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H L Weiss

Publications and source records attributed to H L Weiss.

32 records · Page 2Linked to original sources

Changes in cyclin dependent kinase inhibitors p21 and p27 during the castration induced regression of the CWR22 model of prostatic adenocarcinoma.

PURPOSE: The expression of the cyclin dependent kinase inhibitors p21 and p27 was examined in prostatic adenocarcinomas following castration. MATERIALS AND METHODS: Male nude mice inoculated with the androgen dependent human prostatic tumor CWR22 were castrated when the tumors reached a volume of 0.8 to 1.1 cm.3 and were sacrificed at 3, 7, 21, 28 and 42 days post-castration. An additional group of mice received a subcutaneous testosterone pellet at 21 days post-castration and was sacrificed at 28 days post-castration. The expression of the Ki-67 antigen, p21 and p27 was examined by immunohistochemistry. RESULTS: The mitotic rate as well as the number of Ki-67 antigen positive cells decreased to 3% of intact control values by 7 days post-castration and were less than 0.01% of intact control values at 21, 28 and 42 days post-castration. The percentage of p21 expressing cells decreased from 15+/-2% in intact controls to less than 1% by 42 days post-castration. In contrast, the percentage of cells that expressed p27 increased from 25+/-3% in intact controls to 51+/-8% at 3 days post-castration and to 80 to 95% at days 7, 21, 28 and 42 days post-castration. Testosterone treatment from 21 to 28 days post-castration resulted in an increase in Ki-67 antigen positive cells to 200% of intact controls and a concomitant reduction in p27 expressing cells to about 50% of intact controls. Castration-induced changes in p27 expression were not observed in the CWR22R tumor, a transplantable relapsed derivative of the CWR22 tumor. CONCLUSION: These findings suggest that p27 expression is regulated negatively by androgens and that increased expression of p27 in CWR22 xenografts may be involved in the suppression of proliferation following castration.

Adenocarcinoma↗

Ep-Cam levels in prostatic adenocarcinoma and prostatic intraepithelial neoplasia.

PURPOSE: The monoclonal antibody (mAb) 323/A3, a second generation high affinity antibody of the 17-1A antibody family, recognizes a 40 kDa transmembrane glycoprotein that has been referred to as Ep-CAM, 17-1A recognized antigen, or EGP40. While Ep-CAM is expressed on the basolateral surface of a variety of epithelia, the strongest expression is frequently detected among several types of carcinoma. In this regard, Ep-CAM may be useful in therapy, in diagnosis, and/or in prognosis. We examined the distribution of Ep-CAM in normal, dysplastic, and malignant prostatic epithelium. MATERIALS AND METHODS: Paraffin sections of prostate tissue from 76 patients with clinically localized (pT2) prostatic adenocarcinoma were immunostained with mouse mAb 323/A3 using the avidin-biotin horseradish peroxidase method. RESULTS: Within benign prostatic epithelium, immunoreactivity typically was low and frequently was restricted to the luminal cells. In contrast, moderate to strong immunostaining was detected frequently in the luminal cells of high grade prostatic intraepithelial neoplasia (PIN). Furthermore, strong immunostaining usually was detected in the cells of adenocarcinomas. The immunostaining in PIN (p<0.0001) and in adenocarcinoma (p<0.0001) was significantly greater than that observed in the normal epithelium. Expression of Ep-CAM did not vary significantly with the Gleason score of tumors or the clinical outcome of patients. Expression of Ep-CAM was demonstrated also in the malignant prostatic cell lines LNCaP, DU145 and PC3 using immunohistochemistry and an immunoblot technique. CONCLUSIONS: These findings suggest that increased levels of Ep-CAM represent an early event in the development of prostatic adenocarcinoma.

Adenocarcinoma↗

Nuclear accumulation of p53 in colorectal adenocarcinoma: prognostic importance differs with race and location of the tumor.

