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Biomedical subjects

M E Wallace

Publications and source records attributed to M E Wallace.

At least 19 recordsLinked to original sources
PubMed2000

Junctional biases in the naive TCR repertoire control the CTL response to an immunodominant determinant of HSV-1.

The enormous diversity of the T cell pool makes it difficult to determine whether inherent biases in the naive TCR repertoire can influence T cell responsiveness. In C57BL/6 mice the cytotoxic T lymphocyte response to an immunodominant HSV-1 determinant (gB) is characterized by a prominent bias in Vbeta element usage, associated with a conserved and preferentially D element-encoded CDR3 sequence. Comparison of naive and gB-specific T cell populations revealed a similar enrichment of germline D element-encoded CDR3 sequences in the preimmune repertoire. Strikingly, eliminating the germline coding of the gB-specific CDR3 sequence caused an almost complete loss of the dominant subset of gB-specific T cells, illustrating that CDR3 biases can significantly alter both the composition and strength of an immune response.

Animals↗
PubMed2000

Comparison of three sampling and analytical methods for the determination of airborne hexavalent chromium.

A field study was conducted with the goal of comparing the performance of three recently developed or modified sampling and analytical methods for the determination of airborne hexavalent chromium (Cr(VI)). The study was carried out in a hard chrome electroplating facility and in a jet engine manufacturing facility where airborne Cr(VI) was expected to be present. The analytical methods evaluated included two laboratory-based procedures (OSHA Method ID-215 and NIOSH Method 7605) and a field-portable method (NIOSH Method 7703). These three methods employ an identical sampling methodology: collection of Cr(VI)-containing aerosol on a polyvinyl chloride (PVC) filter housed in a sampling cassette, which is connected to a personal sampling pump calibrated at an appropriate flow rate. The basis of the analytical methods for all three methods involves extraction of the PVC filter in alkaline buffer solution, chemical isolation of the Cr(VI) ion, complexation of the Cr(VI) ion with 1,5-diphenylcarbazide, and spectrometric measurement of the violet chromium diphenylcarbazone complex at 540 nm. However, there are notable specific differences within the sample preparation procedures used in three methods. To assess the comparability of the three measurement protocols, a total of 20 side-by-side air samples were collected, equally divided between a chromic acid electroplating operation and a spray paint operation where water soluble forms of Cr(VI) were used. A range of Cr(VI) concentrations from 0.6 to 960 microg m(-3), with Cr(VI) mass loadings ranging from 0.4 to 32 microg, was measured at the two operations. The equivalence of the means of the log-transformed Cr(VI) concentrations obtained from the different analytical methods was compared. Based on analysis of variance (ANOVA) results, no statistically significant differences were observed between mean values measured using each of the three methods. Small but statistically significant differences were observed between results obtained from performance evaluation samples for the NIOSH field method and the OSHA laboratory method.

Air Pollutants↗
PubMed1999

The cytotoxic T-cell response to herpes simplex virus type 1 infection of C57BL/6 mice is almost entirely directed against a single immunodominant determinant.

Many virus infections give rise to surprisingly limited T-cell responses directed to very few immunodominant determinants. We have been examining the cytotoxic T-lymphocyte (CTL) response to herpes simplex virus type 1 (HSV-1) infection. Previous studies have identified the glycoprotein B-derived peptide from residues 498 to 505 (gB(498-505)) as one of at least three determinants recognized by HSV-1-specific CTLs isolated from C57BL/6 mice. We had previously found that in vitro-derived CTLs directed to gB(498-505) show a characteristic pattern of T-cell receptor (TCR) usage, with 60% of gB(498-505)-specific CD8(+) T cells expressing BV10(+) TCR beta chains and a further 20% expressing BV8S1. In this report, we confirm that this TCR V-region bias is also reflected in the ex vivo response to HSV-1 infection. A high proportion of activated CD8(+) draining lymph node cells were found to express these dominant V regions, suggesting that a substantial number of in vivo responding T cells were directed to this one viral determinant. The use of an HSV-1 deletion mutant lacking the gB(498-505) determinant in combination with accurate intracellular gamma interferon staining allowed us to quantify the extent of gB-specific T-cell dominance. Together, these results suggested that between 70 and 90% of all CD8(+) HSV-1-specific T cells target gB(498-505). While deletion of this determinant resulted in an attenuated CD8(+) T-cell response, it also permitted the emergence of one or more previously unidentified cryptic specificities. Overall, HSV-1 infection of C57BL/6 mice results in an extremely focused pattern of CD8(+) T-cell selection in terms of target specificity and TCR expression.

Animals↗
PubMed1997

Antigen-specific CD8+ T cell subset distribution in lymph nodes draining the site of herpes simplex virus infection.

