Food-borne and water-borne infections and the gastroenterologist.
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Food Microbiology↗
Biomedical subjects
M B Cohen
Publications and source records attributed to M B Cohen.
Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El tor inaba three months after vaccination.
CVD 103-HgR is a live oral cholera vaccine strain constructed by deleting 94% of the gene for the enzymatically active A subunit of cholera toxin from classical Inaba Vibrio cholerae O1 569B; the strain also contains a mercury resistance gene as an identifying marker. This vaccine was well tolerated and immunogenic in double-blind, controlled studies and was protective in open-label studies of volunteers challenged with V. cholerae O1. A randomized, double-blind, placebo-controlled, multicenter study of vaccine efficacy was designed to test longer-term protection of CVD 103-HgR against moderate and severe El Tor cholera in U.S. volunteers. A total of 85 volunteers (50 at the University of Maryland and 35 at Children's Hospital Medical Center/University of Cincinnati) were recruited for vaccination and challenge with wild-type V. cholerae El Tor Inaba. Volunteers were randomized in a double-blind manner to receive, with buffer, a single oral dose of either CVD 103-HgR (2 x 10(8) to 8 x 10(8) CFU) or placebo (killed E. coli K-12). About 3 months after immunization, 51 of these volunteers were orally challenged with 10(5) CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Ninety-one percent of the vaccinees had a >/=4-fold rise in serum vibriocidal antibodies after vaccination. After challenge, 9 (39%) of the 23 placebo recipients and 1 (4%) of the 28 vaccinees had moderate or severe diarrhea (>/=3-liter diarrheal stool) (P < 0.01; protective efficacy, 91%). A total of 21 (91%) of 23 placebo recipients and 5 (18%) of 28 vaccinees had any diarrhea (P < 0.001; protective efficacy, 80%). Peak stool V. cholerae excretion among placebo recipients was 1.1 x 10(7) CFU/g and among vaccinees was 4.9 x 10(2) CFU/g (P < 0.001). This vaccine could therefore be a safe and effective tool to prevent cholera in travelers.
Administration, Oral↗
Validation and characterization of a human volunteer challenge model for cholera by using frozen bacteria of the new Vibrio cholerae epidemic serotype, O139.
Until recently, all epidemic strains of Vibrio cholerae were of the O1 serotype. Current epidemics have also been caused by a new serotype, Vibrio cholerae O139. Although the pathogenesis and clinical features of O139 cholera are similar to those of O1 cholera, immunity to serotype O1 does not confer immunity to serotype O139. Therefore, prior to beginning vaccine efficacy studies, we sought to validate the use of a large standardized frozen inoculum of virulent V. cholerae O139 4260B for use in a human volunteer challenge model. Healthy volunteers (n = 25) were recruited for an Internal Review Board-approved inpatient dose-escalation challenge. Our goal was to identify a dose at which the cholera attack rate and the geometric mean purge were sufficient for determining vaccine efficacy against moderate and severe disease. At a dose of 10(5) CFU, 8 of 10 volunteers experienced purging and had a positive stool culture for V. cholerae. However, at this dose, the geometric mean stool volume of 2,175 g was insufficient by study criteria. At a dose of 10(6) CFU, 14 of 15 volunteers experienced purging, with a geometric mean stool volume of 5,621 g. Disease severity was significantly greater in volunteers with blood group O than those with non-O blood types (10,353 g versus 3,555 g, P < 0.001). Following challenge, all volunteers demonstrated a significant rise in antitoxin antibodies but the serum vibriocidal titer was attenuated compared to that seen after challenge with an O1 strain. This model provides a reproducible illness of sufficient severity for testing the efficacies of new O139 or combined O1-O139 vaccines.
Antibodies, Bacterial↗
Telomerase activity in human solid tumors. Diagnostic utility and clinical applications.
Telomerase is expressed in almost all human malignant processes but not in benign and normal tissues, with the exception of germline and stem cells. Because of its prevalent expression and potential as a target for cancer therapy, telomerase is the subject of intense investigation, and numerous papers have been published. We present the most recent findings on the association between telomerase activity and human malignancies, recent developments in methods of telomerase detection, telomerase utility in monitoring of patients with cancer for residual or recurrent disease, and potential usefulness of telomerase in treatment of cancer.
Humans↗
Family history and prostate cancer risk in a population-based cohort of Iowa men.
