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Biomedical subjects

M Cano

Publications and source records attributed to M Cano.

At least 91 records · Page 5Linked to original sources

The effects of estrogens on tumor growth and on prolactin and growth hormone mRNA expression in rat pituitary tissues.

Estrogens inhibit tumor growth and modify PRL and GH expression in the MtT/W15 transplantable rat pituitary tumor. The effects of estradiol (E2) and diethylstilbestrol (DES) on PRL and GH mRNA levels were investigated. Estrogens increased GH mRNA levels and decreased PRL mRNA levels as detected by in situ hybridization and Northern blot hybridization with oligonucleotide probes, while inhibiting tumor growth. Similar changes in immunoreactive GH and PRL were seen in the tumor cells. The pituitary glands of tumor-bearing rats treated with estrogen for 3 weeks were increased in weight with a concurrent increase in pituitary PRL mRNA when analyzed by dot blot hybridization. These results indicate that estrogens have an inhibitory effect on the growth of the MtT/W15 tumor and increase GH protein and mRNA levels, while causing PRL protein and mRNA levels to decrease. The pituitaries of tumor-bearing rats concomitantly undergo PRL cell hyperplasia with an increase in PRL mRNA. These results also demonstrate a paradoxical effect of estrogens on different pituitary tissues.

Animals↗

Ultrastructural characteristics of the fetal and neonatal rat urinary bladder.

The embryologic and neonatal development of the normal rat urinary bladder was investigated in Sprague-Dawley rats by light, transmission, and scanning electron microscopy from day 11 of gestation through 21 days of age. The epithelium at day 11 of gestation is composed of small, loosely-connected, rounded cells with occasional short microvilli on their surfaces. The large polygonal cells characteristic of the adult bladder begin to appear by day 15, but the microridges are not apparent until day 17. By day 20, the epithelium appears morphologically similar to the adult bladder. Several morphological features are observed at different times of gestation which are not seen in the normal adult bladder, but they have been found in bladder tumors. During days 12-15 of gestation, most of the luminal lining cells of the bladder epithelium have a single central cilium. Cilia are also occasionally seen at days 11, 16, and 17 of gestation. Occasional cells with long tentacles are present from days 13-16 of gestation. Cells that appear to form bridges between cells are also seen from day 14 of gestation and continue to be observed through day 11 after birth. No cells with distinctive pleomorphic microvilli, a feature of rapidly proliferating bladder epithelial cells in the hyperplastic or tumorous epithelium of the adult, were seen at any time during gestation or after birth. Small foci of superficial layer sloughing occurred at the time of birth, but were rapidly replaced by one day after birth. It is apparent from this study that the bladder epithelium is a rapidly changing, proliferating tissue in utero and continuing for a brief period after birth.

Animals↗

Distribution of chromogranin A and secretogranin I (chromogranin B) in neuroendocrine cells and tumors.

The distribution of chromogranin A and secretogranin I (chromogranin B) in normal and neoplastic human endocrine tissues was analyzed with two human monoclonal antibodies against chromogranin A, anti-bovine antiserum against chromogranin A, and an anti-rat antiserum against secretogranin I. Western blotting analyses showed both chromogranin A and secretogranin I in normal adrenals, pheochromocytomas, a pituitary adenoma, and in normal pituitary glands, but not in a bladder carcinoma. Rat adrenal medullary and anterior pituitary tissues reacted with the polyclonal chromogranin A and secretogranin I antisera, but not with the two monoclonal chromogranin A antibodies. All antibodies reacted with most of the neuroendocrine cells and tumors examined. Pituitary prolactinomas contained immunoreactive secretogranin I, but not chromogranin A. Analysis of the distribution of chromogranin A and secretogranin I in pancreatic islet cells showed that chromogranin A was found predominantly in the glucagon-producing A cells, whereas secretogranin I was present in less than 5% of islet cells. These results indicate that chromogranin A and secretogranin I are both useful in the characterization of some neuroendocrine cells and neoplasms.

