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Biomedical subjects

F Walker

Publications and source records attributed to F Walker.

At least 37 records · Page 2Linked to original sources
PubMed2001

Prevalence of high-grade dysplasia and cancer in the anal canal in human papillomavirus-infected individuals.

BACKGROUND & AIMS: The incidence of anal cancer is higher in patients with anal canal condyloma, a sexually transmitted disease, than in the general population. We determined the prevalence of anal dysplasia and cancer in patients with anal canal condyloma with respect to human immunodeficiency virus (HIV) status, immunity status, and human papillomavirus types. METHODS: In 174 consecutive patients (114 HIV positive, 60 HIV negative) with anal canal condyloma, lesions were cured, and the patients were then followed up prospectively. Langerhans cells (LCs) in normal anal mucosa were quantified, and viruses (Epstein-Barr virus, cytomegalovirus, human simplex virus 1, and various human papillomavirus [HPV] types) were characterized on inclusion. During follow-up (median 26 months), relapsed condylomas were resected and examined histologically. HIV load and CD4 T-lymphocyte counts in serum were determined at each visit. RESULTS: Several factors differed significantly between HIV-positive and HIV-negative patients: LCs/mm anal tissue (15 vs. 30), oncogenic HPV (27% vs. 13%), other current anal infections (44% vs. 0%), and sex ratio (93% vs. 73% male). During follow-up, condylomas relapsed in 75% of the HIV-positive patients, with 19 high-grade dysplasias (HGDs) and 1 invasive carcinoma, but in only 6% of HIV-negative patients, with 1 HGD. Male sex, HIV positivity, and <15 LCs/mm tissue were independent risk factors for condyloma relapse. HIV positivity, HGD before inclusion, and condyloma relapse were independent risk factors for HGD and cancer. Serum HIV load was associated with relapse, whereas CD4 T-lymphocyte counts were not. CONCLUSIONS: The prevalence of HGD and carcinoma is higher in HIV-positive than in HIV-negative patients, probably because of HPV activity. HIV-positive patients with high serum HIV load and/or a history of anal dysplasia should be examined by anoscopy, and condylomas should be analyzed histologically.

Adult↗
PubMed2001

Expression of CD44 standard and isoforms V3 and V6 in uterine smooth muscle tumors: a possible diagnostic tool for the diagnosis of leiomyosarcoma.

Alterations of CD44 proteins, a family of cell adhesion molecule, have been linked with tumorigenesis, carcinogenesis, and prognosis in various neoplasms. Our aims were to evaluate and compare CD44 isoforms expression patterns in normal myometrium, uterine leiomyomas, and leiomyosarcomas and to correlate CD44 expression with clinicopathologic parameters. Fresh (n = 15) and formalin-fixed, paraffin-embedded (n = 76) tissues samples of myometrium, leiomyomas, and leiomyosarcomas were used for immunoblotting and immunohistochemistry, respectively. Semiquantitative evaluation was made after immunostaining. Monoclonal antibodies were used. By immunoblotting in myometrium and leiomyomas samples, we observed a band at 85 kd, corresponding to the apparent molecular weight of CD44s, and bands at 140 kd with the monoclonal antibodies against CD44v3 and CD44v6. In leiomyosarcomas, CD44s and CD44v6 were detected, but not CD44v3. By immunohistochemistry, decreased CD44s expression was found in leiomyomas and leiomyosarcomas (73.9% +/- 16.6% and 82.1% +/- 20.7%, respectively) compared with myometrium (97.3% +/- 6.2%; P < .0001). No CD44v6 staining was detected in myometrium, leiomyomas, and leiomyosarcomas. No CD44v3 expression was detected in leiomyosarcomas, whereas myometrium and leiomyomas expressed CD44v3. For the diagnosis of leiomyosarcoma, the absence of CD44v3 staining had a sensitivity, specificity, and positive and negative predictive values of 100%. In patients with recurrence of leiomyosarcomas, CD44s expression was decreased (P = .03). We conclude that CD44s immunostaining in leiomyosarcomas may have prognostic significance. The loss of CD44v3 expression could be used as a putative diagnostic tool for uterine leiomyosarcomas.

Adult↗
PubMed2001

The perinatal thyroid in iodine deficient regions: risks of radioiodines--hazards of stable iodine overload. A study in the newborn rat.

Administration of large quantities of stable iodine is an effective means of reducing the radiation burden on the thyroid in the event of a nuclear power-plant accident. Such administration may involve countries with low baseline dietary iodine intake. It is questioned whether stable iodine overload is safe, and in particular, what are its effects in newborn infants? Iodine-deficient newborn rats were submitted to a single acute administration of stable iodine (100 microg) on the second day of life. The effects on thyroid structure were studied, after 24 hr and after 7 days, using light microscopy. Compared to controls, the thyroids of animals submitted to stable iodine overload showed, 7 days after treatment, signs of acute toxicity including marked desquamation of epithelial cells and rupture of a large number of thyroid follicles. Our findings in iodine deficient newborn rats suggest that stable iodine overload may have side effects during perinatal life. This prophylactic measure should, therefore, be accompanied by follow-up of thyroid function. Thyroid hormones are critical for brain development, during the first period of life.

Animals↗
PubMed2001

Volunteerism under the magnifying glass.

Are you making a concerted effort to seek out and attract those volunteers who can really add value to your cause? Do you place as much emphasis on recruiting volunteers for the long-term as you do when hiring employees? Arguably, the answers to all of these questions should be a resounding "yes."

Fund Raising↗
PubMed2000

c-Raf-1 RBD associates with a subset of active v-H-Ras.

