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Biomedical subjects

K Cooper

Publications and source records attributed to K Cooper.

At least 55 records · Page 3Linked to original sources

Spindle epithelial tumour with thymus-like element (SETTLE): the predominantly monophasic variant.

AIMS: To describe two cases of spindle epithelial tumour with thymus-like element (SETTLE) which are composed predominantly of spindle cells. In addition, to highlight some unusual histological features in SETTLE and discuss its separation from histological mimics. METHODS AND RESULTS: The thyroid masses were in a 4-year-old boy and a 25-year-old male. Both patients were euthyroid and were well except for thyromegaly. The specimens were formalin fixed, and immunohistochemistry was performed on this material using a panel of antibodies following microwave antigen retrieval. Morphologically, the dominant pattern was of sheets of spindle cells arranged in several patterns. There was mild pleomorphism and occasional mitoses. There were very small foci of squamous epithelium and occasional ductular structures. The stroma was composed of fibrous tissue and isolated areas of calcification were noted. The spindle cells showed strong and diffuse immunoreactivity with AE1/3, CAM5.2 and vimentin. CONCLUSION: We describe two cases of SETTLE that are composed mainly of spindle cells and only a very focal ductular component. In addition, calcification was noted within the stroma in one of the cases. These predominantly spindle examples of SETTLE must be separated from synovial sarcoma, which is a more mitotically active, aggressive tumour displaying only patchy immunopositivity with epithelial markers.

Adult↗

The role of the human papilloma virus in esophageal cancer.

Esophageal squamous cell carcinoma (ESCC) demonstrates wide regional variation in incidence and causal associations. Human papillomavirus (HPV) has been implicated in ESCC, particularly the sub-types 16 and 18. Transforming proteins E6 and E7 from these high risk sub-types, interact with p53 protein and Rb protein respectively, leading to loss of function of these tumor suppressor gene products. These interactions further lead to inactivation of the growth suppressive effects of the p53 and Rb proteins, resulting in abnormal proliferative states. p53 protein expression has been found in both HPV-positive and -negative tumors, indicating that HPV and p53 protein expression are not mutually exclusive and can occur together in the same tumor. It has been observed that HPV plays a more significant role in esophageal carcinogenesis in geographic areas with a high prevalence of the disease. A variation in the association between HPV and ESCC worldwide may be due to environmental and geographic factors, or to genetic susceptibility to esophageal HPV infections. Variations in the sensitivity of techniques used in the detection of the virus and in the methodology for processing the tumor tissues, may also be responsible for global differences. Esophageal carcinogenesis is a complex multistep process with a multifactorial etiology. Infection with oncogenic HPV types may be an integral part in a multistep process that leads to ESCC.

Carcinoma, Squamous Cell↗

Primary extrarenal Wilms' tumor of the uterus presenting as a cervical polyp.

Extrarenal Wilms' tumor is rare in any site, and only three cases arising within the uterus have been reported. Two of the previous cases were in adolescent girls, appearing as polypoid vaginal masses, and the third was in a 22-year-old woman who had menometrorrhagia. An extrarenal Wilms' tumor in an 11-year-old girl that initially appeared as a 10-cm polyp protruding through the cervix is described. Triphasic differentiation with mesenchymal stroma showing rhabdomyoblastic differentiation both morphologically and immunohistochemically was demonstrated. Epithelial differentiation with focal glomerular differentiation also was present. Most of the primary tumor and almost the entire recurrent tumor were composed of blastemal cells. The diagnosis of an extrarenal Wilms' tumor should be entertained when examining a polypoid tumor of the cervix or a polypoid mass within the vagina in an adolescent patient.

Biomarkers, Tumor↗

Identification of HHV8 in early Kaposi's sarcoma: implications for Kaposi's sarcoma pathogenesis.

