Search PubMed⌕ Search

Biomedical subjects

D W Brown

Publications and source records attributed to D W Brown.

At least 127 records · Page 7Linked to original sources

Polymerase chain reaction for detection of herpesvirus simiae (B virus) in clinical specimens.

A polymerase chain reaction (PCR) was designed which is specific to Macaca fascicularis (cynomolgus monkey) isolates of B virus. The PCR primers produced the expected 188 basepair product from the Cyno 2 strain and seven other cynomolgus monkey isolates of B virus. Oligomer hybridization with a 31-mer oligonucleotide was used to confirm the origin of this product. The PCR failed to amplify DNA of Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, and other alphaherpesviruses (herpes simplex virus types 1 and 2, four SA 8 isolates and three rhesus isolates of B virus). PCR testing of swabs obtained from four orally-infected cynomolgus monkeys confirmed the presence of B virus DNA in samples previously shown to be positive by culture. In addition, PCR detected B virus in several swabs from infected monkeys that were culture negative. Total DNA extracts from the trigeminal and sacral ganglia of these animals were tested by nested PCR and B virus DNA was detected in the trigeminal ganglia of 3 of the 4 orally-infected cynomolgus monkeys. Nested PCR did not detect B virus DNA in total DNA extracts obtained from the brains of the four monkeys.

Animals↗

Abnormal fluctuations of acetylcholine and serotonin.

Abnormal fluctuations of acetylcholine and serotonin might cause, or be correlated with, a variety of symptoms. This communication cites evidence which suggests that fluctuations of serotonin might have a causative role in migraine, mania, and depression and that fluctuations of acetylcholine might have a causative role in epilepsy, catalepsy, and Kleine-Levin attacks.

Acetylcholine↗

Crick and Mitchison's theory of REM sleep and neural networks.

Crick and Mitchison proposed that a reverse learning mechanism in REM sleep removes certain undesirable modes of interaction in neural networks within the cerebral cortex. If their theory is correct then abnormalities of reverse learning might account for some aspects of schizophrenia, mania, and depression. The theory of reverse learning might lead to an understanding of why lithium salts terminate manic episodes.

Animals↗

Norwalk-like viruses: demonstration of genomic diversity by polymerase chain reaction.

A reverse transcription-polymerase chain reaction (RT-PCR) amplification procedure was developed for the detection of Norwalk-like viruses in fecal specimens. Ninety-nine fecal specimens collected in the United Kingdom and containing small round-structured virus particles as determined by electron microscopy were tested. They came from 50 outbreaks and 16 sporadic cases of viral gastroenteritis. RT-PCR products of the appropriate size for Norwalk virus RNA were detected in 15 specimens from three outbreaks, suggesting that viruses closely related to Norwalk virus have not been circulating widely in the United Kingdom in recent years. From four isolates, the RT-PCR amplification products of two genomic regions were sequenced and the degree of genomic variation was compared. DNA sequencing of the PCR products revealed strong similarities among strains from the United Kingdom (approximately 97% for both regions amplified) but significant differences from Norwalk virus (67 to 78%). All of the viruses detected by RT-PCR were classified as serotype UK2 by solid-phase immune electron microscopy or enzyme-linked immunosorbent assay. These findings provide evidence of a genomic relationship between Norwalk virus and serotype UK2 small round-structured viruses.

Base Sequence↗

Competitive radioimmunoassay to detect antibodies to herpes B virus and SA8 virus.

A monoclonal competitive radioimmunoassay (CompRIAm) which detects antibody to herpesvirus simiae (B virus) in monkey and human sera and antibody to SA8 virus in monkey sera but not antibody to herpes simplex virus in human sera is described. Of 232 serum samples from wild-caught cynomolgus monkeys, 117 serum samples were positive when tested by CompRIAm. The results were in close agreement (97.5%) with B virus neutralizing antibody results on the same sera. Sera from 97 wild-caught rhesus monkeys and 92 wild-caught baboons were also tested. The CompRIAm was able to differentiate between sera that had neutralizing antibody to B virus and SA8 virus and those that did not, although the discrimination was not as clear as that in the tests on cynomolgus monkey sera. Sequential sera from two humans with confirmed cases of B virus infection were tested by CompRIAm. B virus antibody was detected in sera from both humans. None of 237 other serum samples from blood donors and patients attending sexually transmitted disease clinics reacted in the CompRIAm.