Inoculation with replicating virus leads to an increase in T cell numbers within lymph nodes that drain the site of infection. This increase has been associated with a nonspecific proliferation of bystander cells, with only a minority thought to be directed to the infectious agent. Such an assumption is largely based on precursor cytotoxic T lymphocyte (CTL) estimations using limiting dilution analysis. Recently, studies using more advanced molecular approaches have suggested that such functionally derived precursor frequencies considerably underestimate the proportion of T cells specific for the antigen under investigation. We have defined T cell receptor sequences characteristic of CTL populations directed to a dominant determinant of the herpes simplex virus (HSV) glycoprotein B (gB). In this investigation, we used this receptor signature as a probe to directly monitor changes occurring within lymph nodes draining the sites of active infection with HSV. We found that although lymph node CD8+ T cell numbers increase as a consequence of HSV infection, the majority of these cells are small resting cells that are not enriched for gB-specific receptors. In contrast, a significant proportion of activated T cells are highly enriched for CTL bearing gB-specific receptors. Our results are therefore consistent with a nonspecific migration of CTL precursors into the lymph nodes draining the site of infection, followed by the activation and proliferation of the antigen-specific subset that normally makes up a small proportion of the naive T cell repertoire.

Amino Acid Sequence↗
PubMed1997

Caffeine dependence in schoolchildren?

Schoolchildren (N = 289) kept a log and calculated their habitual caffeine consumption (principally in soft drinks). On 2 successive days, they completed a 20-item checklist adapted from the Profile of Moods Scale. On Day 2, they abstained from caffeine. Complete data were obtained for 175 children. A low-consumption group (10 mg or less daily) was compared with a high-consumption group (50 mg or more daily). The high-consumption group reported more stimulation than did the low-consumption group on Day 1 and more dysphoric symptoms during abstinence on Day 2. The results of this open-label pilot trial suggest that a large-scale double-blind placebo-controlled trial would be worthwhile.

Affect↗
PubMed1996

Canine epilepsy: a genetic counselling programme for keeshonds.

The predisposition of keeshonds (Dutch barge dogs) to an idiopathic epilepsy appears to be determined by a single autosomal recessive gene. The pedigrees of 15 litters which included animals diagnosed as epileptic ('fitters') were compared with those of 34 contemporary, normal animals. The pedigrees of all the fitters traced back, on both the paternal and maternal sides, to a common ancestor. Subsequently, further pedigrees and details of litters were gathered. If both parents of a fitter were heterozygous ('carriers'), the progeny (120 in number) of all known carrier x carrier matings would be expected to have a ratio of three phenotypically normal animals to one fitter, that is, 90:30. The ratio observed (91:29) was not significantly different. The Keeshond Club has published a list from which the identities of carriers can be inferred, with the intention that known carriers should be excluded from breeding. A genetic counselling programme has been in operation since 1989, which is based on advising breeders on the probability that the offspring of proposed matings would be fitters or carriers; advice has been given on 77 proposed matings. The mean probability that the proposed matings would result in carriers has declined significantly, and this is consistent with a decline in the frequency of the gene for this form of epilepsy in the breed.

Animals↗
PubMed1995

Control of paint overspray in autobody repair shops.

Commercially available controls for reducing worker exposure to paint overspray were evaluated in six autobody shops and a spray-painting equipment manufacturer's test facility. Engineering control measures included spray-painting booths, vehicle preparation stations, and spray-painting guns. The controls were evaluated by measuring particulate overspray concentrations in the worker's breathing zone, visualizing the airflow in spray-painting booths and vehicle preparation stations, and measuring airflow volumes and velocities. In addition, respirator usage observations were collected at five of the autobody repair shops, and quantitative fit tests were conducted on existing respirators at three shops. Several conclusions were drawn from this study. Downdraft spray-painting booths provide lower particulate overspray concentrations measured on the worker than crossdraft and semidowndraft spray-painting booths. In the latter two booths, the spray-painting gun can disperse as much as half the paint overspray into the incoming fresh air, increasing worker overspray exposure. Vehicle preparation stations have no walls to contain the overspray and, commonly, a single exhaust fan removes air from the painting area. Airflow patterns suggest that these do not control the paint overspray. Switching from a conventional spray-painting gun to a high-volume low pressure spray-painting gun reduced the particulate overspray concentration by a factor of 2 at a manufacturer's test facility. However, this change did not significantly affect solvent concentrations. Finally, respirator usage in five of the six shops studied was inappropriate. Respirators were poorly maintained and/or did not fit the workers, perhaps due to the absence of a formal respirator program.

Air Pollutants, Occupational↗
PubMed1993

Tail short variable: characterization of a new mouse mutant, and its possible analogy to certain human vascular disruption defects.

