Biomedical subjects
Publications and source records attributed to D L Page.
A 29-year-old black woman had a peculiar variety of chronic pancreatitis that initially presented as a solid, discrete mass in the head of the pancreas. It mimicked carcinoma and exemplifies the diagnostic and therapeutic dilemma produced by such "pseudotumors" of the pancreas.
A histological review of 1003 invasive breast carcinomas identified 51 tumours in which the invasive component showed a predominantly cribriform pattern. These separated into two groups; 35 which showed exclusively cribriform or cribriform with a limited extent of tubular invasive elements only, designated 'classical' invasive cribriform carcinoma and 16 which also contained areas of less well differentiated invasive carcinoma, designated 'mixed' invasive cribriform carcinoma. At follow-up, 10 to 21 years after diagnosis, none of the 35 patients with classical invasive cribriform carcinoma had died as a result of this initial carcinoma and 30 remained alive. Of the 16 remaining patients, whose tumours showed areas of less well differentiated carcinoma, only six remained alive. However, the adjusted 10 years survival rate of these patients in this mixed group was significantly better than that of invasive carcinoma in Edinburgh. Invasive cribriform carcinoma in its classical form, is a histological subgroup of invasive carcinoma with the same excellent prognosis as that of invasive tubular carcinoma.
Administration of the antioxidant vitamin E to rats, prior to administration of either streptozotocin or alloxan, provided protection against the diabetogenic effect of both these agents. This was demonstrated by their response to a glucose load, their pancreatic insulin content and light microscopy findings. In addition, rats whose antioxidant state was depleted, by being maintained on a vitamin E and selenium-deficient diet, demonstrated increased diabetogenic susceptibility to normally nondiabetogenic doses of streptozotocin. These findings provide indirect support for the suggestion that the chemical agents streptozotocin and alloxan may exert their diabetogenic effect by acting as oxidants or free radical producers.
Twenty-eight women with ductal carcinoma in situ (DCIS) of the breast treated by biopsy only were identified in a histologic review of 11,760 biopsies performed between 1950 and 1968. Seven of the 25 women followed for more than three years developed invasive breast carcinoma, all in the same breast with a previously detected DCIS. Average follow-up interval for the 18 women not developing invasive carcinoma was 16 years. The invasive carcinomas presented clinically from three to ten years (average, 6.1) after the biopsies demonstrating DCIS. Four women with invasive carcinoma developed distant metastases following mastectomy. This study suggests that 28% of women treated with biopsy only for DCIS presenting as an incidental histologic finding will develop invasive carcinoma in a follow-up period of approximately 15 years.
On review of the histology of 1050 primary breast carcinomas, 103 cases of infiltrating lobular carcinoma were identified and clinical and survival data collected in each case. The tumours were then separated into four groups on the basis of histological pattern and these groups shown to have significantly different survival times. Assessment of the presence of in situ carcinoma, elastosis and intracytoplasmic lumina was performed in each case and the effect of these features on survival investigated. In addition to stage of disease at presentation, the major significant factor in predicting survival of patients with this type of invasive carcinoma is histological type.
We have investigated the appearance of specific nonhistone proteins during azo dye-induced hepatocarcinogenesis in the rat. Groups of animals fed azo dye-containing diet were sacrificed at approximately 3-week intervals, portions of their livers were examined histologically, and the remaining material was fractionated into chromatin and cytoplasmic fractions. Livers of the azo dye-fed animals exhibited histological changes that have been classically attributed to the course and development of cancer; by 28 to 30 weeks of treatment, nearly all animals had developed hepatomas. Heterogeneous rabbit antisera were prepared to dehistonized chromatin from several azo dye-induced hepatomas. These antisera were then used to assess various chromatins for the appearance of antigens specific for neoplasia during inducing carcinogenesis using immunodetection of antigens separated electrophoretically and transferred to nitrocellulose. Changes in the immunoreactivity of liver chromosomal proteins during carcinogen treatment were evident after 3 weeks, and the antigenic profiles of various chromatin samples gradually assumed the characteristics of the hepatoma. The transformation was accompanied by qualitative changes in chromosomal protein antigens, and although these antigenic species were not directly quantitated, noticeable enrichment of tumor-specific species occurred with treatment time. Immunotransfer assays of cytoplasmic fractions indicated most antigens to be specific for chromatin. Normal tissue chromatin exhibited minimal immunoreactivity, and slightly more antigenic homology was noted with regenerating liver and most transplantable tumor chromatins. Interestingly, the transplantable tumor Walker 256 carcinosarcoma was highly enriched in antigens recognized by antisera to azo dye hepatoma dehistonized chromatin. These studies establish a define chronological correlation between the chemical induction of cancer and sequential changes in the immunological specificity of nonhistone protein antigens.
Antiserum to dehistonized chromatin from human colon adenocarcinoma cell line HT-29 was raised in rabbits and used for the immunodetection of colon tumor-associated nuclear antigens. Quantitative microcomplement-fixation studies indicated that the antiserum had reactivity similar to those of chromatins of two human colon adenocarcinoma cell lines (HT-29 and LoVo) and with nonneoplastic colon. Immunocytochemical localization showed the chromatin antigens to be evenly dispersed throughout the nucleus. Immunochemical staining of electrophoretically separated chromosomal proteins transferred to nitrocellulose sheets revealed several intensely staining antigens predominantly in the molecular weight range of 62,000 to 75,000. When the antiserum was immunoabsorbed with nonneoplastic human colon chromatin, two antigens with molecular weights of 67,000 and 92,000 were identified only with the tumor chromatins. Antiserum immunoabsorbed with either LoVo or HT-29 chromatin failed to show any immunoreactivity, suggesting that these tumor-associated proteins, or antigenic sites residing on these proteins, are identical in both colon tumor cell lines.
