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Biomedical subjects

A Joseph

Publications and source records attributed to A Joseph.

At least 109 records · Page 6Linked to original sources

Urinary and tissue levels of scatter factor in transitional cell carcinoma of bladder.

PURPOSE: We previously reported increased titers of scatter factor in urine of 20 patients with transitional cell carcinoma of the bladder compared to noncancer and cancer control groups. Scatter factor was also found in bladder tumor extracts but the number of samples examined was too small for detailed analysis. We report a followup study of larger numbers of patients with transitional cell carcinoma and controls. MATERIALS AND METHODS: The scatter factor content of urine samples and bladder tissue extracts was measured by enzyme-linked immunosorbent assay. Values were normalized per milligram creatinine or tissue protein. Statistical analysis was performed using the Mann-Whitney U test or, for multiple comparisons, the Kruskal-Wallis H test. RESULTS: Patients with transitional cell carcinoma of the bladder (52) had higher urinary scatter factor titers than did 24 normal subjects (p < 0.001) or 14 with benign prostatic hypertrophy (p < 0.001), 49 with prostate cancer (p < 0.001) and 13 with other genitourinary tract cancers (p < 0.01). Transitional cell carcinoma cases with clinicopathological evidence of disease had greater urinary scatter factor levels than those with no evidence of disease at urine sampling (p < 0.01). However, patients with transitional cell carcinomas in remission still had much greater urinary scatter factors than did normal subjects (p < 0.001). In contrast, patients with active prostate cancer had urinary scatter factor levels similar to those in remission. Patients with muscle invasive or high grade transitional cell carcinomas tended to have higher urinary scatter factor levels than patients with nonmuscle invasive or low grade tumors, respectively, but the differences were not significant. Greater levels of scatter factor were present in tissue extracts of muscle invasive transitional cell carcinomas than in nonmuscle invasive tumors (p < 0.001) or nontumor tissue (p < 0.02). Invasion was more closely related to tissue scatter factor content than tumor grade, since high grade noninvasive transitional cell carcinomas had a scatter factor content similar to that of low grade noninvasive transitional cell carcinomas. CONCLUSIONS: These studies suggest that scatter factor may be a marker of bladder cancer, urinary scatter factor titers tend to reflect disease activity and particularly high tissue titers of scatter factor are found in muscle invasive cancers. A larger prospective study will be necessary to determine the clinical significance of elevated scatter factor titers in transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell↗

Sanitation for rural communities: first win the people's support.

A latrine project in an Indian village which failed because the inhabitants were scarcely brought into its planning and execution is contrasted with a moderately successful scheme in another village where a concerted effort was made to educate the community about the value of latrines and to obtain the people's participation.

Community Participation↗

Scatter factor expression and regulation in human glial tumors.

Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a cytokine that induces cell motility in vitro and angiogenesis in vivo. SF appears to be a determinant of the malignant phenotype in certain systemic cancers. We detected SF in extracts prepared from human gliomas, with the highest levels found in malignant tumors. Human glioblastoma cells expressed both SF and its receptor (c-met protein) in vivo, as demonstrated by immunohistochemistry. Consistent with these observations, we found moderate to high levels of production of immunoreactive and biologically active SF by cultured human glioblastoma cells (3 of 8 lines) and by neural microvascular endothelial cells (NMVEC) (3 of 3 lines). SF stimulated the proliferation of glioblastoma and NMVEC cell lines by paracrine or autocrine mechanisms. Conditioned medium (CM) from both glioblastoma and NMVEC cells contained SF-inducing factor (SF-IF) activity, defined by its ability to stimulate SF production in an indicator cell line (MRC5 human fibroblasts). This activity consisted of a high-molecular-weight (> 30 kDa), heat-sensitive component and a low-molecular weight (< 30 kDa), heat-stable component. Furthermore, glioblastoma CM stimulated NMVEC SF production, and NMVEC CM stimulated glioblastoma cell SF production, by 3- to 6-fold in each case. Our findings demonstrate that SF-dependent interactions between glioma cells, and between glioma cells and endothelium, can contribute to the heterogeneous proliferative and angiogenic phenotypes of malignant gliomas in vivo.

Brain↗

Significance of lymphocytic sister chromatid exchange frequencies in ovarian cancer patients.

Very few studies report the analysis of sister chromatid exchanges in ovarian cancer patients. We tested the null hypothesis that SCE frequency increases with the advancing stages of ovarian cancer and follows a Poisson distribution. As controls we examined age- and sex-matched healthy volunteers who had no such past history. An increased average SCE frequency was observed in ovarian cancer patients (6.34 +/- 0.09) vis-à-vis controls (4.47 +/- 0.12). Further, the data also suggested a stage-wise increase in the SCE frequency.

Adult↗

Monitoring of antibiotic use in a primary and tertiary care hospital.

