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Biomedical subjects

D Jenkins

Publications and source records attributed to D Jenkins.

At least 199 records · Page 11Linked to original sources

Possible cofactors in the etiology of cervical intraepithelial neoplasia. An immunopathologic study.

Previous work in our department demonstrated a reduction in the numbers of Langerhans' cells in cervical epithelium showing histologic changes of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). In conjunction with a localized reversal of the T4:T8 ratio of T-lymphocytes, that finding provides evidence of the association of epithelial immunosuppression with both HPV infection and CIN. To investigate whether that phenomenon occurs primarily because of HPV alone or might be caused by a cofactor (e.g., cigarette smoking, oral contraceptive use, chlamydial infection), we performed a study of the effect of those cofactors on the immune defenses of the cervical epithelium. In a study of Langerhans' cells we showed that infection with HPV type 16 and current cigarette smoking both exert effects that cause a reduction in those cells. That diminution of the major antigen-presenting cells in cervical epithelium may constitute a mechanism that explains the observed role of those agents in the etiology of cervical neoplasia.

Antigens, CD1↗

The metabolic consequences of the correction of acidosis in uraemia.

Chronic renal failure is associated with increased protein turnover, and recent evidence suggests that this may be due to the accompanying acidosis. Patients with stable chronic renal failure maintained on protein restriction were given sodium bicarbonate supplementation for 8 weeks. This resulted in improvements in acid-base status, plasma urea and uric acid levels, independent of changes in glomerular filtration rate. Acidosis is a potentially reversible toxic effect of chronic renal failure and its correction produces sustained metabolic benefit.

Acidosis, Renal Tubular↗

Effect of cigarette smoking on cervical epithelial immunity: a mechanism for neoplastic change?

Langerhans' cells in cervical epithelium in colposcopic biopsy specimens were identified by immunocytochemical staining for S100 protein and T6 (CD1) antigen, and their density was quantified. Possible cofactors for the development of cervical neoplasia were examined for any effect on the cell counts per unit area. Current cigarette smoking was associated with a significant decrease in the Langerhans' cell population in both normal epithelium and lesions due to cervical intraepithelial neoplasia. Ex-smokers tended to have cell counts between those of smokers and non-smokers. There was a dose-response relation between number of cigarettes smoked daily and effect on cell counts. These findings of a local immunological effect of smoking on cervical epithelium may explain the means by which cigarette smoking contributes to the development of cervical neoplasia.

Cell Count↗

Trans-racial studies implicate HLA-DQ as a component of genetic susceptibility to type 1 (insulin-dependent) diabetes.

Type 1 (insulin-dependent) diabetic patients and control subjects of Afro-Caribbean Negroid racial origin were investigated by serological HLA-DR-typing and restriction fragment length polymorphism analysis using DNA probes corresponding to the DQ alpha, DQ beta and DR beta chain genes. Combined analysis indicated that four DR antigens are positively associated with the condition in Negroid subjects - DR3, 4, 7 and w9. DR3 and 4 are also associated in Caucasians, but the relative risk for DR3 is lower in Negroid subjects. The DR7 association is specific for the Negroid race, and DRw9 is only weakly associated in Caucasoid subjects. Restriction fragment length polymorphism analysis demonstrated a DQ beta restriction pattern in Negroid subjects which is absent from Caucasoid subjects. This pattern was associated with DRw9 and a subset of DR7, and was markedly increased in frequency in diabetic patients compared with control subjects (48.7% vs 10.4%, respectively; p less than 10(-4). In the absence of this pattern, DR7 showed no positive association. DR3 in Negroid subjects was associated with two distinct DQ alpha-DQ beta patterns, only one of which was positively associated with diabetes. A DQ beta pattern, in linkage disequilibrium with different DR antigens in different races, conferred a consistent protective effect against the development of Type 1 diabetes. Trans-racial genetic analysis thus supports a primary role for DQ in susceptibility to Type 1 diabetes.

Black People↗

Protein A immunoadsorption therapy in HIV-related immune thrombocytopenia: a preliminary report.

Nine homosexual patients with immune thrombocytopenia were treated with autologous plasma that had been perfused over silica-immobilized Staphylococcus aureus protein A (SpA). Pretreatment platelet counts ranged from 10,000 to 98,000 cells/mm3 (mean: 54,000 cells/mm3). Six patients responded to therapy. Platelets increased by a mean of 95,000 cells/mm3 (p less than 0.007) and reached normal levels (greater than 150,000 cells/mm3) in four patients. Increased platelet counts are presently sustained in these four individuals after 5 months of follow-up. Increases in platelet counts significantly correlated with decreases in platelet-associated IgG (PAIgG), platelet-directed IgG (PDIgG), and immune complexes (CIC). PAIgG and PDIgG declined by a mean of 67% (p less than 0.003) and 58% (p less than 0.007), respectively. CIC decreased by a mean of 37% (p = 0.02). Complement was concomitantly activated in all four examined patients. C3a and C5a increased 23-fold and 2.6-fold, respectively, while total hemolytic complement decreased by 50%. Activated complement components and removal of CIC and IgG thus may contribute to the platelet-enhancing activity of SpA immunoadsorption therapy.

Acquired Immunodeficiency Syndrome↗

What is colitis? Statistical approach to distinguishing clinically important inflammatory change in rectal biopsy specimens.

