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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 577 records · Page 32Linked to original sources

Deficits in iodine-labelled 3-quinuclidinyl benzilate binding in relation to cerebral blood flow in patients with Alzheimer's disease.

A loss of acetylcholine is one of the most consistent neurochemical findings in Alzheimer's disease (AD) post-mortem, but the debate concerning receptor abnormalities is unresolved. The aim of this investigation was to measure the density of acetylcholine muscarinic receptors in AD patients at various stages in the disease (N = 8) by synthesising a radio-iodinated version of quinuclidinyl benzilate QNB, a potent muscarinic antagonist. Deficits were identified by comparison with a control data set obtained from four elderly volunteers and then compared to the deficit in total functional activity in the same brain regions measured using the cerebral perfusion tracer technetium-99m hexamethylpropylene amine oxime. Iodine-123 (R,R)quinuclidinyl benzilate (QNB) was synthesised using a CuI assisted nucleophilic aromatic exchange reaction. 160 MBq of the radioligand (specific activity 400 Ci/mmol: dose 90 ng/kg) was administered to each subject. Diagnosis of AD was made using the CAMDEX and DSMIIIR criteria with a physical examination, full blood screen, CT and chest X-ray. All subjects were scanned at 21 h post injection on an SME810 emission tomograph. 123I(R,R)QNB activity in the controls was found to be consistent with the known distribution of muscarinic receptors with no activity in the cerebellum and low activity in the thalamus. In the AD patients deficits in 123I-QNB binding which exceeded the corresponding total functional regional perfusion deficit were not found in six of the patients and were observed only in the two most severely affected patients, both of whom were untestable on the cognitive battery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Detection and characterization of a novel bisegmented double-stranded RNA virus (picobirnavirus) from rabbit faeces.

In two separate studies rabbits were fed orally with human and rabbit "picobirnaviruses". Polyacrylamide gel electrophoresis (PAGE) of nucleic acid extracted from faecal samples collected from inoculated rabbits revealed the presence of discrete equimolar bands, typical of picobirnaviruses, in several specimens. The genome profiles detected in both studies differed significantly from that of the inoculum suggesting that passage of the inoculated picobirnaviruses had not taken place and that the bands were a co-incidental finding. The presence of rabbit picobirnaviruses was confirmed by characterization of the genome bands, as dsRNA by enzyme digestion and by their co-sedimentation in caesium chloride (CsCl) gradients with 32 nm virus particles at a buoyant density of 1.39 g/ml. Picobirnavirus genome segments varied in size in a range between 2.3-2.6 kilo base pairs (kbp) and 1.6-1.9 kbp for the slow and fast migrating bands, respectively. Immune electron microscopy of the picobirnavirus particles revealed round or slightly hexagonal particles with a smooth surface and a mean diameter of 30.7 nm. In one rabbit, an immune response, temporally associated with picobirnaviruses excretion, was demonstrated by immune electron microscopy (IEM) supporting the view that picobirnaviruses may be vertebrate viruses. Two antigenically distinct picobirnavirus strains were defined by IEM.

Animals↗

Storage temperature and differing methods of sample preparation in the measurement of urinary albumin.

Microalbuminuria is a predictor of persistent proteinuria, renal failure and cardiovascular disease and therefore accurate determination of urinary albumin concentration is important. We examined the stability of albumin in urine under different conditions of storage, temperature and sample preparation. There was no significant difference in urinary albumin concentration between fresh urine and urine stored at either 4 degrees C or 20 degrees C for up to 7 days. Similarly in urine samples from diabetic patients there was no significant difference in albumin concentration at levels ranging from 1.3 to 1999.3 mg/l between fresh urine at 4 degrees C and urine stored frozen for 1 week, 1 month or 6 months. Neither storage temperature (-20 degrees C or -40 degrees C) nor centrifugation of sample prior to assay made a significant difference to the albumin concentration. Multiple freezing and thawing of urine samples during 6 weeks of storage at -20 degrees C made no difference to albumin concentrations. Storage of urine samples in either polypropylene, polystyrene or borosilicate glass tubes did not result in a significant change in urinary albumin concentration after either 1 week or 1 month at -20 degrees C although, after 1 month of storage, urinary albumin concentrations tended to be lower by an average of approximately 7%. In tubes to which gelatine had been added this was reduced to 4%. We conclude that fresh urine can be kept at 4 degrees C or 20 degrees C for up to 7 days. Frozen urine samples can be stored for up to 6 months before assay without any loss of albumin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

Trichinella spiralis infection in pigs in the Bolivian Altiplano.