BACKGROUND: Although several studies have been conducted to examine the role of p53 genetic abnormalities and their prognostic value in colorectal carcinoma, the incidence of nuclear accumulation of p53 and the prognostic importance of nuclear accumulation of p53 in African-American and white patients have not been investigated separately. Therefore, the authors evaluated the prognostic significance of p53 nuclear accumulation in these two racial groups. METHODS: Nuclear accumulation of p53 was evaluated immunohistochemically in archival tissue specimens from 204 African-American and 300 white patients with primary colorectal adenocarcinomas who had undergone surgery. Survival times from colorectal adenocarcinoma were analyzed using Kaplan-Meier survival estimates and the Cox proportional hazards model for nuclear accumulation of p53 with adjustments for other confounding demographic and clinical variables. RESULTS: Approximately equivalent proportions of distal (54%) and proximal adenocarcinomas (47%) were positive for nuclear accumulation of p53 in African-American patients. In contrast, distal colorectal adenocarcinomas from white patients more frequently were positive for nuclear accumulation of p53 than adenocarcinomas of the proximal colon (63% vs. 38%, respectively). Nuclear accumulation of p53 was found to be a strong predictor of poor survival in white patients (hazard ratio = 6.77; P = 0.0001) but not in African-American patients with primary adenocarcinomas of the proximal colon. Nuclear accumulation of p53 was not of prognostic value in patients of either race with primary adenocarcinomas of the distal colorectum. CONCLUSIONS: Nuclear accumulation of p53 is a valuable indicator of poor prognosis only for white patients with adenocarcinomas of the proximal colon. The current study also suggests that the role of p53 dysregulation in colorectal adenocarcinomas may vary with the anatomic location of the tumor and the race of the patient. These findings suggest that the demographic characteristics of patients should be considered in the evaluation of prognostic markers of colorectal neoplasia.

Adenocarcinoma↗

Serum retinol and HIV-1 RNA viral load in rapid and slow progressors.

Few studies have addressed the relation between serum vitamin A levels and HIV disease progression. Thirty HIV-infected women in Rwanda were studied over a time span of 26 to 99 months. Fourteen subjects seroconverted and died of HIV-related disease at a mean of 44 months (range, 26-69 months) after their first HIV-positive test and were termed "rapid progressors," (RPs). A comparison group of 16 "slow progressors" (SPs) were HIV-positive at the time of their first HIV serology and had asymptomatic HIV infections at a mean of 96 months (range, 93-99 months) after their first HIV serology. Baseline mean serum retinol values were the same in RPs and SPs: 0.65 + 0.08 micromol/L versus 0.67 + 0.09 micromol/L (p = .7). Lower serum retinol levels were observed in RPs compared with SPs for the second and third measurements, obtained at a median of 12 and 24 months past baseline: 0.51 + 0.07 micromol/L versus 0.76 + 0.14 micromol/L (p = .3) and 0.44 + 0.09 micromol/L versus 0.64 + 0.08 micromol/L (p = .08), respectively. Median retinol levels for the third sample measurement were similar in RPs with lower viral load (LVL) and SPs (0.49 micromol/L and 0.52 micromol/L, respectively) compared with only 0.19 micromol/L in RPs with higher viral load (HVL; p = .02). A trend toward decreasing serum retinol levels and increasing HIV-1 RNA viral load was observed at the third sample measurement (p = .04). Subjects with LVL, higher serum retinol levels (> or =0.70 micromol/L), or both had more favorable rates of survival than subjects with HVL, low serum retinol levels (<0.70 micromol/L), or both. Although sample size does not permit definitive conclusions, this study demonstrates an association of high HIV load, rapid progression, and low serum retinol late but not early in disease progression.

Adult↗

Serum retinol and HIV-1 RNA viral load in rapid and slow progressors.