Animals↗

Infection of peripancreatic lymph nodes but not islets precedes Kilham rat virus-induced diabetes in BB/Wor rats.

A parvovirus serologically identified as Kilham rat virus (KRV) reproducibly induces acute type I diabetes in diabetes-resistant BB/Wor rats. The tissue tropism of KRV was investigated by in situ hybridization with a digoxigenin-labelled plasmid DNA probe containing approximately 1.6 kb of the genome of the UMass isolate of KRV. Partial sequencing of the KRV probe revealed high levels of homology to the sequence of minute virus of mice (89%) and to the sequence of H1 (99%), a parvovirus capable of infecting rats and humans. Of the 444 bases sequenced, 440 were shared by H1. KRV mRNA and DNA were readily detected in lymphoid tissues 5 days postinfection but were seldom seen in the pancreas. High levels of viral nucleic acids were observed in the thymus, spleen, and peripancreatic and cervical lymph nodes. The low levels of infection observed in the pancreas involved essentially only endothelial and interstitial cells. Beta cells of the pancreas were not infected with KRV. These findings suggest that widespread infection of peripancreatic and other lymphoid tissues but not pancreatic beta cells by KRV triggers autoimmune diabetes by perturbing the immune system of genetically predisposed BB/Wor rats.

Animals↗

Physical plant staffing for health care facilities.

No single set of guidelines exists or even applies for determining physical plant staffing for each and every health care facility. However, one possible method is outlined in this document, with procedures to apply to most situations. The method should also help provide justification for staffing needs, and includes the results of a nationwide survey on the issue.

Maintenance and Engineering, Hospital↗

Investigation of an outbreak of rotavirus infection in geriatric patients by serotyping and polyacrylamide gel electrophoresis (PAGE).

An outbreak of rotavirus diarrhoea amongst patients on two wards in a geriatric unit was investigated using polyacrylamide gel electrophoresis (PAGE) and serotyping. There had been no contact between the patients on different wards but some interchange of staff had occurred so it was important to exclude the possibility that the rotavirus had been spread by staff. Two strains of rotavirus were shown to be present, one on each ward. Differences in the electropherotypes and serotypes were demonstrated, showing conclusively that transfer of virus between the wards had not occurred. Thus, serotyping and PAGE are of value in the investigation of rotavirus outbreaks in the hospital setting where cross-infection between wards is suspected.

Adult↗

An M-antibody capture radioimmunoassay (MACRIA) for detection of JC virus-specific IgM.

A solid-phase M-antibody capture radioimmunoassay (MACRIA) for detecting JC-specific IgM is described. The assay is based on a JC-specific monoclonal antibody (17.7.6) and Nonidet P40-treated, glycine-extracted antigen. MACRIA is more sensitive for JC IgM detection than haemagglutination inhibition (HI) following serum fractionation on a sucrose density gradient, and can be applied to large numbers of sera. The specificity of the assay was confirmed by examining sera from several acute virus infections and also those containing rheumatoid factor. Sera collected from renal transplant recipients with known active JC virus infection were found to contain more than 5 units of JC IgM. In this group of patients JC IgM represents either primary or reactivated JC infection. JC IgM was detected by MACRIA in 15 of 100 unselected blood donors, indicating that JC IgM is frequently produced in healthy seropositive individuals. Thirteen of the 15 sera positive from blood donors contained only low levels of JC IgM (< 5 units), but the specificity of all these results was confirmed in a blocking assay. It is suggested that these low levels of JC IgM may occur in up to 28% of seropositive individuals and result from active JC antigenic stimulation in healthy immunocompetent adults.

Aged↗

JC virus associated meningoencephalitis in an immunocompetent girl.

