Search PubMedSearch

Biomedical subjects

A K Shamsuddin

Publications and source records attributed to A K Shamsuddin.

At least 19 recordsLinked to original sources

Immunocytochemical localization of benzo(a)pyrene-DNA adducts in human tissue.

Specimens of human lung, uterine cervix, ovary, and placenta were studied for the presence of benzo(a)pyrene 7,8-diol 9,10 epoxide (BPDE)-DNA adducts by using rabbit anti-BPDE-DNA antibody and light microscopic immunocytochemistry. BPDE-DNA antigenicity was detected in the bronchial epithelial cells, cervical epithelium, oocytes, luteal cells, corpora albicans, and hyalinized media of arteries within the ovaries and trophoblastic cells of the placental villi. In conjunction with immunoassay detection of BPDE-DNA adducts in human peripheral blood lymphocytes, this study demonstrates that a variety of human tissues can metabolize and bind the ubiquitous carcinogen benzo(a)pyrene. The identification and localization of this carcinogen-DNA antigenicity in various tissues and cells may not only help in monitoring exposed persons but also give insight to organ site carcinogenesis, transplacental carcinogenesis, and teratogenesis.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

Is the corneal posterior cell layer truly endothelial?

The posterior cell layer of the normal human cornea or "endothelium" was investigated by electron microscopy and immunocytochemistry. Ultrastructurally, the cells lacked the characteristic marker for endothelial cells (Weibel-Palade body). Immunoperoxidase studies demonstrated these cells to be negative for factor VIII antigen, but strongly positive for keratine, vimentin, S-100 protein, and neuron-specific enolase. The anterior epithelial cell layer showed identical immunoreactivity. These studies strongly suggest that the posterior cell layer of the cornea lacks ultrastructural and immunocytochemical markers of endothelial cells and both the anterior and posterior cell layers share similar cell markers. The authors propose that the posterior cell layer of the cornea should, therefore, not be misnamed as "endothelium."

Cells

Malignant conversion and metastasis of mouse skin tumors: a comparison of SENCAR and CD-1 mice.

The progression of papillomas to squamous cell carcinomas (malignant conversion) was studied in the skin of SENCAR and Charles River CD-1 mice, using a three-stage treatment protocol. After initiation with 7,12-dimethylbenz(a)anthracene (DMBA) (stage 1) and limited promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) (stage II), papilloma-bearing mice were treated (stage III) with either tumor initiators, such as urethane, N-methyl-N'nitro-N-nitrosoguanidine (MNNG) or 4-nitroquinoline-n-oxide (R-NQO), the promoter TPA, or solvent (acetone). Similar final carcinoma yields were found in the mice treated in stage III with TPA or acetone, although carcinomas developed earlier in the TPA-treated mice. In contrast, treatment with tumor initiators in stage III increased both the rate of appearance and the final yield of carcinomas. Similar results were obtained in both SENCAR and CD-1 mice. A papilloma stage appears to be necessary for carcinoma development since elimination of TPA treatment in stage II greatly reduced the incidence of both papillomas and carcinomas in both stocks of mice. The heterogeneity of papillomas with regard to progression to carcinomas is demonstrated by the low rate of conversion of TPA-dependent papillomas and the high rate of conversion of persistent papillomas in CD-1 mice. The carcinomas that develop using the three-stage regimen vary in metastatic potential. In CD-1 mice, the frequency of metastases to lymph nodes were similar in groups treated in stage III with MNNG, urethane, 4-NQO, TPA, or acetone, but treatment with urethane substantially increased metastases to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ultrastructural features of normal mouse colon epithelium. Unique characteristics of a species.

Ultrastructural studies of the colon epithelium of normal C57Bl/Ha and ICR/Ha mice revealed some unique characteristics not seen in human or rat colon. The most striking feature was the presence of a unique type of intracytoplasmic organelle with crystalline internal structure. These organelles measured 1-2 micron in diameter, usually rounded or oval showing marked variation in size and shape. They were surrounded by a single layer of trilaminar plasma membrane and their core structure was mildly electron dense with markedly dense crystalline substructure. Grimelius silver stain done at ultrastructural level revealed these to have staining properties identical to neuroendocrine granules. Approximately 1-5% of the epithelial cells of mouse colon were usually filled with these organelles. But occasionally they were also present in the endocrine cells of colon. The other striking feature of the mouse colon epithelium is the presence of an inordinate number of bacteria. These rod shaped bacteria were present deep inside crypts in large numbers. They were also present within the goblet type of mucous cells and the so-called columnar cells of the surface epithelium. A third unique feature of mouse colon was the presence of mitotic figures in cells with conspicuous mucous vacuoles. This contrasts with human and rat colon where mitosis occurs in cells with little or no mucus. Since the ultrastructural morphology of the normal mouse colon is distinctly different from the human and rat, caution must be exercised in extrapolating colon carcinogenesis data from mouse to human.

