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Biomedical subjects

D Jenkins

Publications and source records attributed to D Jenkins.

At least 19 recordsLinked to original sources
PubMed1992

Mild cervical dyskaryosis: safety of cytological surveillance.

How best to manage women who are found on cervical screening to have mild dyskaryosis remains controversial. Cytological surveillance misses some lesions picked up by colposcopy, but colposcopy is emotionally traumatic for women, the majority of whom will have a normal result. To determine what proportion of lesions are missed by cytological surveillance, and whether any abnormalities persist after colposcopy, we studied, by means of colposcopy and biopsy, the prevalence of cervical intraepithelial neoplasia (CIN) and subclinical human papillomavirus infection (HPVI) in two groups of patients who had had a first smear showing mild dyskaryosis at least 24 months earlier. One group was recruited from a centre practising cytological surveillance, with colposcopy for patients showing persistent or progressive cytological abnormality. The other group all had early colposcopy and treatment. Of 214 patients recruited into the cytological surveillance group, 70 (33%) had been referred for colposcopy within 24 months. Colposcopy of the remaining 144 (after a mean interval of 27 months from presentation) revealed that 54 (38%) were disease free, 64 (44%) had HPVI/CIN1, 8 (6%) had CIN2, and 18 (12%) had CIN3. A smear at that time identified 12 of the 18 (67%) with CIN3 as needing close cytological follow-up (1 patient) or prompt referral for colposcopy (11 patients). 137 women in the early colposcopy group attended for the study colposcopy (after a mean interval of 32 months from presentation). 37% were found to have some abnormality persisting after an earlier colposcopy, but none had CIN3. Cytological surveillance of mild dyskaryosis resulted in a 12% risk of patients having a small CIN3 lesion after 2 years, but this risk was reduced to 4% by the addition of a third repeat smear 12 months after the second. With such a policy only about a third of women would require colposcopy, and the risk of missing serious underlying precancerous changes would be low.

Adult↗
PubMed1992

32P-postlabelling analysis of DNA from human tissues.

DNA extracted from human lung, bladder, liver, pancreas, cervix and breast tissue samples taken at autopsy (37 sample sets) was analysed by the nuclease P1 enhancement modification of the 32P-postlabelling assay for levels of aromatic carcinogen DNA adducts. Results were combined with those from a previous study for statistical analysis of 56 sample sets (32 male+24 female). A strong trend was seen for increased adduct levels in the lung DNA of smokers and a weak association for the bladder DNA of smokers compared to non-smokers. Aromatic adducts were also detected in other tissues.

Carcinogens↗
PubMed1992

An investigation of Japanese subjects maps susceptibility to type 1 (insulin-dependent) diabetes mellitus close to the DQA1 gene.

Insulin-dependent diabetic and control subjects of Japanese origin were HLA-DRB1, -DQB1, and -DQA1 typed using restriction fragment length polymorphism analysis and sequence-specific oligonucleotide gene probing. The DQA1 allele DQA1*0301 was positively associated with the disease [48/52 (92%) diabetic patients versus 44/64 (69%) control subjects, Pc less than 0.03, RR = 4.97]. Alleles of the DRB1 and DQB1 genes showed no significant association with the disease. The frequency of DQB1 genotypes encoding the amino acid aspartic acid at position 57 of the DQ beta chain did not differ significantly between subjects with insulin-dependent diabetes mellitus (IDDM) and controls. These findings suggest that a susceptibility allele for IDDM in the Japanese is more closely associated with the DQA1 gene than the DQB1 gene.

Alleles↗
PubMed1992

The gene organization of the human beta 7 subunit, the common beta subunit of the leukocyte integrins HML-1 and LPAM-1.

