported have occurred in immunologically compromised patients, most frequently renal transplant recipients. CMV retinitis is associated with a distinctive ophthalmoscopic appearance and, in the majority of cases, was the first clinical manifestation of systemic viral infection. Severe and permanent visual deficits are characteristic. Since retinitis is a reliable sign of disseminated disease and ophthalmoscopic examination a rapid method of establishing its presence, recognition of this manifestation should allow earlier diagnosis of serious CMV infection.


The natural history of hypertrophic gastrophy (Menetrier's disease). Report of a case with 16 year follow-up and review of 120 cases from the literature. We describe a 33 year old man who presented with epigastric pain, weight loss and hematemesis. Roentgenograms of the upper gastrointestinal tract and endoscopy demonstrated giant rugal folds, and the diagnosis of hypertrophic gastropathy was confirmed by operative biopsy. This patient's symptoms and abnormalities noted on the roentgenograms persisted until his death 16 years later. Postmortem examination confirmed the persistence of hypertrophic gastropathy and revealed, in addition, a hepatocellular carcinoma metastatic to the stomach and regional lymph nodes. A review of 120 previously reported cases of hypertrophic gastropathy with special attention to its natural history indicates that the chronic nature of this patient's illness is typical. In addition, the chance of gastric carcinoma developing in these patients is appreciable. Since the reported long-term results of operative therapy appear favorable, patients with persistent and sufficiently distressing symptoms should be considered for gastric resection.


An epidemiologic study of cancer of the cervix, vagina, and vulva based on the Third National Cancer Survey in the United States. Cases of invasive and in situ carcinoma of the lower female genital tract as reported in the Third National Cancer Survey in the United States were analyzed according to age, race, and geographic distribution. Results indicate that the incidence rates of in situ and invasive carcinoma of the cervix were greater in black than in white women, with a relative risk rate for black women of approximately two for both types of cervical carcinoma. For white women, the age-specific rates for invasive carcinoma of the cervix remained relatively constant after age 45, while for black women the age-specific rates for invasive carcinoma continued to increase after age 45. For both races, the patterns of age-specific incidence rates for in situ and invasive carcinoma of the cervix were not similar to those for carcinoma of the vagina or vulva. The pattern of age-specific incidence rates of adenocarcinoma of the cervix did not resemble those for in situ or invasive squamous cell carcinoma of the cervix. The rates for adenocarcinoma of the cervix demonstrated patterns similar to those for intraductal carcinoma of the breast. Results of the study are discussed in relationship to the field theory of carcinogenesis as developed for the lower female genital tract.


Cytomegalovirus retinitis secondary to chronic viremia in phagocytic leukocytes. We studied the relationship between the duration and intensity of cytomegalovirus viremia, cytomegalovirus complement fixing antibody, and cytomegalovirus retinitis in 61 renal transplant recipients. Five (8%) patients had chronic viremia which lasted more than six months. Two of the five developed typical cytomegalovirus retinitis and a severe fungal infection after intensive viremia of more than 11 months' duration. Retinitis did not develop in 22 patients with short-term viremia. Infectious cytomegalovirus was largely associated with polymorphonuclear leukocytes, but the virus was associated with monocytes during the immature granulocytic response accompanying one patient's terminal illness.


Effect of polychlorinated biphenyl (PCB) on the thyroid gland of rats. Ultrastructural and biochemical investigations. Polychlorinated biphenyls (PCB) produced ultrastructural lesions in thyroid follicular cells and reductions in serum thyroxine levels in rats that were time- and dose-dependent. The acute effects (4 week) of PCB (50 and 500 ppm) consisted of an accumulation of lysosomal bodies and colloid droplets in follicular cells with abnormalities of microvilli on the luminal surface. The chronic administration (12 week) of PCB (50 and 500/250 ppm) resulted in a striking distention of many follicular cells with large lysosomal bodies with strong acid phosphatase activity and colloid droplets, blunt and abnormally branched microvilli, and mitochondrial vacuolation. These ultrastructural alterations in follicular cells were associated with a highly significant reduction in serum thyroxine with both the low and the high dose of PCB. Follicular cells remained responsive to the lowered thyroxine level after feeding PCB for 4 and 12 weeks and underwent moderate compensatory hypertrophy and hyperplasia. Thyroid follicles were smaller than in controls and were lined by more columnar cells that occasionally formed papillary projections into the colloid. Residual ultrastructural alterations persisted for 12 weeks following cessation of feeding the compound, and serum thyroxine levels were significantly lower than in control rats. However, 35 weeks after discontinuing PCB, thyroid follicular cells were similar to those in controls and serum thyroxine levels had returned to normal. The striking ultrastructural lesions in follicular cells produced by feeding PCB to rats appeared to contribute to the lowering of serum thyroxine levels, in combination with the known stimulation of peripheral thyroxine metabolism by these compounds. Certain metabolic alterations produced by PCB intoxication in experimental animals and human beings may be related to an alteration in thyroid function.


Role of cyclic 3',5'-GMP in modulation of cellular uptake of phosphate. The role of cGMP in regulating renal cortical phosphate uptake was investigated in rats. Cyclic GMP (1 mM) produced a 27.7% +/- 1.4 (SE) increase in 32PO4 uptake by isolated renal cortical tubules (P less than 0.001) and cAMP (1 mM) a 28.7% +/- 1.4 increase (P less than 0.001), but their effects were not additive. Acetylcholine (Ach) (1 mM), in the presence of theophylline (T) (10 mM), increased cGMP in cortical slices from 24.1 pmol/g wet wt +/- 1.3 to 76.5 +/- 5.2 (P less than 0.001), but had no effect on cAMP, and Ach (1 mM) in the presence of T (1 mM) increased 32PO4 uptake 19.1% +/- 1.1 (P less than 0.001). Addition of Ca2+ to the incubation medium in the presence of T (10 mM) significantly increased cGMP in cortical slices from 7.4 pmol/g wet wt +/- 0.6 (0 Ca2+ plus EGTA, 0.5 mM) to 24.1 +/- 1.3 (1 mM Ca2+) and caused a 52.2% +/- 2.7 rise in 32PO4 uptake (P less than 0.001). Cyclic AMP was decreased by the addition of Ca2+. In summary, cGMP and cAMP stimulate 32PO4 uptake by renal cortex, and Ach and Ca2+ increase both cGMP and 32PO4 but do not increase cAMP. These data suggest that cGMP may play a role in regulating cellular uptake of phosphate.


Development-dependent responses of ovarian follicles to FSH and hCG. Ovarian follicles removed from immature rats (preantral follicles) and immature rats treated in vivo with follicle stimulating hormone (FSH) (antral follicles) released progesterone in vitro in response to either human chorionic gonadotropin (hCG), hFSH, or DBcAMP in a time- and concentration-dependent fashion. Antral follicles produced approximately 20 times more progesterone than preantral follicles in response to both FSH and hCG at 10(-7) M and approximately 5 times more progesterone in  response to 8 X 10(-3) M DBcAMP. After in vitro incubations, follicles were transplanted beneath the kidney capsules of recipient rats to assess their ability to luteinize after hormonal stimulation. Only antral follicles incubated with hCG, hFSH, and DBcAMP formed ectopic corpora lutea. Adenylate cyclase activity in preantral and antral follicle granulosa cells increased in response to both 10 mM KF and 10(-6) M hFSH with no major differences observed between membranes prepared from preantral or antral follicle granulosa cells. These results demonstrate that follicular maturation is associated with major changes in the ability of the granulosa cells to produce progesterone and luteinize in response to hormonal stimulation and that these changes may be, in part, independent of a functional hormone-responsive adenylate cyclase system.


Effect of leukocytic endogenous mediators on endocrine pancreas secretory responses. Crude mediators from stimulated rabbit peritoneal leukocytes (LEM) engender numerous physiologic alterations in rats, which are similar to those observed during infection. One hour after the intraperitoneal injection of crude LEM, plasma insulin and glucagon concentrations are elevated; at 2 h the hormonal alterations are manifested by a 30% increase in hepatic cyclic adenosine 3',5'-monophosphate (cAMP), glycogen depression, and uptake of 14C-labeled nonmetabolizable amino acid analogues (AA). Plasma hormone concentrations reach maximum levels by 5 h and decline by 24 h. The hepatic concentrations of AA parallel the insulin and glucagon responses and correlate with the inverse of insulin/glucagon molar ratio. In spite of mobilization of hepatic glycogen evident at 5 h, plasma glucose concentrations were transiently depressed. Plasma insulin, glucagon, and hepatic AA concentrations were dose dependent. Plasma insulin and glucagon responses to crude LEM may explain increases in hepatic cAMP, uptake of AA, and glycogenolysis as well as hypoglycemia. These data partially characterize the role of crude LEM, provide an explanation for the stimuli-inducing hyperglucagonemia and hyperinsulinemia during infection. They implicate the endocrine pancreas as a factor regulating the host's metabolic response to infection.


