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Biomedical subjects

M E Bailey

Publications and source records attributed to M E Bailey.

At least 37 records · Page 2Linked to original sources

Schizophrenia and GABAA receptor subunit genes.

Alterations in gamma-aminobutyric acid (GABA) neurotransmission have been indirectly implicated in the pathogenesis of schizophrenia. Using nine multiplex pedigrees, we tested for linkage between schizophrenia and simple sequence repeat polymorphisms for the GABAA receptor alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, beta 1 and beta 3 subunit genes. Evidence of linkage was not found when assuming either autosomal dominant or autosomal recessive inheritance. The non-parametric sib pair test also did not reveal significant evidence of deviation from expected segregation ratios.

Genes, Dominant↗

Further evidence for clustering of human GABAA receptor subunit genes: localization of the alpha 6-subunit gene (GABRA6) to distal chromosome 5q by linkage analysis.

GABAA receptors are hetero-oligomeric ion-channel complexes that are composed of combinations of alpha, beta, gamma, and delta subunits and play a major role in inhibitory neuro-transmission in the mammalian brain. We report here a microsatellite polymorphism within the human alpha 6-subunit gene (GABRA6). Mapping of this marker in a human-hamster hybrid cell-line panel and typing of the repeat in the Centre d'Etude du Polymorphisme Human (CEPH) reference families enabled the localization of this gene to chromosome 5q and established its linkage to the GABAA receptor alpha 1-subunit gene (GA-BRA1) with a maximum lod score (Zmax) of 39.87 at a theta of 0.069 (males) and 0.100 (females). These results reveal the clustering of GABRA6, GABRA1, and the GABAA receptor gamma 2-subunit gene (GABRG2) on distal chromosome 5q.

Animals↗

Pulmonary histopathology in cocaine abusers.

Lung histopathology was reviewed from 52 autopsies with positive toxicologic tests for cocaine from the medical examiners' offices in Dallas and Austin, TX. The median patient age was 34.7 years, and the male to female ratio was 2:1. Twelve individuals primarily used the drug intravenously and six primarily smoked it, but in most patients usage history was not known. The most frequent manner of death was accidental, consisting predominantly of cocaine overdoses. Other frequent manners of death included both natural causes and homicides. Subjects with chest trauma were excluded from the study. Twenty-three age-matched control cases with negative cocaine histories and toxicologic tests also were obtained from medical examiner autopsies. Histopathologic findings in the cocaine abuse group included acute hemorrhage, 58% (P = .05); chronic hemorrhage, 40% (P < .01), interstitial pneumonitis/fibrosis, 38% (P < 0.01); congestion, 88% (P < .01); and intra-alveolar edema, 77% (P < .01). These changes were remarkably consistent regardless of locale or method of use. Our findings demonstrate that pulmonary hemorrhage is more frequent than suggested by clinical hemoptysis and that chronic pulmonary diseases such as interstitial fibrosis may develop in long-term users.

Adult↗

Analysis of GABAA receptor subunit genes in multiplex pedigrees with manic depression.

The gamma-aminobutyric acid (GABA) neurotransmitter system has been implicated in the pathogenesis of manic depression. Tests of this hypothesis can now be carried out due to the recent characterization of simple sequence repeat polymorphisms for the GABAA receptor alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, beta 1, beta 3 and gamma 2 subunit genes. Using both parametric and non-parametric methods, we tested for linkage between manic depression and these polymorphisms in six multi-generational pedigrees. No evidence of linkage was found.

Adolescent↗

The SON gene encodes a conserved DNA binding protein mapping to human chromosome 21.

We report the identification and characterization of a clone for the DNA binding protein SON, which we have isolated from a human keratinocyte cDNA library. Using this clone we have found that the SON gene is expressed in different cell types and that homologous sequences can be detected in vertebrate and insect genomic DNA. Using the polymerase chain reaction (PCR) to amplify SON sequences from a panel of somatic cell hybrids we have assigned the gene encoding human SON to chromosome 21. By use of hybrids containing regions of chromosome 21 the localization has been refined to 21q 22.1-q22.2.

Amino Acid Sequence↗

Parathyroid hormone related peptide gene expression in human fetal and adult heart.