Trichinella spiralis infection has been reported sporadically in several areas in Central and South America. However, several countries, including Bolivia, have not reported trichinellosis in animals or humans. A small survey of pigs slaughtered in an abattoir in Bolivia was undertaken during September 1991, to determine the presence of Trichinella spiralis. In a group of 100 pigs slaughtered consecutively on a single day and tested using the pooled digestion method, two of eight pools (25%) were positive. Twenty-one of 188 pigs (11.2%) from ten communities slaughtered consecutively on a second day tested positive for the presence of antibodies to Trichinella spiralis using an enzyme-linked immunosorbent assay. It was concluded that trichinellosis is present in pigs in Bolivia and the rate of infection may be quite high.

Abattoirs↗

Increases in serum prolactin levels associated with syncopal attacks.

Numerous investigators have found that serum prolactin levels increase after tonic-clonic and partial complex seizures, but the effect of syncope on prolactin levels has been studied little. Serum prolactin levels were measured following unexpected syncopal attacks in patients seeking emergency treatment in a community hospital. Levels sampled 18 to 60 minutes after syncopal episodes were increased in 8 of 11 cases. Follow-up prolactin levels, measured 17 to 222 days later, were normal in all eight cases in which they were initially increased. Most subjects had concurrent illness. Although the current study does not clarify whether it was the syncope, the concurrent illness, or both that caused the prolactin elevations, it implies that measurement of this hormone will not help the clinician in distinguishing between seizures and syncopal attacks.

Adolescent↗

The tyrosine kinase connection: how GPI-anchored proteins activate T cells.

How can crosslinking of cell-surface glycosylphosphatidylinositol-anchored proteins activate T cells when the proteins do not reach the cytosol? Recent results show that glycosylphosphatidylinositol-anchored proteins associate with tyrosine kinases of the src family. Kinase activity is stimulated when glycosylphosphatidylinositol-anchored proteins are crosslinked. How the proteins are linked across the membrane, however, remains an intriguing mystery.

Animals↗

The immunofluorescent era of membrane traffic.

In recent years immunofluorescence microscopy has been increasingly used to study membrane traffic. In this article seven electron microscopists, all with considerable experience in using light microscopy, take a critical look at the immunofluorescence approach and argue that results obtained with this method are often overinterpreted.

Journal Article↗

Hyoid bone tumour mass presenting with cervical nodal metastasis.

This paper presents a quite unique case report of a patient presenting with the combination of cervical metastatic lymphadenopathy and a hyoid bone tumour mass. The differential diagnosis and treatment is discussed, with emphasis on the importance of immunohistochemistry and electron microscopy in the management of such a case.

Bone Neoplasms↗

The development of a spinal injuries unit in Armenia.

A severe earthquake in December 1988 in Armenia, resulted in a large number of spinal cord injuries. A rehabilitation facility was urgently established in Yerevan by the Red Cross with volunteers from various countries outside the then Soviet Union. A programme of training of Armenian doctors, nurses and therapists was established, and a new purpose built spinal unit planned. The new unit was opened in August 1992 and should serve as a model for similar units throughout the Commonwealth of Independent States.

Armenia↗

Enteric disease in early childhood inhibits microvillus expression by potential stem cells.

1. Enterocyte development of microvillus structure has been measured in intestinal biopsies obtained from children suffering from coeliac disease, cow's milk protein intolerance and microvillus atrophy, and the results compared with similar measurements carried out in control children. 2. All types of enteric disease caused a significant 30% reduction in the length of microvilli present on undifferentiated basal crypt enterocytes, here referred to as potential stem cells. 3. Microvillus growth measured in control enterocytes took place mainly over the basal third of the villus. There was then little further change in structure during subsequent enterocyte migration to the villus tip. 4. Microvillus length in diseased tissue remained more or less constant during enterocyte migration to the crypt-villus junction. Microvillus length then decreased slightly during subsequent enterocyte migration over stunted villi. 5. The present results are discussed in relation to the supposed properties of potential stem cells. Comparisons are also made between profiles of microvillus development measured in healthy children and mature adults.

Adult↗

Tetrameric assembly of CHIP28 water channels in liposomes and cell membranes: a freeze-fracture study.