JC virus is most commonly acquired during childhood, and no clinical illness has been associated with primary infection, which is assumed to be asymptomatic. The only disease associated with JC virus to date is progressive multifocal leucoencephalopathy (PML), which is usually caused by viral reactivation in immunocompromised adults. A chronic meningoencephalitis associated with an active JC virus infection in an immunocompetent 13 year old girl is described.

Adolescent↗

Radioimmunodetection of occult carcinoembryonic antigen-producing cancer.

This study evaluates the ability of 111In-labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody (Mab) ZCE-025 to detect sites of occult cancer in patients with elevated serum CEA who have negative or equivocal CT scans. One hundred forty patients suspected of having occult cancer were evaluated. Except for elevated CEA levels, all had negative work-ups, including negative or inconclusive CT scans. Eighty-two patients (59%) had positive scans and 58 (41%) had negative scans. Seventy-five of the 82 patients with positive scans had confirmation of at least one Mab-positive lesion (91% positive predictive value). Thirty-eight of the 58 patients with negative scans had negative follow-up (66% negative predictive value). The Mab scan correctly identified at least one site of tumor in 75 of the 95 patients with recurrent or metastatic disease (79% sensitivity) and correctly predicted the absence of disease in 38 of 45 patients (84% specificity).

Aged↗

Carbamazepine-induced increases in total serum cholesterol: clinical and theoretical implications.

To assess the effect of carbamazepine (CBZ) upon total serum cholesterol, we examined 38 inpatients with affective illness and one with multiple personality disorder who received a course of CBZ monotherapy. CBZ therapy yielded significant increases in total serum cholesterol that became evident during the second week of therapy, persisted throughout therapy, and reversed in the first few weeks after discontinuation of therapy. CBZ-induced increases in total cholesterol appeared independent of initial mood state, diagnostic subtype, baseline cholesterol or thyroid indices; CBZ levels, doses, and level-to-dose ratios; and the degree of change in mood and thyroid indices. CBZ induction of enzymes mediating cholesterol synthesis is a possible mechanism of the increase in total cholesterol observed with CBZ therapy. Although preclinical studies suggest possible influence of cholesterol on neurotransmitter regulation and behavior, clinical studies have yielded conflicting data. There are insufficient data to support a role for cholesterol in the anticonvulsant and psychotropic mechanisms of CBZ. The increase in total serum cholesterol seen with CBZ therapy is likely due to an increase in the high density lipoprotein fraction and is thus not likely to be clinically problematic in relationship to atherosclerosis.

Adult↗

Saliva antibody testing and vaccination in a mumps outbreak.

Saliva antibody testing was performed to describe the epidemiology of an outbreak of mumps and identify susceptible children. Thirty-three out of 171 children (19%) were designated susceptible. A past history of mumps illness was found to be unreliable. No further cases of mumps were notified after 28 susceptible children were given MMR vaccine. The use of MMR vaccination may have contributed to the control of this outbreak and its use should be considered where a defined population is expected to have a significant proportion of susceptible individuals.

Antibodies, Viral↗

Fluorescence anisotropy decay of ethidium bound to nucleosome core particles. 1. Rotational diffusion indicates an extended structure at low ionic strength.

The fluorescence decay of ethidium intercalated into the DNA of nucleosome core particles increases in average lifetime from about 22 ns in H2O to about 39 ns in D2O. This increase, combined with the acquisition of large amounts of data (on the order of 10(8) counts per decay), allows measurement of anisotropy decays out to more than 350 ns. The overall slow rotational motions of the core particle may thereby be more clearly distinguished from the faster torsional motions of the DNA. In 10 mM NaCl at 20 degrees C, we recover a long correlation time of 198 ns in D2O (159 ns when corrected to a viscosity of 1.002 cP), in agreement with the value of 164 ns obtained in H2O. These values are consistent with hydrodynamic calculations based on the expected size and shape of the hydrated particle. To support our conclusion that this long correlation time derives from Brownian rotational diffusion, we show that the value is directly proportional to the viscosity and inversely proportional to the temperature. No significant changes in the rotational correlation time are observed between 1 and 500 mM ionic strength. Below 1 mM, the particle undergoes the "low-salt transition" as measured by steady-state tyrosine fluorescence anisotropy. However, we observe little change in shape until the ionic strength is decreased below approximately 0.2 mM, where the correlation time increases nearly 2-fold, indicating that the particle has opened up into an extended form. We have previously shown that the transition becomes nonreversible below 0.2 mM salt.

