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Biomedical subjects

J H Smith

Publications and source records attributed to J H Smith.

At least 19 recordsLinked to original sources
PubMed1992

Anal intraepithelial neoplasia: part of a multifocal disease process.

Invasive carcinomas of the anogenital epithelium share a common aetiological factor--human papillomavirus (HPV) type 16. Although genital intraepithelial neoplasia may be multifocal, there have been no studies of the prevalence of anal intraepithelial neoplasia in women with intraepithelial neoplasia of the genital tract. We tested the hypothesis that women with high-grade cervical intraepithelial neoplasia are at higher risk of disease in the anus than are control women of similar age with no history of anogenital neoplasia. 29 (19%) of 152 women with cervical intraepithelial neoplasia grade III had histological evidence of anal intraepithelial neoplasia. Of the 29 patients, 11 had grade III anal lesions; 2 of those women had concomitant invasive anal squamous-cell carcinomas. Only 7% (8/115) women with high-grade lesions of the cervix alone had evidence of anal intraepithelial neoplasia; by contrast, 57% (21/37) of those with more than one focus of intraepithelial neoplasia (cervix plus vulva, vagina, or both) had anal lesions. HPV 16 DNA was identified in 18 (51%) of 35 anal biopsy samples in the study group. No evidence of anal intraepithelial neoplasia was found in the control group (50 women), although 2 patients had grade I cervical lesions. HPV 16 DNA was identified in 12 (24%) of biopsy samples from the cervix and 7 (14%) from the anus in the control group; all 7 women with anal HPV 16 had concomitant cervical infection. The role of anal examination in the assessment of women with any focus of genital intraepithelial neoplasia requires further investigation.

Adult↗
PubMed1992

Delay in fixation does not affect the immunoreactivity of proliferating cell nuclear antigen (PCNA).

The effect of delayed fixation on the immunoreactivity of proliferating cell nuclear antigen (PCNA) was investigated using eight breast carcinomas. Topologically shuffled samples of each tumour were immersed in fixative at times of 0.5, 1, 2, 4, 6, 18, and 24 h after surgical removal. In addition to a PCNA index (percentage of positive cells per 1200 tumour cells), a semi-quantitative PCNA grading system was used, based on estimates of more than or less than 50 per cent of positive tumour cells at each time interval. The PCNA index of six tumours increased by a mean of 10 per cent with a fixation delay of 24 h. The PCNA grade of all eight tumours showed no change with delayed fixation.

Antigens, Neoplasm↗
PubMed1992

Reassessment of the rate of fixative diffusion.

The diffusion of fixatives is slow. Early work using plasma gels and animal tissues showed the distance penetrated by a fixative to be a simple function of the fixation time but this relation has not been established in human tissues. The rates of diffusion into whole human spleens were measured for three primary fixatives over periods ranging from one to 25 days. A positive correlation was demonstrated between penetration distance (mm) and fixation time (hours). The diffusion rates were slower than those in previous studies. These results have possible implications for the handling of surgical specimens.

Diffusion↗
PubMed1992

Assessment of specimen fixation in a surgical pathology service.

The quality of specimen fixation was examined within a routine diagnostic histopathology service. For each specimen the adequacy of fixation was assessed and the transit time between operating theatre and the laboratory was measured. Preliminary fixation was found to be inadequate in 25% of specimens and some form of manipulation to assist fixation was required in 36% of specimens. The mean transit time was 22 (SD 10.7) hours. Specimen fixation and transport are additional factors to consider in quality assurance of histopathology.

England↗
PubMed1992

Nd:YAG laser endometrial ablation: histological aspects of uterine healing.

Laser ablation of the endometrium performed under hysteroscopic control is a novel procedure for the conservative management of menorrhagia in cases of dysfunctional uterine bleeding. The effect this has on the uterine cavity and the mechanism of reepithelialisation and endometrial regeneration have been examined by means of histological examination of endometrial biopsies and four hysterectomy specimens obtained for various indications at varying time intervals after laser endometrial ablation. During the first 3 months, fragments of necrotic and granulation tissue are found surrounded by a limited polymorph response. By 3 months, the uterine cavity appears to be completely reepithelialised. After 6 months, areas of normal-appearing endometrium may persist, but in other areas there is an attenuated cuboidal surface epithelium closely applied, to the underlying myometrium. Stromal fibrosis reminiscent of Asherman syndrome is also apparent.

