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Biomedical subjects

A M Shamsuddin

Publications and source records attributed to A M Shamsuddin.

At least 55 records · Page 3Linked to original sources
PubMed1985

Carcinoma in situ in nonpolypoid mucosa of the large intestine. Report of a case with significance in strategies for early detection.

A case of carcinoma in situ of the flat, nonpolypoid mucosa of the large intestine in a 32-year-old man is reported. This case is of unusual importance because it was detected by endoscopy and was effectively managed; it sheds further light into the histogenesis of large intestinal carcinomas; and it points to alternate strategies for early detection and prevention of large intestinal carcinomas.

Adult↗
PubMed1985

Transformation of human bronchial epithelial cells transfected by Harvey ras oncogene.

Transfection of normal human bronchial epithelial (NHBE) cells with a plasmid carrying the ras oncogene of Harvey murine sarcoma virus (v-Ha ras) changed the growth requirements, terminal differentiation, and tumorigenicity of the recipient cells. One of the cell lines isolated after transfection (TBE-1) was studied extensively and shown to contain v-Ha ras DNA. Total cellular RNA from TBE-1 cells hybridized to v-Ha ras structural gene fragment probes five to eight times more than RNA from parental NHBE cells. The TBE-1 cells expressed phosphorylated v-Ha ras polypeptide p21, showed a reduced requirement for growth-factor supplements, and became aneuploid as an early cellular response to v-Ha ras expression. As the transfectants acquire an indefinite life-span and anchorage independence they became transplantable tumor cells and showed many phenotypic changes suggesting a pleiotropic mechanism for the role of Ha ras in human carcinogenesis.

Animals↗
PubMed1985

Microscopic analysis of the mastoid bone in chronic serous otitis media.

The pathologic changes of the middle ear and mastoid bone mucosa in two pediatric patients with long standing chronic serous otitis media were studied by electron and light microscopy. The embryological development of the eustachian tube, middle ear cleft, and mastoid bone suggests a common physiological and anatomical continuity. The histological changes by light and electron microscopy in these patients demonstrates the metaplastic changes of the basal cell of the mucosa differentiating into mucous and keratin cells. These metaplastic changes are associated with the exudative process known as chronic serous otitis media.

Biopsy↗
PubMed1985

Distribution of blood group antigens A, B, H, Lewisa, and Lewisb in human normal, fetal, and malignant colonic tissue.

In humans, most blood group substances (BGS) are expressed throughout the fetal colon but are absent from the distal portion of adult colon. Cancers of the distal colon frequently reexpress BGS thereby suggesting that these antigens behave as oncofetal antigens at this organ site. We used a sensitive immunoperoxidase method with monoclonal antibodies directed against blood groups A, B, O (H), Lewisa and Lewisb to systematically evaluate BGS expression in fetal colon, normal adult colon from immediate autopsies of kidney donors, mucosa adjacent to cancer (transitional mucosa) and colorectal cancer tissues. In normal colon, BG-A, B, H, and Lewisb were expressed in proximal but not distal colon, whereas Lewisa was distributed uniformly throughout the colon. In colon cancer, and fetal colon, the proximal-distal gradient of BG-A, B, H, and Lewisb expression was abolished because of enhanced distal expression of these antigens. In cancer tissues, three patterns of altered BGS expression emerged: (a) incompatible expression of BG-A or BG-B (over 50% of patients); (b) deletion of BGS; and (c) precursor BG-H accumulation (80% of 25 tumors). BGS staining of transitional mucosa closely resembled that of the adjacent tumor except that no examples of BGS deletion were encountered in transitional mucosa. The goblet cell secretory vacuole accounted for most of the BGS expression in normal colon, but cancer cells demonstrated differentiation-dependent antigenic expression such that well-differentiated tumors expressed BGS on cell apical membranes and glandular contents, but poorly differentiated cancers exhibited diffuse cytoplasmic staining. These findings confirm the oncofetal nature of BGS in distal colon cancer, and provide immunohistochemical evidence for a diverse repertoire of altered antigen expression in colon cancer. Further investigation is needed to elucidate the possible genetic and biochemical mechanisms involved.

ABO Blood-Group System↗
PubMed1984

Induction of squamous differentiation of normal human bronchial epithelial cells by small amounts of serum.

