PubMed Health⌕ Search

Biomedical subjects

T M Brown

Publications and source records attributed to T M Brown.

At least 19 recordsLinked to original sources
PubMed2006

Disrupted neuronal activity rhythms in the suprachiasmatic nuclei of vasoactive intestinal polypeptide-deficient mice.

Vasoactive intestinal polypeptide (VIP), acting via the VPAC(2) receptor, is a key signaling pathway in the suprachiasmatic nuclei (SCN), the master clock controlling daily rhythms in mammals. Most mice lacking functional VPAC(2) receptors are unable to sustain behavioral rhythms and lack detectable SCN electrical rhythms in vitro. Adult mice that do not produce VIP (VIP/PHI(-/-)) exhibit less severe alterations in wheel-running rhythms, but the effects of this deficiency on the amplitude, phasing, or periodicity of their SCN cellular rhythms are unknown. To investigate this, we used suction electrodes to extracellularly record multiple- and single-unit electrical activity in SCN brain slices from mice with varying degrees of VIP deficiency, ranging from wild-type (VIP/PHI(+/+)) to heterozygous (VIP/PHI(+/-)) and VIP/PHI(-/-) animals. We found decreasing proportions of rhythmic cells in SCN slices from VIP/PHI(+/+) ( approximately 91%, n = 23) through VIP/PHI(-/+) ( approximately 71%, n = 28) to VIP/PHI(-/-) mice (62%; n = 37) and a parallel trend toward decreasing amplitude in the remaining rhythmic cells. SCN neurons from VIP/PHI(-/-) mice exhibited a broad range in the period and phasing of electrical rhythms, concordant with the known alterations in their behavioral rhythms. Further, treatment of VIP/PHI(-/-) slices with a VPAC(2) receptor antagonist significantly reduced the proportion of oscillating neurons, suggesting that VPAC(2) receptors still become activated in the SCN of these mice. The results establish that VIP is important for appropriate periodicity and phasing of SCN neuronal rhythms and suggest that residual VPAC(2) receptor signaling promotes rhythmicity in adult VIP/PHI(-/-) mice.

Action Potentials↗
PubMed2002

Delirium.

Explore the source record for details and available documents.

Aftercare↗
PubMed2002

Effects of vasoactive intestinal polypeptide on neurones of the rat suprachiasmatic nuclei in vitro.

The suprachiasmatic nuclei (SCN) of the hypothalamus house the main circadian pacemaker in mammals. Vasoactive intestinal polypeptide (VIP) is the most abundant neuropeptide in the SCN and has been shown to phase-shift the electrical activity rhythm of SCN cells in vitro. However, the effects of VIP on the cellular activity of rat SCN neurones are unknown. In this study, we examined the acute effects of VIP on the extracellularly recorded spontaneous firing rate of SCN neurones in an in-vitro hypothalamic slice preparation. Furthermore, with the use of receptor-selective agonists and antagonists, we determined which receptors might mediate the effects of VIP in the SCN. Approximately 50% of cells responded to VIP; the main type of response was suppression in firing rate, although a few cells were activated. Suppression responses to VIP were mimicked by the VPAC(2) receptor agonist Ro 25-1553 and blocked by the selective VPAC(2) receptor antagonist PG 99-465. The PAC(1) receptor agonist maxadilan evoked responses from 40% of SCN cells, and activations to this agonist were not altered by PG 99-465. Responses to VIP were not blocked by antagonists to ionotropic glutamate receptors, but the duration of suppression was modulated by the GABA(A) receptor antagonist bicuculline. Our data indicate that VIP alters the electrical activity of rat SCN neurones in vitro, via both VPAC(2) and PAC(1) receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

A single gene (yes) controls pigmentation of eyes and scales in Heliothis virescens.

A yellow-eyed mutant was discovered in a strain of Heliothis virescens, the tobacco budworm, that already exhibited a mutation for yellow scale, y. We investigated the inheritance of these visible mutations as candidate markers for transgenesis. Yellow eye was controlled by a single, recessive, autosomal factor, the same type of inheritance previously known for y. Presence of the recombinant mutants with yellow scales and wild type eyes in test crosses indicated independent segregation of genes for these traits. The recombinant class with wild type scales and yellow eyes was completely absent and there was a corresponding increase of the double mutant parental class having yellow scales and yellow eyes. These results indicated that a single factor for yellow eye also controlled yellow scales independently of y. This gene was named yes, for yellow eye and scale. We hypothesize that yes controls both eye and scale color through a deficiency in transport of pigment precursors in both the ommochrome and melanin pathways. The unlinked gene y likely controls an enzyme affecting the melanin pathway only. Both y and yes segregated independently of AceIn, acetylcholinesterase insensitivity, and sodium channel hscp, which are genes related to insecticide resistance.