Measurements of mucosal dimension, architecture, and cell counts in both lamina propria and epithelium were made on rectal biopsy specimens from 20 patients with irritable bowel syndrome ("normal" controls); 54 patients with ulcerative colitis, Crohn's disease, and non-specific proctitis; eight patients with small bowel Crohn's disease; and 34 in whom the rectal biopsy specimen was not diagnostic. Discriminant analysis was applied to multiple variables based on the measurements, and three variables were identified as of high predictive value. The most powerful discriminant was increased lamina propria cellularity in all forms of chronic colitis. The ratios of surface length to mucosal length and of surface epithelial height to crypt epithelial height also emerged as discriminants. Chronic inflammatory bowel disease was distinguished from normal in 95% of cases with a definite pathological diagnosis, and 85% of borderline cases were correctly classified as either normal or inflammatory when judged by the final diagnosis after follow up. This study provides a basis for automated diagnosis of rectal biopsy specimens and provides objectively validated criteria which can also be applied in routine histological diagnosis.

Adult↗

An unusual interpodocyte cell junction and its appearance in a transplant graft kidney.

In a case of focal and segmental glomerulonephritis unusual cell junctions were discovered between podocytes. These most closely resembled lesions described in aminonucleoside induced nephrosis in rats and were unlike anything previously seen in our experience. Shortly after renal transplantation nephrotic syndrome recurred and biopsy specimens showed recurrent focal and segmental glomerulonephritis, with the appearance of these unusual interpodocyte junctions in the graft kidney. This may be related to circulating factors in the blood of the patient.

Female↗

Detection of human papillomavirus DNA sequences by in situ DNA-DNA hybridisation in cervical intraepithelial neoplasia and invasive carcinoma: a retrospective study.

Human papillomavirus (HPV) infection of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma was investigated using in situ DNA-DNA hybridisation on histological sections of formalin fixed, paraffin embedded tissue to assess the technique's sensitivity and to assess retrospectively the association between HPV16 and invasive cervical carcinoma. HPV DNA was detected in 16 of 33 biopsy specimens of CIN. Cells containing viral DNA were more numerous than those positive for viral structural proteins. HPV DNA was also present in less differentiated cells deeper in the epithelium. The detection rate in CIN was lower than that reported for other hybridisation techniques such as Southern blotting. In a retrospective study of biopsy specimens of invasive squamous carcinoma of the cervix HPV16 DNA, the virus most commonly associated with cervical malignant disease, was found in 20 of 25 cases, including those dating from as far back as 1932. The level of sensitivity was similar to that reported for other hybridisation techniques. DNA positive cells were focally distributed in the invasive tumours, and most tumour cells were negative for viral DNA, a result consistent with the low copy number found in malignant cells. It is concluded that HPV16 is not a new virus but that its prevalence is a result of changes in sexual behaviour and that in situ hybridisation is useful in the localisation of HPV DNA replication in CIN and invasive carcinoma.

DNA, Viral↗

Chronic renal failure; an important feature of the Laurence-Moon-Biedl syndrome.

Two cases of end stage renal failure occurring in association with the Laurence-Moon-Biedl syndrome are reported. Abnormalities in renal function and morphology are increasingly recognized in these patients in whom uraemia is an important cause of morbidity and early mortality. The presence of renal impairment, occurring as frequently as any of the pentad of features that characterize the syndrome, has important implications for the prognosis and long term management of these patients.

Adult↗

Subclinical penile human papillomavirus infection and dysplasia in consorts of women with cervical neoplasia.

Fifty men whose sexual partners were 50 women with histologically proved cervical intraepithelial neoplasia (CIN) grade III (severe dysplasia or carcinoma in situ) were studied. A further 25 men whose current regular sexual partners were 25 women with chlamydial cervicitis were recruited as controls. If either of the partners in either group had genital condylomata acuminata or a known history of similar lesions, the couple was excluded from the study. Abnormal penile epithelium, which was detected by colposcopy after application of 5% acetic acid to the penile skin, was reported in 25 men in the study group compared with three in the control group. Histologically proved subclinical penile infection with human papillomavirus (HPV) was present in 23 men in the study group compared with three in the control group (p less than 0.01). Of the 50 men in the study group, four had histologically proved severe penile dysplasia or carcinoma in situ with evidence of HPV infection, the disease being subclinical in each case and diagnosed on histology of a specimen obtained by colposcopically directed biopsy. HPV DNA was detected on filter hybridisation of penile scrapes from 15 of the 23 men in the study group with histologically proved penile HPV infection, HPV16 DNA being detected in 10 of them. HPV DNA was detected on DNA-DNA hybridisation of biopsy material in seven of 18 men with histologically proved penile HPV infection. Five of these biopsy specimens were positive for HPV16 DNA. Only one man in the control group had HPV DNA detected in a penile scrape. This patient had histologically proved subclinical penile HPV infection. Such lesions may represent an important male reservoir of HPV types implicated in genital squamous carcinogenesis in both sexes.

Adult↗

Pseudoepitheliomatous, keratotic, micaceous balanitis. A clinical lesion with two histologic subsets: hyperplastic dystrophy and verrucous carcinoma.

A 58-year-old man presented with a 4-year history of a slowly enlarging, hyperkeratotic plaque on his glans penis that was compatible with a clinical diagnosis of pseudoepitheliomatous, keratotic, micaceous balanitis. The lesion had been treated unsuccessfully on three occasions with superficial shave excisional biopsies. Complete surgical excision produced excellent cosmetic and functional results with no evidence of recurrence at 3- and 6-month follow-up. A diagnosis of verrucous carcinoma was made on histologic examination of the excised material. Pseudoepitheliomatous, keratotic, micaceous balanitis is a distinctive clinical entity that represents a histologic spectrum ranging from hypertrophic-hyperplastic penile dystrophy to verrucous carcinoma.

Balanitis↗