The integrin beta 7 subunit associates with two alternative alpha subunits termed alpha HML-1 and alpha 4 to give the lymphocyte activation and homing receptors HML-1 and LPAM-1. Overlapping genomic clones that encoded the human beta 7 subunit gene were isolated from cosmid and phage lambda libraries. The coding portion of the gene spanned approximately 10 kb and was composed of 14 exons. Exon 1 (123 bp) encoded 5' untranslated sequences; exon 2 (204 bp) encoded the initiation codon, signal peptide, and 50 amino acid residues of the N-terminus of the mature protein; 7 exons (exons 3-9), ranging in size from 90 bp to 242 bp, encoded most of the extracellular domain proximal to the four cysteine-rich repeats; the region corresponding to the beta 3 arginine-glycine-aspartic acid (RGD)-binding domain was divided amongst exons 4 and 5; the four cysteine-rich repeats were encoded by 3 exons (exons 10-12) with intron insertion into the first and third repeats; exon 13 (209 bp) provided a spacer between the cysteine-rich domains and the transmembrane domain; exon 14 (161 bp) encoded the transmembrane domain and exactly half of the cytoplasmic domain; the remainder of the cytoplasmic domain and most of the 3' untranslated region was contained in the largest 313 bp exon 15. Comparison of integrin beta subunit genes revealed that the gene organization of beta 7 was almost identical to that of beta 2, but had diverged from that of beta 3. Amplification of integrin DNAs directly from genomic DNA, using PCR primers based on beta subunit consensus sequences corresponding to the beta 3 RGD-binding domain, yielded partial gene sequences for the beta 3, beta 5, and beta 6 subunits only. Inspection of the amplified sequences revealed that, as for beta 3, the regions in beta 5 and beta 6 corresponding to the beta 3 RGD-binding domain lacked the intron present in beta 7, beta 1, and beta 2, which divides this region in beta 2 into two subdomains that contribute to subunit assembly. This study provides genetic evidence for at least two major branches to the integrin beta subunit evolutionary tree, with beta 7, beta 2, and probably beta 1 in one branch, and the cytoadhesin beta 3 and probably also beta 5 and beta 6 in the other.

Amino Acid Sequence↗
PubMed1992

HLA class II gene polymorphism contributes little to Hashimoto's thyroiditis.

UNLABELLED: Previous studies of HLA and Hashimoto's thyroiditis have shown weak associations between the disease and various HLA-DR antigens. OBJECTIVE: To define better the contribution of HLA class II alleles to susceptibility to Hashimoto's thyroiditis. DESIGN AND MEASUREMENTS: Comparison of HLA-DRB, DQA and DQB restriction fragment length polymorphisms in patients with Hashimoto's thyroiditis and control subjects, and meta-analysis of this and other published studies. PATIENTS: Fifty Caucasian patients with Hashimoto's thyroiditis and 93 racially-matched control subjects. RESULTS: A 4.6 kb Taq 1 DQA restriction fragment length polymorphism occurred in 60% of patients compared with 35.5% of controls, Pc < 0.025. No other restriction fragment length polymorphism was significantly associated with the disease. Meta-analysis of several studies demonstrated weak, positive associations between the disease and DR3 and DR4. An association with DR5 was not significant. CONCLUSIONS: DR antigens are unlikely to determine disease susceptibility directly. These findings indicate that any contribution of HLA genes to inherited susceptibility to Hashimoto's thyroiditis is small and requires confirmation in family studies.

Disease Susceptibility↗
PubMed1992

CIN 3: the role of lesion size in invasion.

OBJECTIVE: To define the relation between the size of a CIN 3 lesion (measured histologically) and invasive squamous carcinoma. DESIGN: Measurement of CIN 3 by computerized planimetry of histological sections from 39 cone biopsies containing microinvasive cancer. Comparison with previous measurements of CIN lesions, associated with different grades of dyskaryosis. RESULTS: Microinvasive carcinoma of the cervix is associated with extensive CIN 3 on the surface and in endocervical crypts. The mean size of CIN 3 lesions showing microinvasion is seven times greater than that for severe dyskaryosis without invasion, (P less than 0.0001) and a 100-fold greater than with mild dyskaryosis (P less than 0.00001). CONCLUSION: Invasive squamous carcinoma of the cervix arises in large CIN 3 lesions and these are associated usually with severe dyskaryosis. We propose a model for the development of high-grade precancer as a small focus within low grade precancer which then undergoes expansion in size, accompanied by apparent progression in cytological grade.