A new mouse mutant, tail short variable (Tsv) produces a reduction deformity of the tail, growth retardation, and, in adults, a mild anemia. Genetic and embryological studies show that on all genetic backgrounds there is variable viability of Tsv/Tsv and Tsv/+ and phenotypic overlap within these and with +/+. A modifier is located to a short segment of chromosome 7, which alters the tail length of Tsv/+ mice up to 15%. The modifier, Tsv, and a coat texture mutant come from the same wild Peru mouse. The tail deformity is associated with, and may be caused by, a vascular disruption of the caudal aorta starting on day 11 of gestation. Thus Tsv appears to be different from each of the thirty known mouse mutants involving the tail. It is suggested that Tsv could be a mouse model for human conditions involving transverse terminal limb defects such as Moebius and de Lange syndromes.

Anemia↗
PubMed1993

Women at high risk of HIV infection from drug use.

The purpose of this project was to study women at high risk for contracting AIDS from intravenous drug use or from sexual contact with addicts. Characteristics of the population, differences between HIV+ and HIV- women, substance abuse in primary caretakers of this high risk population, and changes in drug use when learning of HIV status were investigated. Subjects were mothers at high risk for contracting HIV, whose children were referred to a pediatric AIDS clinic of a large urban hospital because of AIDS risk factors. HIV testing revealed that 27 women were HIV+ and 13 were HIV-. The most common source of infection reported by the HIV+ women was sexual contact (17 subjects), with the remainder reporting that they were unsure of the source or reported intravenous drug use as their source of infection. There were significant differences between HIV+ and HIV- mothers with regard to the presence and impact of substance abuse in their own primary caretakers before age 16. Substance abuse in the parents of subjects was apparently reflected in behaviors reflecting health risk in subsequent generations. Subjects did not report changes in AIDS risk behavior when informed of their own HIV status or that of their children.

Adult↗
PubMed1992

Remodelling of angular deformity after femoral shaft fractures in children.

We reviewed 28 children with unilateral middle-third fractures of the femoral shaft who had an angular deformity after union of 10 degrees to 26 degrees. At an average follow-up of 45 months (20 to 66), we measured remodelling of the proximal physis, the distal physis and the femoral shaft. The average correction was 85% of the initial deformity. We found that 74% of correction occurred at the physes and only 26% at the fracture site. Neither the direction nor the magnitude of the angulation much influenced the degree of remodelling. Younger children remodelled only a little better than older children. We conclude that in children under 13 years of age, malunion of as much as 25 degrees in any plane will remodel enough to give normal alignment of the joint surfaces.

Bone Remodeling↗
PubMed1992

Sertoli-Leydig cell tumor of the ovary: a rare cause of amenorrhea.

A 15-year-old girl presented to a primary care clinic with secondary amenorrhea, masculinization, and rapidly increasing abdominal girth. Evaluation revealed a large pelvic mass, which was found at laparotomy to be a bilateral Sertoli-Leydig cell tumor producing androgens and high levels of alpha-fetoprotein (AFP). The patient underwent bilateral salpingo-oophorectomy. Other pelvic structures were uninvolved. The postoperative course was unremarkable, with testosterone and AFP levels in the normal range. A thorough literature search revealed no cases in which bilateral Sertoli-Leydig cell tumors were associated with high AFP levels. This case was unusual in its pathology, dramatic in its presentation, and valuable in its implications regarding the work-up of amenorrhea in young women.

Adolescent↗
PubMed1987

Recognition of 'trembler', a hypomyelinating condition in the Bernese mountain dog.

An account is given of a hypomyelinating condition, 'trembler', in the Bernese mountain dog. The condition is manifested clinically as a tremor of the limbs and head which becomes more intense with excitement or stress and which disappears with sleep. The tremor, which is first noticeable between two and eight weeks old, may persist throughout life but decline with age. Examination of plastic embedded tissue obtained post mortem from two, nine-week-old animals showed hypomyelination of the spinal cord. Preliminary examination of breeding data suggests that the condition may be inherited as an autosomal recessive.

Animals↗
PubMed1986

Aneuploidy in the embryonic progeny of females heterozygous for the Robertsonian chromosome (9.12) in genetically wild Peru-Coppock mice (Mus musculus).

The spontaneous appearance of a Robertsonian translocation in a laboratory colony of genetically wild Peru-Coppock mice gave the opportunity to study potential meiotic nondisjunction soon after the formation of the new chromosome and also in a hitherto untested combination of genotype and environment Metaphase II scores from the progenitor male had indicated a nondisjunction rate of approximately 10%, a figure that was confirmed by the finding of an estimated 12-16% total trisomic and probable monosomic zygotes in chromosomal studies of Day 9 embryos from heterozygous females. The chromosome studies also showed the presence of a significant excess of normal embryos that were heterozygous for the Robertsonian chromosome.

Aneuploidy↗