Neurons in medullary areas controlling ACTH: atrial input and rostral projections. To examine hindbrain pathways mediating release of adrenocorticotropin (ACTH) in response to hemodynamic changes we tested, in 19 cats (chloralose/urethan), 70 neurons in ACTH-active areas of the medulla for their response to volume pulsation (+/- 1 ml, 1 Hz, 60 s) of the right atrium (RA) or to hemorrhage (3 ml/kg per 30 s), and to electrical stimulation in ACTH-active areas of the dorsal rostral pons (DRP). The activity of 16 neurons was increased (P less than 0.05) by RA. Of these, 6 were driven antidromically from the locus subcoeruleus (LSC), and were located in the lateral solitary nucleus and in posteromedial nucleus intercalatus (NI). The activity of 11 neurons was decreased by RA. Of these, 5 were driven antidromically from LSC and lateral ventral tegmental nucleus and were located in anterolateral NI. No rostral projections were found to more medial sites in DRP. Responses to the first trial of RA were rapid, but slowed and attenuated with repeated trials. Responses to hemorrhage were rapid and in the opposite direction, but did not attenuate. The results suggest that pathways displaying rate sensitivity project from the right atrium via B-receptors to the DRP.


Structure-function relationships of peptide fragments of gastrin and cholecystokinin. This study evaluates the structure-function relationships of the C-terminal peptide fragments of gastrin and cholecystokinin (CCK) in the biliary system and the stomach. Dogs with chronic biliary and gastric fistulas were used. Administration of the common fragments of CCK and gastrin with four and five amino acids and the active fragments of CCK with six through eight amino acids without sulfation of tyrosine in position 7 failed to alter hepatic bile flow from control values while significantly stimulating gastric hydrogen ion output. Administration of the seven and eight amino acid peptide fragments of CCK with sulfation of tyrosine in position 7 significantly increased hepatic bile flow. Administration of the sulfated octapeptide with 4 microgram/kg per h of nonsulfated octapeptide did not result in the inhibition of the choleresis produced by the sulfated peptide. The gastric hydrogen ion response produced by the administration of the nonsulfated and sulfated peptide was equal to that of the nonsulfated peptide alone. These results suggest that in the biliary system the receptor is highly specific as sulfation of the peptide fragment of CCK is essential for combining with the receptor, whereas in the stomach the receptor has little specificity and combines with all of the peptide fragments evaluated.


Barrier and uptake mechanisms in the cerebrovascular response to noradrenaline. Cerebral blood flow (CBF) was measured in 20 baboons by the intra-arterial xenon-133 injection method. The CBF responses to intra-arterial infusions of noradrenaline (NA) were determined. These responses were normally found to be vasodilator and mediated by beta adrenoreceptors. After infusion of substances blocking extraneuronal uptake of NA or opening of the blood-brain barrier, this vasodilation was either abolished or converted to an alpha-receptor mediated vasoconstriction. This suggests that normally the cerebral circulation is protected against noradrenergic vasoconstriction by mechanisms reducing the concentration of NA in the tunica media to below threshold for alpha-adrenoreceptor stimulation.


Malignant salivary gland neoplasms of the lip. The charts of fourteen patients with malignant salivary gland tumors of the lip were reviewed. These patients represented 1 per cent of all patients seen during this same period of time with malignant salivary gland tumors. No specific etiologic factors were implicated except that the tumors occurred predominantly in white males. The overall results of treatment were poor, perhaps secondary to delay in diagnosis, very biologically aggressive tumors, or inadequate or improper treatment. Hopefully, the 20 per cent survival can be improved with planned combined sequential surgery and radiation in those selected high risk patients.


Pattern of angiomas in the Igbos of Nigeria. Almost all angiomas fall into three main groups--hemangioma, lymphangioma, and glomangioma. Fifty-one such angiomas were found in approximately 7500 surgical specimens examined at a central laboratory serving the Igbos of Nigeria. The youngest patient was aged 19 days and the oldest 70 years. Most patients presented in the first two decades of life and both sexes were equally affected. Hemangiomas greatly outnumbered the other angiomas; most were cavernous and tended to thrombose, fibrose, or calcify. Lymphangiomas frequently exhibited lymphoid tissue, some showing germinal centers. Glomangiomas occurred mostly in the upper extremity as small, painful masses.


Temporary remission of hypoglycemia in a dog with an insulinoma after treatment with streptozotocin. Temporary remission of hypoglycemia was achieved in a dog with an insulinoma by treatment, using streptozotocin. Nephropathy, manifested as a renal tubular defect, and hepatopathy were associated with the administration of streptozotocin.


Equine rhinopneumonitis virus (herpesvirus type 1): attenuation in stable monkey cell line. An isolate of virulent equine herpesvirus (EHV) type 1 was adapted to Vero stable cell line by 13 serial passages at 37 C and 50 serial passages at 26 C. Characteristics of the attenuated EHV-1 were found to be avirulent, but immunogenic in horses if injected intramuscularly. The attenuated virus was regularly isolated from peripheral leukocytes in inoculated horses, but was not recovered from nasal turbinate tissues. A mild leukopenia was noticed. The attenuated virus produced characteristic large syncytia on primary isolation in rabbit kidney (RK13) or Vero cells at 37 C in contrast to cell rounding observed with virulent EHV-1. The syncytial marker was stable through 20 serial passages in Vero cells at 37 C. New application of double immunodiffusion test for distinguishing between EHV-1 and EHV-2 also is described.


Inactivation of equine infectious anemia virus by chemical disinfectants. Twelve chemicals and commercial disinfectants were tested for inactivation of equine infectious anemia virus. In the presence of 10% bovine serum, all chemicals inactivated 4 log10 (based on 0.1 ml) of the virus within 5 minutes at 23 C. A reduction of at least 4 log10 was observed when the virus was exposed for 1 minute to substituted phenolic disinfectants (3 commercial preparations and sodium orthophenylphenate), halogen derivatives (iodophor and sodium hypochlorite), chlorhexidine, and 70% ethanol. Sodium hydroxide (5%), 2% formalin, and 2% glutaraldehyde were slower to inactivate the virus, but achieved 4 log10 reduction in titer by 5 minutes' contact time. The susceptibility of the equine infectious anemia virus to chemical disinfectants is similar to that of other enveloped viruses.


Leukocyte migration-inhibition procedure for transmissible gastroenteritis viral antigens. Swine exposed to transmissible gastroenteritis viral antigens developed humoral and cell-mediated immunity. Migration of leukocytes from exposed swine was inhibited in the presence of the sensitizing antigens, whereas migration of leukocytes from nonexposed swine was not inhibited in the presense of these same antigens. In virus-neutralization-positive animals, it was not possible to correlate degree of inhibition with virus-neutralization titer. Inhibition was observed 7 days after exposure and was found to persist for at least 35 days.


Diabetes, blood lipids, and the role of obesity in coronary heart disease risk for women. The Framingham study. Diabetes and a low high-density lipoprotein cholesterol level are associated with each other and with a higher coronary heart disease risk in women. Moreover, both are strongly associated with obesity. These findings are reported from the Framington Study, in which persons aged 49 to 82 were characterized, after overnight fast, for blood lipids by the method of Fredrickson and Levy and then followed for the subsequent development of coronary heart disease. Low-density lipoprotein cholesterol was also associated with coronary heart disease risk in women, but fasting triglycerides were not associated with risk after allowing for the association with high-density lipoprotein cholesterol and diabetes. A low high-density lipoprotein cholesterol in the presence of diabetes appeared to raise the coronary heart disease risk in women relative to that of men.