Adrenal Medulla↗

[Newborn infants of mothers addicted to heroin. Study of 45 cases].

Authors have studied 45 babies born during past five years to drug-addicted mothers. Increase in number han been remarkable: from 0.095 per thousand live births in 1980 to 1.57 in 1984. There was and 16.3% incidence for preterm infants, 34.8% for low birth weight and 18.6% were small for gestational age. One third (30.2%) suffered infections, mostly sepsis. Morbidity was high in these babies, caused mainly by prematurity. Drug withdrawal syndrome appeared in 26 babies (60.4%) at an age of 13 +/- 10 hours. Fifteen of these babies (57.6%) required pharmacological treatment during 10 +/- 7.3 days, with a good response, and only two cases needed treatment for more than a month. There were no deaths in the neonatal period. In our experience children of heroin addicted mothers form a group difficult to study because their parents give not reliable data, they have high morbidity and true problems begin when they leave hospital.

Adolescent↗

Scanning electron microscopic exfoliative urinary cytology in patients with malignant and nonmalignant diseases of lower urinary tract.

The possible clinical usefulness of scanning electron microscopic observation of urinary cytologic specimens has been suggested for selected patient populations. To begin to determine the specificity and sensitivity of the procedure, cytologic specimens (48 catheterized urine and 49 bladder washings) from 85 patients with bladder tumor or nonmalignant urologic diseases were observed by scanning electron microscopy (SEM) and compared with observations by light microscopy. This study provides evidence that SEM exfoliative cytology in catheterized urine and/or bladder washings has considerable specificity for low-grade, low-stage bladder tumors, but may not be sufficiently sensitive for use in routine urologic practice. However, this procedure may be of use in following patients with previously resected low-grade, low-stage bladder tumors for the early detection of recurrences.

Carcinoma, Transitional Cell↗

Effect of dose on the induction of urothelial proliferation by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide and its relationship to bladder carcinogenesis in the rat.

The effect on urothelial proliferation of a urinary bladder carcinogen, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), fed to male F344 rats at doses of 0.2, 0.1, 0.05, 0.01, 0.005 and 0.001% of diet for 4 or 10 weeks was evaluated by autoradiography, using [3H-methyl]thymidine, and by histopathology. At week 4, hyperplasia was induced in 10/11 and 6/11 rats given 0.2% and 0.1% FANFT, respectively. The dose-related increase of labeling index in the bladder epithelium was significant for the groups given 0.01% or higher doses of FANFT. At week 10, histopathologic lesions were observed in groups given 0.05% or higher doses of FANFT. This was accompanied by a significant increase in labeling index for these groups. The results are consistent with the long-term carcinogenicity studies conducted with the same dose levels of FANFT. The interrelationships between numbers of cells (hyperplasia), cell proliferation (labeling index) and cancer induction are discussed utilizing a computerized model of bladder carcinogenesis.

Animals↗

Preparation methods for light microscopic and ultrastructural studies of fetal rat bladder.

Little is known about in utero urinary bladder embryogenesis and the development of the urothelium of laboratory animals. Previous scanning and transmission electron microscopy studies in rats and mice have indicated that the highly specialized superficial cells of the urothelium complete their differentiation at a very late stage of fetal development or shortly after birth. Limitations in methodology in the past have precluded extensive examination of earlier stages of bladder development. Innovations in preparatory procedures of the bladder of rat fetuses have been developed which make possible detailed scanning and transmission electron microscopic and light microscopic examination of cloaca and urinary bladder as early as day 11 of gestation.

Animals↗

Quantitation of scanning electron microscopic urinary cytology.