Animals↗

Effect of group thawing on post-thaw viability of bovine spermatozoa packaged in .5-milliliter French straws.

The objective of this study was to determine the effects of thawing groups of 2, 5, 10, 15, or 20 .5-ml French straws on post-thaw spermatozoal viability. Thermostatically controlled and nonthermostatically controlled thawing baths were compared. Using a split-plot design, semen from 10 bulls was extended in egg yolk citrate, frozen, and then thawed (in the respective groups) at 36 degrees C in two types of thawing baths. Motility and percentage of intact acrosomes were determined immediately after thawing (0 h) and again after 4 h of incubation at the respective temperature of each thawing bath. Neither percentage of intact acrosomes nor motility was influenced by the number of straws thawed at 0 h (P greater than .05). Thawing bath had no effect (P greater than .05) on motility or percentage of intact acrosomes at 0 h. Bull variation was significant in both the 0- and 4-h evaluations. After 4 h of incubation, there was a significant (P less than .05) straw number x thawing bath interaction. When 15 or 20 straws were thawed in the thermostatically controlled bath there was a reduction (P less than .05) in motility and percentage of intact acrosomes. However, in the nonthermostatically controlled bath there was no reduction in motility and percentage of intact acrosomes as the size of straw group increased. Our results indicate that, when using a nonthermostatically controlled thawing bath, semen packaged in .5-ml straws can be thawed in groups of 20 without an effect on post-thaw sperm viability.

Analysis of Variance↗

Herpesvirus simiae (B virus) antibody response and virus shedding in experimental primary infection of cynomolgus monkeys.

Four cynomolgus monkeys (Macaca fascicularis) were inoculated in the lips and tongues with B virus. Virus shedding and antibody responses were monitored for up to 50 days postinfection. Virus was isolated from the oral cavities of all monkeys at 6 days postinfection despite the absence of observable lesions. Virus was not isolated from genital swabs or serum. Antibodies to both B virus and herpes simplex virus were detected by neutralization between days 8 and 12. Virus-specific IgM and IgG antibodies were measured by antibody capture radioimmunoassay. IgM was first detected on day 6; by contrast, IgG did not appear until day 12. Antibodies reactive in a competitive radioimmunoassay appeared by day 12 and peaked at 30 to 40 days postinfection. This study provides data on which to base the diagnosis of primary B virus infection in cynomolgus monkeys.

Animals↗

Endogenous opiate response to pain in rheumatoid arthritis and cortical and subcortical response to pain in normal volunteers using positron emission tomography.

Identification of the main areas in the brain that respond specifically to the "suffering" components of pain has been achieved by using serial dynamic measurements of blood flow as an index of synaptic activity. Specific response to a repeated painful thermal stimulus as compared to a non-painful thermal stimulus in normal male volunteers identified the anterior cingulate cortex and the thalamus contralateral to the side of stimulation as the main sites of significant response. It was concluded that it was these areas where pain was likely to be experienced. Changes in opioid receptor binding in the brain was measured using 11C-diprenorphine and positron emission tomography in three patients with rheumatoid arthritis. In the two patients with active rheumatoid arthritis substantial changes in opioid receptor binding in the brain are described. The significance of these findings are discussed.

Arthritis, Rheumatoid↗

Melanin-concentrating hormone: a structural and conformational study based on synthesis, biological activity, high-field NMR, and molecular modeling techniques.

A series of Melanin-concentrating hormone (MCH) fragments have been synthesized and their biological activities compared with the parent peptide. The substructural units, 5-14 linear and 5-14 cyclic, have been used as models for MCH-- H-Asp1-Thr-Met-Arg-Cys-Met-Val-Gly-Arg HO-Val17-Glu-Trp-Cys-Pro-Arg-Tyr-Val in 1H-nmr conformational studies. Conformational features predicted by molecular dynamics analyses find support in the nmr experiments.

Amino Acid Sequence↗