Arthritis associated with apatite crystals. Needle-shaped crystals of 75 to 250 A diameter have been identified by transmission electron microscopy in clumps within synovial fluid mononuclear cell vacuoles in a variety of joint diseases. These crystals, similar to those previously associated with calcific periarthritis, were seen in acute undiagnosed arthritis and in exacerbations of osteoarthritis where they may be inducing a synovitis similar to that seen with urate and pyrophosphate crystals in gout and pseudogout. By light microscopy purple staining cytoplasmic inclusions or extracellular globules can suggest the presence of clumps of these crystals. Apatite clumps can also occasionally appear as small birefringent chunks or rods and thus might mimic urate or calcium pyrophosphate. Ultrastructural appearance, electron probe analysis, and X-ray diffraction pattern were those of apatite. Experimental injection of hydroxyapatite crystals into dog knee joints produces inflammation supporting the potential role for these crystals in joint disease.


Serum angiotensin-converting enzyme in leprosy and coccidioidomycosis. Serum angiotensin-converting enzyme levels were found to be elevated in 71.4% of 42 leprosy patients, both treated and untreated, but in only one of 13 patients with disseminated coccidioidomycosis. The elevations with leprosy were present in association with each of the three major categories: lepromatous, borderline, or tuberculoid. Sulfone therapy had no immediate effect on the elevated serum levels, although long-term sulfone therapy appeared to result in lowering of the level. Corticosteroid therapy had a more immediate and dramatic effect on reducing the elevated angiotensin-converting enzyme level in leprosy. This assay cannot distinguish between sarcoidosis and leprosy or between the various categories of leprosy, but it can help differentiate sarcoidosis from fungal or tuberculous disease. Elevated levels of serum angiotensin-converting enzyme have now been associated with three diseases states: sarcoidosis, Gaucher's disease, and leprosy.


Hypersensitivity to adrenergic stimulation after propranolol withdrawal in normal subjects. The cardiac response to isoproterenol after propranolol withdrawal was studied in six normal persons. Serial isoproterenol infusions were done before and after oral propranolol administration, 160 mg daily for 2 days. Changes in electromechanical systole corrected for heart rate (QS2I) and pulse pressure were used to assess the inotropic response to isoproterenol, and changes in heart rate were used to assess the chronotropic response. As shown in previous studies, the negative inotropic effect of propranolol lasted only 12 to 15 h, while the negative chronotropic effect lasted 24 to 36 h. After the disappearance of blockade a hypersensitivity to isoproterenol was found 24 to 48 h after propranolol withdrawal in all three measured determinants. The explanation of this phenomenon most likely lies in the nature of adrenergic receptors that become activated during long-term blockade.


Alveolar cell carcinoma in identical twins. Similarity in time of onset, histochemistry, and site of metastasis. Identical male twins had alveolar cell carcinoma with nearly synchronous onset and similar histopathologic features, both metastatic to the brain. The hypothesis is advanced that there are genes shared by these twins that determine not only the susceptibility of pulmonary cells to malignant transformation but also the character of the resultant neoplasm, including its histologic features and metastatic behavior.


[Plasmidic resistance of "Haemophilus sp." to aminoglycoside antibiotics: isolation and study of a new phosphotransferase (author's transl)]. Plasmid mediated phosphorylating activities have been found in Haemophilus sp. strains resistant to some aminoglycoside antibiotics. The enzymes responsible for this phenomenon have been purified and studied. They belong to the group of aminoglycoside phosphotransferases which are able to phosphorylate these antibiotics on the 3'- or 5"-hydroxyl group. The first enzyme studied is closely related to APH(3')I whereas the second one is different from the former on the basis of substrate specificities and physicochemical properties. We propose to call this second enzyme APH(3')Ib as compared to APH(3')I which will be called APH(3')Ia.


[Effect of different salts and their concentration on polymyxin M biosynthesis by Bac. polymyxa Ross]. The effect of various concentrations of ammonium sulfate, sodium and potassium chlorides and sulfates on biosynthesis of polymyxin M by Bac. polymyxa Ross. on media containing wheet meal as the carbon source was studied. The culture growth, antibiotic accumulation and consumption of the main nutrients was studied as dependent on the level of the salts in the medium. The highest productivity was observed on media with the salt concentrations amounting to 1--2 per cent except sodium sulfate: changes in the concentration of the latter had practically no effect on the activity of the fermentation broth.


[Nerve-blocking properties of antibiotics]. Comparative data on the neuroblocking activity of antibiotics of various groups in acute experiments on albino mice and narcotized cats are presented. It was found that according to the impairments in the neuro-muscle conductivity the drugs were arranged in the following descending order: polymyxin B, neomycin, gentamicin, streptomycin, lincomycin and kanamycin. The streptomycin derivatives were approximately 2 times less toxic than streptomycin. The problems of the mode of action of the antibiotics on conductivity of excitation in the neuro-muscle synapses are discussed.


Rapid detection and quantitation of Clostridium perfringens enterostoxin by counterimmunoelectrophoresis. Conditions for detection and quantitation of Clostridium perfringens enterotoxin by counterimmunoelectrophoresis are described. As little as 0.2 microgram of enterotoxin per ml could be detected. The test was found to be rapid, sensitive, specific and easy for the detection and quantitation of enterotoxin.


Increased spore yields of Clostridium perfringens in the presence of methylxanthines. The methylxanthines caffeine, theophylline, and isobutylmethylxanthine greatly increased spore yields of Clostridium perfringens strains FD-1, PS52, and PS49 when grown on Duncan-Strong medium or on a new casein-digest medium. Four other strains (KA3, and National Collection of Type Cultures strains 8798, 8238, and 10240) failed to show any significant increase when tested under similar conditions. The degree of sporulation increase was influenced by the carbohydrate energy source in some strains but not in others. Strain PS52 showed a large increase in spore yield when dextrin was the energy source but only a slight increase when raffinose served as the energy source. Strain FD-1 showed similar increases in spore yield with either dextrin or raffinose.


Dialysis technique for containment of microbial populations inoculated into food systems. A technique utilizing dialysis tubing was developed for the containment of microbial populations introduced into a food system. The entrapment of the inoculum was accomplished while reducing interference with interactions between the sample and the surrounding environment.


Thermal inactivation of ileal loop-reactive Clostridium perfringens type A strains in phosphate buffer and beef gravy. The thermal resistance of spore crops produced from each of two ileal loop-reactive strains of Clostridium perfringens type A was determined in two suspending vehicles consisting of 0.067 M (pH 7.0) phosphate buffer and a commercial beef gravy. D115.6 values obtained in buffer and enumerated after pretreatment with sodium ethylenediaminetetraacetate and recovery in plating medium containing lysozyme were two- to threefold greater than those obtained without this treatment. D115.6 values obtained with beef gravy were less than those obtained in buffer with or without lysozyme; however, the D98.9 and D104.4 values were 1.3 to 2 times greater than those obtained in buffer with lysozyme. The z values were within the ranges reported by previous investigators.


Arenavirus concentration by molecular filtration. Liter volumes of a human arenavirus pathogen (Machupo) and a nonpathogen (Tacaribe) were concentrated 30 to 100 times in less than 90 min without significant loss of particle infectivity.


Synthesis of prostaglandins by psoriatic skin. The biosynthesis of prostaglandins (PG) in biopsies from 9 patients with psoriasis was studied. The involved as well as the uninvolved psoriatic skin showed a statistically significant decrease of the ability to synthesize PG's. In PGE1-equivalents the concentration (mean +/- S.E.M.) was 4.41 +/- 0.48 ng/g wet weight in the psoriatic lesion, 5.41 +/- 0.64 ng/g wet weight in uninvolved psoriatic skin in the presence of exogenous arachidonic acid in the incubation medium as compared with 9.02 +/- 1.59 in normal human skin. When the skin was incubated without excess of exogenous precursor acid the activity formed was similarly significantly lower in psoriatic skin as compared with normal skin. A disturbed balance between E and F PG synthesis was not demonstrated, which might have accounted for the postulated altered intracellular ratio of cyclic AMP to cyclic GMP in psoriatic skin.


