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Biomedical subjects

J Brown

Publications and source records attributed to J Brown.

At least 19 recordsLinked to original sources
PubMed2001

MEK kinase activity is not necessary for Raf-1 function.

Raf-1 protein kinase has been identified as an integral component of the Ras/Raf/MEK/ERK signalling pathway in mammals. Activation of Raf-1 is achieved by RAS:GTP binding and other events at the plasma membrane including tyrosine phosphorylation at residues 340/341. We have used gene targeting to generate a 'knockout' of the raf-1 gene in mice as well as a rafFF mutant version of endogenous Raf-1 with Y340FY341F mutations. Raf-1(-/-) mice die in embryogenesis and show vascular defects in the yolk sac and placenta as well as increased apoptosis of embryonic tissues. Cell proliferation is not affected. Raf-1 from cells derived from raf-1(FF/FF) mice has no detectable activity towards MEK in vitro, and yet raf-1(FF/FF) mice survive to adulthood, are fertile and have an apparently normal phenotype. In cells derived from both the raf-1(-/-) and raf-1(FF/FF) mice, ERK activation is normal. These results strongly argue that MEK kinase activity of Raf-1 is not essential for normal mouse development and that Raf-1 plays a key role in preventing apoptosis.

Animals↗
PubMed1991

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.

A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene.

Alzheimer Disease↗
PubMed1979

Fungal peritonitis and malignancy: report of two patients and review of the literature.

Two patients developed isolated Candida albicans peritonitis in association with intraabdominal malignancy. Although additional factors predisposing to the development of fungal peritonitis were present, we postulate that tumor-related local factors permitted fungi to cross the gut wall and to enter the peritoneum, where the host immune status determined whether the infection spread. These two cases are the sixth and seventh reported cancer patients who developed fungal peritonitis, but the first two who had the fungal infection localized to the peritoneum; and this is the first report known to us specifically associating intraabdominal malignancy and fungal peritonitis. Patients who develop fungal peritonitis may have a primary or metastatic intraabdominal malignancy, and fungi should be considered as a cause of peritonitis in cancer patients.

Abdominal Neoplasms↗
PubMed1979

Incidence of abnormal haemoglobin traits among Gambian children.

The electrophoretic mobility of haemoglobin from 343 Gambian children between the ages of two months and ten years has been investigated. The incidence of Hb-S and Hb-C traits is described and compared with earlier reports on the distribution of these traits in The Gambia. One child was identified as having the rare haemoglobin, Hb-A + N.

Child↗
PubMed1979

Extended pelvic lymphadenectomy for prostatic cancer.

Thirty patients with clinically localized prostatic carcinoma underwent extended pelvic lymph-adenectomy, including the presacral and presciatic (lateral sacral) areas. The first echelon of pelvic nodes to be involved by metastases was the external iliac, obturator, presacral and presciatic. The deep presacral-presciatic nodes were involved almost as often as the more superficial external iliac-obturator group. Metastases limited only to the deep pelvic nodes were found in 14 per cent of the cases.

Adenocarcinoma↗
PubMed1979

Selective antagonism by benzodiazepines of neuronal responses to excitatory amino acids in the cerebral cortex.

1 The recently discovered benzodiazepine receptor exists in high concentration in the cerebral cortex. We have, therefore, examined the effects of diazepam and chlordiazepoxide on cortical neurone responses to excitatory and inhibitory amino acids and acetylcholine, in the cortex of rats anaesthetized with urethane.2 Chlordiazepoxide applied by microiontophoresis reduced the responses to glutamate and aspartate but acetylcholine responses were unaffected on most cells even by much higher doses of benzodiazepine. gamma-Aminobutyric acid (GABA) and taurine responses were unaffected on most cells, but were reduced on 4 of 25 units. After intravenous diazepam, responses to GABA and taurine were reduced on 3 cells and unchanged on 11.3 On Purkinje cells in the cerebellum a number of cells (5 of 16) exhibited a substantial increase in responses to GABA and taurine following intravenous or iontophoretic application of benzodiazepines.4 It is suggested that the highly selective reduction of excitatory amino acid responses in the cerebral cortex may be of particular relevance to the behavioural effects of benzodiazepines.

