Case reports--desideratum or rubbish?
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Biomedical subjects
Publications and source records attributed to R R Pascal.
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A malignant giant cell tumor of the carpal bones metastatic to the lung in a 23-year-old woman is described. Findings from ultrastructural and cell marker studies support the concept that this tumor is of histiocytic origin.
The dimensions and composition of the small intestine were studied in fed aged (27 month) and young adult (4 to 5 months) male Fischer rats maintained under barrier-reared, controlled conditions. In the proximal intestine (duodenum and jejunum) of aged rats there was no reduction in mucosal mass, protein, or deoxyribose nucleic acid, and the villus epithelium had similar dimensions and cell number as in young rats. The ileum of old rats had a 20% larger villus epithelium than those of young rats, suggesting that the function of the proximal intestine in aged rats might be impaired. In the proximal intestine of old rats, the proliferative zone was expanded, crypt depth and cell number were approximately 20% greater than in young rats. Because previous studies have shown no effect of aging upon epithelial cell migration in proximal intestine and villus height in young and old animals was not different, decreased survival of newly formed crypt epithelial cells is likely. These observations must be taken into account in the analysis of nutritional requirements and intestinal function.
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Epithelial cell migration in animal gut classically is measured by autoradiography after systemic administration of tritiated thymidine. A migration rate is calculated from observations of the leading edge of villus epithelial cells containing labeled nuclei at varying time periods after tritiated thymidine injection. This method is very accurate, but laborious, time consuming, and costly. A new, simplified method for measuring epithelial cell measurement of [3H] deoxyribonucleic acid specific activity in frozen sections of intestine cryostat-cut from villus tip to crypt base. The leading edge of [3H]deoxyribonucleic acid can be detected reproducibly (coefficient of variation 11.25%). Autoradiographic and chemical methods for determining the leading edge of labeled cells compared favorable (r=0.848). Epithelial cell migration rates in barrier-reared Fisher 344 aging (27 mo) and young control (4-5 mo) rats were compared and no differences were detected in duodenum, jejunum, or ileum. Labeled epithelial cells reached the villus tip sooner in the ileum than in duodenum or jejunum. However, crypt-villus column heights were greater in duodenum and jejunum and the calculated epithelial cell migration rate was faster in upper intestine than in the ileum. Although ileal epithelial cells are shed from the villus sooner than cells in the upper intestine, the rate of cell migration in ileum is slower.
The relationship of adenomatous polyps and hyperplastic polyps to carcinomas of the colon and rectum are discussed. There is a continuum of neoplastic alterations from adenomas to invasive carcinomas, which is defined. Clinically relevant prognostic factors in adenomas containing cancer are evaluated. Degree of differentiation, depth of invasion, and the relative amount of carcinoma are important factors.
Certain tumors of the female genital tract have a very probability of expressing CEA activity. These include endocervical carcinomas and ovarian Brenner tumors. This information may be helpful in allowing one to distinguish among several diagnostic possibilities on a given biopsy. CEA detection apparently fails to distinguish between endometrial hyperplasias versus endometrial carcinomas. Gonadal stromal tumors of the ovary are generally negative, whereas the common epithelial tumors (depending on the histological type) have a reasonable probability of having detectable antigen. Since plasma CEA levels have had a demonstrated usefulness in following patients who were known to have elevated CEA levels prior to the removal of their primary tumor in the endometrium, ovary, and cervix, it is valuable to have an estimate of probability that a tumor will express CEA in evaluating the results of plasma radioimmunoassays for this antigen.
It has been postulated that in some patients with obstructive and reflux uropathy proteinuria develops through an intermediate mechanism of immune complex glomerulonephritis involving antigenic material of renal tubular epithelium. A patient with a unilateral ureterocele and nephrotic syndrome underwent bilateral renal biopsies during surgical correction of the obstruction. The obstructed kidney showed mild pyelonephritis, but both kidneys showed a glomerulopathy with electron-dense deposits in the mesangial and paramesangial regions associated with positive immunofluorescence for immunoglobulin M (IgM) and the third component of complement (C3). An IgM antibody was eluted from the biopsy specimens and it reacted by indirect immunofluorescence with normal renal tubular epithelium and with the patient's renal tubular epithelium. The eluate also reacted with pre-eluted glomeruli of the patient, but not with normal glomeruli. All antibody activity could be removed from the eluate by pre-incubation with normal kidney. It is concluded that the unilateral renal obstruction produced tubular injury so that as yet unidentified antigens were recognized by the immune system. The resultant antibody response gave rise to circulating immune complexes which were then deposited in glomeruli with subsequent glomerular damage and nephrotic syndrome.