Biopsy↗
PubMed1992

Susceptibility to IDDM in a Chinese population. Role of HLA class II alleles.

MHC associations with IDDM in a Chinese population were studied to investigate genetic susceptibility to the disorder. The frequency of HLA-DR3 was significantly higher in the diabetic patients (19/49 [38.7%] vs. control subjects, 11/105 [10.5%], Pc less than 1.3 x 10(-3), RR = 5.3 [CI 2.3-12.1]), whereas DR4 was not (11/49 [22.4%] vs. 28/105 [26.7%], NS). The frequency of DR3/4 heterozygosity was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 0/105 [0%], P = 1.7 x 10(-3), RR = 31.5 [CI 3.8-263.6]). The frequency of DR3/9 heterozygosity also was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 2/105 [1.9%], P = 0.03, RR = 6.2 [CI 3.0-12.7]). No significant associations were noted between DQB1 alleles and IDDM. Among DR4-positive subjects, the frequency of DQB1 allele DQB1*0302 was higher in the diabetic patients (10/11 [90.0%] vs. control subjects, 12/24 [50%], Pc less than 0.05, RR = 7.0 [CI 1.3-38.0]), and the frequency of DQB1*0401 was significantly lower in the diabetic patients (2/11 [18.2%] vs. control subjects, 16/24 [66.7%], Pc = 0.04, RR = 0.1 [CI 0.02-0.46]). No DR4 subtype was associated significantly with IDDM. The frequency of DQA1*0501, a DQA1 allele, was higher in diabetic patients (22/41 [53.7%] vs. control subjects, 20/95 [21.1%], Pc less than 3 x 10(-3), RR = 4.3 [CI 2.0-9.3]). The frequency of DQA1*0301, which has been associated consistently with IDDM in other ethnic groups, was not significantly higher in the diabetic patients in this study (27/41 [65.9%] vs. control subjects, 53/95 [55.8%], NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1992

Investigation of the mode of inheritance of insulin-dependent diabetes mellitus in Japanese subjects.

Previous studies have shown that insulin-dependent diabetes mellitus is positively associated with HLA-DR4 and HLA-DR9 in Japanese populations. It was proposed that susceptibility to the disease is determined by a single HLA allele associated with both DR4 and DR9. DR genotypes in a Japanese population with insulin-dependent diabetes mellitus were determined by DRB/DQB RFLP analysis. A single disease-susceptibility-allele model was tested by the antigen-genotype-frequency-among-patients method. Recessive and additive inheritance of a single susceptibility allele were rejected. The DR9-associated disease-susceptibility allele in Japanese subjects is distinct from both the DR3- and DR4-associated susceptibility alleles in white Caucasians. The data suggest further complexity in the inheritance of HLA-associated susceptibility to insulin-dependent diabetes mellitus.

Adult↗
PubMed1991

CD1a and S100 antigen expression in skin Langerhans cells in patients with breast cancer.

Langerhans cells (LCs) are dendritic, antigen-presenting cells found in the epidermis. This study investigates the effect of early breast cancer on the expression of CD1a and S100 antigens by these cells. LCs were counted and expressed as cells/mm of epithelial basement membrane on biopsies from the skin overlying the tumour and from biopsies distant from the tumour. A control study was performed on normal breast skin, not adjacent to a lesion, from women with benign breast disease. The LC count of 18 patients undergoing biopsy for benign breast disease indicated a mean of 26 cells/mm [95 per cent confidence interval (CI) 23-29] and a S100/CD1a ratio of 70 per cent. In 35 cases of early breast cancer, the CD1a-positive LC count in the epidermis overlying the carcinoma (mean 26/mm; 95 per cent CI 23-29) was similar, but the count made on biopsies distant from the tumour (mean 21/mm; 95 per cent CI 19-23) was significantly smaller. The percentage ratio of S100/CD1a was 71 per cent over the carcinoma and 84 per cent in the distant biopsies. The changes were not associated with the presence of nodal metastases or the oestrogen and progesterone status of the primary tumour. The reduction in LC numbers provides a link between decreased monocyte function and the decreased skin hypersensitivity responses found in patients with breast cancer.