Few studies have addressed the relation between serum vitamin A level and HIV disease progression. Thirty HIV-infected women in Rwanda were studied over a time span of 26 to 99 months. Fourteen subjects seroconverted and died of HIV-related disease at a mean of 44 months (range, 26-69 months) after their first HIV-positive test and were termed "rapid progressors," (RPs). A comparison group of 16 "slow progressors" (SPs) were HIV-positive at the time of their first HIV serology and had asymptomatic HIV infections at a mean of 96 months (range, 93-99 months) after their first HIV serology. Baseline mean serum retinol values were the same in RPs and SPs: 0.65 + 0.08 mmol/L versus 0.67 + 0.09 micromol/L (p = .7). Lower serum retinol levels were observed in RPs compared with SPs for the second and third measurements, obtained at a median of 12 and 24 months past baseline: 0.51 + 0.07 mmol/L versus 0.76 + 0.14 mmol/L (p = .3) and 0.44 + 0.09 mmol/L versus 0.64 + 0.08 mmol/L (p = .08), respectively. Median retinol levels for the third sample measurement were similar in RPs with lower viral load (LVL) and SPs (0.49 mmol/L and 0.52 mmol/L, respectively) compared with only 0.19 mmol/L in RPs with higher viral load (HVL; p = .02). A trend toward decreasing serum retinol levels and increasing HIV-1 RNA viral load was observed at the third sample measurement (p = .04). Subjects with LVL, higher serum retinol levels (> or =0.70 mmol/L), or both had more favorable rates of survival than subjects with HVL, low serum retinol levels (<0.70 mmol/L), or both. Although sample size does not permit definitive conclusions, this study demonstrates an association of high HIV load, rapid progression, and low serum retinol late but not early in disease progression.

Adult↗

Relationships between socioeconomic status and race-specific cervical cancer incidence in the United States, 1973-1992.

The association between low socioeconomic status (SES) in minority groups and higher incidence and mortality from cervical cancer was examined using two large U.S. databases. With cases from 1973 to 1992, all registries of the Surveillance, Epidemiology, and End Results (SEER) (except Hawaii) were used to calculate incidence rates of in situ and invasive cervical cancers by race group. SES indicators were derived from the Regional Economic Information System, Department of Commerce. Higher levels of SES indicators were related to decreased risk and lower incidence of invasive cancers in all race groups, but especially white and black populations, and to increased incidence of situ cancer in these populations. Results suggest that higher SES status is related to a decrease in invasive cervical cancer, but an increase in in situ cervical cancer in recent years. These findings may explain the racial differences in cervical cancer incidence and help target intervention programs.

Adolescent↗

Changes in the leukocyte phenotype profile of goats infected with the caprine arthritis encephalitis virus.

The proportions of different sub-populations of leukocytes in five healthy goats and five goats infected with the caprine arthritis encephalitis virus (CAEV) were examined using immunofluorescence and flow cytometry. A panel of monoclonal antibodies that identified a monocytegranulocyte marker (GMI); the CD4, CD8, IgM, MHC Class I, MHC Class II and T19 antigens, and the gamma delta (gamma delta) T cell receptor was used. We observed a significant (P = 0.016) reduction in the proportion of monocytes in the peripheral blood of infected (5.98%) compared with healthy control goats (9.92%). There was also a decrease in the proportion of CD4+ T lymphocytes that approached significance (P = 0.076) accompanied by a slight increase in the proportion of CD8+ T lymphocytes, in infected compared with uninfected animals. Consequently, three of the five infected animals had lower CD4:CD8 ratios than any of the healthy animals and two of these three ratios were inverted. Approximately 14% of T cells in the peripheral blood of healthy goats was identified as gamma delta T cells and all expressed the T19 antigen. A significantly elevated level of gamma delta T cells (P = 0.030) and an elevated level of T19 cells were observed in infected, compared with healthy animals. The proportion of leukocytes expressing surface IgM (B cells) was also elevated, although not significantly, in CAEV-infected compared to healthy controls. The changes in peripheral blood leukocyte subsets in infected goats suggest that immune responses to the infection are probably altered in these animals with eventual progression to severe disease and death.

Animals↗

Brain edema in meningiomas is associated with increased vascular endothelial growth factor expression.

