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Biomedical subjects

D Jenkins

Publications and source records attributed to D Jenkins.

At least 181 records · Page 10Linked to original sources

DNA adducts in different tissues of smokers and non-smokers.

Purified DNA from human lung, liver, bladder, pancreas, breast and cervix has been analysed for DNA adducts using the nuclease P1 modification of the 32P post-labelling technique. Tissues were obtained at autopsy from 13 men and 6 women. Relatives were asked to provide information on smoking history for deceased subjects. All tissues examined except the breast had detectable adducts. In lung, bladder and pancreatic tissue a characteristic pattern of adducts was seen which has previously been reported as typical of cigarette-smoke-induced damage. Smokers and former smokers tended to have higher adduct levels than non-smokers in the tissues examined but this was only significant for the lung. There appeared to be considerable variation in adduct levels among smokers which could not be accounted for by duration or daily consumption level. Certain smokers had high adduct levels in all tissues examined, whilst in others high levels were only seen in some tissues. All cervical samples examined had detectable adducts. These results confirm the finding that cigarette smoking is associated with DNA damage in the lung and suggest that similar damage may be related to tobacco-induced neoplasms of other tissues.

Aged↗

Identification of susceptibility loci for type 1 (insulin-dependent) diabetes by trans-racial gene mapping.

A major component of inherited susceptibility to Type 1 (insulin-dependent) diabetes mellitus has been mapped to the major histocompatibility complex. Certain gene alleles in this region determine susceptibility and resistance to the disease. Mapping of susceptibility is hindered by the limitations of conventional tissue typing techniques, and by strong linkage disequilibrium within this part of the genome. Recombinant DNA technology and trans-racial studies have been used to allow finer mapping of genetic predisposition to Type 1 diabetes. These techniques have localised alleles encoding susceptibility and resistance to the DQ region. Other alleles determining disease susceptibility remain poorly localised.

Diabetes Mellitus, Type 1↗

Analysis of MHC class II DNA polymorphisms in Negroid subjects.

Study of the MHC class II region is complicated by strong linkage disequilibrium between DR and DQ. Comparison of DR-DQ haplotypes between different races partly resolves this problem. We present the results of an analysis of DRB, DQA and DQB restriction fragment length polymorphisms in serologically DR-typed subjects of Negroid origin. Clearly distinguishable DRB RFLPs were observed for DR1,2,5,7 and w8. DR4,9 and w10 were uncommon in this group. DR3 was associated with two extended haplotypes, one characterised by the DQw4 allele, the other by the DQw2 allele. A recently recognised DQB RFLP (DQB 2c) was associated with DR7 and also occurred on DR5 and DR9 haplotypes. Both DR5 and DRw6 were heterogeneous in their DR-DQ relationships. Negroid subjects exhibit DR-DQ relationships distinct from other races. These provide scope for further study of MHC class II associations with disease.

Black People↗

Leprotic involvement of peripheral nerves in the absence of skin lesions. Case report and literature review.

In the absence of clinically apparent cutaneous lesions, primarily neural leprosy is uncommon. Primarily neural leprosy presents clinically as a peripheral neuropathy that most frequently affects motor nerves and that occasionally involves sensory nerves as well. The long incubation period for leprosy and its occurrence outside endemic areas often lead to delayed diagnosis. We present a case of glove and stocking hypoesthesia, weakness of the flexor muscle of the right great toe, palpable thickening of the right popliteal nerve, and hypoesthetic but normal-appearing areas on the back, which developed in a Trinidadian immigrant who lived in Canada for 16 years. A skin biopsy specimen obtained from a visibly normal but hypoesthetic area on the back demonstrated a few acid-fast bacteria in small dermal nerves, in arrector pili smooth muscle, and in rare perivascular histiocytes, associated with a sparse mixed inflammatory cell infiltrate. The patient responded well to therapy with dapsone, rifampin, and clofazamine. A classification and review of primarily neural leprosy is presented. Our patient represents the first reported case of primarily neural borderline lepromatous leprosy in Canada.

Diagnosis, Differential↗

A histological and immunohistological study of cervical intraepithelial neoplasia in relation to recurrence after local treatment.