Acetylcholinesterase↗
PubMed2001

Typing of Chlamydia trachomatis strains from urine samples by amplification and sequencing the major outer membrane protein gene (omp1).

OBJECTIVES: To develop a novel protocol for the extraction, amplification, and sequencing of Chlamydia trachomatis MOMP gene (omp1) from urine, a non-invasive source, and apply it to an epidemiological study on the distribution of C trachomatis strains in a population of pregnant women in Thailand. METHODS: The C trachomatis DNA was extracted from culture stocks and urine using a slightly modified commercially available kit, the High Pure PCR Template Preparation Kit (Roche Molecular Biochemicals, IN, USA). The PCR and sequencing primers used for the amplification and sequencing of the omp1 were designed based on the nucleotide sequence of multiple C trachomatis strains found in GenBank. The protocol for the extraction, amplification, and sequencing was tested on laboratory culture stocks of reference strains of all C trachomatis serovars and on urine samples collected in a cross sectional study designed to assess the prevalence of C trachomatis infections in the cities of Bangkok and Chiang Rai, Thailand. RESULTS: The omp1 gene was successfully amplified and sequenced from 18 laboratory C trachomatis reference strains and from 45 C trachomatis positive urine clinical samples collected from asymptomatic pregnant women. Among clinical samples, we found nine different C trachomatis genotypes: F (11, 25%), D (10, 22.6%), H (5, 11.7%), K (5, 11.7%), E (4, 9.3%), Ia (3, 7%), B (3, 7%), Ja (2, 4.5%), and G (1, 2.3%). One specimen generated an omp1 DNA sequence pattern indicating the presence of a mixed infection with at least two different serovars. CONCLUSIONS: Urine is a convenient and reliable source for genotyping C trachomatis strains. A clear advantage of urine over traditional samples, such as cervical swabs, is that urine is a non-invasive source which makes collection easier and thus facilitates the enrolment of patients in clinical and epidemiological studies. In addition to typing, urine is increasingly used for diagnosis of C trachomatis infection by several commercially available nucleic acid amplification assays which represents a distinct advantage for collecting, transport, storage, and laboratory handling of samples.

Bacterial Outer Membrane Proteins↗
PubMed2001

Preemptive biopreparedness: can we learn anything from history?

The treat of bioterrorism is in the public eye again, and major public health agencies are urging preparedness efforts and special federal funding. In a sense, we have seen this all before. The Centers for Disease Control and Prevention grew substantially during the Cold War era in large part because Alexander Langmuir, Chief Epidemiologist of the CDC, used an earlier generation's anxieties to revitalize the CDC, create an Epidemic Intelligence Service, and promote epidemiologic "surveillance" as part of the nation's defense. Retrospective investigation suggests that, while Langmuir contributed to efforts promoted by the Department of Defense and the Federal Civil Defense Administration, the United States did not have real cause to fear Communist biological warfare aggression. Given clear historical parallels, it is appropriate to ask, What was gained and what was lost by Langmuir's central role in that first instance of American biopreparedness? Among the conclusions drawn is that biopreparedness efforts fed the Cold War climate, narrowed the scope of public health activities, and failed to achieve sustained benefits for public health programs across the country.

Biological Warfare↗
PubMed2001

Detection of eastern equine encephalitis virus in infected mosquitoes using a monoclonal antibody-based antigen-capture enzyme-linked immunosorbent assay.

Surveillance of mosquito populations for virus activity is not often performed by small, vector-control districts because they do not have the financial resources to use virus isolation, or newer methods such as the polymerase chain reaction. Consequently, development and refinements of rapid, sensitive, and simple enzyme-linked immunosorbent assays (ELISAs) applicable to a wide variety of public health settings are justified. We have developed an antigen-capture ELISA for the detection of eastern equine encephalitis (EEE) virus in mosquitoes that uses both monoclonal capture and detector antibodies. The sensitivity of this assay is 4.0-5.0 log10 plaque-forming units/ml, which is comparable to previously published EEE antigen-capture assays developed with polyclonal antibody reagents. This test identifies only North American strains of EEE virus and does not react with either western equine encephalitis or Highlands J viruses. Test sensitivity was enhanced by sonicating mosquito pools, treating them with Triton X-100, and increasing the time and temperature of antigen incubation. The conversion of this ELISA to a monoclonal antibody-based format should result in a readily standardizable and transferable assay that will permit laboratories lacking virus isolation facilities to conduct EEE virus surveillance.