Using scanning electron microscopy (SEM), differences in cell surface morphology are identifiable between normal urothelium and malignant urothelia including the presence of pleomorphic microvilli (PMV). PMV have been reported in carcinomas of the urinary bladder, and they appear early in the pathogenesis of these tumors in animal models. Preliminary studies in our laboratory and others' demonstrated similar changes in tissue and cytologic specimens from patients with bladder cancer. We observed and evaluated normal and neoplastic cells of the human bladder by SEM in a preliminary assessment of surface topography with regard to tumor growth, grade, and stage. However, while these SEM observations indicated that differences between normal and abnormal urothelia could be readily recognized, the distinction between the various types of atypical cells was not as clearly defined. Data collected so far indicates that changes in the surface topography of the exfoliated cells may possibly vary both in relation to tumor grade and stage. Based on these qualitative observations, we expanded our approach by using a computerized image analysis system directly interfaced with the SEM. The measurements which can be made include cell surface area, diameter, length, width, perimeter, orientation and number of PMV per unit area. Statistical analysis is also performed. The boundaries between cells are not recognizable by the system, making the single cells present in cytologic specimens ideal for evaluation. Uniform short microvilli are readily distinguished from PMV. Preliminary evaluation of 23 patients has distinguished specimens from malignant cases compared to patients with benign lesions.

Autoanalysis↗

Bladder freeze ulceration and sodium saccharin feeding in the rat: examination for urinary nitrosamines, mutagens and bacteria, and effects on hepatic microsomal enzymes.

We previously demonstrated that long-term feeding of sodium saccharin, a non-mutagen, induced bladder carcinomas when administered to F344 male rats with regenerative hyperplasia of the urothelium induced by the freeze-ulceration technique, even without prior chemical initiation (Cohen et al. Cancer Res. 1982, 42, 65). In the present study, we examined the urine of rats subjected to freeze ulceration of the bladder and then fed sodium saccharin at 5% in the diet to evaluate the possibility of a mutagen being generated as a result of ulceration and/or saccharin feeding. Urine was collected into a syringe by aspiration from the urinary bladder after ligating the urethra for 2 hr at intervals from day 0 to day 14 after ulceration. After ulceration and/or sodium saccharin feeding, the urine showed no bacterial contamination, no mutagenic activity in the standard Ames assay, no production of nitrosamines, and no nitrosating environment. In addition, no significant changes in activities of liver microsomal enzymes (i.e. cytochrome P-450, NADPH-cytochrome c reductase, aniline hydroxylase, or ethylmorphine N-demethylase) were observed in rats fed sodium saccharin for 1, 5 or 14 days. Thus, freeze ulceration, and the consequent regenerative hyperplasia of the epithelium, compared with sodium saccharin feeding do not involve the administration of an exogenous mutagenic substance or the generation of a detectable mutagen in the urine.

Administration, Oral↗

Comparative studies on expression of tumor-associated antigens in human and induced pancreatic cancer in Syrian hamsters.

The expression of blood-group-related antigens (BGRAs) in experimental primary pancreatic cancer induced by N-nitrosobis(2-oxopropyl)amine (BOP) treatment of Syrian hamsters and homologous subcutaneous transplants of this primary cancer in the cell line, PC-1, established from the primary cancer and intrapancreatic transplanted PC-1 cells were studied by histochemical and biochemical methods. Human primary pancreatic cancer; the human pancreatic cancer cell line, HPAF; and its subclones, CD11 and CD18, also were studied on a comparative basis. Histochemical analysis of BGRAs demonstrated that A, B, H, Leb, Lex, Ley, and T antigen were expressed both in vivo and in vitro in hamster and human materials in similar patterns. However, Lea, CA 19-9 and sialylated Tn antigens were not found in hamster-derived tissues. SDS-PAGE and Western blotting procedures using anti-A antigen revealed similar major bands in the membrane fractions of both human and hamster pancreatic cells between 97 and 200 kdalton. Among other human pancreatic cancer-associated antigens, TAG-72, CA 125, and 17-1A were detected immuno-histochemically in the hamster tumors both in vivo and in vitro, in a pattern similar to that seen in human pancreatic cancer. Tumor antigen DU-PAN-2, associated with human pancreatic cancer, was found infrequently in hamster pancreatic cancer specimens. These results indicate that the experimental hamster pancreatic cancer model provides a unique tool for investigating antigenicity of pancreatic cancer, particularly in relation to diagnosis and therapy.

Animals↗