Animals

Detection of benzo(a)pyrene:DNA adducts in human white blood cells.

Metabolic activation of benzo(a)pyrene (BP) to its ultimate carcinogenic form, 7 beta, 8 alpha-diol-9 alpha, 10 alpha-benzo(a)pyrene epoxide (BPDE), and the binding of BPDE to DNA are important steps in BP carcinogenicity in experimental animals. Since people of certain occupations are exposed to high concentrations of BP, we have used enzyme-linked immunosorbent assay and ultrasensitive enzymatic radioimmunoassay to measure BPDE:DNA adducts in white blood cells from 2 of these occupational groups. Seven of 28 samples from roofers and 7 of 20 samples from foundry workers were positive for BPDE:DNA adducts (range, 2 to 120 fmol BPDE/50 micrograms DNA). In a group of nine volunteers without these industrial exposures to BP, the two positive DNA samples were from cigarette smokers. Control DNA obtained from human lymphocyte cell line RPMI 4265 was negative. These results indicate that the metabolic activation of BP and formation of BPDE:DNA adducts occurs in humans.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

Mucinous colloid adenocarcinoma of colon in Fischer-344 rats. Light microscopy, histochemistry and ultrastructure.

Azoxymethane (AOM) induced mucinous colloid adenocarcinomas of the colon have been studied by light microscopy, histochemistry and transmission electron microscopy. This neoplasm constituted 2.6% of the induced carcinomas. Histogenetically they were formed directly from the flat mucosa without going through a benign polyp-cancer sequence. By light microscopy, the neoplasms were characterized by lakes of abundant extracellular mucin within which were cells often distended with intracellular mucin. Histochemically, this mucin was composed of a mixture of neutral and acidic mucopolysaccharide, the latter being predominantly sialomucin. Ultrastructurally, the cells exhibited a mixed differentiation. The majority of the cells were hyperdistended with mucin, resembling the goblet cells. Other cells contained abundant rough endoplasmic reticulum, free polysomes and very little intracellular mucin. There were a few endocrine cells as well as mucous cells with dense core granules. It seems that similar to the normal colon, the neoplastic colon also contains cells at various stages of differentiation. A hypothesis to explain these events in colon carcinogenesis is proposed.

Adenocarcinoma, Mucinous

Detection of putative adduct with fluorescence characteristics identical to 2,3-dihydro-2-(7'-guanyl)-3-hydroxyaflatoxin B1 in human urine collected in Murang'a district, Kenya.

Food samples collected in Murang'a district, Kenya are known to be contaminated with a mycotoxin, aflatoxin B1 (AFB), and a positive correlation exists between the dietary intake of AFB and the incidence of liver cancer. When urine samples collected in this district were analyzed for the presence of 2,3-dihydro-2-(7'-guanyl)-3-hydroxyaflatoxin B1 (AFB-GuaI) by h.p.l.c., 6 of 81 samples had a detectable level of a compound whose fluorescence spectrum was identical to chemically synthesized AFB-GuaI as confirmed by photoncounting fluorescence spectrophotometry. These results are an indication of interaction between the ultimate carcinogenic form of AFB and cellular nucleic acids in vivo and further support the hypothesis that AFB may play an important role in the etiology of human liver cancer.

Aflatoxin B1

Experimental Staphylococcus epidermidis endocarditis in rabbit model.

To study the natural course of catheter-induced endocarditis secondarily infected with Staphylococcus epidermidis, 29 rabbits had catheters introduced surgically through the carotid artery to the aortic valve. Forty-eight hours later the catheters were removed from five rabbits. The rabbits were inoculated intravenously with 10(8) colony-forming units of S epidermidis. Autopsies done at various intervals showed all rabbits with indwelling catheters had noticeable aortic valve vegetations with positive cultures for S epidermidis. In the group with catheters removed after 48 hours, less severe valvular lesions were noted. Metastatic seeding to kidneys, spleen, and liver were noted in both groups. Because of low cure rate in the treatment of S epidermidis endocarditis, this rabbit model could be used to study antibiotic regimens for valvular endocarditis.

Animals

Ultrastructural pathology in Hashimoto's thyroiditis.

