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Biomedical subjects

T J Aitman

Publications and source records attributed to T J Aitman.

31 records · Page 2Linked to original sources
PubMed1991

Genetic analysis of autoimmune type 1 diabetes mellitus in mice.

Two genes, Idd-3 and Idd-4, that influence the onset of autoimmune type 1 diabetes in the nonobese diabetic mouse have been located on chromosomes 3 and 11, outside the chromosome 17 major histocompatibility complex. A genetic map of the mouse genome, analysed using the polymerase chain reaction, has been assembled specifically for the study. On the basis of comparative maps of the mouse and human genomes, the homologue of Idd-3 may reside on human chromosomes 1 or 4 and Idd-4 on chromosome 17.

Animals↗
PubMed1991

Mononucleotide repeats are an abundant source of length variants in mouse genomic DNA.

Microsatellite sequences, such as dinucleotide repeats, show a high degree of polymorphism in eukaryotic DNA. These sequences are convenient as genetic markers and can be analyzed by the polymerase chain reaction (PCR). We have assessed the frequency of length variants in 18 mononucleotide repeats in mouse DNA and find that the variability is similar to that reported for dinucleotide repeats. Nine of the 18 repeat sequences (50%) have three or more alleles in the strains tested. Ten of these repeat sequences have been mapped using strain distribution patterns (SDPs) in recombinant inbred (RI) strains.

Animals↗
PubMed1991

Additional microsatellite markers for mouse genome mapping.

Mouse sequence information from the EMBL and GenBank databases, published sequences and genomic clones have been analyzed for simple repetitive elements or microsatellites. Each microsatellite has been amplified by the polymerase chain reaction (PCR) as a single locus marker. PCR primers were designed from unique sequence flanking each repeat. Size variation of PCR products less than 750 base pairs (bp) between mouse strains has been determined using ethidium bromide-stained acrylamide or agarose gels. A further 74 newly characterized microsatellites are presented in this paper, bringing to 185 the total we have analyzed. Of these, 157/185 (85%) have more than one allele, 143/178 (80%) vary in length between C57BL/6J and Mus spretus, and 82/168 (49%) vary between DBA/2J and C57BL/6J. Microsatellites provide informative single locus probes for linkage analysis in the construction of a genetic map of the mouse genome.

Animals↗
PubMed1991

The generation of a library of PCR-analyzed microsatellite variants for genetic mapping of the mouse genome.

Forty-three sequences containing simple sequence repeats or microsatellites were generated from an M13 library of total genomic mouse DNA. These sequences were analyzed for size variation using the polymerase chain reaction and gel electrophoresis without the need for radiolabeling. Seventy-two percent of the sequences showed allelic size variations between different inbred strains of mouse and the wild mouse, Mus spretus; and 53% showed variation between inbred strains. Thirty-seven percent were variant between B6/J and DBA/2J, and 81% of these were resolved using minigel agarose electrophoresis alone. This approach is a useful way of generating the large number of variants that are needed to create high resolution maps of the mouse genome.

Animals↗
PubMed1990

Comparison of fine needle aspiration cytology, radioisotopic and ultrasound scanning in the management of thyroid nodules.

In 175 patients presenting with thyroid nodules, the diagnostic value in management of fine needle aspiration and cytology (FNAC), pertechnetate (99mTc) scanning and ultrasound imaging was examined. In 82 patients, the diagnosis was confirmed at operation; in the remaining 93, there was a follow-up period of at least 2 years. Thyroid cancer was found in 13 patients. For FNAC the sensitivity, specificity and positive predictive value for thyroid cancer were 92%, 85% and 41% respectively compared with 82%, 34% and 11% for 99mTc pertechnetate scanning, 75%, 61%, 19% for ultrasound and 73%, 58% and 19% for combined pertechnetate and ultrasound scanning. In 14% of patients, the aspirates were inadequate for cytology at the first examination. FNAC is therefore the preferable initial investigation and usually gives results adequate for a decision on surgical or medical management. With medical management and follow-up, ultrasound is of value in defining the nodule and the appearance of the rest of the gland.

Biopsy, Needle↗
PubMed1989

Insulin-like growth factor I gene expression in the rat ovary is confined to the granulosa cells of developing follicles.