AIMS: Kaposi's sarcoma is a vascular tumour of uncertain pathogenesis possibly caused by an infectious agent, identified in high risk groups. Accumulating solution phase polymerase chain reaction (PCR) and seroepidemiological data suggest that a previously undescribed herpes DNA virus (human herpesvirus 8 (HHV8)) is the causative agent. Using a unique cohort of early Kaposi's sarcoma, the precise cell type infected with HHV8 in such lesions was identified to elucidate further the role of HHV8 in the pathobiology of Kaposi's sarcoma. METHODS: Sixteen cases of early Kaposi's sarcoma (derived from skin and lymph node) were assessed for the presence of HHV8 using both standard solution phase PCR and TaqMan PCR to the KS330 Bam region of HHV8. In situ amplification was also performed on a selected group in an attempt to identify the candidate infected cells. RESULTS: Using both conventional solution phase and TaqMan PCR, 87% of cases were positive. In addition, HHV8 amplicons were localised in situ to endothelial and spindle cell proliferations in early Kaposi's sarcoma. The HHV8 viral load varied from lesion to lesion. CONCLUSIONS: The presence of HHV8 in early lesions supports a role for HHV8 in the pathogenesis of Kaposi's sarcoma. Coupled with recent seroepidemiological studies, these results suggest that HHV8 is the aetiological agent of Kaposi's sarcoma. Its precise interaction with other factors known to be involved in the development of Kaposi's sarcoma, including cytokines and anti-apoptosis genes, requires elucidation.

Adolescent↗

HHV-8 is not associated with follicular dendritic cell tumours.

Follicular dendritic cell tumours are rare malignancies derived from the follicular dendritic cells of lymphoid follicles. These tumours have been associated with Epstein-Barr virus infections and with the hyaline vascular subtype of Castleman's disease. Because many examples of Castleman's disease have been associated with Kaposi's sarcoma associated herpes virus (HHV-8), this study uses polymerase chain reaction technology to examine five cases of follicular dendritic cell tumours for HHV-8. One of these cases had previously been documented to arise from pre-existing Castleman's disease. HHV-8 DNA was not detected in any of the follicular dendritic cell tumours examined, or in the original case of Castleman's disease. These findings suggest that HHV-8 plays no role in the aetiology of follicular dendritic cell tumours and the cause of this tumour remains obscure.

Adolescent↗

Hyperparathyroidism: a seven-year follow-up.

Hyperparathyroidism (HPT) is a common finding in patients with end-stage renal disease (ESRD). Most chronic peritoneal dialysis (CPD) patients with HTP can be successfully managed with phosphate binders, calcium supplements, and calcitriol therapy. Noncompliance with diet, prescribed binder, or calcitriol therapy may also lead to HPT. We reviewed New Haven CAPD unit patients who failed medical therapy and required parathyroidectomy (PTX) for control of severe HPT [sustained immunoreactive parathyroid hormone (iPTH) level > 600 pg/mL]. From 1990 to 1997, 18 out of 620 patients (3.0%) required PTX. Time on dialysis prior to PTX was 44.8 +/- 17.5 (mean +/- SD) months with a range of 13 to 71 months. The mean age was 43.6 +/- 11.8 years with a range of 30 to 66 years. There were 10 females and 8 males. Of the 18 patients, 14 had total parathyroidectomy with arm implants, and 4 had subtotal PTX. Seven of 18 patients had iPTH levels of < 100 pg/mL at 1 year post-PTX (5 patients with arm implants, 2 with subtotal PTX). Three patients required partial arm implant PTX to correct recurrent HPT. Pulse oral calcitriol (POC) was prescribed in 10 patients post PTX to maintain iPTH at target levels. Parathyroidectomy was necessary to correct HPT in 18 of 620 CPD patients from 1990 to 1997. The majority of these patients had excellent results after their PTX. Intact PTH levels of < 100 pg/mL for 1 year or more were noted in 5 of 14 patients with arm implants, and 2 of 4 patients with subtotal PTX. The significance of a persistent iPTH of < 100 pg/mL has yet to be determined in CPD patients.