A retrospective histological study was performed on 23 patients who had presented with recurrent cervical intraepithelial neoplasia (CIN) 18 months or more after apparently adequate local destructive treatment and a comparable control group of 23 patients who had no recurrence at 18 months. All recurrences were in women with CIN 3. Detailed examination of pretreatment biopsies showed that there were significant differences in both the extent of crypt involvement (P less than 0.01) and maximum depth of CIN (P less than 0.01) between the recurrent groups and the comparison group of women without recurrence. There was also a significant difference in mitotic count between the two groups (P less than 0.01). Immunocytochemical staining for Langerhans' cells or human papilloma virus common antigen showed no significant difference between the two groups. A mitotic count of 35 per ten high-power fields or a depth of crypt involvement greater than 1.7 mm in the pretreatment biopsy was invariably associated with recurrence and identified 13/22 (59%) cases of recurrent disease. The histological reporting of these features may be of value in predicting a group of women at high risk of recurrence of CIN after local treatment.

Antigens, Viral↗

Ulcerative colitis: one disease or two? (Quantitative histological differences between distal and extensive disease).

Cell counts and measurements of mucosal architecture were made on rectal biopsies from nine patients with total colitis, eight with left sided colitis, 15 with distal colitis, and 11 with proctitis. The mean total lamina propria cell count in proctitis and distal colitis approached twice that of extensive left sided and total colitis (p less than 0.001) and in distal proctocolitis the cell numbers are further increased in the chronic over the acute phase. This difference was not explained by age, duration, activity, or treatment. The predominantly increased lymphoid and mononuclear cell infiltrate in distal proctocolitis indicates a different pattern of immune response, suggesting a separate process from extensive colitis or a more intense reaction resulting in localisation of disease.

Adolescent↗

Prevalence of Toxoplasma gondii antibodies in dingoes.

Serum samples from 62 dingoes (Canis familiaris dingo) trapped in five areas of southeastern New South Wales, Australia were tested for antibodies to Toxoplasma gondii. Six (10%) of the dingoes had direct agglutination test titers for T. gondii of greater than or equal to 1:64, and four of these animals had T. gondii-specific IgM, suggesting recent exposure.

Agglutination Tests↗

Linear relationship between DNA adducts in human lung and cigarette smoking.

Human lung and bladder DNA has been isolated and purified from either surgical or autopsy specimens. Smoking history details were obtained from patients or their close relatives. Each DNA sample was investigated using the nuclease P1 digestion modification of the 32P-postlabelling procedure. Data are presented for 48 lung and 19 bladder specimens. The samples were subdivided into three groups for data analysis, viz. smokers, former smokers and nonsmokers. The mean adduct levels (adducts per 10(8) nucleotides) in lung samples were: [see text] The chromatographic pattern of bladder DNA adducts for smokers was similar to that for smokers' lung DNA, although less intense. Adduct levels in former smokers tended to be lower than in smokers, although loss of adducts appeared to require several years after cessation of smoking. These findings support a link between DNA adduct levels and cigarette smoking, for both the lung and the bladder. For the former tissue there was a strong linear correlation between adduct levels and the number of cigarettes smoked.

Aged↗

Maternal mortality.

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Developing Countries↗

Identification of susceptibility loci for insulin-dependent diabetes mellitus by trans-racial gene mapping.

INSULIN-dependent (type I) diabetes mellitus (IDDM) follows an autoimmune destruction of the insulin-producing beta-cells of the pancreas. Family and population studies indicate that predisposition is probably polygenic. At least one susceptibility gene lies within the major histocompatibility complex and is closely linked to the genes encoding the class II antigens, HLA-DR and HLA-DQ (refs 3, 4). Fine mapping of susceptibility genes by linkage analysis in families is not feasible because of infrequent recombination (linkage disequilibrium) between the DR and DQ genes. Recombination events in the past, however, have occurred and generated distinct DR-DQ haplotypes, whose frequencies vary between races. DNA sequencing and oligonucleotide dot-blot analysis of class II genes from two race-specific haplotypes indicate that susceptibility to IDDM is closely linked to the DQA1 locus and suggest that both the DQB1 (ref. 7) and DQA1 genes contribute to disease predisposition.

Chromosome Mapping↗

Secretory carcinoma of the breast in adults: emphasis on late recurrence and metastasis.