Acetylcholine↗
PubMed1979

Lesions of swine lymph nodes as a diagnostic test to determine mycobacterial infection.

Decisions as to the disposition of swine carcasses with lesions attributable to a mycobacterial infection are based upon a lesion criterion which is used as a diagnostic test by federal meat inspectors. Using this criterion, a federal meat inspector classified 58 of 100 pigs as "passed for cooking" and the other 42 pigs passed. Of the 58 pigs passed for cooking and the 42 pigs passed, mycobacterial isolations were made from the lymph nodes of 33 and 15 of the animals, respectively. The lesion criterion as a diagnostic test has the following attributes: 70% sensitive; 53% specific; 23% index of performance; 57% positive accuracy; and 67% negative accuracy.

Animals↗
PubMed1979

Influence of pork consumption on human infection with Mycobacterium avian-intracellulare.

The hypothesis that eating pork from animals infected with organisms of the Mycobacterium avium-intracellular complex is a significant cause of human mycobacteriosis was examined by skin testing students with purified protein derivative from M. intracellulare to determine their sensitivity to M. avium-intracellulare. No significant differences in sensitivity could be demonstrated between those individuals who had never eaten pork and those who ate pork routinely. It was concluded that sensitivity to purified protein derivative from M. intracellulare in this population did not involve eating pork.

Animals↗
PubMed1979

Importance of hepatic portal circulation for insulin action in streptozotocin-diabetic rats transplanted with fetal pancreases.

The importance of the hepatic portal circulation in the response to insulin was assessed in streptozotocin-diabetic rats transplanted with syngeneic fetal pancreases. Partial reversal of diabetes was accomplished by transplantation of two or three fetal pancreases beneath the capsule of the kidney; complete reversal followed shunting of the venous drainage from the transplants to the liver. Plasma glucose after streptozotocin of 509+/-31 mg/dl (mean+/-SEM) fell after transplantation to 395+/-23 and after the shunt to 143+/-5 mg/dl. Urine volume fell from 84+/-4 to 50+/-5 ml/d and then to normal (17+/-1 ml/d) after the shunt. Glucose excretion which was 8.1+/-0.3 g/d after streptozotocin fell after transplantation to 4.8+/-0.3 g/d and after the shunt completely disappeared from the urine. The disappearance rate of glucose injected into the circulation, which was 0.50+/-0.07%/min in untreated diabetes, increased to 1.39+/-0.38%/min after transplantation and to 2.52+/-0.31%/min after the shunt, not different from normal controls (2.79+/-0.25). Plasma immunoreactive insulin (IRI) was below normal (25-35 muU/ml) and unresponsive to glucose in untreated diabetic rats. After transplantation IRI levels ranged from 73-223 muU/ml and there was no rise after glucose injection. After the shunt both the basal IRI (36+/-5 muU/ml) and the peak response to glucose at 10 min (58+/-7 muU/ml) were the same as in normal controls (42+/-4 and 62+/-7 muU/ml, respectively). The fall in IRI after the shunt is explained by increased extraction of insulin passing into the liver and also diminished secretion. After removal of the transplants plasma glucose and urine values returned almost to pretransplant levels. Secretion of insulin by transplanted pancreases into the liver enhances the effectiveness probably by increased extraction and action and reveals the importance of the normal route for insulin delivery.

Animals↗
PubMed1979

Drowning and near-drowning involving children: a five-year total population study from the City and County of Honolulu.