A family history of prostate cancer has been associated with prostate cancer risk in most prior studies, and more limited data suggest that a family history of breast cancer may also be important; however, there are no data from a population-based cohort study of prostate cancer incidence that adjusts for major confounders. We conducted follow-up through 1995 on 1557 men, ages 40-86 years, who were randomly selected (81% response rate) as cancer-free controls for a population-based case-control study conducted in Iowa from 1987-1989. Family history of cancer in parents and siblings was obtained using a mailed questionnaire. Incident cancers and deaths were ascertained through linkages to state and national databases; 101 incident cases of prostate cancer were identified. At baseline, 4.6% of the cohort reported a family history of prostate cancer in a brother or father, and this was positively associated with prostate cancer risk after adjustment for age [relative risk (RR) = 3.2; 95% confidence interval (CI), 1.8-5.7] or after multivariate adjustment for age, alcohol, and dietary factors (RR = 3.7; 95% CI, 1.9-7.2). Risk was greater if a brother had prostate cancer (RR = 4.5; 95% CI, 2.1-9.7) than if a father had prostate cancer (RR = 2.3; 95% CI, 1.0-5.3). Also at baseline, 9.6% of the cohort had a family history of breast and/or ovarian cancer in a mother or sister, and this was positively associated with prostate cancer risk (age-adjusted RR = 1.7; 95% CI, 1.0-3.0; multivariate RR = 1.7; 95% CI, 0.9-3.2). Men with a family history of both prostate and breast/ovarian cancer were also at increased risk of prostate cancer (RR = 5.8; 95% CI, 2.4-14). There was no association with a family history of colon cancer. Exclusion of well-differentiated, localized tumors did not alter these findings. These data from an incidence study confirm that a family history of prostate cancer is a strong prostate cancer risk factor after adjustment for dietary and other risk factors, and suggest that selection and recall bias have not had an important influence on most case-control study results. These data also support the idea that a family history of breast cancer may also be a prostate cancer risk factor.
Adult↗
Fas-mediated apoptosis in human prostatic carcinoma cell lines occurs via activation of caspase-8 and caspase-7.
We previously demonstrated that treatment with cycloheximide (CHX) converted the phenotype of Fas-resistant human prostatic carcinoma cell lines to Fas-sensitive and that resistance to Fas-mediated apoptosis was due to a dominant-negative protein(s). In this study, we investigated the sequential activation of caspase family members, to gain insight into the likely site of action of the suppressor protein(s). We did not find Tyr-Val-Ala-Aspase activity in any of the cell lines examined. Time-dependent Asp-Glu-Val-Aspase activity was detected during Fas-mediated apoptosis in Fas-sensitive cell lines PC3 and ALVA31. Asp-Glu-Val-Aspase activity in Fas-resistant cell lines DU145 and JCA1, was detected only under combined treatment with CHX and anti-Fas agonistic mAb. In experiments with caspase inhibitors we show that Fas-mediated apoptosis in PC3 is mainly executed by the caspase-3 subfamily, but another member(s) of the caspase family may be involved in Fas-mediated apoptosis in ALVA31, DU145, and JCA1. Western blot analysis revealed that Fas-ligation activated caspase-7, but not caspase-3. The activated form of caspase-8 was detected in DU145 only after 4 h of simultaneous treatment with CHX and anti-Fas mAb, whereas in PC3 caspase-8 was found to be activated after 1 h of Fas-ligation. We have also found that treatment with staurosporin did not activate caspase-8, whereas staurosporin induced apoptosis at the same levels in both Fas-resistant and Fas-sensitive cell lines. These results suggest that an inhibitory protein(s), which suppresses apoptosis in Fas-resistant cell lines, presumably acts at the apex of apoptotic cascade by preventing the activation of caspase-8.
Apoptosis↗
Cytologic criteria for the brush diagnosis of gastric adenocarcinoma.
BACKGROUND: The cytologic diagnosis of gastric adenocarcinoma often is difficult, and the role of gastric brushing in the detection of gastric malignancy is controversial. The purpose of this study was to identify the key cytologic criteria that are most useful for establishing a diagnosis of adenocarcinoma in gastric brushing specimens. METHODS: One hundred gastric brushings were reviewed retrospectively. Fifty of the specimens were obtained from patients with histologically confirmed benign lesions. The other 50 specimens were obtained from patients with histologically confirmed gastric adenocarcinoma. All 100 brushing specimens were reviewed without knowledge of the histologic diagnosis. Each specimen was assessed for the presence or absence of 16 different cytologic features that have been identified in the published literature as being useful for separating benign conditions from malignancy. A multiple logistic linear regression analysis was performed to determine which combination of criteria was the most useful for diagnosing gastric adenocarcinoma. RESULTS: Three key cytologic criteria were identified as being the most useful for diagnosing gastric adenocarcinoma: single atypical cells with intact cytoplasm, eccentric nuclei, and atypical naked nuclei. When at least 2 of these cytologic criteria were present, the sensitivity and specificity for detecting adenocarcinoma were 88% and 100%, respectively. Two minor cytologic criteria also were identified: nuclear hyperchromasia and nuclear molding. CONCLUSIONS: Our statistical analysis demonstrates that gastric adenocarcinoma can be diagnosed with a high degree of accuracy using gastric brushing specimens when specific cytologic criteria are applied.