Assessment of the role of surgery for control of lung cancer. When morphologically stratified, the classification of patients according to surgical stage provides an objective basis for evaluating the results of surgical treatment. In a review of 794 patients according to surgical staging criteria, the data supported concepts regarding differences in the behavior of each cell type as well as major differences in survival between each stage of disease. The overall cumulative five-year survival was 37% for squamous cell carcinoma, 27% for adenocarcinoma, and 27% for undifferentiated large cell carcinoma. Fewer than 1% of patients with undifferentiated small cell carcinoma survived. Survival for patients with surgical Stage I disease was 53%, for Stage II 29%, and for Stage III 16%. The results of surgical treatment for patients with limited disease extent are much better than is generally realized. Fifty to 60% of such patients in this series survived five years. Survival studies by surgical stage permit resonable estimates of the presence of occult metastatic disease and supply insights necessary to the design and appropriate selection of adjunctive therapeutic programs.


Dissociation of lipolysis from the levels of cyclic AMP in rat epididymal fat cells. Two compounds, theophylline and 8-aza-9-furfuryl-adenine (SQ 4665), were found to maximally stimulate lipolysis in preparations of rat epididymal fat cells in the absence of exogenous hormones. Cyclic AMP levels in lipocytes maximally stimulated by either agent alone were unchanged from control levels. In contrast, lipolysis stimulated by either epinephrine alone or in combination with several cyclic nucleotide phosphodiesterase inhibitors correlated well with increases in the levels of cyclic AMP observed. These results suggest the presence of a non-cyclic AMP dependent pathway for the stimulation of lipolysis in rat epididymal fat cells.


Vascular alpha adrenotropic responses of the isolated rabbit kidney at 15 degrees C. Rabbit kidneys were isolated and perfused with a balanced salt solution at 15 degrees C. The effects of norepinephrine (NOR) and phentolamine (P) were tested after fastly or slowly induced cooling. Vascular alpha receptor effects were enhanced by a slow cooling rate (0.6 degrees C/min), but blocked or impaired by a faster cooling rate (6 degrees C/min). Kidney function was severely impaired at this temperature as it would be expected.


[Precipitation antibodies against poliovirus in patients with poliomyelitis]. Sera from 26 children bearing poliomyelitis caused by virus tipe I and from 47 cases with paralysis of different etiology (non-poliomyelitic) were tested against antigen of poliovirus types I, II and III with an agar-immunoprecipitation reaction. All sera with neutralizing antibodies with titres of 1:1250 gave positive results in immunodifusion tests. The percentage of positiveness decrease with lower titres. No false positive reactions were found. Immunodiffusion test with antigens of poliovirus were positive in 100% of sera from patients with poliomyelitis and only in 30% in sera from patients with non polio paralysis.


[Cytochemical labeling of proteolytic enzymes in Entamoeba histolytica]. Trophozoites were obtained from fecal mucous in patients bearing colonic amebiasis. The tripsin inhibitor of soya bean was coupled to peroxidase according to Nakane and Kawokoi method. Amebae were incubated with couple and reactions were developed following Karnowsky's technic. There was a specific labeling of proteolitic enzymes on plasma membrane, the wall of digestive vacuoles and intracytoplasmic vacuoles of the trophozoites. Such a distribution of proteolitic enzymes agreed with digestive and invasion functions of E. histolytica.


Induction of polymyxin resistance in Pseudomonas fluorescens by phosphate limitation. Shift of Pseudomonas fluorescens NCMB 129 from a a phosphate rich into a phosphate limited medium results in a reduction of the membrane phospholipids phosphatidylethanolamine, phosphatidylglycerol and cardiolipin. Concomitantly a positively charged ornithine amide lipid is synthesized. The gradual increase of this lipid is paralleled by an increasing resistance to polymyxin B. The binding capacities of intact cells, and isolated inner and outer membranes for the antibiotic are reduced in the resistant organisms. It is discussed that the observed effect could be circumstantial evidence that the positively charged polymyxin B needs negatively charged receptors in biological membranes in order to exert its antibiotic activity.


Micromorphology of Gram-negative hydrogen bacteria. II. Cell envelope, membranes, and cytoplasmic inclusions. The fine structure of the cell envelope, of membrane systems and of cytoplasmic inclusions of Gram-negative aerobic hydrogen bacteria has been studied. The results have been tabulated, and three main groups could be recognized: Group 1: Alcaligenes eutrophus, A.paradoxus, A.ruhlandii, Pseudomonas facilis,   P.flava, P.pseudoflava, P.palleronii, and Aquaspirillum autotrophicum; Group 2: "Corynebacterium" autotrophicum and strains MA 2 and SA 35; Group 3: Paracoccus denitrificans. Special structures related to the chemoautotrophic way of life of the hydrogen bacteria were not observed.


Evidence against involvement of endorphins in sexual arousal and orgasm in man. In a double-blind study, intravenous injection of naloxone, at a dose sufficient to saturate the opiate (endorphin) receptors, had no effect on sexual arousal, penile erection, ejaculation, or orgasm in a human subject. Apparently, endorphins are not involved in these phenomena.


Fluphenazine decanoate, oral fluphenazine, and placebo in treatment of remitted schizophrenics. II. Rating scale data. This study of patients with remitted chronic schizophrenia in an aftercare clinic was designed to test whether such patients require maintenance antipsychotic medication. A previous report showed that the group receiving active medication, fluphenazine decanoate and oral fluphenazine, had far fewer relapses; but the former group had a high incidence of akinesia. This present report presents rating scale data substantiating these two findings: (1) patients terminated on clinical grounds because of a schizophrenic relapse showed rating scale changes consistent with that diagnosis; and (2) the patients removed due to severe akinesia showed a worsening on items selected a priori to measure akinesia, and when compared to survivors on the same items, showed significant differences--thus confirming our clinical judgments.


Life events and schizophrenia. I. Comparison of schizophrenics with a community sample. In exploring the relationship of life events and psychiatric impairment in a group of 132 posthospitalized schizophrenics living in the community, schizophrenics are contrasted with 132 nonpatient community subjects matched on age, race, sex, and social class. Schizophrenics were significantly more psychiatrically impaired than their nonpatient counterparts and experienced significantly more life events. The overall correlation between life events and psychiatric impairment is weaker in the schizophrenic group than in the control group. However, our findings underscore the association between these variables found in previous studies. In terms of specificity, schizophrenics experienced significantly more events in the interpersonal, health, work, legal, and community crisis areas of activity, and more events categorized as exits from the social field and socially undesirable. On the psychological control dimension, schizophrenics experienced significantly more life events categorized both as "controlled" and "uncontrolled". We discuss the findings in relation to studies exploring the relationship of life events to illness onset and show the implications for the delivery of mental health services to schizophrenics living in the community setting.


[On the organization of the mature human placenta (author's transl)]. By means of macroscopic, histologic and enzyme histochemical methods the concept of Schuhmann and Wehler (1971) that the mature human placenta shows a morphological organization coincides with bloodflow-units was examined. The investigation deals with the existence and distribution of terminal villi which can be distinguished on the basis of histological and enzyme histochemical peculiarities. 90 placentas were available, 3 of which were premature. In 6 cases one half of the placenta or the whole organ was cut into serial sections. Mature placentas. Per dissected placenta on an average 6--7 regions with cavities in the intervillous space could be observed, which might correlate to the "placentones" postulated by Schuhmann and Wehler (1971). Using histological techniques at random scattered areas of different size of so-called "immature" villi exist in the near of the basal plate; a relation between these areas and the placentones cannot be seen. All enzymes investigated possess a lower activity in the syncytiotrophoblast of the immature villi than in the mature ones. The demonstration of phosphatases and lysosomal enzymes reveals groups of mature villi with increased activity; they form a patchy enzyme pattern. With the exception of dehydrogenases there is no relation between villi with special enzyme activities and the placentones. Premature placentas. The younger the placenta, the larger is the volume of immature villi. Result. At present a organization of the human placenta into morphological units which correlates to the bloodflow (placentones) cannot be seen. A principle of segmentation which bases on differences between the terminal villi cannot be demonstrated.


Stimulated neutrophil locomotion: chemokinesis and chemotaxis. All leukocytes are capable of responding chemotactically (oriented locomotion) and chemokinetically (stimulated nondirected or random locomotion) to a variety of chemical agents. A brief review of the in vitro and in vivo methods of studying neutrophil movement and our present knowledge of chemotactic factors is presented as well as a discussion on the mechanisms of stimulated movement. Two clinically important instances of defects in neutrophil movement, ie, the Chédiak-Higashi syndrome and a case of actin dysfunction, are herein described.