OBJECTIVE: Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), an endothelial cell-specific cytokine, induces proliferation of endothelial cells and increases vascular permeability dramatically. All gliomas secrete significant amounts of VEGF, whereas meningiomas are variable in expression. Thus, we sought to determine whether the extent of VPF/VEGF expression in meningiomas correlated with differences in brain edema associated with these tumors. METHODS: Meningioma tissue samples from 37 patients (15 men, average age 65 +/- 13 yr; 22 women, average age 60 +/- 10 yr) who underwent surgery at or were referred to the University of Alabama Hospital were examined retrospectively for the extent of expression of immunoreactive VPF/VEGF. Additionally, peritumoral edema was assessed on a blinded basis radiographically from preoperative magnetic resonance imaging scans. Selected specimens were examined by in situ hybridization to document the source of VPF/VEGF. RESULTS: The predominant meningioma subclassifications were transitional (57%) or meningothelial (27%) subtypes. VPF/VEGF immunoreactivity ranged from 0 to 3.5, with a median value of 2 on a subjective 5-point scale; magnetic resonance imaging-assessed edema ranged in extent from 0 to 4 (subjective 5-point scale), with a median value of 2.5. The correlation of determination (R2) of magnetic resonance imaging-assessed tumor edema rating and VPF/VEGF staining intensity rating was 0.6087 (r = 0.78; P = 0.0001). In situ hybridization localized VPF/VEGF messenger ribonucleic acid in meningioma cells and not in normal parenchymal brain cells. CONCLUSION: These data suggest that meningioma-associated edema may be a result of the capacity of meningioma cells to produce VPF/VEGF locally, leading to increased tumor neovascularization and enhanced vascular permeability.

Adult↗

The use of sequential self-obtained vaginal smears for detecting changes in the vaginal flora.

BACKGROUND AND OBJECTIVES: The ability to study daily changes in the vaginal flora may provide insight into the pathogenesis of bacterial vaginosis. Because culture of the vaginal fluid is tedious and expensive, the utility of self-obtained vaginal smears for documenting changes in the flora was evaluated. GOALS: To validate the adequacy of self-collected vaginal fluid Gram stains and use them to monitor vaginal flora. STUDY DESIGN: Ten asymptomatic premenopausal women collected daily vaginal smears for 30 days. The smears were Gram stained and interpreted using a standardized scoring system (Nugent criteria). In addition, results from self- and clinician-obtained vaginal smears from 18 women were compared to validate the adequacy of self-obtained smears. RESULTS: Two women had asymptomatic bacterial vaginosis. One woman, who was postpartum, had intermediate flora that toward the end of the collection period changed to Lactobacillus predominant. The remaining seven women exhibited two patterns. One was Lactobacillus morphotypes only; the second consisted of Lactobacillus-predominant days interspersed with days with moderate to high numbers of Gardnerella/Bacteroides morphotypes. There was a significant correlation of the point of change in the flora of this group with menses. CONCLUSIONS: The adequacy of self-collected vaginal fluid Gram's stains was validated. Changes in vaginal flora were demonstrated over a 30-day period by use of this methodology.

Female↗

Cancer incidence among predominantly black, rural-poor populations in southern states.

BACKGROUND: A seven-county, predominantly black, rural-poor population in Alabama is targeted for a program aimed at improving access to state-of-the-art cancer care. This paper presents combined age-adjusted cancer incidence rates for predominantly black, rural counties in North Carolina and Georgia similar to the Alabama counties and compares these rates with Surveillance, Epidemiology, and End Results (SEER) incidence rates. METHODS: Cancer incidence data from 1990 to 1993 were obtained from the Georgia Center for Cancer Statistics for 10 rural counties with predominantly black populations. Likewise, cancer incidence data from 1990 to 1993 were obtained for seven rural-poor counties in North Carolina from the North Carolina Central Cancer Registry. SEER incidence rates from 1990 to 1992 were obtained for nine SEER sites. RESULTS: The overall cancer incidence rate from North Carolina and Georgia is lower by 22% than the SEER rate. Cancer incidence rates for cancers of the breast, colon/rectum, lung, and prostate were at least 15% lower than the SEER rates, while the invasive cervical cancer rate was 1.78 times higher than the SEER rate. CONCLUSION: Blacks comprise about 50% of the population in these counties. In contrast, the SEER population is predominantly white, and the black population is primarily urban. Estimates of the number of cancer cases in black, rural-poor populations based on SEER incidence rates is not reflective of the cancer experience in these populations.