Although the etiology of human breast cancer is unknown, certain epidemiological parameters such as risk of breast cancer development. Concurrent, retrospective and prospective studies have shown that one particular component of benign breast disease -- epithelial hyperplasia, may be responsible for the increase in risk. Several classification have been devised for epithelial hyperplasia of the human breast using light microscopy. By scanning electron microscopy epithelial hyperplasia in ducts has several patterns: focal hyperplasia, simple columnar bridging, complex bridging and solid hyperplasia. Although these patterns may be seen in non-cancerous ducts in both malignant and non-malignant cases, alterations in microvillus structure and number have only been seen to date in malignant cases.
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An 18-year-old man with a history of Cushing's disease was treated with a total right and a near total left adrenalectomy in 1956. Pathologic examination of the operative specimen revealed bilateral adrenal hyperplasia. After 13 years, recurrence of symptoms of cortisol excess necessitated cobalt irradiation to the pituitary, which was without clinical effect. After an initial response to the adrenolytic agent, o,p'-DDD, partial relapse occurred. At this time, the recognition of an abdominal mass prompted abdominal exploration revealing a huge adrenal myelolipoma containing adrenal cortical cells distributed diffusely throughout the tumor. Symptoms of adrenal insufficiency developed, and adrenal steroid secretion did not respond to exogenous adrenocorticotropic hormone postoperatively. The case illustrates that adrenal myelolipomas may become very large with continued stimulation by adrenocorticotropic hormone, may contain significant amounts of adrenal cortical tissue, and may be associated with clinical hypercortisolism.
The clinical and pathologic features of four sebaceous carcinomas primary located in the eyelids were studied in detail. The neoplasms occurred in four patients of ages 62 to 76 years, were often misdiagnosed at initial excision, and recurred in all four cases. Three of the four cases required orbital exenteration, and preauricular lymph node metastases developed in two. The tumors were characterized by variable histologic growth patterns and evidence of sebaceous differentiation. Pagetoid spread of the neoplastic cells in the overlying epithelium was found in all four cases. Recognition of the pagetoid growth pattern in biopsy material was essential in correctly diagnosing two of the four cases. It is one of the important features enabling sebaceous carcinoma to be distinguished from basal cell carcinomas showing sebaceous differentiation.
Existing views on prorenin are conflicting and its physiological activation mechanism is not clear. In an attempt to obtain clearcut views on the molecular properties of prorenin in human plasma, the renin zymogen (prorenin) was separated from active renin by two steps of affinity chromatography and it was demonstrated that prorenin is a completely inactivate zymogen contrary to the existing information. Inactive prorenin has an apparent molecular of 56,000 contrary to 46,000-43,000 of partially active prorenin. Isolated and acid-treated human prorenin was shown to be activated by kallikreins from human urine and plasma. This activation was completely blocked by Trasylol. Hog pancreatic kallikrein also activated human prorenin. The kallikrein mediated activation of prorenin indicates the existence of a new link between the vasoconstricting renin-angiotensin system and the vasodilating kallikreinkinin system.
Forty-one patients with adrenal cortical tumors were evaluated retrospectively for the presence of histologic and non-histologic features associated with malignant behavior. The patients who survived operation were followed at least five years. The association of these features with subsequent metastasis was examined by both parametric and nonparametric statistical methods. Twelve criteria were statistically significant in predicting subsequent metastasis. The most significant of these were: clinical evidence of weight loss, broad fibrous bands traversing the tumor, a diffuse growth pattern, vascular invasion, tumor cell necrosis, and tumor mass. The tendency toward metastasis for each tumor was expressed in indices that correlated well with diagnoses made by conventional histologic means, but were more accurate in predicting subsequent clinical behavior than nonquantitative methods of evaluation.
Technetium-99m-stannous pyrophosphate scintiphotos were evaluated for diagnosing and quantitating myocardial infarct (MI) extension in sedated dogs. Infarction and extension were produced by serial left anterior descending coronary artery ligations at 0 and 48 hours. We compared serial scintiphoto data with regional myocardial blood flow (MBF) (microsphere technique) and infarct histopathology. In eight control dogs, the scintigraphic MI area was stable at 24, 48, and 72 hours. In each of 11 dogs undergoing extension, the MI area increased after the 48-hour occlusion, averaging a 48.9% increase (p less than 0.001). Grossly, most extensions were mixtures of confluent necrosis and moderate (patchy) necrosis. MBF to confluent infarct tissue decreased significantly, allowing the documentation of extension by totaling the grams of newly flow-deprived tissue, but patchy infarct tissue had little flow deprivation, making it difficult to quantitate this type of extension accurately by flow criteria alone. Rarely, extension could be diagnosed using conventional histologic criteria. We concluded that the scintiphoto MI area was related quantitatively to infarct weight in both control and extension. However, it was not possible to determine that an increase in the MI scintiphoto area was an accurate predictor of the degree of extension using independent flow or pathologic criteria.
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Non-histone protein-DNA complexes isolated from human lung tissue were used to immunize New Zealand rabbits. Quantitative microcomplement fixation and immunocytochemistry revealed a specific chromatin antigen(s) in the human granulocyte nucleus. The study demonstrates the feasibility of employing antisera against chromosomal non-histone protein-DNA complexes for the immunochemical identification of cell types.
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