Recently we reported a low calcium (110 microM) serum-free medium (LHC-1) for clonal growth of normal human bronchial epithelial (NHBE) cells. NHBE cells within colonies are small (mean surface area = 1,250 mu2) rarely migratory, have few tonofilaments, and multiply with an average population doubling time of 28 h. We have also noted that adding small amounts of blood-derived serum to LHC-1 medium (as little as 2%) significantly decreased the clonal growth rate. We have now found that the growth inhibiting effect of serum is due to the induction of squamous (terminal) differentiation. Serum quickly increases the size of the cells (mean surface area = 4,900 mu2). In addition, the cells acquire numerous desmosomal junctions and an extensive network of keratin bundles. In contrast, human lung carcinoma cells multiply rapidly at clonal density in LHC-1 medium containing as much as 8% serum. Although high concentrations of calcium ions in the medium are known to induce squamous differentiation of epidermal keratinocytes in the absence of serum, high levels of Ca2+ (up to 1,000 microM) increased the number of desmosomal junctions, but did not significantly affect the clonal growth rate or size of the NHBE cells. However, high concentrations of calcium (above 450 microM) were found to potentiate serum differentiation-inducing activity. On the other hand, cholera toxin (10 ng/ml) inhibited the differentiation-inducing activity of serum. These results show that squamous differentiation of NHBE cells can be induced by serum and the potency of these serum factors can be modulated. In addition, the data show that lung carcinoma cells differ from their normal counterparts by not undergoing differentiation in the presence of serum.

Blood Physiological Phenomena↗
PubMed1984

Comparative studies of primary, metastatic and transplanted colon adenocarcinomas of Fischer 344 rats.

Morphological and histochemical characteristics of two sets of metastatic and transplanted adenocarcinomas were compared to those of the parent primary colon carcinomas induced by azoxymethane (8 mg/kg/week) in Fischer 344 rats. The histochemical features of the primary carcinomas and their respective metastatic and transplanted carcinomas were similar; however, there were marked morphological differences between these lesions. The primary adenocarcinomas were both well-differentiated glandular and mucinous colloid in type. Histochemically, both the types showed marked diminution of sulfomucin and increased sialomucin in the primary lesions as well as in the secondary sites. By light microscopy, the general histological pattern of the primary carcinoma was maintained by the secondary lesions. Compared to normal colon epithelia, the primary carcinoma showed mildly increased exfoliation of cells, and the transplanted carcinomas demonstrated profound exfoliation of epithelial cells in the glandular lumen, whereas the metastatic carcinomas showed moderate exfoliation. The three basic cell types of colon (undifferentiated cells, mucous cells and endocrine cells) were seen in variable proportions in the primary and secondary lesions with inconsistent pattern of cellular differentiation in the secondary lesions of the same primary. In the liver, intercellular junctions were seen between the metastatic carcinoma cells and the host hepatocytes indicating establishment of physical and probably biological communication between the metastatic cancer cells and the host cells.

Adenocarcinoma↗
PubMed1984

Large intestinal carcinogenesis. I. Promotional effect of dietary fatty acid isomers in the rat model.

For evaluation of the promotional effects of dietary trans-fatty acids on large intestinal carcinogenesis, 120 inbred female F344 rats were divided into 6 groups and fed a 25% elaidic acid diet, a 25% oleic acid diet, or a regular (4.5% fat) chow diet. Ninety animals, 30 per dietary group, received weekly im injections of azoxymethane (2 mg/kg; CAS: 25843-45-2). None of the 30 saline-injected control animals, 10 per dietary group, fed any of the three diets developed tumors. There were twice as many animals with adenocarcinoma of the large intestine from the trans-fatty acid diet group as compared with either the cis-fatty acid diet group or regular diet groups. Chi-square analysis showed that the difference between the incidence of large intestinal carcinomas was not significant between the cis- and trans-fatty acid diets. The difference between the regular diet and trans-fatty acid diet groups was not significant at the 5% level (P = .08). A higher, but nonstatistically significant, incidence of nephroblastomas and squamous ear duct neoplasms was also observed in carcinogen-treated animals maintained on each of the high-fat diets as compared with the incidence of both in treated animals fed the regular chow diet.