Clinical, histopathological, and biochemical findings in Fabry's disease. A case report and family study. An extensive enzymatic and morphological study was performed in a 38-year-old patient with Fabry's disease (FD). The quantitative evaluation of the enzyme alpha-galactosidase was shown to be important in identifying the genetic distribution of FD in the family tree of the patient under study. An enzymatic activity less than 0.5 nanomole/hr/10(6) cells and ranging from 2.2 to 1.1 nanomoles/hr/10(6) cells was found in the affected males and the heterozygous females, respectively. alpha-galactosidase activity in the patient's leukocytes correlates well with the histopathological findings of the kidney and skin biopsy specimens, thus demonstrating the need for both of these special examinations for a correct diagnosis of FD.


Adenomyoma: a precursor of extrauterine Müllerian adenosarcoma? One patient had an extrauterine pelvic Müllerian adenosarcoma that recurred on multiple occasions and was originally diagnosed as a benign lesion. Caution is needed in the initial interpretatrion of such lesions as "adenofibromas." We have compared this lesion with a benign adenomyoma of the uterus from a second patient and suggest that such benign neoplasms serve as precursors for Müllerian adenosarcoma in some cases. Light and electron microscopic observations in the first case as well as data from the literature support this hypothesis.


Acidophil stem cell adenoma of the human pituitary. Among 87 pituitary adenomas, four neoplasms had a superficial resemblance to undifferentiated cell adenomas and some fine structural features of both sparsely granulated adenomatous growth hormone and prolactin cells. Misplaced exocytosis, fibrous bodies, and multiple centrioles were sometimes revealed within the same cell and usually were accompanied by oncocytic transformation, mitochondrial alterations, and abnormal centriologenesis. The patients had normal or low blood growth hormone levels and elevated or normal prolactin values. All the tumors that were tested contained immunoreactive growth hormone and prolactin, irrespective of the blood hormone levels. The four tumors could represent a hitherto unclassified adenoma type and derive from the common, committed precursor of the two acidophils. The term acidophil stem cell adenoma is proposed to designate this entity.


Multiple tumors after androgen therapy.

Multiple tumors after androgen therapy. A case of multiple small well-differentiated hepatomas with early peliosis hepatis, multiple pancreatic islet cell tumors, and a renal medullary interstitial cell tumor following five years of androgen and prednisone therapy for idiopathic aplastic anemia is reported in a patient who died shortly after allogeneic bone marrow transplantation. The hepatic tumors were well differentiated, and the pancreatic tumors were of mixed ribbon and islet cell pattern. Therapeutic and experimental implications and the relevant literature are briefly summarized.


Dominant lethal mutations in male mice.

Dominant lethal mutations in male mice. Dominant lethal mutations are due to chromosome aberrations as demonstrated by analysis of first cleavage. With a sample size of 40-45 mice per dose the induction of dominant lethal mutations by 10 mg/kg of methyl methanesulfonat (MMS) can be detected in spermatids in the mating interval 9-12 days posttreatment (6-11%). In the same mating interval a dose of 150 mg/kg of MMS induces 100% dominant lethal mutations. MMS and other chemical mutagens can be characterized by their different spermatogenic response. The germ cell stage specific induction of dominant lethal mutations by chemical agents is very likely due to their different pathways and therefore, to different effects on the structural and macromolecular changes during spermatogenesis. The feasibility of standardizing test protocol for the dominant lethal assay in mice, based on collaborative studies, is discussed. The reproducibility of results and the sensitivity of the induction of dominant lethal mutations in the collaborative studies demonstrate the usefullness of the method for mutagenicity screening.


The role of mammals in the future of chemical mutagenesis research. Radiation genetics has demonstrated that mutagenesis is a complex process affected by many factors. The ABCW hypothesis, that mutation frequency per rad over a wide range of organisms, from microbes to man, is linearly related to DNA content, ignores the fact that, within the mouse alone, different cell stages exhibit a range of mutation rates greater than that listed for the whole evolutionary tree. Also ignored are the findings that the important effects of dose rate and some other factors in the mouse were not predictable even from Drosophila. A much greater maze of complexities has already been found in chemical mutagenesis. This is illustrated even by the results obtained from testing of a single drug. Thus, it is clear that the attempt to extend the ABCW hypothesis to chemicals will be of little, if any, predictive value. Similarly, such concepts as the REC (roentgen-equivalent-chemical), designed to express the mutagenic risk from a chemical by a single unit quantitatively related to radiation damage, are defeated by the extreme qualitative differences in response. Unifying theories and simple non-mammalian tests that reliably predict the results in mammals cannot be expected to materialize until much more information has been collected on transmitted mutations induced in mammalian germ cells.


Cell receptors for paramyxoviruses.

Cell receptors for paramyxoviruses. Treatment of chick embryo fibroblasts, calf kidney and BHK cells for 30 minutes with the enzyme neuraminidase from Vibrio cholerae causes an enhancement of the per cent of attached NDV virions. This enhancement does not depend on the multiplicity of infection. The quantity of spontaneously eluted and cellbound virus is two times greater than the quantity of the same virus derived from control cells. N-acetyl-neuramin lactose inhibits the effect of Vibrio cholerae neuraminidase. After prolonged action of this enzyme, the quantity of adsorbed NDV diminishes. Treatment of the same cells with neuraminidase from influenza virus decreases the per cent of adsorbed NDV with respect to controls. The other paramyxovirus--bovine parainfluenza 3 virus adsorbs also more intensively on cells treated with Vibrio cholerae neuraminidase. It is suggested that partial hydrolysis of NANA molecules causes a rearrangement of the cell surface charged groups and thus allows a more effective contact between paramyxoviruses and the cell.


The effect of ultraviolet light on primary herpes simplex virus infection in the mouse. The effect of irradiation with UV light on herpes simplex virus infection in the mouse ear was investigated. Irradiation 2 days before infection had no effect on the titre of virus in the skin 3 days after infection. In ears irradiated 24 hours or immediately before infection virus titres measured 3 days after infection were depressed. Irradiation 2 days after infection enhanced virus titres. The dose of irradiation used did not directly inactivate herpes simplex virus in the ear. The results are discussed with reference to theories of herpes simplex reactivation.


[Immunohistochemical characteristics of cells of the adenohypophysis producing adrenocorticotropic hormone]. By means of immune fluorescence and histochemical methods, adenohypophyseal corticotropocytes from intact rats and the rats subjected to immobilization stress were studied. The data obtained demonstrated that according to their tinctorial properties, corticotropocytes are chromophobic adenocytes and some of them contain small aldehyde-fuchsinophil and PAS-positives granules. After an acute stress, corticotropocytes secrete ACTH into the intracellular space, and the cytoplasmic processes secrete it into the pericapillar space. Under a prolonged stress, the latter phenomenon prevails.


[Malignant glomus tumor of the jejunum with distant metastases]. An autopsy observation of a malignant glomal tumor (angioleiomyomatotic variant) of rare localization (jejunum) with degeneration, outgrowth through the intestinal wall, and numerous metastases (regional, paratracheal and bifurcational lymph nodes, the liver, lungs) in a man of 65 is described.


Alternating proptosis. A case report of acute orbital myositis defined by the computerized tomographic scan. A 27-year-old woman had a two-week course of acute painful right proptosis with ptosis, medial conjunctival injection, and restriction of eye movements--particularly abduction. One month later, a similar remitting painful left proptosis with complete limitation of abduction developed. Computerized tomographic x-ray scanning showed marked contrast enhancement of both medial rectus muscles, documenting the presumptive diagnosis of acute orbital myositis without recourse to invasive diagnostic techniques. Myositis is a common component of idiopathic orbital inflammatory disease (orbital pseudotumor), but awareness of the rare patient with acute inflammation clinically localized to the extraocular muscles will decrease confusion with cranial nerve and cavernous sinus disease.


Dapsone-induced peripheral neuropathy.

Dapsone-induced peripheral neuropathy. Peripheral neuropathy is a rare complication of dapsone therapy. This neuropathy appears primarily to be of the motor type, and recovery occurs on discontinuation of the drug therapy. The patient in  this report developed a marked motor deficit as well as a selective marked loss of vibration sense shortly after the initiation of a relatively low dose of dapsone. Recovery was rapid on cessation of the therapy. This patient was found to be a slow acetylator of isoniazid, and therefore is probably a slow acetylator of dapsone. The possible mechanisms of the neurotoxicity of dapsone and the role of altered metabolism are discussed.