The in vivo intraovarian synthesis of insulin-like growth factor-I (IGF-I) has been studied in the rat by Northern blot, dot blot hybridization, and in situ hybridization histochemistry. Ovarian IGF-I mRNA transcript sizes (7.0 kilobases (kb), 1.6 kb, and a group from 0.4-0.9 kb) were similar to those in liver and other tissues. The proportion of ovarian IGF-I to tubulin messenger RNA (mRNA) was increased to 176% of control values by treatment with diethylstilbestrol, while the ratio in liver was decreased to 64.4%. In situ hybridization identifies the major in vivo site of IGF-I synthesis in the ovary as the granulosa cells of developing follicles. IGF-I mRNA was present in the granulosa cells of developing preantral and antral follicles, but was not seen in atretic follicles or corpora lutea. In preovulatory follicles high levels of IGF-I mRNA were confined to the antral cell layers and to the cells of the cumulus oophorus. High levels of tubulin gene expression within follicles were seen in a similar distribution to that for IGF-I but 80-90% of corpora lutea also strongly expressed the tubulin gene. Interstitial cells, including thecal cells, express the tubulin gene at low levels but do not express the IGF-I gene. The distribution of IGF-I mRNA is the same as that previously observed for mitotically active granulosa cells, and therefore offers strong support for the view that IGF-I in the ovary acts by an autocrine-paracrine mechanism to promote granulosa cell replication.

Animals↗
PubMed1988

Prazosin in the treatment of chronic asthma.

The role of prazosin, an alpha 1 adrenoceptor blocker, was investigated in patients with chronic stable asthma who continued to have symptoms despite conventional treatment. Forty patients were entered into a double blind, placebo controlled, crossover trial to examine the effect of adding oral prazosin (2 mg twice daily) to previous medication for three weeks. Sixteen patients withdrew from the study. The remaining 24 patients showed no significant change in peak expiratory flow, FEV1, forced vital capacity (FVC), FEV1/FVC ratio, diary card symptom scores, or dose of beta sympathomimetic.

Adolescent↗
PubMed1981

Relationship of gold and penicillamine therapy to diffuse interstitial lung disease.

Seven cases of diffuse interstitial lung disease (DILD) are reported with an unequivocal temporal relationship between the development of the lung disease and treatment with gold (6 cases) and penicillamine (1 case). They were characterised clinically by the sudden onset of dyspnoea and crepitations and radiologically by diffuse bilateral pulmonary shadowing. Most showed evidence of hypersensitivity such as eosinophilia, a raised serum IgE level in response to gold, proteinuria, thrombocytopenia, or an immediate postinjection reaction. DILD is a serious complication of treatment with gold and penicillamine that is commoner than generally realised.

Adult↗
PubMedDate not supplied

Bioactivity of growth hormone releasing hormone (1-29) analogues after SC injection in man.

The bioactivity of growth hormone releasing hormone 1-29 [GHRH(1-29)NH2] has been compared with that of an agonist analogue [Ac-D-Tyr1,D-Ala2]-GHRH(1-29)NH2, in normal male volunteers. Using a submaximal dose of 3 micrograms/kg administered subcutaneously, peak growth hormone (GH) response and area under the GH curve were similar for the native and agonist analogue. In addition, no significant differences were found in peak GHRH(1-29) immunoreactivity, area under the GHRH(1-29) curves or plasma disappearance rates of the two peptides. The results suggest that, in keeping with the relative activities of other "superactive" analogues tested so far, the greatly enhanced activity of [Ac-D-Tyr1,D-Ala2]-GHRH(1-29)NH2 observed in the rat is not found in humans. It is possible that this species difference is due to differences in the interaction of GHRH peptides with the rat and the human somatotroph GHRH receptor.

Growth Hormone↗
PubMedDate not supplied

Serum IGF-I levels and growth failure in juvenile chronic arthritis.

The association between growth failure and serum IGF-I levels has been assessed in 32 children with Juvenile Chronic Arthritis (JCA) aged 5-16 years. A spectrum from normal growth to severe growth failure was included in the study population. Height Standard Deviation Score (SDS) ranged from -5.79 to +1.41 (median -1.22) and Height Velocity from 0.72-8.85 cm/yr (median 3.81 cm/yr). Known risk factors for growth failure (disease activity, steroid treatment, vertebral collapse) were confirmed. Additionally, height SDS was significantly correlated with serum IGF-I levels (rs = 0.49; p = 0.008); height velocity was significantly, although less strongly correlated with IGF-I levels (rs = 0.41; p = 0.027). There was no correlation between IGF-I levels and either of two indices of nutritional status, or between IGF-I levels and current steroid dose. The correlation of serum IGF-I with parameters of growth failure may be due to either insufficient secretion of growth hormone (GH) or defective GH action. In view of the recently increased availability of GH for treatment of short stature, it is important to distinguish between these two mechanisms.

Adolescent↗