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Biomedical subjects

H M Thomas

Publications and source records attributed to H M Thomas.

At least 19 recordsLinked to original sources

Chromosome pairing in Lolium perenne x L. temulentum diploid hybrids: genetic and cytogenetic evaluation.

A Lolium perenne genotype (E5/2/5/10), which had been selected for low chiasma frequency over a number of generations and which was suspected of containing one or two heterozygous dominant genes with a significant effect on chiasma frequency, was crossed with L. temulentum (Ba3081) to create a hybrid population of 47 diploid plants. The mean chiasma or paired arm (PA) frequency of homoeologous chromosomes at meiosis in the population was 9.1/cell (1.3 PA/chromosome pair) with a distribution skewed towards high PA frequency. More than 90% of the hybrid chromosomes paired at meiosis in spite of the disparity in chromosome length and DNA quantity between the two species. Overall, the distribution of PAs between chromosomes for a given number of PAs/cell favoured the production of rod bivalents over ring bivalents and univalents, indicating that there is a mechanism present that maximizes the total number of bivalent associations formed. Molecular marker analysis using AFLPs and isoenzymes did not identify any clear major gene effect on PA frequency in the hybrid population. It was concluded that the control of PA frequency in E5/2/5/10 was not a simple genetic mechanism.

Chromosomes↗

Immunological responses to respiratory syncytial virus infection in infancy.

OBJECTIVES: To determine whether there is evidence of immunological responses in infants with respiratory syncytial virus (RSV) bronchiolitis by measuring inflammatory mediators in peripheral blood and, if found, whether these related to the severity of illness. PATIENTS AND METHODS: Blood was taken from 94 children with RSV infection during the acute episode and 10 or more days later when the child was well. Control serum samples were obtained from well children of similar ages. Serum samples were assayed for mediators of lymphocyte activity (interleukin-4 (IL-4), soluble interleukin-2 receptor (sCD25), soluble intercellular adhesion molecule-1 (sICAM-1), eosinophil activity (eosinophil cationic protein) and neutrophil activity (myeloperoxidase). Symptoms were assessed as very mild (coryza only), mild (symptoms of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: IL-4 concentrations were at the lower limits of detection of the assay. The concentrations of sCD-25 were greater in samples from patients with acute illness than from convalescent patients and both were greater than in control samples. sICAM-1 concentrations were similar in samples from patients with acute illness and convalescent patients, but both were greater than in samples from controls. Eosinophil cationic protein concentrations were lower in samples from patients with acute illness than in those from convalescent patients; there was no difference between samples from convalescent and control patients. Myeloperoxidase concentrations were similar in all samples. There was no correlation between the severity of infection and the concentrations of any inflammatory mediators. CONCLUSIONS: There is evidence of an inflammatory response in the peripheral blood of infants with acute bronchiolitis which may affect lymphocytes and eosinophils, but an association between this response and the severity of illness was not shown here.

Acute Disease↗

Respiratory syncytial virus genotypes and disease severity among children in hospital.

OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.

Acute Disease↗

Pulmonary artery smooth muscle cell [Ca2+]i and contraction: responses to diphenyleneiodonium and hypoxia.

To investigate mechanisms of inhibition of hypoxic pulmonary vasoconstriction (HPV), we studied pulmonary artery smooth muscle cell (PASMC) responses to hypoxia, utilizing diphenyleneiodonium (DPI), which blocks HPV. We measured cell contraction in primary cultures of rat PASMC grown on collagen gels and cytosolic free Ca2+ concentration ([Ca2+]i) in PASMC grown on glass. DPI (5 and 20 microM) caused contraction of PASMC and increased [Ca2+]i. Omission of extracellular Ca2+ diminished the DPI-induced PASMC contraction and greatly reduced the increase in [Ca2+]i. DPI substantially inhibited KCl-induced PASMC contraction (1 microM DPI) and the increase in [Ca2+]i (5 microM DPI). Severe hypoxia contracted PASMC and quadrupled [Ca2+]i. DPI, 1 microM, substantially inhibited hypoxic contraction, but neither 1 nor 5 microM DPI diminished the hypoxia-induced increase in [Ca2+]i, which was greatly attenuated by 20 microM DPI. These data show 1) that DPI increases [Ca2+]i, accounting for DPI-induced PASMC contraction and 2) that 1 and 5 microM DPI inhibit the hypoxia-induced contraction but not the hypoxia-induced increase in [Ca2+]i, suggesting that DPI inhibits hypoxic PASMC contraction downstream of the Ca2+ signal by desensitizing the contractile apparatus and indicating a potential control point for modulation of HPV.