Endocrine influences on ulceration and regeneration in the alkali-burned cornea. Subconjunctival dibutyryl 3',5' cyclic adenosine monophosphoric acid (DBcAMP) produced a statistically significant reduction of ulceration in the alkaliburned rabbit cornea. No effect on epithelial cell growth was observed. DBcAMP also caused a statistically significant acceleration of corneal neovascularization in the first two weeks postburn. Medroxyprogesterone acetate also affected the development  of corneal ulcers postalkali burn, but in a less well-defined manner. Dinoprost and indomethacin did not seem to influence this lesion. Cyclic adenosine monophosphoric acid may therefore possess a potential for use in the alkali-burned human eye.


Treatment of hypercholesterolaemia with oral lecithin. An open clinical trial was performed to evaluate the plasma cholesterol-lowering potential of oral lecithin in large doses (20--30 g/day), with or without supplementary clofibrate. Three healthy subjects and seven patients with hypercholesterolaemia were studied over periods ranging from eight weeks to 11 months. In one-third of healthy subjects and in 3/7 patients, lecithin therapy led to a significant fall in plasma cholesterol concentration (10--18% fall). Combination of lecithin and clofibrate in two of the patients led to still lower plasma cholesterol levels (21 and 22% fall). Most of the change in plasma cholesterol concentration, when it occurred, was due to a reduction in beta lipoproteins. Evidence is presented that oral lecithin may reduce plasma cholesterol levels by acting as a source of linoleic acid.


Lymphoid leukosis: interrelations among virus infections in hens, eggs, embryos, and chicks. Hens from a commercial source were selected because they were infected with lymphoid leukosis virus (LLV). LLV was detected in vaginal swabs from 17 viremic hens and from 27 of 44 hens that were not viremic. All hens that were positive on the vaginal swab test (VST) produced one or more eggs with virus in albumen or in embryos, whereas in comparable tests, virus was detected only in eggs from 5 of 17 hens that were negative on VST. Congenital transmission of LLV was erratic and neither the VST nor tests for virus in egg albumen prior to incubating eggs identified all hens that transmitted infection. For example, 14 hens negative on VST produced 50 eggs negative for virus in albumen and yet one of the embryos from these eggs was infected. Eggs from other hens had infectious virus in albumen and about half of the embryos from these were infected. Tests for virus in cloacal swabs from one-day-old chicks were as sensitive as tests on embryos for detecting congenital transmission. Titers of LLV in the meconium of congenitally infected chicks were as high as 10(7) infectious units per ml. The cloacal swab test should be a valuable adjunct to the VST and tests on egg albumen in programs designed to eradicate lymphoid leukosis from chickens.


Pathogenicity of low-virulence Marek's disease viruses in normal versus immunologically compromised chickens. To learn whether "low virulence" isolants of Marek's disease (MD) virus have a low inherent oncogenic potential, 3 isolants (CU-1, CU-2, S-11) were given to genetically susceptible S-strain or P-line birds with or without immunosuppressive treatments. Based on lesion incidence and type during an 8-10-week experimental period, embryonal (17-day) bursectomy and neonatal cyclophosphamide (CY) treatment were without effect on CU-1 and CU-2 infections in P-lines. S-11 virus was virulent for P-lines, and CY treatment reduced MD incidence as reported by others for virulent virus infections. Neonatal thymectomy or infection in ovo (at 8 days of incubation) or use of the more susceptible S-strain chicks all increased the incidence of MD induced by CU-1 and CU-2 viruses. It was concluded that the "low virulence" of these viruses is a reflection of an adequate immune response by the host.


Serological response of chickens exposed to a type 1 avian adenovirus alone or in combination with the adeno-associated virus. The avian adenoviruses (AV) are common infectious agents of poultry and other avian species throughout the world (1,4,8). Limited observations suggest that the adeno-associated virus (A-AV) coinfects many of the chickens that carry AV (8). The presence and persistence of these infections in a flock is often determined by serological methods. In the current study, the immune response of chickens to type 1 AV alone and to a dual exposure, AV plus A-AV, was followed over a 12-week period with a variety of serological tests. The study also determined the duration of the viral infections.


Subcellular distribution of superoxide dismutases in human neutrophils. Influence of myeloperoxidase on the measurement of superoxide dismutase activity. We have identified two distinct pools of superoxide dismutase in fractions of human peripheral neutrophils obtained by the isopycnic fractionation of homogenates of the latter with linear sucrose gradients. Superoxide dismutase activity, observed with polyacrylamide gels impregnated with Nitro Blue Tetrazolium, was present in: (1) the mitochondrial fraction [density (rho) 1.169g/ml], containing the high-molecular-weight KCN-resistant enzyme, and (2) the cytoplasm fraction, containing the low-molecular-weight KCN-sensitive enzyme. Superoxide dismutase activity, observed with a quantitative assay involving cytochrome c, was present in: (1) the mitochondria, (2) the cytoplasm, and (3) the azurophil-granule fractions (rho=1.206 and 1.222g/ml). No substantial enzyme activity was observed in specific-granule fractions (rho=1.187g/ml) or in the membranous fraction (rho=1.136g/ml) in either assay. The apparent superoxide dismutase activity observed in the azurophil granules with the cytochrome c assay was attributable not to true superoxide dismutase but to myeloperoxidase, an enzyme found solely in the azurophil granules. In the presence of H(2)O(2), human neutrophil myeloperoxidase oxidized ferrocytochrome c. Thus, in the cytochrome c assay for superoxide dismutase, the oxidation of ferrocytochrome c by myeloperoxidase mimicked the inhibition of reduction of ferricytochrome c by superoxide dismutase. When myeloperoxidase was removed from azurophilgranule fractions by specific immuno-affinity chromatography, both myeloperoxidase and apparent superoxide dismutase activities were removed. It is concluded that there is no detectable superoxide dismutase in either the azurophil or specific granules of human neutrophils. Mitochondrial superoxide dismutase, 15% of the total dismutase activity of the cells, occurred only in fractions of density 1.160g/ml, where isocitrate dehydrogenase and cytochrome oxidase were also observed.


Collagen synthesis in the muscle of developing chick embryos. Radioactive protein was prepared from the leg muscle of chick embryos, 11, 14, 16 and 17 days old, each injected with radioactive proline and incubated for 30, 60 or 90 min afterwards. The radioactive protein was incubated with collagenase purified by chromatography on a Sephadex G-100 column. Under this condition, only collagen is digested into products soluble in trichloroacetic acid. The relative rate of collagen synthesis was determined by comparing the amount of radioactivity released into the supernatant fraction and that in the residue, by the method of Diegelmann & Peterkofsky [(1972) Dev. Biol. 28, 443--453]. The results show that the rate of collagen synthesis remains at approx. 10% of the rate of synthesis of other non-collagenous proteins during the development of chick embryonic muscle from 11 to 17 days. This suggests that the synthesis of collagen and that of other proteins are co-ordinately regulated at these stages of development.


Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. 1. The subcellular distribution of adenine nucleotides, acetyl-CoA, CoA, glutamate, 2-oxoglutarate, malate, oxaloacetate, pyruvate, phosphoenolpyruvate, 3-phosphoglycerate, glucose 6-phosphate, aspartate and citrate was studied in isolated hepatocytes in the absence and presence of glucagon by using a modified digitonin procedure for cell fractionation. 2. In the absence of glucagon, the cytosol contains about two-thirds of cellular ATP, some 40-50% of ADP, acetyl-CoA, citrate and phosphoenolpyruvate, more than 75% of total 2-oxoglutarate, glutamate, malate, oxaloacetate, pyruvate, 3-phosphoglycerate and aspartate, and all of glucose 6-phosphate. 3. In the presence of glucagon the cytosolic space shows an increase in the content of malate, phosphoenolpyruvate and 3-phosphoglycerate by more than 60%, and those of aspartate and glucose 6-phosphate rise by about 25%. Other metabolites remain unchanged. After glucagon treatment, cytosolic pyruvate is decreased by 37%, whereas glutamate and 2-oxoglutarate decrease by 70%. The [NAD(+)]/[NADH] ratios calculated from the cytosolic concentrations of the reactants of lactate dehydrogenase and malate dehydrogenase were the same. Glucagon shifts this ratio and also that of the [NADP(+)]/[NADPH] couple towards a more reduced state. 4. In the mitochondrial space glucagon causes an increase in the acetyl-CoA and ATP contents by 25%, and an increase in [phosphoenolpyruvate] by 50%. Other metabolites are not changed by glucagon. Oxaloacetate in the matrix is only slightly decreased after glucagon, yet glutamate and 2-oxoglutarate fall to about 25% of the respective control values. The [NAD(+)]/[NADH] ratios as calculated from the [3-hydroxybutyrate]/[acetoacetate] ratio and from the matrix [malate]/[oxaloacetate] couple are lowered by glucagon, yet in the latter case the values are about tenfold higher than in the former. 5. Glucagon and oleate stimulate gluconeogenesis from lactate to nearly the same extent. Oleate, however, does not produce the changes in cellular 2-oxoglutarate and glutamate as observed with glucagon. 6. The changes of the subcellular metabolite distribution after glucagon are compatible with the proposal that the stimulation of gluconeogenesis results from as yet unknown action(s) of the hormone at the mitochondrial level in concert with its established effects on proteolysis and lipolysis.