Animals↗
PubMed1984

Large intestinal carcinogenesis. II. Histogenesis and unusual features of low-dose azoxymethane-induced carcinomas in F344 rats.

The histogenesis of large intestinal carcinomas was studied by use of a low dose (2 mg/kg/wk) of azoxymethane [(AOM) CAS: 25843-45-2] administered im to inbred F344 rats. No evidence of benign polyp was seen, and the carcinomas in this model did arise directly from the flat mucosa. In marked contrast to the standard dose (8 mg/kg/wk) studies, low-dose AOM carcinogenesis yielded the following unusual features: a) There was a very high incidence of readily metastasizing mucinous adenocarcinomas that were extremely aggressive and easily transplantable; b) the carcinomas, microscopic and macroscopic, were localized predominantly in the proximal large intestine; c) foci of atypical early neoplastic (or so-called dysplastic) crypts as well as early carcinomas were frequently associated with the lymphoid aggregates in the intestinal wall; d) Paneth cells were commonly seen to be associated with these atypical crypts and/or early carcinomas associated with the lymphoid aggregates; and e) there was a virtual lack of the dilated, distorted, or hyperdistended crypts in noncarcinomatous epithelia. The significance of the lack of dilated, distorted, hyperdistended crypts and the similarity of this finding with the findings in the low incidence of colon cancer in the Japanese population are discussed.

Animals↗
PubMed1984

Large intestinal carcinogenesis. III. Studies in low-incidence (Japanese) patients.

Recent studies have demonstrated that at the early stages of carcinogenesis of the large intestine(s) (LI), severely dilated crypt(s) (SDC) appear followed by atypical and/or neoplastic crypt(s) (ANC) and, subsequently, carcinomas. Thus both SDC and ANC appear to be premalignant changes and are probably initiated foci. Since the Japanese in Japan (JIJ) show a much lower rate of large intestinal carcinomas (LIC) compared to people in the Western Hemisphere, a study was designed to answer the question: Is the difference between the rates due to a difference in initiation or promotion? If the difference is due to less initiation, large intestinal epithelium of JIJ should contain fewer initiated foci. For testing this hypothesis, a retrospective histopathologic study was conducted on 100 LI of JIJ resected at the Cancer Institute, Tokyo, Japan, between 1977 and 1978, and mucosae remote from carcinomas were examined for SDC and ANC. In sharp contrast to a 100% incidence of SDC in the cases in the United States, only 1 of 100 LI of patients with LIC at the Cancer Institute demonstrated the presence of SDC. However, ANC was seen in 10 of 100 LI (10%), a figure comparable to that in the United States (7%). The extreme rarity of SDC in JIJ represents lesser initiation of that type. The presence of a comparable number of ANC in JIJ indicates that ANC is the predominant morphologic type of initiated foci in JIJ. This study suggests that not only promotional agents but also different initiating factors may be responsible for the difference in incidence and prevalence of LIC in the two populations. Comparative studies of parallel experimental animal models with the use of high and low doses of azoxymethane support this conclusion.

Adolescent↗
PubMed1983

Improved enzyme immunoassays using biotin-avidin-enzyme complex.

Using the characteristic of a high-affinity complex between enzyme-conjugated avidin and biotin, we improved the techniques of enzyme-linked immunosorbent assay and ultrasensitive enzymatic radioimmunoassay. The method included biotinylation of a specific antibody, complexing of a biotinylated antibody with avidin-alkaline phosphatase conjugate, and addition of the antibody-conjugate complex (with or without a standard amount of antigen for competitive or noncompetitive assays, respectively) to the microtiter wells containing antigen in the solid phase. Once biotinylated, antibodies could be stored for several months. Complexing of biotinylated antibody with avidin-alkaline phosphatase conjugate could also be performed once, and the stock solution could be used for several days. Thus, the steps of enzyme immunoassays were reduced to the addition of only antibody-conjugate complex and enzyme substrate. The improved assays, biotin-avidin-linked enzyme immunoassay and biotin-avidin-linked ultrasensitive radioimmunoassay, were simpler, quicker, less expensive, and more sensitive than their standard counterparts.

Alkaline Phosphatase↗
PubMed1983

Comparative study of the morphologic, histochemical, and proliferative changes induced in the large intestine of ICR/Ha and C57BL/Ha mice by 1,2-dimethylhydrazine.