Adult↗
PubMed1991

Tumour necrosis factor-beta polymorphism is unlikely to determine susceptibility to type 1 (insulin-dependent) diabetes mellitus.

Tumour necrosis factor gene polymorphism has been proposed as a determinant of Type 1 (insulin-dependent) diabetes mellitus. Tumour necrosis factor-beta gene polymorphisms were analysed in 40 North Indian Asian Type 1 diabetic patients and 63 control subjects. A 5.5 kilobase gene fragment was significantly increased among the patients (82.5% vs 52%, pc less than 0.01). A 10.5 kilobase fragment was significantly reduced among the patients (70% vs 90.5%, pc less than 0.02). The 5.5 kilobase fragment was associated with DR3, and was not significantly increased among DR3-positive patients compared with DR3-positive control subjects. The 5.5 kilobase/5.5 kilobase genotype was increased among the diabetic subjects (30% vs 9.5%, pc less than 0.03). The 10.5 kilobase/10.5 kilobase genotype was reduced among the diabetic subjects (17.5% vs 47.5%, pc less than 0.02). The 5.5 kilobase/10.5 kilobase genotype was not significantly associated with disease. These findings contrast with those in a white Caucasian population, suggesting that tumour necrosis factor-beta polymorphisms do not predispose to Type 1 diabetes directly, but are in linkage disequilibrium with disease susceptibility alleles at other MHC loci.

Diabetes Mellitus, Type 1↗
PubMed1991

Allele-specific gene probing supports the DQ molecule as a determinant of inherited susceptibility to type 1 (insulin-dependent) diabetes mellitus.

Trans-racial analysis of disease associations has improved mapping of MHC-linked susceptibility to Type 1 (insulin-dependent) diabetes mellitus. In this study the contributions of the MHC class II DQA1 and DQB1 genes were investigated. Sequence-specific oligonucleotide gene probing in Type 1 diabetic and control subjects of North Indian origin supported the DQw1.18 allele of the DQB1 gene as a determinant of inherited protection against Type 1 diabetes (RR = 0.12, pc less than 0.05). The A3 allele of the DQA1 gene was positively associated with the disease, (RR = 3.6, pc less than 0.05), as was the DQw2 allele of the DQB1 gene (RR = 4.6, pc less than 0.01). Trans-racial comparison of these disease associations indicates that DQ alleles may directly determine an element of inherited susceptibility to Type 1 diabetes.

Alleles↗
PubMed1991

HLA-DQA1 and -DQB1 alleles associated with genetic susceptibility to IDDM in a black population.

Transracial analysis provides a method of distinguishing primary associations between insulin-dependent diabetes mellitus (IDDM) and HLA class II alleles from those secondary to linkage disequilibrium. Blacks show DR-DQ relationships that are different from other races and are a useful group in which to investigate HLA-D region associations with IDDM. In this study, the frequencies of HLA-DQA1 and -DQB1 alleles in Afro-Caribbean IDDM and control subjects were compared. Alleles were identified with sequence-specific oligonucleotide probing. The DQA1 allele A3 was positively associated with IDDM (relative risk [RR] = 25.3, corrected P [Pc] less than 7.0 x 10(-6). The DQB1 alleles DQw2 and DQw8 were also positively associated (RR = 4.7, Pc less than 6.5 x 10(-3) and RR = 12.3, Pc = 3.4 x 10(-3), respectively). The A1.2 and DQw6 alleles were negatively associated (RR = 0.16, Pc less than 3.5 x 10(-3) and RR = 0.15, Pc = 2.4 x 10(-2), respectively). These findings were compared to data from other races. The positive associations with A3 and DQw2 are consistent with all racial groups investigated. The negative association with DQw6 is present in all racial groups in which it is a common allele. These findings suggest that DQ alleles, and hence DQ molecules, may directly affect predisposition to IDDM.

Alleles↗