A study of all serious childhood immersion accidents (both drowned and near-drowned cases) is reported from Hawaii. This is a total population-based survey of 140 consecutive cases (0--15 years) occurring during the five-year period (1973--1977. Age-specific, sex-specific, and osmolality-specific (salt versus fresh water) data are presented both for survivors and fatalities. The overall annual drowning rate of 3.1 per 100,000 children at risk is low, for a water-oriented society. The survival rate following loss of consciousness in the water is 73 per cent. There is no evidence from this study that osmolality affected the probability of survival. The rank order of importance of drowning sites is swimming pools, surf, sheltered salt water bathing, domestic bath tubs, fresh water streams, salt water canals, and garden fish ponds. Specific accident rates, by sex, outcome, and site of immersion are also presented. No secular trend in the rate of drowning was observed in this study. Comparison with the only other available total population survey (Australia) of childhood immersions reveals common epidemiological and demographic patterns in modern urban societies and suggests that safety regulations play a role in reducing swimming accidents and fatalities in children.

Adolescent↗
PubMed1979

Direct Coombs antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. I. Incidence and class specificity.

Gambian children with past or present Plasmodium falciparum malaria were investigated for the incidence of Coombs positivity using monospecific antisera. Approximately 50% were positive and the most frequent form of erythrocyte sensitization was with C3d. Other specificities, EIgG, EIgGC3d and EIgGC4bC3d were less common. Erthyrocytes were never found sensitized with IgA or IgM. There was no correlation between a positive test and age, tribal status or level of parasitaemia at presentation, although a positive test was often found in association with anaemia. Sensitized erythrocytes were present in the circulation for a period of up to 6 weeks following initial observation. The mechanism of erythrocyte sensitization is not known, but the results suggest a Type III complex-mediated hypersensitivity involving parasite antigen-antibody complexes. It is likely that these reactions contribute to the pathogenesis of the anaemia in falciparum malaria.

Anemia↗
PubMed1979

Isolation of Klebsiella pneumoniae from the urogenital tract of experimentally infected mares.

K. pneumoniae capsule type 68 infused into the uterus of 4 mares was recovered up to 15 weeks after inoculation. The insertion of a tampon for 10 min was more effective than a swab technique in detecting the organism in the uterus. The clitoral fossa and the urethral orifice when sampled by the swab technique were also found to be infected for a comparable period. K. pneumoniae was isolated from the clitoral specimens more often and more consistently than from either urethral or uterine specimens.

Animals↗
PubMed1979

Bathtub drownings: report of seven cases.

The domestic bathtub is an important site for infant drownings. A total population study of drowning and near-drowning accidents involving Honolulu infants has enabled the risks to be specified with greater detail. A series of seven consecutive bathtub immersion accidents is presented. The "at risk" profile comprises highly mobile families of lower socioeconomic status; usually younger siblings in larger families are involved and often the father had immediate care of the infant at the time of the accident. Another case of bathtub immersion as a form of nonaccidental injury is described. In five of the other six cases reported, the drowned child was left attended by an older sibling. Preventive strategies are discussed.

Accidents, Home↗
PubMed1979

Increased survival in experimental dog heatstroke after reduction of gut flora.

A study was undertaken to determine if gut flora contribute to the pathophysiology of experimental canine heatstroke. Fifty animals in four groups were anesthetized with sodium pentobarbital (25 mg/kg) intravenously. An air temperature of 42-46 degrees C was maintained adjacent to the dog with a water-heated blanket for approximately 2 h until rectal temperatures rose to 43.5 +/- 0.4 degrees C. Animals were then cooled passively in room air (28 degrees C, 20% RH) until death or until 18 h elapsed, and were euthanized. Reduction of intestine stool and bacterial contents with antibiotics, cathartics, and enemas prior to heatstroke increased the incidence of 18-h survival from 20.0% to 70.6%; antibiotics administered after heatstroke did not alter the incidence of survival over control values. These data suggest that gut flora, presumably through endotoxemia, contribute to the evolution of heatstroke pathophysiology.

Animals↗