Channel forming integral protein of 28 kD (CHIP28) functions as a water channel in erythrocytes, kidney proximal tubule and thin descending limb of Henle. CHIP28 morphology was examined by freeze-fracture EM in proteoliposomes reconstituted with purified CHIP28, CHO cells stably transfected with CHIP28k cDNA, and rat kidney tubules. Liposomes reconstituted with HPLC-purified CHIP28 from human erythrocytes had a high osmotic water permeability (Pf0.04 cm/s) that was inhibited by HgCl2. Freeze-fracture replicas showed a fairly uniform set of intramembrane particles (IMPs); no IMPs were observed in liposomes without incorporated protein. By rotary shadowing, the IMPs had a diameter of 8.5 +/- 1.3 nm (mean +/- SD); many IMPs consisted of a distinct arrangement of four smaller subunits surrounding a central depression. IMPs of similar size and appearance were seen on the P-face of plasma membranes from CHIP28k-transfected (but not mock-transfected) CHO cells, rat thin descending limb (TDL) of Henle, and S3 segment of proximal straight tubules. A distinctive network of complementary IMP imprints was observed on the E-face of CHIP28-containing plasma membranes. The densities of IMPs in the size range of CHIP28 IMPs, determined by non-linear regression, were (in IMPs/microns 2): 2,494 in CHO cells, 5,785 in TDL, and 1,928 in proximal straight tubules; predicted Pf, based on the CHIP28 single channel water permeability of 3.6 x 10(-14) cm3/S (10 degrees C), was in good agreement with measured Pf of 0.027 cm/S, 0.075 cm/S, and 0.031 cm/S, respectively, in these cell types. Assuming that each CHIP28 monomer is a right cylindrical pore of length 5 nm and density 1.3 g/cm3, the monomer diameter would be 3.2 nm; a symmetrical arrangement of four cylinders would have a greatest diameter of 7.2 nm, which after correction for the thickness of platinum deposit, is similar to the measured IMP diameter of approximately 8.5 nm. These results provide a morphological signature for CHIP28 water channels and evidence for a tetrameric assembly of CHIP28 monomers in reconstituted proteoliposomes and cell membranes.

Animals↗

Recipient vessels in head and neck microsurgery: radiation effect and vessel access.

Historical cohort analysis compared free-flap survival rates in 226 irradiated and 108 nonirradiated head and neck reconstructions. The failure rate for the irradiated flaps (3.5 percent) did not differ significantly from that for the nonirradiated group (2.9 percent). A case-control study of the failed irradiated flaps revealed infection and lag time between radiotherapy and surgery as the only factors significantly associated with free flap failure. Salvage techniques (vein grafting, cephalic transposition, and Corlett looping) for recruiting recipient vessels into radically ablated head and neck beds are reviewed.

Adult↗

Alpha interferon in the treatment of chronic hepatitis C infection in thalassaemia major.

Hepatitis C virus (HCV) is responsible for the majority of cases of post transfusion non-A non-B (NANB) hepatitis in thalassaemia major (TM). Twelve multi-transfused TM patients with serological, biochemical, histological and molecular biological evidence of HCV infection have been treated for 6 months with recombinant alpha-interferon (IFN). Ten (83%) responded as assessed by a fall of at least 50% of pre-treatment serum transaminase levels. Histological improvement was observed in 6/7 responders tested. Natural killer (NK) cell activity 24 h after the first dose of IFN was significantly increased in responders as compared to non-responders (P < 0.05). HCV RNA disappeared from serum in 5/12 and from liver tissue in 2/5 of the responders. The degree of induction of peripheral blood mononuclear cell 2'5' oligoadenylate synthetase messenger RNA (2-5 OAS mRNA), an enzyme induced by IFN, after the first dose of IFN did not correlate with response. IFN was generally well tolerated. We conclude that the response rate in multi-transfused TM patients infected with HCV and treated with IFN is similar to that in non-multi-transfused patients.

Adolescent↗

Intravaginal misoprostol as a cervical ripening agent.

OBJECTIVE: To determine if misoprostol (exogenous prostaglandin E1 PGE1) used vaginally was of value in improving the Bishop score, leading to an early safe vaginal delivery in women in whom the cervix is unripe and delivery is indicated. DESIGN: A double-blind clinical trial. SETTING: Antenatal and labour wards of the University Hospital of the West Indies, Jamaica. SUBJECTS: Forty-five women in the third trimester with various obstetric indications for induction of labour and with no contra-indications to prostaglandins. INTERVENTIONS: The women were randomly assigned to receive treatment or a placebo. The treated group had 100 micrograms misoprostol inserted vaginally while the placebo was similarly inserted. MAIN OUTCOME MEASURES: Efficacy of the misoprostol was measured by the increase in the Bishop score 12 h after giving the treatment, the time between insertion and delivery, the need for oxytocin, and the outcome of the pregnancy. RESULTS: The prostaglandin was superior to the placebo in ripening the cervix and inducing labour. The change in Bishop score was 5.3 in the misoprostol group compared with 1.5 in the placebo group (P < 0.001). The mean time from insertion to delivery was 15.6 h in the former while it was 43.2 h in the placebo group (P < or = 0.001). The need for oxytocin was also significantly less in the women receiving the prostaglandin compared with those who received the placebo (29% vs 62%, P < 0.02). There was no difference in the two groups in the delivery outcome in terms of complications, Apgar scores and mode of delivery. CONCLUSIONS: Intravaginal misoprostol is an effective and cheap method of inducing labour in the third trimester.

Administration, Intravaginal↗