OBJECTIVE: The aim was to investigate the expression of parathyroid hormone related peptide (PTHrP) gene in the human fetal and adult heart. METHODS: Molecular biological techniques were employed as well as immunocytochemistry and western blot analysis using rabbit polyclonal anti-PTHrP(1-34) and anti-PTHrP (56-86) on normal human fetal and adult heart tissues. Northern blot analysis of both normal human fetal and adult heart total RNA, using a human full length cDNA probe, and polymerase chain reaction analysis of normal human fetal and adult heart cDNAs with exon specific oligonucleotides were carried out. RESULTS: Positive staining was detected with both anti-PTHrP(1-34) and anti-PTHrP(56-86) in fetal heart at 12 weeks of gestation. In both fetal and adult hearts, multiple putative PTHrP proteins were observed with apparent molecular mass of 14-125 kDa. Multiple hybridising PTHrP mRNA isoforms (1.4, 2.1, 3.2, and 4.5 kb) were detected in both fetal and adult heart total RNAs. The fetal and adult heart cDNAs amplified from the cDNA libraries showed the presence of the 5' non-coding exon II and coding exons III-IV but not the 5' non-coding exon Ic. CONCLUSIONS: PTHrP is expressed in normal human fetal and adult hearts suggesting that it has a function as an endogenous modulator of the cardiovascular system.

Adult↗

Antioxidant defenses in the bile duct-ligated rat.

Changes in pro-oxidant and antioxidant balance in the serum and liver were studied in an experimental model of obstructive jaundice in the rat. The results showed a decrease in plasma vitamin E concentration (P < 0.01) and a threefold reduction in liver vitamin E concentration (P < 0.001). There was also a threefold reduction in levels of the liver enzymes glutathione peroxidase (P < 0.01) and glutathione transferase (P < 0.001), together with a six-fold reduction in catalase activity (P < 0.001). The serum selenium level decreased by 35% in the jaundiced rats (P < 0.05). The total liver glutathione level decreased to half the control value (P < 0.01). The malonyldialdehyde level, the measure of lipid peroxidation used in this study, doubled (P < 0.01). The results suggest a shift in the pro-oxidant/antioxidant balance in favor of lipid peroxidation. The possible etiology of this change and its relationship to human cholestasis are discussed.

Animals↗

Prevention of postoperative renal dysfunction in patients with obstructive jaundice: a multicentre study of bile salts and lactulose.

The role of preoperative lactulose and bile salts in the prevention of postoperative renal failure in patients with obstructive jaundice has been evaluated in a prospective randomized trial. One hundred and two patients undergoing surgery for obstructive jaundice (bilirubin greater than 100 mumols/l) were randomized into three groups: those receiving preoperative oral lactulose (n = 35), those receiving oral sodium deoxycholate (n = 32) and a control group of patients receiving no specific treatment (n = 35). All patients received intravenous fluids commencing the night before surgery. One patient in the control group and none in the treatment groups developed postoperative renal failure. Postoperative deterioration of renal function in patients with normal preoperative function was significantly more common in the control group than in the treatment groups (chi 2 = 8.1, d.f. = 2, P less than 0.02). The incidence of renal failure and impairment was lower in this control group than that reported in previous studies. This may be due to the introduction of adequate preoperative hydration. Additional protection occurs by the preoperative administration of either lactulose or sodium deoxycholate.

Acute Kidney Injury↗

The 'topping-up' effect: differences between low- and non-alcoholic lager on blood ethanol.

The peak blood alcohol levels attained in male and female subjects after consumption of 3 pints of regular lager (4.2%) over a 30 min period was 73.5 +/- 6.9 mg% in males and 113 +/- 17 mg% in females. Peak values occurred at 60 and 90 min post-ingestion in males and females, respectively. Consumption of 3 pints of low-alcohol lager gave a maximum blood alcohol level of 13 mg% while there was no measurable blood alcohol content after three pints of non-alcohol lager. 'Topping-up' with a non-alcohol lager after 2 pints of regular lager leads to significantly lower blood alcohol levels when compared with 'topping-up' with low-alcohol lager over a comparable time in males but not in females.

Alcohol Drinking↗

Prevention of endotoxaemia in obstructive jaundice--a comparative study of bile salts.

Systemic endotoxaemia is associated with postoperative renal dysfunction in obstructive jaundice, and can be prevented by the pre-operative administration of certain bile salts. In order to find the most effective bile salt for use in this condition, a comparison of the anti-endotoxic activities of different bile salts was performed. Bile salts were incubated in vitro with endotoxin and the resultant endotoxin level was measured with a quantitative limulus assay. The in vivo effects of different oral bile salts on the intestinal absorption of radiolabelled endotoxin from rats with obstructive jaundice were compared. The in vitro and in vivo anti-endotoxic activities of bile salts related to their known detergent activities. Deoxycholic acid and its conjugates were the most effective and should be the bile salts of choice for further clinical evaluation in obstructive jaundice in man.