Prophylactic and curative use of antibiotics was studied prospectively in 87 consecutive medical and surgical cases of a tertiary care hospital and in 98 cases of a primary care hospital. Based on Kunins' criteria, antibiotic prophylaxis was found to be more inappropriate in the primary care hospital (49%) than in the tertiary care hospital (34%). Antibiotic therapy, however, was more appropriate at the primary level; 67% as opposed to 60% at the tertiary level. This resulted in a similar overall level of inappropriate antibiotic use in the two hospitals. Surgical prophylaxis was started postoperatively in 68% of the primary care hospital cases. Though prophylaxis was always perioperative in the tertiary care hospital, the postoperative duration was more than 7 days in one third of the cases. The nosocomial infection rate in those given prolonged prophylaxis was higher than those who received antibiotics for less than 72 hours. Antibiotics were started empirically in 78% of tertiary hospital care cases and 100% of cases in the primary hospital. Though culture sensitivity was done in 80% of the tertiary care cases, more than half the specimens were sent after multiple doses of antibiotics were started. The choice of antibiotic did not always correlate with the sensitivity report. Though cost-effective drugs were chosen in 50% of cases, in more than 20% of cases expensive drugs were started. The study highlights the need for an antibiotic audit and suggests the necessity of having an ongoing peer audit.

Anti-Bacterial Agents↗

Scatter factor binds to thrombospondin and other extracellular matrix components.

Scatter factor (SF) is an angiogenic growth factor that stimulates motility and invasion of carcinoma cells. SF is present in the extracellular matrix (ECM) of breast cancers, where it might act to promote tumor cell invasion and angiogenesis. To investigate how SF is incorporated into the ECM, we studied the binding of SF to various ECM components using a solid-phase binding assay based on the SF enzyme-linked immunosorbent assay. We found that SF binds to a variety of ECM molecules, with different binding capacities. The highest SF binding capacities were observed for thrombospondin-1 (TSP-1), fibronectin (Fn), and heparan sulfate proteoglycan, although SF did not bind to albumin. Mature two-chain SF and precursor single-chain SF bound approximately equally well to TSP-1 and Fn. Moreover, two SF alpha-chain peptides (NK1 and NK2) both bound to TSP-1 and Fn, suggesting that the whole SF molecule is not required for binding. Based on binding competition assays, TSP-1 exhibited higher affinity for SF than did nine other ECM molecules, including Fn and heparan sulfate proteoglycan. Although heparin in solution potently inhibited the binding of SF to TSP-1-coated surfaces, even very high concentrations of heparin could not elute SF already bound to TSP-1. SF binding was modulated by binding interactions among ECM molecules (TSP-1-Fn, TSP-1-collagen I, and Fn-collagen I), suggesting that the matrix capacity to bind SF depends upon its exact composition. SF bound in a dose-dependent fashion to ECMs secreted by three human breast carcinoma cell lines. Binding of SF to matrices from all three cell lines was significantly inhibited by preincubation of the matrices with antibodies against TSP-1, whereas antibodies against several other ECM components were less effective or ineffective in inhibiting SF binding. In addition, TSP-1 markedly inhibited chemotaxis of microvascular endothelial cells toward SF and SF-induced angiogenesis in the rat cornea neovascularization assay. Our findings suggest that 1) SF interacts with a variety of ECM components, 2) high affinity SF-TSP-1 interactions may mediate the binding of SF to the breast cancer matrix, and 3) the SF-TSP-1 interaction may contribute to modulation of angiogenesis. Possible implications of these findings for tumor angiogenesis are discussed.

Animals↗

Glutaric aciduria type I in the Arab and Jewish communities in Israel.

Mutation analysis was performed in eight families (16 patients) with glutaric aciduria type I (GA-I), which were all the families diagnosed in Israel in the years 1987-1994. Six families were of Moslem origin and two were non-Ashkenazi Jews. The entire coding region of the cDNA of the glutaryl-CoA dehydrogenase gene was sequenced in one patient of each family. Seven new mutations were identified in 15 of 16 mutated alleles, including six point mutations: T416I (4 alleles), G390R (1 allele), and S305L, A293T, L283P, and G1O1R (2 alleles each). In addition, a 1-bp deletion at position 1173 was identified in two alleles. These findings do not provide a molecular basis for the clinical variability in GA-I families. The occurrence of multiple novel mutations in a small geographic area may be explained by their recent onset in isolated communities with a high consanguinity rate.

Adult↗

Scatter factor protein levels in human breast cancers: clinicopathological and biological correlations.

Scatter factor (SF) is an invasogenic and angiogenic cytokine the cellular receptor of which is encoded by a proto-oncogene (c-met). We measured the immunoreactive SF content (nanograms of SF per milligram of protein) in tissue extracts from 166 breast cancers and correlated the values with various known prognostic parameters. Invasive cancers had nearly four times greater SF content than did ductal carcinoma in situ, and the difference was statistically significant (P < 0.02, two-tailed t-test). However, there were no significant differences in SF content among different histological types of invasive cancer. Invasive cancers that had spread to axillary lymph nodes exhibited higher SF content than did invasive cancers without regional spread (P < 0.02), but the difference in SF content between node-positive and node-negative tumors was not as great as that between invasive and ductal carcinoma in situ tumors. There was a trend toward increased SF content in larger primary tumors as compared with smaller tumors, but statistical comparison revealed borderline significance (0.05 < P < 1.0). There was no significant correlation between SF content and other parameters, including estrogen receptor, progesterone receptor, DNA ploidy, S phase, or Scarff-Bloom-Richardson score. We also measured the content of von Willebrand factor (a marker of blood vessels) and interleukin-1 beta (a pro-inflammatory cytokine) in the same tumor extracts. SF content showed a strong positive correlation with von Willebrand factor content (P < 0.001) but did not appear to be correlated with interleukin-1 beta. These findings suggest that SF is correlated with several other clinicopathological indicators of aggressive tumor behavior, consistent with the hypothesis that SF is a biological factor that may play a role in breast cancer pathogenesis.