A patient with carcinoma of the prostate and metastases developed the nephrotic syndrome following hormonal therapy. A decrease in the dose of estrogens was associated with decreased proteinuria, but when therapy was increased the nephrotic syndrome became more severe. Renal biopsy performed when proteinuria was present showed subendothelial electron dense deposits, complement by immunofluorescence, and a morphologic pattern of membranoproliferative glomerulonephritis. There was evidence of resorption of the deposits by endothelial cells. Microspherical particles resembling those described in prostatic cancer were found in the glomeruli. On the basis of previous reports it is concluded that circulating tumor antigen-antibody complexes produced glomerulonephritis, the severity of which was related to the amount of soluble antigen released by tumor cell destruction. Apparent phagocytosis of immune complexes by glomerular endothelial cells was believed to account for the reversibility of the nephrotic syndrome. The role of the virus-like particles in the process is as yet unclear.
A patient dying of gastric carcinoma was one of a group of cancer patients examined for the presence of glomerular immune complex deposits not associated with the nephrotic syndrome. The deposits were distributed in the mesangial and subendothelial regions. This distribution is found in experimental animals with neoplasia and glomerulopathy as well as in over 30 per cent of humans with cancer. Immunofluorescence showed IgG and C3 in the patient's glomeruli. Carcinoembryonic antigen was identified in the patient's glomeruli by the immunoperoxidase staining method. An IgG antibody was eluted from the kidney and found to be reactive with the patient's tumor, as well as another patient's colonic carcinoma. This reactivity was blocked by preincubation of the tumor substrate with anticarcinoembryonic antigen. Thus, both a tumor associated antigen and a corresponding antibody were shown to be contained in the glomerular deposits. It is concluded that circulating immune complexes of high molecular weight containing carcinoembryonic antigen produced by the gastric carcinoma led to the formation of subendothelial deposits without significant renal damage. This is in contrast to the usual finding of membranous glomerulonephritis among cancer patient with the nephrotic syndrome and more closely resembles the animal models. Whereas tumor reactive antibodies can be found in the glomeruli of patients with cancer, a specific tumor associated antigen to which the antibody is reactive has only occasionally been demonstrated.
In a study of 1270 consecutive autopsies there were 314 patients with malignant neoplasms arising in sites other than the kidney and central nervous system. In over 50 per cent of these there was significant renal damage related to cancer. Renal damage was produced by direct involvement of one or both kidneys by the neoplasm or by indirect effects. The latter included ischemic damage, metabolic injury, immunologic injury, and effects of therapy directed at the malignant tumor. In patients with cancer, tumor bulk and invasion of vital organs do not always explain the clinical deterioration and cause of death. Recognition of the indirect effects of tumors on the kidney and other organ systems is essential to the understanding of the generalized host response to malignant disease.
The present communication is a brief review of the origins, theory, and applications of a relatively new immunohistochemical technique that can be performed on routinely fixed, paraffin embedded tissues in which visualization by bright field light microscopy is feasible and which thus can be readily adapted to routine diagnostic work. The chief concern of this presentation is the practical diagnostic application of the immunoperoxidase technique, a method whose reputation as a sensitive investigative tool is well established.
Immunoglobulin-containing eluates, prepared from kidneys of Paris RIII mammary tumor-bearing mice approximately 10 months old, were incubated with frozen sections of mouse mammary tumor and normal lactating mammary gland and examined by immunofluorescence. The eluates diffusely strained the tumor but did not stain the nonneoplastic lactating mammary gland. Mammary tumor and normal lactating mammary gland were both stained by an antiserum to mammary tumor virus (MuMTV). The euglobulin portion of the eluates, when fractionated on a Sephadex G-200 column, yielded an IgG fraction which was shown by immunodiffusion to react with Paris RIII mammary tumor extract and with anti-mouse globulin but not with nonneoplastic mouse tissue extracts. Since the lactating mammary glands of these animals contain MuMTV, the antibody-containing fraction eluted from the kidneys appeared to be tumor directed rather than virus directed.
A total of 58 pulmonary lesions from 48 patients were examined for carcinoembryonic antigen (CEA). The three-layer immunoperoxidase procedure for antigen detection was used with a monospecific anti-CEA antiserum. The control serum was the same antiserum with its specificity removed by affinity chromatography. Normal goat serum was also used as a control. Carcinoembryonic antigen was present in the majority of pulmonary adenocarcinomas and generally absent in the squamous cancers. The major exception was in the well-differentiated squamous lesions where CEA was occasionally found in the keratinizing areas. Of special interest was the finding of CEA in all areas of intraepithelial squamous neoplasia studied.
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