Aedes↗
PubMed2000

Failure of routine HIV-1 tests in a case involving transmission with preseroconversion blood components during the infectious window period.

CONTEXT: Current screening practices for blood donations have been successful in reducing human immunodeficiency virus (HIV) transmission through receipt of contaminated blood products. However, HIV-infected blood donations made prior to seroconversion and before high levels of viral replication occur could test negative using both serologic antigen and antibody tests. Testing based on nucleic acid amplification (NAT) is being implemented to screen for HIV-infected blood donated during this period, yet the issue of single vs minipool donation screening remains unresolved. OBJECTIVES: To determine HIV-1 genetic linkage between virus in 2 HIV-1-infected recipients of blood components and virus in the donor, who was HIV antigen and antibody negative at the time of donation; to screen the blood donor's plasma with HIV NAT assays, including those currently proposed for use in US blood donation screening. DESIGN AND SETTING: Case study conducted in October 1997 involving the Communicable Disease Centre, Singapore General Hospital, and the Singapore Blood Transfusion Service, Singapore. SUBJECTS: The blood donor and the 2 recipients of donor platelets and red blood cells. MAIN OUTCOME MEASURES: Genetic analysis of the HIV-1 p17 coding region of gag and the C2V5 region of env to determine the genetic relatedness of virus from the donor and recipients; reactivity in quantitative and qualitative assays, and reactivity in donor screening HIV NAT assays in single donation and minipool screening contexts. RESULTS: Direct DNA sequencing demonstrated identical HIV-1 subtype E viral sequences in the donor and recipients. Based on comparisons of a qualitative and quantitative assay for HIV-1 RNA levels, a low level of viremia (range, 5-39 copies/mL in plasma) was estimated to be in the donor's undiluted blood at the time of donation. Additional testing using donor-screening NAT assays showed consistent detection of HIV RNA in the undiluted donor plasma whereas detection was inconsistent at the 1:16 and 1:24 dilution levels currently used in minipool screening of blood donations in the United States. CONCLUSIONS: Transmission of HIV from a blood donor to a platelet recipient and a red blood cell recipient occurred in the preseroconversion infectious window period. The viral load in the implicated donation was estimated to be less than 40 copies/mL of plasma. Current US minipool HIV NAT screening protocols may not be sufficiently sensitive to detect all infectious window-period donations. JAMA. 2000;284:210-214

AIDS Serodiagnosis↗
PubMed2000

Molecular epidemiology of HIV-1 in Switzerland: evidence for a silent mutation in the C2V3 region distinguishing intravenous drug users from homosexual men. Swiss HIV Cohort Study.

OBJECTIVES: To study the molecular epidemiology of HIV-1 strains found in Switzerland and to determine possible genetic linkages among strains sorted by risk group or geographic region. DESIGN: A cross-sectional, clinic-based survey of HIV-1 molecular sequences and linked patient history from Swiss people. METHODS: Specimens were collected from 215 HIV-1-infected people in HIV outpatient clinics of four tertiary referral centers (Lausanne, St. Gallen, Zurich, and Basel) between May and August 1996, mainly from homosexual men, injecting drug users (IDU), and heterosexually infected people. In addition, specimens collected between 1991 and 1995 in the HIV outpatient clinic at University of Geneva were included into this survey. These specimens were collected primarily for an ongoing, prospective cohort (Swiss HIV Cohort Study). Direct C2V3C3 sequences of the env gene were determined from 158 samples of peripheral blood mononuclear cells. Genetic data were analyzed with the available patient history on each specimen. RESULTS: As found in other previous studies in Europe, primarily subtype B viruses were identified, whereas seven (4%) of 158 were non-subtype B: one subtype D, four subtype A, and two subtype E. Five of seven non-B subtypes occurred in immigrants from African or Asian countries and all seven were found exclusively in individuals who had been infected by heterosexual contact. No significant clustering of strains within different study sites or risk groups was found. A silent mutation (LAI env 834) occurred significantly more often in IDU than in homosexual men (p<.001). CONCLUSIONS: Although the lack of significant clustering of strains by risk group or geographic region may result from early introduction of subtype B viruses in Switzerland, the strong association of a silent mutation with IDU suggests that, early in the epidemic, there was a unique founder virus among IDUs. The HIV epidemic in Switzerland is still predominantly caused by subtype B viruses.

Amino Acid Sequence↗
PubMed2000

Drug-induced delirium.

Drug-induced delirium (DID) is a common and debilitating clinical problem. Identifying and treating the causes of DID is becoming easier as knowledge of the pharmacodynamic and pharmacokinetic fates of drugs increases. This article reviews basic pharmacological mechanisms and risks of DID, and ways to manage these risks.

Brain↗