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Biomedical subjects

William J Castellani

Publications and source records attributed to William J Castellani.

5 recordsLinked to original sources
PubMed2006

Potential deployment of angiotensin I converting enzyme inhibitors and of angiotensin II type 1 and type 2 receptor blockers in cancer chemotherapy.

There is significant evidence that both angiotensin I converting enzyme inhibitors (ACEI) and type 1 and type 2 angiotensin 2 (A2) receptor blockers may inhibit tumor growth. The finding is supported by many reports where these two classes of drugs showed cytostatic effects on the cultures of several lines of both normal and neoplastic cells. These drugs often transformed the cellular biochemical structures, especially in neoplastic cell lines. The same drugs also delayed the growth of different types of tumors in a variety of experimental animals (breast and lung carcinoma in mice; sarcomas, squamous cell carcinomas and hepatocellular carcinomas in rats), and there are a few reports of successful treatment of a limited number of cases of Kaposi sarcoma and gliomas with these drugs. Retrospective studies in hypertensive subjects treated with ACEI or A2 receptor blockers also seem to indicate that the incidence and growth of different neoplasms was delayed when these patients were compared to hypertensive patients receiving alternate medications. There is strong indication that the pharmacologic effect of these drugs may be exerted by reduction or inhibition of the synthesis of angiotensin 2. A2 is a powerful mitogen and its effect on cellular growth is exerted through stimulation of many factors, including transforming growth factor beta (TGFbeta), epidermal growth factor (EGF), smooth muscle actin (SMA), and tyrosine kinase. A2 also regulates apoptotic mechanisms and angiogenesis. The pharmacologic action of most of these drugs, however, is not necessarily limited to downregulaton of A2. Many ACEI, especially those containing the sulfhydryl (SH group), possess antioxidant or metalloprotease inhibitory properties per se. These experimental and retrospective data justify clinical testing of these drugs in appropriate randomized trials. Several such trials are currently in process. If these trials confirm the experimental and retrospective studies, these agents will provide a significant contribution to the therapeutic treatment of many malignancies in humans.

Angiotensin II↗
PubMed2006

Myelopoiesis in the liver of stillborns with evidence of intrauterine infection.

CONTEXT: Chorioamnionitis is the maternal and fetal response to an ascending intrauterine infection. The fetal response is manifested by funisitis and chorionic vasculitis, or as neutrophils within pulmonary spaces. Human hematopoiesis occurs in the liver primarily during the 6th to 22nd weeks of gestation. OBJECTIVE: To establish the relationship between the presence of an intrauterine infection and the degree of fetal hepatic myelopoiesis in second- and third-trimester fetuses. DESIGN: Liver and lungs from 49 fetal autopsies, 20 to 41 weeks of gestational age, and their associated placentas and membranes were analyzed for evidence of intrauterine infection and hepatic myelopoiesis. Hematoxylin-eosin-stained sections from fixed tissues were evaluated for the presence of amnionic fluid infection, defined by the presence of acute chorioamnionitis or funisitis. The degree of portal hematopoiesis, myelopoiesis and intra-alveolar neutrophils was assessed semiquantitatively with hematoxylin-eosin-stained sections and immunohistochemically with antimyeloperoxidase. The Kruskal-Wallis 1-way analysis of variance and the Wilcoxon-Mann-Whitney test were used to determine the significance of any observed difference. RESULTS: The degree of portal and lobular myelopoiesis was significantly greater with the presence of inflammation in both the membranes and umbilical cord, and correlated with the presence of intra-alveolar neutrophils (P < .001). A high correlation between the hematoxylin-eosin and immunohistochemistry assessment of myeloid cells was noted. CONCLUSIONS: There is increased portal and lobular myelopoiesis in 20-week to 41-week gestational age fetal livers that is associated with intrauterine ascending infection. The presence of increased portal or lobular myelopoiesis suggests the presence of an active fetal response to an intrauterine ascending infection.

Adult↗
PubMed2003

Salivary gland disease in HIV/AIDS and primary Sjögren's syndrome: analysis of collagen I distribution and histopathology in American and African patients.

BACKGROUND: Salivary gland disease (SGD) in HIV/AIDS is clinically and histopathologically very similar to Sjögren's Syndrome (SS), although the mechanism of tissue damage is unknown. The aim of this study is to determine the prevalence of SGD in primary SS and in HIV/AIDS in USA and in West African patients, and to seek distinguishing histopathologic features that may help to elucidate underlying mechanisms. METHODS: Histologic sections of minor salivary glands from 164 HIV-positive and -negative patients from Cameroon and the US, and from 17 US patients with primary SS, were evaluated following salivary gland biopsy for inflammatory changes. To confirm the presence of fibrosis, collagen I, which is the most abundant collagen type, was assessed immunohistochemically in H&E-stained sections. RESULTS: Forty-eight per cent of patients with HIV from Cameroon had severe SGD, while it was only in 6% of patients from the US. Patients with HIV in the US had less fibrosis and collagen I deposits than Cameroonians. Seventy-six per cent of US HIV-positive patients had received anti-retroviral therapy, while none of the African patients had. SS and AIDS patients had a tendency for lymphocytes to locate in a perivascular rather than in a periductal distribution. CONCLUSIONS: The prevalence of SGD and the presence of fibrosis and collagen I in Cameroonians with HIV is significantly higher than in HIV-positive American patients, and is similar to US patients with primary SS. The impact of patient selection, anti-retroviral therapy, and pathogenic mechanisms on salivary gland pathology is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Expression of cyclin D1 in normal, metaplastic, hyperplastic endometrium and endometrioid carcinoma suggests a role in endometrial carcinogenesis.

CONTEXT: Endometrioid carcinoma is often preceded by characteristic histopathologic lesions known as endometrial hyperplasia. Estrogen appears to be involved in the development of endometrioid carcinoma. Other mechanisms of endometrial carcinogenesis include mutations in p53 and PTEN tumor suppressor genes and overexpression of cyclin D1. However, the pattern of cyclin D1 expression is not well defined in normal, hyperplastic, neoplastic, and metaplastic endometrium. DESIGN: Cyclin D1 immunohistochemical analysis was used to evaluate 108 fixed, paraffin-embedded endometrial biopsy specimens and uterine resections obtained from 108 patients. Specimens included proliferative and secretory endometria, simple and complex hyperplastic lesions, and endometrioid adenocarcinoma. Normal and metaplastic surface epithelia were also evaluated independently of glandular morphologic features. RESULTS: Cyclin D1 was significantly overexpressed in glands with complex hyperplasia and endometrioid adenocarcinoma compared with proliferative or secretory endometrium and simple hyperplasia. Significant overexpression was also noted in papillary, syncytial, and squamous metaplasias compared with normal surface epithelium or epithelium with tubal metaplasia. CONCLUSION: Overexpression of cyclin D1 increases from normal endometrium to hyperplasia and carcinoma, suggesting that it may play a role in endometrial carcinogenesis. Overexpression of cyclin D1 in endometrial glands was independent from overexpression of cyclin D1 in surface metaplastic epithelium.

Carcinoma, Endometrioid↗