Secretory (so-called juvenile) carcinoma of the breast, first described in children, occurs also in adult women, predominantly in the third decade. Less commonly it is seen in older age groups, up to the eighth decade. We report five patients with this tumour; one, a female aged 73, is the oldest age at which the tumour has been recorded, and one is the first report in an adult male in whom the disease recurred after 20 years, only the second recorded death attributable to this tumour type. Secretory carcinoma in adults is potentially more aggressive than in childhood. Nodal metastases are more frequent and sometimes more extensive. Recurrence of tumour after surgery developed in four of our five patients at 3, 8, 15 and 20 years. Slow growth and delayed recurrence are characteristic of many of these tumours. Death from systemic metastases is rare, but may ensue either rapidly or following a long latent period after treatment. Prolonged follow-up is needed to assess accurately the biological behaviour of this tumour.

Adult↗

An explanation for the problem of false-negative cervical smears.

False-negative cervical cytology due to sampling error is a well-recognized problem. Forty-seven women with histologically proven cervical intraepithelial neoplasia (CIN) were studied. All had two cervical smears performed at a mean interval of 3 months. At the time of the second smear, cervicography, colposcopy and biopsy were performed. The area of acetowhite cervical lesions and of the total visible atypical transformation zone (ATZ) were measured from the cervical photographs. The 17 women in whom one or both smears showed no dyskaryosis were found to have a significantly smaller proportion of their ATZ affected by CIN. It is suggested that this finding can account for the sampling error which causes false-negative cervical cytology. New screening techniques, such as cervicography, may offer a method of detecting and assessing these relatively smaller cervical lesions.

Biopsy↗

Cytological status and lesion size: a further dimension in cervical intraepithelial neoplasia.

Quantitative histological study of 84 laser cone biopsies showed a highly significant correlation between the grade of a cervical smear and the size of the lesion for all grades of cervical intraepithelial neoplasia (CIN) (CIN I P = 0.004; CIN II P = 0.0001; CIN III P = 0.003; total CIN P less than 0.0001); 10 of 34 (29%) of women with CIN III and mild dyskaryosis or less had significantly smaller lesions than 23 of 36 (63%) of women with CIN III and moderate or severe dyskaryosis. Repeat cytology identified as severe dyskaryosis all those with large CIN III lesions. Lesion size has been neglected in studies of the natural history of CIN and in the assessment of cytological screening, but offers an explanation for the apparent discrepancies between cytological, colposcopic and histological assessment of progression of CIN.

Biopsy↗

Langerhans cell population in early invasive squamous cell carcinoma of the uterine cervix.

Langerhans cell counts were performed using indirect immunoperoxidase staining for S100 protein in 10 cases of early invasive squamous cell carcinoma of the cervix and 20 controls from routine hysterectomy specimens. There was a significant (p < 0.01) reduction in the number of Langerhans cells per unit sectional area of tumour tissue compared to the normal cervical epithelium. The density of Langerhans cells in the 3 patients with tumour metastasis in pelvic lymph nodes was further reduced. The low density of Langerhans cells in invasive squamous cell carcinoma compared to the normal state may reflect poor local immunosurveillance and may be related to progression and spread of the tumour.

Adult↗

T-cell and plasma cell populations in coeliac small intestinal mucosa in relation to dermatitis herpetiformis.

Differential lymphocyte and plasma cell counts and measurements of mucosal architecture were studied in small intestinal biopsies from 17 controls and 17 patients with untreated uncomplicated coeliac disease of whom five also had dermatitis herpetiformis. Intraepithelial T-cell and plasma cell counts and measurements of mucosal architecture were not significantly different in the two coeliac groups but both groups differed from the controls. Lamina propria T-cell counts were significantly higher in the patients who also had dermatitis herpetiformis than in uncomplicated coeliac disease, with a significant increase in the Leu 2 (CD8) positive (cytotoxic/suppressor) T-cell subset. This suggests a specific abnormality of T-cell control of immune responsiveness in the pathogenesis of the skin manifestations of dermatitis herpetiformis which is not found in uncomplicated coeliac disease.

Adolescent↗

New scans from old: digital reformatting of ultrasound images.

Two-dimensional images obtained using ultrasound have been digitized from videotape recordings and stored within a maximum of 240 digital memory planes to form a three-dimensional data set using a commercially available image processing unit. This data set has been manipulated to produce images in planes perpendicular to the original scan set. The reformatted images represent not only the scans that could have been obtained by rotating the scan head but also demonstrate planes that are not accessible by conventional scanning. The system has been evaluated with a tissue-equivalent phantom to determine the geometric accuracy of the reformatting process. Clinical material has also been used to evaluate the practical value of such a technique and to highlight difficulties that may be encountered in its routine use.

Abdomen↗