Biomarkers, Tumor↗

A systematic tool to assess urinary incontinence parameters: a closer look at unfamiliar parameters.

The Joseph Continence Assessment Tool, originally published in 1993, is further evaluated in terms of content validity. Nine nurses in practice and 9 nurses expert on the topic of incontinence evaluated each component of the tool as to whether they seemed quite relevant, somewhat relevant, or not relevant. The total results and a discussion of items that seemed somewhat or not relevant are presented.

Humans↗

Expression of scatter factor in human bladder carcinoma.

BACKGROUND: Scatter factor (SF) is a protein secreted by stromal (supporting) cells that induces disruption of intercellular junctions and stimulates motility and invasiveness of carcinoma cells. SF is also a potent inducer of angiogenesis (new blood vessel formation), a process required for tumor growth and dissemination. Invasion and angiogenesis are characteristics of biologically aggressive tumors, suggesting that the accumulation of SF within tumors might promote progression to a more malignant phenotype. PURPOSE: This study was designed to determine if SF is overexpressed in carcinoma of the bladder and to evaluate the potential mechanisms that might account for such overproduction. METHODS: We measured the SF content in urine from 20 patients with carcinoma of the bladder and various control groups. We also measured expression of SF in bladder tumor extracts, histologic sections of tumors, and cell culture models, using a variety of techniques, including enzyme-linked immunosorbent assays, immunohistochemistry, and Western and Northern blot analyses. Statistical comparisons were performed using two-tailed t tests. RESULTS: Urinary SF content was found to be significantly elevated in patients with bladder carcinoma as compared with normal control subjects (P < .001), patients with benign prostatic hypertrophy (P = .0055), and patients with prostate carcinoma, another genitourinary malignancy (P = .002). Extracts of bladder cancers, especially those from high-grade, invasive tumors, contained very high levels of SF. Both SF and its proto-oncogene (c-met)-encoded receptor were detected in bladder carcinoma tissue sections by immunostaining. Three different bladder carcinoma cell lines produced no detectable SF but produced very high titers of a high-molecular-weight (> 30 kd), heat-sensitive protein that stimulates SF production by stromal cell types. High titers of a similar SF-inducing activity were detected in vivo, in bladder carcinoma extracts, and in the urine of patients with bladder carcinoma. CONCLUSIONS: Our results suggest that SF is overproduced in bladder carcinomas and accumulates within the tumor and in the urine. Overproduction of SF may result from an abnormal urothelial-stromal interaction in which dysplastic or carcinomatous urothelium secretes factors that stimulate SF expression by bladder wall stromal cells. IMPLICATION: Quantitation of SF in the urine and tumor deserves further study as a possible marker of urothelial malignancy.

Blotting, Northern↗

Sphincterotomy: long-term complications and warning signs.

Transurethral sphincterotomy is a commonly performed operation in spinal cord injury patients. Sixty-three patients who have had transurethral sphincterotomy were evaluated at our spinal cord injury unit for the risk and possible predictors of long-term outcome associated with this procedure. In addition to history and physical examination, all patients had urine culture, blood urea and creatinine, intravenous pyelogram and/or KUB with renal ultrasound, 4 channel videourodynamics, voiding cystourethrogram, and cystocopy when indicated. Their mean age was 53 years, and their level of injury was cervical 32, thoracic 25, and lumbar 6. The mean time since injury was 27 years (3-50), and the mean follow-up since their last sphincterotomy was 11 years (2-30). The mean number of sphincterotomies was 1.74 (1-4). Urine culture revealed bacteruria (asymptomatic) in 48 and sterile urine in 15 patients. Renal function was normal in 61 patients and abnormal in 2 patients. Videourodynamics revealed detrusor hyperreflexia in 60, detrusor areflexia in 3, abnormal detrusor compliance in 9, and detrusor sphincter dyssynergia in 34 patients. The mean Leak point pressure was 36.4 cm H2O (5-100), and the mean maximum detrusor pressure was 54.7 cm H2O (12-100). Nineteen (30%) patients had significant upper tract complications including; renal calculi, atrophic kidney, vesicoureteral reflux, and renal scarring with impaired renal function. Fifty percent of upper tract complications developed more than 2 years after sphincterotomy. Thirty patients had lower tract complications including; recurrent symptomatic urinary tract infection, bladder stones, urethral diverticulum, urethral stricture, bladder neck stenosis, and recurrent epididymitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Follow-Up Studies↗