The mouse model of 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis was studied to determine the susceptibility of different anatomic segments of the large intestine in ICR/Ha (susceptible) and C57BL/Ha (resistant) mice. In ICR/Ha mice numerous exophytic macroscopic neoplasms were found in the distal colon and rectum after 15 weekly injections of DMH (20 mg/kg). The proximal colon was free of any microscopic or macroscopic neoplasms. In contrast, C57BL/Ha mice given the same treatment showed no macroscopic neoplasms. However, foci of dysplastic crypts were observed throughout the large intestine of C57BL/Ha mice with highest incidence in the distal colon and rectum. In some areas dysplastic crypts were clearly invading the muscularis mucosae and were, therefore, microscopic carcinomas (microcarcinomas). Thus C57BL/Ha mice were not totally resistant to the neoplastic stimulus of DMH, and the susceptibility of the large intestine is site-specific in both mouse strains.

1,2-Dimethylhydrazine↗
PubMed1983

Differential control by platelet factors of squamous differentiation in normal and malignant human bronchial epithelial cells.

Recently, we developed a nutritionally optimal medium for rapid clonal growth (greater than 1 population doubling/day) of normal human bronchial epithelial (NHBE) cells. Adding fetal bovine or adult human blood-derived serum to this medium depresses the clonal growth rate of NHBE cells in a dose-dependent fashion. In contrast, 10 representative lines of human lung carcinomas either replicate poorly or fail to grow at all when inoculated at clonal density in serum-free medium, and their rates of multiplication increase in direct proportion to the amount of blood-divided serum added to the optimized medium. Thus, the growth factor requirements of these lung carcinoma cell lines are significantly different from those of their normal counterparts. Blood-divided serum reduces the clonal growth rate of NHBE cells by specifically inducing the normal cells, but not lung carcinoma cells, to undergo squamous differentiation. The differentiation-inducing activity was found in platelet lysates. In addition, a growth-inhibiting activity that did not induce squamous differentiation of NHBE cells was also identified in partially purified commercial preparations of platelet-derived growth factor. This observation was in marked contrast to results using human bronchial fibroblasts and human lung carcinoma cell lines; the growth rate of the former was significantly stimulated by commercial preparations of platelet-derived growth factor, whereas the growth rates of the tumor cell lines were unaffected. These results indicate that an aberration in the cellular differentiation as assayed in vitro is positively correlated with cancer and suggests that decreased responsiveness to inducer(s) of differentiation may be a major aspect of bronchial cell carcinogenesis.

Bronchi↗
PubMed1982

A comparative study of the normal histochemical and proliferative properties of the large intestine in ICR/Ha and C57Bl/Ha mice.

The histochemical staining, labeling index and incorporation of [3H] thymidine [TdR] in large intestinal epithelium were compared in four anatomically distinct segments from ICR/Ha and C57Bl/Ha mice. This comparison was done because the incidence of 1,2-dimethylhydrazine (DMH)-induced carcinomas is different for different anatomic segments as well as for the two strains. Within each strain, the amount of [3H] TdR incorporated into mucosal DNA was found to vary less than 20% at each anatomic site of the large intestine. However, there were site-specific differences in the depth of the proliferative populations within the crypts. In autoradiograms from both strains, the crypts of the proximal colon showed maximal [3H] TdR labeling of nuclei in mid-crypt cells, some of which contained mucin. In contrast, the distal colon and rectum were characterized by maximal nuclear labeling in a population of undifferentiated cells near the base of each crypt. In distal ICR/Ha colon, the proportion of labeled nuclei at each crypt depth corresponded to the [3H] TdR labeling of DNA that had been isolated from frozen sections cut sequentially. As visualized with alcian blue-periodic acid Schiff (AB-PAS) and high iron diamine-alcian blue (HID-AB) stains, the epithelial mucin showed site-specific differences, but the differences between the two strains of mice were not remarkable. In contrast to the human and rat large intestine, the acidic mucin in the mouse large intestine was predominantly sialomucin. However in the cecum and mid-distal colon, there was a predominance of sulfomucin. In the various anatomic segments of both strains, the histochemical staining, labeling index and incorporation of [3H]TdR were remarkably similar considering the large differences in susceptibility to chemically-induced neoplastic change.