Ultrastructural studies of the thyroid tissue in two cases of Hashimoto's thyroiditis demonstrated that the inflammatory cells do not pass through the follicular cells. Indeed these cells travelled between the epithelial cells in a manner similar to the neutrophil emigration (diapedesis) through the vessel wall in acute inflammation. Inflammatory infiltrates were composed of lymphocytes, plasma cells, or transformed lymphocytes that showed features intermediate between those of lymphocytes and plasma cells. These inflammatory cells were observed to travel from the stroma to the follicular lumen in a vectorial manner - similar to neutrophilic chemotaxis in acute inflammation. The basement membrane around the thyroid follicles remained intact around some follicles whereas it was reduplicated or focally increased in thickness around others. The basement membrane material seemed to have been secreted by the follicular cells, and strands of early collagen fiber formation were seen within the excess basement membrane material. The follicular cells showed evidence fo sublethal injury characterized by prominent defects of the rough endoplasmic reticulum or the mitochondria. Cells from areas that appeared as foci of squamous metaplasia by light microscopy showed an increased number of cytoplasmic filaments (120 to 160 A), bundles of tonofilaments, large desmosomes, an increased number of desmosomes, and intracellular desmosomes. The colloid content of the follicles was diminished, and it seemed that instead of secreting the protein colloid, the follicular cells in Hashimoto's thyroiditis were producing either excessive proteinaceous material similar to colloid or other types of proteins such as basement membrane material or keratin.

Humans

Preneoplastic and neoplastic changes in colonic mucosa in Crohn's disease.

In order to further substantiate the associated risk of colonic adenocarcinoma in cases of Crohn's disease, colonic mucosa from 12 patients with documented Crohn's disease was studied. All of the cases exhibited a wide spectrum of mucosal changes. These changes included the following: dilation and distortion of the crypts, cellular basophilia with decreased mucus, Paneth's cell metaplasia, variable degrees of atypia, and carcinoma in situ. These findings are consistent with the increased incidence of carcinoma of the colon in cases of Crohn's disease.

Cell Transformation, Neoplastic

Rectal mucosa. Malignant and premalignant changes after radiation therapy.

A spectrum of changes that range from crypt basophilia through varying degrees of dysplasia and carcinoma in situ have been observed in the flat, nonraised mucosa of the rectum in patient who received pelvic irradiation for carcinoma of the cervix. This case demonstrates (1) the morphological evidence of the relationship between radiation and large-bowel carcinoma, (2) that large-bowel carcinoma may arise directly from the flat mucosa without having to go through a benign polyp-cancer sequence, (3) that early carcinoma arising from the flat mucosa may clinically resemble radiation proctocolitis, and therefore, (4) that increased vigilance in needed for the follow-up of patients who undergo pelvic irradiation.

Aged

Colon epithelium. I. Light microscopic, histochemical, and ultrastructural features of normal colon epithelium of male Fischer 344 rats.

Although the colon of the inbred F344 rat is not distinctly demarcated into ascending, transverse, and descending segments as in the human colon, it can roughly be divided into ascending and descending portions that show distinct light microscopic, histochemical, and ultrastructural features. The ascending colon is characterized by a "herringbone" pattern of mucosal folds and test-tube-shaped uniform crypts that contain mucous cells (MC) with abundant mucin (acidic mucopolysaccharide--mostly sialomucin) in the lower one-third of the crypt, whereas the upper one-third contains two putative cell populations: 1) MC containing large globules of neutral mucopolysaccharide or sulfomucin and 2) columnar cells (CC), the full capabilities of which are unknown. The descending colon has longitudinal folds and contains sparse MC with small mucous granules at the lower one-third of the crypt, whereas the upper one-third contains numerous goblet cells. Neutral mucopolysaccharide is sparse and the acidic mucin is exclusively sulfated. Histochemically, the descending segment of the rat colon resembles the human descending colon in that the predominant type of mucus is sulfomucin. Ultrastructurally, the cell types observed in both the ascending colon and the descending colon are: a) MC, b) CC, c) endocrine cells, and d) undifferentiated cells.

Animals

Colon epithelium. III. In vitro studies of colon carcinogenesis in Fischer 344 rats. N-methyl-N'-nitro-N-nitrosoguanidine-induced changes in colon epithelium in explant culture.

Colon explants from the inbred F344 rat descending colon pretreated in vivo with azoxymethane and maintained in explant culture were exposed to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). One week after the MNNG treatment, the colon crypts showed marked crowding, hypercellularity, and stratification of cells. Nine weeks after the treatment, the explants showed epithelial papillary projections on the surface epithelium and within the crypts, in addition to hypercellularity and stratification. The control untreated explants maintained a single layer of epithelium during the entire culture period. Ultrastructurally, the treated cells showed an unusual concentration of free polysomes and thin and thick filaments, multiple and bizarre nucleoli, nuclear indentations and pseudoinclusions, and intracellular lumina. Sulfomucin was the predominant component in the control untreated explants as well as in the normal descending colons of rats and humans. One week after treatment the crypts of the carcinogen-treated explants showed an increase in sialomucin, and by 9 weeks after treatment, they showed mostly sialomucin. These features, compared and correlated with those of the parallel in vivo animal model as well as with human material, lend additional support to de novo histogenesis of colon carcinoma.

Animals