Membrane cholesterol and cell fusion of hen and guinea-pig erythrocytes. 1. The cholesterol content of hen erythrocytes was modified by treating the cells with phospholipid liposomes. 2. Depletion of cellular cholesterol, by using liposomes of dipalmitoylglycerophosphocholine or phosphatidylcholine from hen erythrocytes, had no effect on the susceptibility of the cells to fusion induced by oleoylglycerol, but markedly decreased fusion induced by Sendai virus. 3. By contrast, enrichment of cellular cholesterol by using liposomes of dipalmitoylglycerophosphocholine and cholesterol increased cell fusion induced by oleoylglycerol, poly(ethylene glycol) and Sendai virus. 4. Virus-induced cell fusion of guinea-pig erythrocytes, which were enriched in cholesterol by feeding a cholesterol-rich diet to the animals, was also enhanced. 5. Hen erythrocytes that were treated with liposomes prepared from egg phosphatidylcholine contained increased quantities of phospholipid phosphorus and fused readily on incubation with retinol, independently of their cholesterol content. 6. It is suggested that cholesterol may enhance cell fusion by acting to facilitate a phase separation of protein-free areas of lipid bilayer, which subsequently provide the sites for cell fusion.


[Studies on the mechanism of action of clonidine (author's transl)]. The effects of 3.7-120 microgram 2-(2,6-dichloro-anilino)-2-imidazoline (clonidine, Catapresan)/kg i.v. on the arterial blood pressure and the central nervous activities of sympathetic and phrenic nerves were studied in 42 anaesthetized cats which had been relaxed and artificially respirated. At the dosage 3.7-30 microgram/kg clonidine produced a moderate fall of blood pressure and a more distinct sympathetic inhibitory effect. At a dosage of 60-120 microgram/kg an increase of the hypotensive action was not observed whereas the central nervous inhibition increased with the dosage. The activity of the respiratory centre remained constant. The pressor effects as well as the sympathetic stimulation effects of nicotine, nicetamide or asphyxia were reduced by the treatment with clonidine. At a dosage of 3.7-30 microgram clonidine/kg, i.e. including the 6fold therapeutic dosage, the inhibition of the evoked sympathetic activity was, however, considerably weaker than the inhibition of the sympathetic activity at rest. Therefore clonidine at a therapeutic dosage probably causes an activation of the central part of the pressor-receptor reflexes and as a result a decrease of the central sympathetic activity and the moderate fall in blood pressure. At a higher dosage the absence of increasing hypotensive effect in spite of increasing sympathetic inhibition is probably caused by a stimulation of peripheral postsynaptic alpha-adrenoreceptors.


Studies of plasma viscosity in primary hyperlipoproteinaemia. Using an Ubbelohde capillary viscometer, viscosity was determined in the plasma of 39 patients with a primary hyperlipoproteinaemia (type IIa, n=13; type IV, n=12; type IIb, n=14), in isolated lipoprotein fractions as well as in sera which differed only in their lipoprotein concentration. Plasma viscosity of the patients with hyperlipoproteinaemia was compared to that of a normolipidaemic control group and correlated with the lipid fractions characteristic of the different hyperlipoproteinaemia types. Plasma viscosity in types IIa, IV and IIb was found to be significantly higher than in the control group. Of the different hyperlipoproteinaemia types, IIa exhibited the lowest and IIb the highest plasma viscosity levels. The elevation of plasma viscosity was correlated with the concentration of lipoproteins (lipid fractions). In viscosity measurements of sera which varied only in lipoprotein concentrations, a correlation between the increase of viscosity and lipoprotein concentration as well as a greater efficiency of VLDL fractions was observed, similar to the viscosity results from isolated lipoproteins.


Elastin sub-fraction as binding site for lipids. Elastin preparations were isolated from human thoracic aorta, from atherosclerotic and from grossly normal regions. A relatively mild procedure was used to avoid hot alkaline extraction and autoclaving. The elastase digest of the aortic elastin was chromatographed on a Sephadex G-100 column and separated into two fractions: A (larger molecular weight) and B (smaller molecular weight). The ratio of fraction A to total aortic elastin increased with age and the development of the atherosclerosis. Amino acid and sugar analyses showed that fraction A consistently contained more polar amino acids, hexose, hexosamine and L-fucose, and less sialic acid, in comparison with fraction B. Part of the elastin preparation was incubated with human low-density lipoprotein; a considerable amount of lipid, especially cholesterol, was transferred from the lipoprotein to the elastin. Estimation of protein and cholesterol in fractions A and B of the elastase hydrolyzate of incubated elastin showed that most of the cholesterol taken up by elastin had been in fraction A. The increased proportion of fraction A in aortic elastin derived from plaque areas appeared responsible for the marked lipid-binding capacity of plaque elastin.


Biochemical and immunological evidence for the presence of an apolipoprotein B-like component in the serum low-density lipoproteins of several animal species. The major component of the protein moiety of human LDL, i.e. apolipoprotein B, has been compared biochemically and immunologically with its counterpart in the LDL of several groups of animals (mammals, birds, snakes and fish). A marked resemblance was found in the amino acid composition of the apo-B fractions from all the phylogenetic groups, although immunological cross-reactivity with human apolipoprotein B occurred only in the case of non-human primate (Old World monkey), non-primate mammalian (pig and guinea pig) and bird (chicken) apo-B components (63%, 24% and about 8% respectively). The cross-reactivity of each animal apo-B component with its human counterpart was 7-14% lower than that observed between the parent LDL's. The resemblance in amino acid composition between the various apo-B preparations suggests that certain structural characteristics are required in this protein in order for it to bind and stabilise the lipid complement of serum LDL.


[Wilms' tumor, multiple intestinal parasitosis and typhoid fever]. The case was that of a 21-month-old infant who presented a great inoperable Wilm's tumor that was treated with vincristine to the point of practically disappearing. Severe typhoid fever that was complicated by multiple intestinal parasitoses (ascariasis, trichuriasis, giardiasis and strongyloidiasis) appeared. Possibly, tumoral necrosis, salmonellosis and the parasitoses formed a sac that opened to the hepatic angle of the colon. Finally, multiple liver metastases were discovered and confirmed pathologically. The patient died 36 hours after surgical reexamination and liver biopsies, from causes not clearly explained. Comments are made on the diagnostic problems originated by rareness of the association of typhoid fever resistant to chloramphenicol, intestinal parasitoses and a great Wilms' tumor and the possible influence of chemotherapy and radiotherapy in the evolution of the case.


[Juvenile nasopharyngeal angiofibroma with intracraneal lesion. Report of a case]. A case of juvenile nasopharyngeal angiofibroma in a 9 years and 8 months old male child is reported. Histologically it is considered a mild tumor, but because of its rapid growth and great surgical risk, it is clinically considered malignant. Surgery is the most important factor.


[Review of 15 cases of hypervitaminosis D]. In our experience, hypervitaminosis D, which at present should only be a historic remembrance in pediatrics, is still a frequent cause of hipercalcemia in childhood. It is easy understand that its appearance should turn out to be a complication in the treatment of hypoparathyroidisms or in vitamin D resistant rickets, but its persistance as a purely iatrogenic diseases is at present inexplicable. The frequency with which we have seen it has led us to review 15 cases where erroneous administration of high doses of vitamin D has resulted in serious clinical, biological and anatomical problems.