Adult↗

Weight dissatisfaction and weight loss attempts among Canadian adults. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To describe the pattern of weight dissatisfaction and weight loss attempts among Canadian adults and the reasons for and methods of weight loss among those trying to lose weight. DESIGN: Population-based, cross-sectional surveys. SETTING: Ten Canadian provinces between 1986 and 1992. PARTICIPANTS: A probability sample of 29,855 men and women aged 18 to 74 years was selected using provincial health insurance registration files; this paper describes the subsample of 19,841 (66%) participants from whom anthropometric data were collected. OUTCOME MEASURES: Discrepancy between actual and desired body mass index (BMI); attempts to lose weight; reasons for losing weight; methods of weight loss used. RESULTS: Whether their weight was in the acceptable range (BMI 20-24 kg/m2) or at a level of increasing risk (BMI > or = 27 kg/m2), women were more likely than men to wish they weighed less and to be trying to lose weight; almost two-thirds of women but less than half the men with BMI > or = 27 kg/m2 were trying to lose weight. Even among those with BMI 20-24 kg/m2, 32% of women (v. 10% of men) were trying to reduce their weight. Weight dissatisfaction and current and past weight loss attempts were all negatively associated with age among women, but were unrelated to age among men. People with higher ratios of waist to hip circumference (WHR), controlling for BMI, were no more likely to be trying to lose weight than those with lower WHR; in fact, for women with BMI 27-29 kg/m2, WHR was negatively associated with prevalence of weight loss attempts. The presence of diabetes, hypertension and hypercholesterolemia was also unrelated to weight loss attempts; regular smokers and sedentary people were less likely to report trying to lose weight, controlling for BMI. Among those currently trying to lose weight, the most commonly mentioned reason was to improve general health, followed by increasing attractiveness. Overall, the most frequently mentioned method of weight loss was dieting, followed by exercise. CONCLUSIONS: Substantial numbers of men whose BMI places them at increased health risk appear to be content with their weight and are not attempting to reduce it. Conversely, women, especially the young and middle-aged, are likely to consider themselves above their desired weight and to be trying to lose weight, even when their weight is within acceptable limits. This reinforces the need to consider differences between men and women in efforts to promote and support healthy weights among Canadians.

Adult↗

Attitudes toward environmental hazards: where do toxic wastes fit?

The public is continually faced with making decisions about the risks associated with environmental hazards, and, along with managers and government officials, must make informed decisions concerning possible regulation, mitigation, and restoration of degraded sites or other environmental threats. We explored the attitudes regarding several environmental hazards of six groups of people: undergraduate science majors, undergraduate nonscience majors, and graduate students in environmental health, in ecological risk assessment, and in nonscience disciplines, as well as nonstudents over 35 yr of age. We had predicted that there would be significant differences in attitudes between science and nonscience majors and as a function of age. Relative concerns could be divided into three discrete classes (in descending order of concern): (1) general ecological problems (cutting tropical forests, polluting groundwater, trash along the coasts, lead in drinking water, and acid rain), (2) radon and nuclear wastes, and finally (3) specific nuclear waste facilities, chromium, fertilizers and pesticides, and electromagnetic waves. For any hazard, attitudes were consistent across groups with regard to ranking the severity of the environmental problem and willingness to expend funds to solve the problems. Attitudes about spending money to develop methods to evaluate risk fell in the middle level of concern. There were no major differences among classes of college-age students, or between them and older nonstudents.

Adult↗

Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized.

BACKGROUND: The goal of this study was to characterize the clinicopathologic features of follicular dendritic cell sarcoma, a very uncommon neoplasm. METHODS: The 17 cases were collected from the consultation and surgical pathology files of the authors, including 8 previously reported cases. The histologic and immunohistochemical features and outcome were analyzed. RESULTS: The patients had a median age of 40 years, with a slight female predominance. Seven patients presented with enlarged lymph nodes, and ten presented with tumor in extranodal sites. Two cases were associated with hyaline-vascular Castleman's disease. The tumors had an average greatest dimension of 6.7 cm. The most common histologic feature was a storiform or fascicular array of spindle, ovoid, or polygonal cells with oval nuclei, delicate nuclear membrane, vesicular or granular chromatin, distinct nucleoli, indistinct cell borders, and frequently fibrillary cytoplasm. There were often scattered multinucleated forms. The tumor cells sometimes formed sheets, circular whorls, follicle-like structures, trabeculae, or pseudovascular spaces. There was a sprinkling of small lymphocytes, with or without cuffing around blood vessels. The neoplastic cells were immunoreactive for CD21 (17 of 17 cases), CD35 (17 of 17 cases), desmoplakin (10 of 17 cases), epithelial membrane antigen (14 of 16 cases), S-100 protein (6 of 17 cases), and CD68 (2 of 17 cases), but not cytokeratin. Ultrastructural studies showed villous processes connected by desmosomes. Only one harbored the Epstein-Barr virus. Among 13 patients with a median follow-up of 3 years, local recurrence occurred in 6, metastasis in 6, and 3 died of disease. CONCLUSIONS: Follicular dendritic cell sarcoma exhibits distinctive histologic features that permit its presumptive recognition, but a firm diagnosis requires confirmation with special studies. Because it has a significant recurrent and metastatic potential (the latter risk having been previously underestimated), it should be viewed as an intermediate grade malignancy. An intraabdominal location is associated with a particularly aggressive clinical course.