Animals↗

Analysis of the human serological immune response to a variable region of the attachment (G) protein of respiratory syncytial virus during primary infection.

The serum antibody responses of babies to the variable carboxy-terminal region of the attachment (G) protein of respiratory syncytial virus (RSV) have been analysed using paired acute and convalescent sera from infants experiencing their first RSV infection with viruses of known genotype. The variable 84-85 carboxy-terminal amino acids of the G protein of six recent isolates of group A RSV were expressed in Escherichia coli as fusion proteins with glutahione S-transferase. About half the infants developed antibodies which recognised these fusion proteins. The patterns of response obtained in enzyme linked immunosorbant assays and immunoblotting assays were closely related to the infecting genotype.

Acute Disease↗

Comparison of ribosomal DNA sites in Lolium species by fluorescence in situ hybridization.

The position of the 18S-5.8S-26S and 5S rRNA genes have been physically mapped on the chromosomes of seven Lolium taxa. 18S-5.8S-26S sites were seen on two pairs of chromosomes in the inbreeding taxa. In the outbreeding taxa six sites were found in the L. multiflorum, seven in L. perenne and nine in L. rigidum var. rigidum. Two 5S sites were found in each of the taxa. In the inbreeders, the 5S sites were found adjacent to the 18S-5.8S-26S sites on chromosome 2. In L. multifiorum and L.perenne the 5S sites were on the short arm of chromosome 3. However, in L. rigidum var. rigidum the 5S rDNA site was found in either of the two positions.

Chromosome Mapping↗

Pharmacological treatment for antisocial personality disorder alcoholics: a preliminary study.

A short time ago, we reported that a subgroup of hospitalized alcoholic men with comorbid antisocial personality disorder (ASP) seemed to benefit significantly from antidepressant medication at the end of a 6-month period in a double-blind, random assignment, placebo-controlled study. In a reanalysis of those data, we divided the ASP alcoholic group (n = 29) into those who did (n = 15) and who did not (n = 14) also satisfy DSM-III-R criteria for an additional current mood and/or anxiety disorder and then compared the 6-month outcomes of these two smaller subgroups. Despite the small ns, the results for most drinking outcome measures indicated: (1) that ASP alcoholics with a current mood/anxiety disorder improved significantly more with pharmacological treatment, relative to placebo; and (2) that ASP alcoholics with no current mood/anxiety disorder failed to respond differentially to pharmacological treatment over the 6-month period. These findings suggest a possibly useful and inexpensive approach to the long-term management of a very difficult-to-treat subgroup of men substance abusers.

Adult↗

A double-blind, placebo-controlled study of nortriptyline and bromocriptine in male alcoholics subtyped by comorbid psychiatric disorders.

This double-blind, placebo-controlled, 6-month follow-up treatment study investigated the efficacy of bromocriptine and nortriptyline in attenuating drinking behavior and psychiatric symptoms in 216 male alcoholic patients subtyped by comorbid psychiatric disorder(s). Three well-defined subtypes were examined: alcoholism only, alcoholism + affective/anxiety disorder, and alcoholism + antisocial personality disorder. It was hypothesized that both medications would relieve negative affective symptoms associated with alcohol use and would be particularly effective for the affective/anxiety subgroup. Contrary to our predictions, the only significant effects found were with the antisocial personality disorder patients who were receiving nortriptyline. One interpretation of the results was that nortriptyline may have reduced impulsive drinking in the antisocial personality disorder subgroup by actions on serotonergic neurotransmission.

Adult↗