Adenocarcinoma↗
5E10: a prostate-specific surface-reactive monoclonal antibody.
We created mAb that reacted solely with prostate epithelial cells. The strategy involved immunizing mice with a mixture of six different prostatic carcinoma cell lines and selecting by flow cytometry only those antibodies that bind whole cells. The primary screening was performed using a mixture of all six prostate cell lines used in immunization together with six non-prostate cell lines in the same tube. Antibodies that gave a bimodal pattern of surface staining were selected for further evaluation. The most attractive clone, designated 5E10, produced IgG1 mAb that recognized four of the six prostatic cell lines and did not react with non-prostate tumor cell lines, peripheral blood and bone marrow mononuclear cells and endothelial and bone marrow stromal cells. 5E10 mAb reacted with both benign and malignant prostate in eight of eight histological samples and no reactivity was noted with non-prostate normal tissues. The 5E10 antigen is a transmembrane glycoprotein with a molecular weight of 110 kDa and the epitope recognized by 5E10 is extracellular. Ongoing studies are exploring the nature of this antigen in more depth.
Animals↗
Rhabdomyosarcoma presenting as a parotid gland mass in pediatric patients: fine-needle aspiration biopsy findings.
BACKGROUND: The head and neck region is one of the most common locations of rhabdomyosarcoma. Salivary gland involvement is usually secondary to advanced disease, and presentation as a primary salivary gland tumor is very rare. METHODS: Three cases of rhabdomyosarcoma presenting as parotid masses, in 2 boys (ages 3 and 7 years) and a girl (age 5 years), were retrieved from the files of 2 institutions. RESULTS: The three patients presented with parotid gland enlargement. Clinically, the enlargements appeared to be inflammatory, and they were treated unsuccessfully with antibiotics. Fine-needle aspiration biopsy (FNAB) was performed on all three patients. The cytologic features varied from one case to another; one case had features of a small round cell tumor, another was composed of a monomorphic population of spindle cells in a metachromatic stroma, and the third case was composed mostly of spindle cells with moderate cellular pleomorphism. Immunohistochemical studies performed in two of the cases confirmed the diagnosis of rhabdomyosarcoma, and ultrastructural studies were confirmatory in the other case. The patients are alive; 2 of them have had no evidence of disease after 6 and 9 years of follow-up, and the third, the most recent patient, has just finished adjuvant chemotherapy. CONCLUSIONS: With the increased use of FNAB for the evaluation of salivary gland masses in children, the authors believe that it is important to recognize the occurrence of rhabdomyosarcoma in this location. Immunohistochemical studies have proved helpful in differentiating rhabdomyosarcoma from other parotid gland tumors and can be readily done on cytologic preparations.
Biopsy, Needle↗
Is the cytologic diagnosis of esophageal glandular dysplasia feasible?
Barrett's esophagus is a premalignant condition in which the normal stratified squamous epithelium of the esophagus is replaced by metaplastic glandular epithelium. Patients with Barrett's esophagus are at increased risk for the development of esophageal adenocarcinoma. Because dysplasia precedes the development of frank adenocarcinoma, the cytologic detection of esophageal glandular dysplasia represents a potentially inexpensive and efficient means of monitoring disease progression to adenocarcinoma and identifying high-risk patients. This article discusses the current status of exfoliative cytology as a screening test for glandular dysplasia of the esophagus.
Barrett Esophagus↗
Cytology of metastatic cutaneous basal cell carcinoma.
Although basal cell carcinoma is the most common malignant skin tumor, it rarely metastasizes. Because of the infrequency of basal cell carcinoma metastases, the cytomorphologic findings have not been well documented. We retrospectively reviewed the cytologic findings of six cases of metastatic basal cell carcinoma from two patients. Five of these specimens were fine-needle aspiration biopsies, and one was a bronchial brush specimen. All cases were confirmed by and compared to either the concurrent tissue biopsy or to a previous surgical specimen. The microscopic findings of these specimens reveal tight clusters of cells with high nuclear to cytoplasmic ratio. The nuclei were crowded and overlapping, and on Diff Quik stain, peripheral palisading of nuclei could be appreciated. The small hyperchromatic nuclei were round to oval with finely granular chromatin. Nucleoli were inconspicuous. Basophilic cytoplasm was scant with indistinct borders. Cytologic findings of basal cell carcinoma have not been well documented in the English literature. Our experience suggests that there are unique cytormorphologic features of metastatic basal cell carcinoma and that in the right setting such a diagnosis can be rendered.