[Rotavirus in children with severe malnutrition]. The study comprised 19 children with severe protein-calorie malnutrition admitted to Hospital Nacional de Niños. With one exception, all of the patients complained of diarrhea at the examination. Samples of stools were collected for bacteriologic, parasitologic and virologic studies. Rotavirus was shown in 4 cases and adenovirus in another 4. Enteropathogenic Escherichia coli, Shigella and Salmonella were isolated in 9 different children. It was possible to demonstrate at least one potentially pathogenic agent in 84% of the total number of cases. In malnourished infants under one year of age, the index of positiveness was 100%. It is set forth that infection is the most important factor in the etiology of diarrhea of the malnourished infant.


The effect of age on the safety factor in neuromuscular transmission in the isolated diaphragm of the rat. An analysis of neuromuscular transmission has been made in phrenic nerve/diaphragm preparations from male rats aged 30 days or 110 days. The amplitude of miniature end-plate potentials was found to decrease with age, being 0.969 +/- SEM 0.058 mV at 30 days and 0.510 +/- SEM 0.031 mV at 110 days. Over the same period, the quantum content of the first end-plate potential of a train of 40 at 10 Hz, increased from 144.5, SEM + 11.1, -10.4 to 346, SEM +41.4, -37.0. A corresponding change was observed also in the average quantum contents of the last 30 end-plate potentials of each train; from 50.6, SEM +3.5, -3.2, to 138.9, SEM + 15.0,--13.6. The safety factor for neuromuscular transmission, calculated from these measured parameters, was found at 30 days to be only 70-80% of that at 110 days. It was estimated that the lower safety factor found in young rats was approximately equivalent to the neuromuscular blocking action of a dose of, at least, 0.0225 mg/kg of d-tubocurarine. Extrapolation of these results to man would support previous reports of increased sensitivity to d-tubocurarine in neonates.


Studies on brain metabolism of biogenic amines. 1. In vitro models (synaptosones, electrically stimulated brain slices and monoamine oxidase (MAO) preparations have been used to identify the sites of action of nomifensine on brain monoamine metabolism. 2. Nomifensine potentiates neurotransmission in noradrenergic and dopaminergic synapses by blocking catecholamine uptake. 3. Nomifensine does not inhibit MAO and does not enhance the release of biogenic amines. 4. Studies on electrically stimulated brain slices suggest that nomifensine does not directly stimulate dopamine (DA) nor noradrenaline (NA) receptor sites. 5. 5-Hydroxytryptamine (5-HT) uptake is not inhibited at "therapeutic" concentrations of nomifensine. 6. Nomifensine differs from the tricyclic antidepressants by virtue of its effect on the dopaminergic system.


Comparison of cell-surface glycoproteins of rat hepatomas and embryonic rat liver. Cell-surface glycoprotein of 3 rat hepatoma strains and late-embryonic liver was metabolically labelled in vivo with [3H]- or [14C]-fucose. Trypsinization of the cells and exhaustive pronase digestion of combined hepatoma-liver trypsinates followed by gel filtration over Sephadex-Biogel mixtures, yielded elution profiles that contained more early-eluting (high-mol.-wt.) glycopeptides for hepatomas than for liver. At least 3 factors were identified which acted to augment the fraction of early-eluting tumour glycopeptides: (a) increase of neuraminidase-sensitive sialic acid, (b) increase of neuraminidase-insensitive sialic acid that was sensitive to mild HCl hydrolysis, and (c) presence of sugar sulphate groups contributing to a restricted extent, relative to possible unknown factor(s). Whether (a), (b) or (c) operated depended on the hepatoma strain or its mode of growth. Notwithstanding these differences in the nature of the increase in early-eluting glycopeptides, the increase itself appears not to be due to growth per se, nor to an embryonic expression, but rather may serve as a marker of tumourigenicity.


Radioiodination studies of tumour cell-surface proteins after different disaggregation procedures. The surface of single cells isolated from solid tumours by either a mechanical or an enzymatic method have been compared, using lactoperoxidase-catalyzed radioiodination of the tyrosine-containing proteins. Qualitatively, the patterns of surface labelling were similar, and duplicate experiments indicated that each method of isolation gave reproducible results. Analysis of incorporated label into 4 defined sections of the electrophoretic pattern illustrated quantitative differences. When the cells were isolated mechanically, the incorporation into low-mol.- wt. components was considerably reduced, whereas that into the high-mol.-wt. components was unaffected. Treatment of enzymatically isolated cells with trypsin also reduced incorporation into low-mol.-wt components.


Null-cell properties of a lymphoid cell line from a child with acute lymphoblastic leukaemia. Cultured cells established from the bone marrow of a child with null-cell acute lymphoblastic leukaemia (ALL) have been studied. After 8 months in vitro, the cytological, cytochemical and immunological properties of the cultured cells were very similar to those of the patient's cells. Many of the cultured cells had morphological and cytogenetic abnormalities often found in acute leukaemia. The cells were EBNA-negative. This unique culture of ALL-derived null cells might provide information as to the aetiology and origin of malignant cells.


Hepatic cell loss and proliferation induced by N-2-fluorenylacetamide, diethylnitrosamine, and aflatoxin B1 in relation to hepatoma induction. Three hepatic carcinogens (aflatoxin B1, diethylnitrosamine (DEN) and N-2-fluorenylacetamide (FAA)) were compared for carcinogenicity, early cell toxicity and parenchymal cell proliferation. The carcinogens were administered to rats for 15 weeks as follows: aflatoxin B1, 1 in 10(6) in pelleted food; DEN, 2 in 10(5) in drinking water; FAA, 3 in 10(4) in pelleted food. The loss of prelabelled DNA and the [H3] TdR pulse-labelling indices (LI) of parenchymal and nonparenchymal cells were determined at various times during the period of carcinogen availability. On a molar basis, aflatoxin B1 was 90 times as carcinogenic as FAA and 24 times as carcinogenic as DEN. However, for about equal magnitudes of hepatic cell proliferation and loss, aflatoxin B1 was the least potent carcinogen. For a given level of carcinogenicity, FAA was more potent than DEN in causing loss of hepatic DNA and in increasing the parenchymal cell labelling index. DEN and aflatoxin B1 produced about the same degree of DNA loss and parenchymal cell labelling, but the former was a more potent carcinogen. When carcinogenicity was compared for approximately equal levels of early hepatic cell destruction and proliferation, the 3 chemicals in the present study could be ranked in descending order of potency as DEN, FAA and aflatoxin B1.


The effect of macrophage poisoning by silica on experimental pulmonary contusion and its benzo-pyrone treatment. The effect of poisoning the macrophages with silica on the fine structure of pulmonary contusion was studied in rats. It was found that this causes an increase in the concentration of protein in the interstitial tissue and in the air spaces. It also causes a consequent increase in the amount of interstitial oedema. While the benzo-pyrones normally cause a considerable reduction both in the protein concentrations and in the amount of oedema, they do not act in these ways when the macrophages are poisoned. These results imply that the macrophages normally lyse some of the protein and that this effect is considerably enhanced by the action of the benzo-pyrones.


Pregnancy complicated by insulinoma. Case report. An insulinoma was excised during pregnancy. The tumor was located by radiography and severe hypoglycaemia made it necessary to administer diazoxide to the mother. The out come in the pregnancy was satisfactory. The rationale and risks of giving diazoxide in pregnancy are discussed.


Hydatidiform mole arising twice during bromocriptine therapy. Case report. A patient with a prolactin secreting pituitary tumour is described, in whom two pregnancies occurred during bromocriptine treatment. Both were hydatidiform moles.


Effect of phosphonoacetic acid in the treatment of experimental herpes simplex keratitis. In the rabbit 5% phosphonoacetic acid ointment suppressed herpetic keratitis as well as 0-5% idoxuridine ointment. After 5 days of treatment quantitative virus titres showed that phosphonoacetic acid was superior to idoxuridine in the inhibition of herpes virus replication. Phosphonoacetic acid was found to be nontoxic to the eye in both clinical and histopathological studies. Recent reports suggest that the mechanism of action of phosphonoacetic acid appears to be the blocking of the virus DNA polymerase, which is essential for the synthesis of herpes virus DNA.