Adult↗
PubMed1991

Is the grading of breast carcinomas affected by a delay in fixation?

The effect of delay in fixation on the modified Bloom and Richardson grade of eight breast carcinomas was investigated. Topologically shuffled samples of each tumour were immersed in fixative at times of 0.5, 2, 4, 6, 18 and 24 h after surgical removal. The grade of each tumour was assessed at delays of 0.5 and 6 h. The tubule formation and nuclear pleomorphism components of the grade showed no change with a delay in fixation of 6 h. The number of mitotic figures declined by a mean of 53% over the same period and this resulted in a decrease in the histological grade of one of the tumours. The implications of these findings for the handling of breast specimens in a diagnostic histopathological laboratory are discussed.

Breast Neoplasms↗
PubMed1991

Altered patterns of gap junction distribution in ischemic heart disease. An immunohistochemical study of human myocardium using laser scanning confocal microscopy.

Arrhythmias are a common and potentially life-threatening complication of myocardial ischemia and infarction in humans. The structural pathways for the rapid intercellular conduction of the electrical impulse that stimulates coordinated contraction in the myocardium are formed by the gap junctions situated at intercalated disks. By raising antibodies to cardiac gap-junctional protein, and using these antibodies in an immunohistochemical procedure in combination with the technique of laser scanning confocal microscopy, we have succeeded in localizing gap junctions, with a clarity not previously possible, through thick volumes of human myocardial tissue. To explore the structural basis for ischemia and infarction-related arrhythmogenesis, antibody labeling and laser scanning confocal microscopy were applied to study the organization, distribution, and other characteristics of gap junctions in the explanted hearts of patients undergoing cardiac transplantation for advanced ischemic heart disease. In areas of myocardium free from histologically detectable structural damage, there was no significant difference in the size of distribution of labeled gap junctions, or in their number per intercalated disk, between left ventricular tissue (in which functional impairment was severe) and right ventricular tissue (in which functional impairment was minimal). However, in myocytes at the border of healed infarcts--zones to which the slow conduction responsible for reentry arrhythmias has been localized--the organization of gap junctions was markedly disordered; instead of being aggregated into discrete intercalated disks, gap-junctional immunostaining was spread extensively over myocyte surfaces. Some infarct zones were bridged by continuous strands of myocytes, coupled to one another by gap junctions, thereby linking healthy myocardium on either side. At their thinnest, these bridges were in some instances no wider than a single attenuated myocyte. The conclusions are 1) a widespread, generalized derangement of gap junction organization does not appear to underlie functional impairment in the ischemic heart, 2) a disorderly arrangement typifies gap junctions in myocytes of the infarct border zone, and this may contribute to alterations in conduction that are capable of precipitating reentry arrhythmias, and 3) delicate chains of myocytes traverse some healed infarcts, apparently forming electrically coupled bridges across what would otherwise constitute blocked zones. The weakest link in this chain can be a single, degenerating myocyte; avoidance of arrhythmia may therefore depend on the continued survival of this single cell.

Antibodies↗
PubMed1979

Metabolism of the liver carcinogen N-nitrosopyrrolidine by rat liver microsomes.

This report represents a study of the total metabolism of the hepatocellular carcinogen, N-nitrosopyrrolidine (NO-PYR), by rat liver microsomes and postmicrosomal supernatant. [2,5-14C]NO-PYR, which is totally extractable from aqueous solution with methylene chloride, is converted to radioactive nonmethylene chloride-extractable products by these fractions. The initial rate of conversion to nonmethylene chloride-extractable products follows simple Michaelis-Menten kinetics with an apparent Km of 3.6 x 10(-4) M NO-PYR. The major products of NO-PYR metabolism by rat liver microsomes and postmicrosomal supernatant have been isolated and identified. One product of metabolism of NO-PYR is 2-hydroxytetrahydrofuran formed by alpha-hydroxylation by the microsomes. In the presence of postmicrosomal supernatant enzymes, this compound exists only as a transient intermediate which is rapidly converted to 1,4-butanediol or gamma-hydroxybutyrate. These compounds may be cycled into general cellular metabolism resulting in the production of CO2. Two minor pathways of metabolism have also been found.

Animals↗