Aged↗
Escherichia coli O157:H7: assessing and minimizing the risk from farm to fork.
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Animals↗
Atypical prostatic stromal lesions.
This commentary addresses the newly proposed classification of the rare atypical prostatic stromal lesions of the prostate. The entity called "prostatic stromal proliferation of uncertain malignant potential" apparently has a benign behavior. The entity "prostatic stromal sarcoma" might have a malignant potential, but its line of differentiation is still unclear.
Diagnosis, Differential↗
Validation of a volunteer model of cholera with frozen bacteria as the challenge.
To evaluate a standardized inoculum of Vibrio cholerae for volunteer challenge studies, 40 healthy adult volunteers were challenged at three different institutions with a standard inoculum prepared directly from vials of frozen, virulent, El Tor Inaba V. cholerae N16961, with no further incubation. Groups of 5 volunteers, with each group including 2 volunteers with blood group O, were given a dose of 10(5) CFU, and 34 of the 40 volunteers developed diarrhea (mean incubation time, 28 h). Transient fevers occurred in 15 (37.5%) of the volunteers. V. cholerae was excreted by 36 of 40 volunteers. Five additional volunteers received 10(4) CFU, and four developed diarrhea but with a lower average purging rate than required for the model. Of the 40 volunteers, 37 developed rises in their vibriocidal and antitoxin titers similar to those in previous groups challenged with freshly harvested bacteria. We conclude that challenge with frozen bacteria results in a reproducible illness similar to that induced by freshly harvested bacteria. Use of this model should minimize differences in attack rates or severity when groups are challenged at different times and in different institutions.
Adolescent↗
Exacerbation of autoimmune hepatitis: another hepatotoxic effect of pemoline therapy.
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Acute Kidney Injury↗
Guanylin mRNA expression in human intestine and colorectal adenocarcinoma.
Guanylin is a mammalian peptide ligand that binds to the enterocyte receptor guanylyl cyclase C and mediates Cl- and HCO3- efflux via the cystic fibrosis transmembrane conductance regulator. To identify the regional localization of guanylin mRNA in the human intestine, we performed in situ hybridization using a guanylin-specific riboprobe. The pattern of guanylin mRNA distribution is complex and includes all epithelial lineages at various points along the duodenal-to-colonic axis. Guanylin mRNA expression is most prominent in the distal small intestine and colon. In the normal colon, guanylin mRNA is robustly expressed in superficial epithelial cells; in colorectal adenocarcinoma, however, guanylin mRNA expression is absent. Guanylin mRNA is detectable in several intestinal tumor cell lines, although at much lower levels than those seen in the human intestine. The pattern of guanylin expression is consistent with the possibility of region-specific functions for guanylin within the human intestine. Furthermore, the diminished expression of guanylin mRNA in adenocarcinoma of the colon and in colon cancer cell lines, along with the chromosomal localization of guanylin to the tumor modifier region 1p34-35, raises the possibility that loss of guanylin activity leads to or is a result of adenocarcinoma formation.
Adenocarcinoma↗
The uroguanylin gene (Guca1b) is linked to guanylin (Guca2) on mouse chromosome 4.
Uroguanylin is an endogenous ligand of the intestinal receptor guanylate cyclase-C (GC-C). Both uroguanylin and the related peptide ligand guanylin bind to GC-C and stimulate an increase in cyclic GMP, inducing chloride secretion via the cystic fibrosis transmembrane conductance regulator. We describe the cloning of the complete mouse uroguanylin gene (Guca1b) and show that Guca1b is tightly linked to the mouse guanylin gene on chromosome 4. The two genes are structurally similar, being composed of three short exons; the uroguanylin gene spans 2.4 kb and the guanylin gene spans 1.7 kb. Uroguanylin mRNA is most prominent in proximal small intestine, whereas guanylin mRNA is predominantly expressed in distal small intestine and colon. The upstream promoter sequence of the mouse uroguanylin gene contains a canonical TATA element at the site of transcription initiation and consensus binding sites for several known transcription factors, including HNF-1 and Sp1 within the first 1 kb. Although the gene structure and coding sequences of uroguanylin and guanylin are similar, the 5' flanking sequences and patterns of expression of these two genes in the intestine are different. It is likely that uroguanylin and guanylin represent gene duplications that have evolved to allow overlapping and complementary patterns of expression in the intestine.
Animals↗