Animals↗
PubMed1982

Microscopic intraepithelial neoplasia in large bowel mucosa.

Early neoplastic changes within the nonpolypoid mucosa of the large bowel have been incidentally discovered in two individuals. One of these patients is a 31-year-old man without any known large bowel disease; the other is a 61-year-old woman with diverticulosis. Only small microscopic foci of several neoplastic crypts were observed in otherwise normal-appearing mucosa. This finding lends support to the concept that cells in the crypts, irrespective of their location either in the flat mucosa, polyps, diverticula, or elsewhere, are susceptible to neoplastic transformation.

Adult↗
PubMed1982

Extrahepatic biliary obstruction and liver failure secondary to myeloma of the pancreas.

An unusual case of multiple myeloma in an 88-year-old patient is described. Besides skeletal involvement, there was myeloma of the thoracic and abdominal lymph nodes and of the liver and pancreas. In the pancreas, the myeloma extensively involved the head and body, and on computerized tomography scan was suggestive of a pancreatic carcinoma. The myeloma caused extrinsic compression of the common bile duct, resulting in severe jaundice and hepatic and renal failure. To the author's knowledge this is the second such case of pancreatic myeloma causing extrahepatic biliary obstruction.

Acute Kidney Injury↗
PubMed1982

Human large intestinal epithelium: light microscopy, histochemistry, and ultrastructure.

Despite numerous reports of morphologic characteristics of premalignant and malignant large intestinal epithelium, the literature lacks comprehensive reports of the morphologic features of the epithelium of the normal large intestine, except of the rectum. Large intestinal epithelium from 41 persons was obtained, and samples from the ascending, transverse, descending, and rectosigmoid areas were studied by light microscopy, histochemical techniques, and transmission and scanning electron microscopy. The morphologic features and histochemical reactions of the various segments of the large intestine are different. Neutral mucopolysaccharide is predominant in the ascending colon, whereas the rectum has predominantly or exclusively acidic mucin. Only three basic epithelial cell phenotypes have been identified: undifferentiated cells, mucous cells, and endocrine cells. The columnar cells at the surface between the crypts appear to be a variant of mucous cells. Compared with other segments, the rectum shows an unusually high concentration of endocrine cells, positively correlating with the high incidence of carcinoid tumors in that segment of the large intestine. The mucous cells in all segments contain large mucous vacuoles and small apical vesicles. The apical vesicles show variable electron density, being most dense in the ascending colon and becoming progressively less dense at the transverse and descending colon and most electron-lucent in the sigmoid colon and rectum. Ultrastructurally, the mucin shows a variable degree of heterogeneity in the proximal segments. This study suggests that some of the previously described ultrastructural features of abnormal large-intestinal epithelium may be only the result of failure to compare the so-called abnormal cells with normal cells from the same region. Well-controlled studies of the abnormal epithelium of a particular segment of large intestine must include the normal epithelium from the identical segment as control in order to make interpretations accurate.

Adult↗
PubMed1982

Morphogenesis of colonic carcinoma. Ultrastructural studies of azoxymethane-induced early lesions in colon epithelium of Fischer 344 rats.

Marked dilation and distortion of the crypts have been observed in the colonic epithelium of Fischer-344 rats after four to six weekly doses of azoxymethane (8 mg/kg). These changes precede malignant transformation in this model and, therefore, may be considered premalignant. Ultrastructural morphologic aspects of these crypts can arbitrarily be divided into three stages: an early stage of increased mucus secretion and "exhausted" appearance of mucous cells; an intermediate stage of severe crypt dilation, with extreme thinning of crypt epithelium and neutrophilic emigration to the mucous pool of the crypt lumen; and a late stage characterized by repopulation of the crypts, with epithelial cells showing an increased nuclear-cytoplasmic ratio and bizarre nuclei and nucleoli. The surface epithelium between the crypts shows increased cell loss and alterations of cell membrane. Similar structure of crypts has been described in the mucosa remote from carcinomas in rats and humans, and in various precancerous changes in humans (ie, ulcerative colitis and Crohn's disease). Therefore, I propose that these lesions are significant in human colon carcinogenesis as well.

Animals↗