Animals↗

Measurement of operative plasma endotoxin levels in jaundiced and non-jaundiced patients.

A study of portal plasma endotoxin levels was performed using a chromogenic limulus amoebocyte lysate (LAL) assay. The assay proved sensitive and reproducible. In only 1 of 25 healthy subjects was the systemic plasma endotoxin level above 100 pg/ml (equivalent Escherichia coli 0111B4). In 30 non-jaundiced patients undergoing surgery the mean (+SEM) portal plasma endotoxin level (60 + 9 pg/ml) was significantly higher (p less than 0.05) than the mean level in the systemic blood (46 + 6 pg/ml), supporting the concept of endotoxin absorption from the intestine into the portal blood. In 20 patients with obstructive jaundice undergoing surgery 42% of portal, 45% of inferior mesenteric and 35% of systemic venous plasma endotoxin levels were above 100 pg/ml. There were significantly higher levels in the portal (p less than 0.05) and inferior mesenteric (p less than 0.05) compared with the systemic blood. Neither the presence of malignancy nor the duration of surgery appeared to influence endotoxin absorption. The significance of raised plasma endotoxin levels in obstructive jaundice is discussed.

Adult↗

Bile salts, endotoxin and renal function in obstructive jaundice.

Surgical treatment for the relief of obstructive jaundice is still complicated by postoperative acute renal failure in almost 10 per cent of patients. Renal failure in the patient with jaundice is associated with the presence of bacterial endotoxin in the peripheral blood, and enteric endotoxin absorption is facilitated by the absence of bile salts from the intestine. Oral replacement of bile salts should prevent endotoxemia and renal failure. Forty-six patients with jaundice were studied. Twelve patients received sodium deoxycholate preoperatively, 12 received chenodeoxycholic acid and 22 acted as controls. Endotoxemia was measured by the limulus test and renal function assessed by 24 hour creatinine clearance. No patient given deoxycholate preoperatively had systemic endotoxemia or postoperative impairment of renal function. Endotoxemia was reduced in the chenodeoxycholic acid group, but not significantly, and renal function was not protected. Sodium deoxycholate is undergoing further evaluation in a multicenter randomized prospective study.

Acute Kidney Injury↗

Experimental and clinical study of lactulose in obstructive jaundice.

The role of lactulose in preventing endotoxaemia in obstructive jaundice has been investigated. A prospective study was performed on 24 consecutive patients with obstructive jaundice undergoing surgery. Twelve patients were given oral lactulose before operation and were compared with twelve controls. Endotoxaemia was reduced in peroperative portal (P less than 0.05) and postoperative systemic (P less than 0.05) blood samples in the lactulose treated group, and a significant fall (P less than 0.05) occurred in the postoperative 24 h creatinine clearances in controls compared with the lactulose treated group. Results from animal experiments in which oral lactulose reduced endotoxin related mortality in obstructive jaundice (P less than 0.05), and the in vitro demonstration of a direct anti-endotoxic action of lactulose suggest that its beneficial action is due in part to an inactivation of endotoxin.

Acute Kidney Injury↗

The Kupffer cell in experimental extrahepatic cholestasis in the rat--a light microscopy, immunohistochemical and electron microscopy study.

Kupffer cell phagocytic function is reduced in the presence of obstructive jaundice. To investigate possible mechanisms we report a study of the rat liver in extrahepatic cholestasis, using light microscopy, immunohistochemistry and electron microscopy, Immunohistochemistry was performed with monoclonal antibodies specific for rat Kupffer cells ED 1, ED 2 and ED 3 and monoclonal antibodies directed against class II antigens of the rat major histocompatibility complex Ox 3 and Ox 6. Extrahepatic cholestasis was produced by bile duct ligation. In bile duct ligated animals light microscopy showed proliferation of bile ductules and an increase in sinusoidal cells. Immunohistochemistry with ED 1, ED 2 and ED 3 demonstrated a marked increase in the number of positive cells, but few of these cells were positive with Ox 3 and Ox 6, whereas the proliferating bile ductules were strongly positive. Electron microscopy revealed two homogeneous granular substances within the sinusoidal lumen and loss of the space of Disse. Despite a reduction in Kupffer cell phagocytic function in obstructive jaundice there is an increase in Kupffer cells, but these cells appear to be in an inactivated state as few express class II antigens on their surface. Furthermore the granular substance within the space of Disse may interfere with function.

Animals↗