Adolescent↗

bcl-2 and p53 protein expression in follicular lymphoma.

Recent studies have shown bcl-2 to be regulated by p53. Other studies have suggested an inverse relationship between p53 and bcl-2 protein expression in breast and colonic cancers and in a variety of subtypes of non-Hodgkin's lymphoma. This study investigates the relationship between bcl-2 and p53 protein expression and the correlation between these findings and the grade and cell type of follicular lymphomas according to the REAL classification. Paraffin-embedded nodal follicular lymphomas (n = 37) were subjected to bcl-2 and p53 immunohistochemistry on tissue sections using a three-step ABC system. Positive immunostaining for both oncoproteins was scored using a three-tiered scale: +, < 10 per cent cells; ++, 10-50 per cent cells; and ++(+), > 50 per cent cells (< 10 per cent was used as a cut-off to define negative tumours). Ninety-seven per cent (36/37) of follicular lymphomas expressed bcl-2 protein in all three grades, manifesting in the small cell (grade 1) through to the large cell (grade 3). p53 protein expression showed a pattern of increasing immunostaining with progression towards the high-grade follicular lymphoma: grade 1 = 6 per cent (1/16); grade 2 = 48 per cent (10/21); grade 3 = 100 per cent (6/6). Five cases comprised varying combinations of grades. This latter finding suggests a role for p53 mutation in the progression/transformation of follicular lymphoma. The mechanism, however, differs from that suggested in breast and colonic cancers, since an inverse relationship between bcl-2 and p53 was not demonstrated in the present study.

Adult↗

Electrophysiological effects of Bacillus sphaericus binary toxin on cultured mosquito cells.

The electrophysiological effects of both trypsinactivated native and 42- and 51-kDa cloned binary toxins of Bacillus sphaericus were investigated on cultured Culex quinquefasciatus cells using the patchclamp technique. Rates of reduction in whole-cell membrane resistance were correlated with increasing native toxin concentration. The 42- or 51-kDa cloned toxin alone at 50 micrograms/ml reduced the resistance. Electrophysiological effects occurred before any changes were visible by phase-contrast microscopy.

Animals↗

Distribution studies in CD-1 mice administered [14C]muconaldehyde.

Trans,trans-muconaldehyde (muconaldehyde, MUC), a microsomal hematotoxic ring-opened metabolite of benzene, has been proposed to play a role in benzene hematotoxicity. In the present study, [14C]muconaldehyde was administered to CD-1 mice and the distribution of [14C]muconaldehyde equivalents was investigated. The study was carried out to evaluate whether [14C]muconaldehyde equivalents could reach the bone marrow. [14C]Muconaldehyde at a dose of 2 mg/kg was administered intraperitoneally (3.4 microCi/mouse) and by intravenous injection (2.7 microCi/mouse). The amount of [14C]muconaldehyde equivalents was measured in the bone marrow, blood, liver, lung, kidney and spleen at 0.25, 0.5, 1, 2, 4, and 24 h after [14C]MUC administration. The results indicate that 0.044% or 0.018% of the total dose administered when given i.v. or i.p., respectively, reached the bone marrow. The elimination of the radioactivity in all organs had at least two phases. The bone marrow, kidney, and lung had a rapid first phase (t1/2 0.5-1.2 h) and a slower second phase (t1/2 2.8-15.7 h). In the liver, a slow first phase (t1/2 3.7 h) was followed by a more rapid second phase (t1/2 1.5 h). The level of radioactivity in blood and bone marrow was significantly higher when [14C]muconaldehyde was administered intravenously compared with intraperitoneally, demonstrating that the route of administration affects the distribution of [14C]muconaldehyde equivalents.

Absorption↗