Adult↗

Using elderly educators to increase colorectal cancer screening.

This article reports on the elderly educator method, a practical and economical intervention that was used for increasing the rate of return of fecal occult blood sampling in colorectal screening among 171 socioeconomically disadvantaged older persons. Two methods that used elderly educators had an overall response rate of more than 60%. Logistic regression shows a statistically significant difference between two methods that used elderly educators and two methods that did not.

Age Factors↗

Effects of acute and chronic body weight gain reductions in the evaluation of agents for efficacy in mammary cancer prevention.

Studies were performed to determine the effects of moderate decreases in body weight gain on mammary carcinogenesis. The levels of depressions in weight gain were those often observed in the evaluation of chemopreventive agents. In the first experiment, the effects of acute and chronic reductions of body weight gain when started after carcinogen treatment were examined in young rats (MNU at 50 days of age). Significant decreases (36%) in mammary cancers occurred in groups of rats that underwent a 12% acute reduction in body weight gain as compared with ad libitum controls. In contrast, chronic weight reductions of up to 12% had minimal effects on cancer multiplicities, while a 15% chronic reduction significantly decreased cancer numbers (26%). A second experiment evaluated the efficacy of toremifene (7.0 mg/kg diet), an estrogen/anti-estrogen, and the effect of toremifene-matched body weight gain reduction that occurred during the study. Toremifene caused a chronic reduction in body weight that resulted in a 10% decrease in final body weight at the end of the study. While toremifene-treated rats exhibited a 67% decrease in the number of mammary cancers, the rats which similarly exhibited a 10% decrease in final body weight showed only a 14% decrease in cancer number. Thus, the weight effects observed with toremifene, similar estrogens/anti-estrogens, and other classes of chemopreventive compounds (where chronic body weight reductions are 10% or less) imply that the body weight reduction has a limited effect on overall chemopreventive activity. A third study examined the effect of chronic body weight gain reduction on mammary cancers induced in older rats (MNU given at 100 days of age). This model more closely resembles the status of the breast tissue of mature women currently enrolled in clinical trials of chemopreventive agents. Under these conditions chronic reductions in body weight up to 15% had minimal effects on mammary carcinogenesis. These data further demonstrated that acute body weight reductions in young rats at the time of carcinogen treatment can be a concern in interpretation of the chemopreventive activity of an agent, but that moderate chronic depressions of body weight gain probably do not play a significant role.

Adenocarcinoma↗

Longitudinal analysis of mammary cancer multiplicity in chemoprevention studies.

BACKGROUND: The effect of chemopreventive agents on cancer multiplicity is of primary interest in animal studies. The nature of data collected from chemoprevention studies may be analyzed by a longitudinal analysis of repeatedly measured cancer multiplicity data. METHODS: We determined the number of mammary cancers over the entire follow-up period for varying doses of two chemopreventive agents. Longitudinal analyses were performed to model the number of cancers over different time intervals. RESULTS: There was a significant increase in the number of cancers between six to seven weeks post-carcinogen administration in the control group. Varying patterns of cancer development were observed at different doses of chemopreventive agents including a delay in onset of tumor growth compared to the control group. CONCLUSION: Longitudinal data analysis complements traditional analyses by providing detailed information regarding the effect of chemopreventive agents on the pattern of tumor development throughout the follow-up period. Importantly, some chemopreventive agents may delay time to appearance of mammary cancers without causing a significant difference in cancer multiplicity.

Animals↗