Mutational analysis of the cRaf-1 Ras binding domain (RBD) identified several point mutants with elevated Ras binding. Detailed examination of the binding kinetics of one mutant (A85K) suggests that it associates with a greater range of isomeric conformers of v-H-Ras than wt-RBD. At limiting v-H-Ras concentrations, saturation binding to A85K-RBD is higher than to wt-RBD. Notably, in assay systems where the RBD concentration is limiting, no difference exists between wt-RBD and A85K-RBD saturation levels in the presence of a sufficiently large molar excess of Ras. The inability of wt-RBD to saturate all bindable Ras/GTP (defined by its binding to A85K-RBD) suggests that Ras/GTP exists as several isoforms and that only a minority of these isoforms are capable of associating with wt-RBD. These findings provide the first experimental evidence in support of functionally distinct Ras/GTP isoforms. We also describe a novel analysis of such isoforms.

Binding Sites↗
PubMed2000

Point mutants of c-raf-1 RBD with elevated binding to v-Ha-Ras.

A mutational analysis of the Ras-binding domain (RBD) of c-Raf-1 identified three amino acid positions (Asn(64), Ala(85), and Val(88)) where amino acid substitution with basic residues increases the binding of RBD to recombinant v-Ha-Ras. The greatest increase in binding (6-9-fold) was observed with the A85K-RBD mutant. The elevated binding for the A85K-RBD and V88R-RBD mutants was also detected with Ras expressed in cultured mammalian cells, namely NIH-3T3 and BAF cells. None of the wild type residues in RBD positions Asn(64), Ala(85), and Val(88) have been previously implicated in the interaction with Ras (Block, C., Janknecht, R., Herrmann, C., Nassar, N., and Wittinghofer, A. (1996) Nat. Struct. Biol. 3, 244-251; Nassar, N., Horn, G., Herrmann, C., Scherer, A., McCormick, F., and Wittinghofer, A. (1995) Nature 375, 554-560). The discovery of elevated binding among the mutants in these positions implies that additional RBD residues can be used to generate the Ras. RBD complex. These findings are of particular significance in the design of Ras antagonists based on the RBD prototype. The A85K-RBD mutant can be used to develop an assay for measuring the level of activated Ras in cultured cells; Sepharose-linked A85K-RBD.GST fusion protein served as an activation-specific probe to precipitate Ras.GTP but not Ras.GDP from epidermal growth factor-stimulated cells. A85K-RBD precipitates up to 5-fold more Ras.GTP from mammalian cells than wild type RBD.

Amino Acid Sequence↗
PubMed2000

Targeted oncogenesis reveals a distinct tissue-specific utilization of alternative promoters of the human mineralocorticoid receptor gene in transgenic mice.

The human mineralocorticoid receptor (hMR) is a nuclear receptor mediating aldosterone action, whose expression is driven by two alternative promoters, P1 and P2, flanking the two first 5'-untranslated exons. In vivo characterization of hMR regulatory regions was performed by targeted oncogenesis in mice using P1 or P2 directing expression of the large T antigen of SV40 (TAg). While transgenic P1.TAg founders rapidly developed lethal hibernomas from brown fat, cerebral primitive neuroectodermal tumors and facial leiomyosarcomas occurred in P2.TAg mice. Quantitative analyses of mouse MR (mMR) and transgene expression indicate that P1 promoter was transcriptionally active in all MR-expressing tissues, directing strong TAg expression in testis and salivary glands, moderate in lung, brain, uterus, liver, and heart but, unlike mMR, rather low in colon and kidney. Importantly, the renal transgene expression colocalized with mMR in the distal nephron. In contrast, P2 promoter was approximately 10 times less potent than P1, with no activity in the brain and colon. Several immortalized cell lines were established from both neoplastic and normal tissues of transgenic mice. These cells exhibited differentiated characteristics and maintained MR expression, thus providing useful models for further studies exploring the widespread expression and functions of MR. Our results demonstrate that hMR gene expression in vivo is controlled by complex regulatory mechanisms involving distinct tissue-specific utilization of alternative promoters.

Adipose Tissue, Brown↗
PubMed2000

Oestrogen receptor alpha in female fetal, infant, and child mammary tissue.

Oestrogen receptor alpha (ER alpha) expression was studied in female mammary tissue from a series of 35 samples obtained post-mortem, ranging from fetuses of 13 weeks' gestation to prepubertal children of 12 years. Immunocytochemistry was performed on formalin-fixed tissue after microwave antigen retrieval. ER alpha was present in epithelial cell nuclei from the 30th week of gestation onwards and was markedly up-regulated shortly after birth. For up to 3 months thereafter, progesterone receptor was also expressed, indicative that the ER alpha was functional. During this period, ER alpha was also present in epithelial cell cytoplasm. From this perspective of the developing breast, it is suggested that an early postnatal component should be added to the prenatal oestrogen hypothesis; further, the significance of ER alpha cytoplasmic staining in the adult breast also merits review.

Adult↗
PubMed2000

Consistency of histopathological reporting of laryngeal dysplasia. The Scottish Pathology Consistency Group.

AIMS: Clinical management of premalignant and malignant lesions of the larynx is dependent on histopathological evaluation. The Scottish Pathology Consistency Group assessed interobserver variation in the evaluation of laryngeal dysplasia. METHODS AND RESULTS: One hundred laryngeal biopsies ranging from normal to invasive carcinoma were assessed. The overall Kappa result of 0.32 was disappointing. However, agreement on those categories which dictate significantly different management was more favourable. The Kappa figure for mild dysplasia versus severe dysplasia/CIS was 0.7, the Kappa figure for mild dysplasia versus severe dysplasia/CIS and invasive carcinoma was 0.77. The Kappa figure for mild and moderate dysplasia versus severe dysplasia/ CIS and invasive carcinoma was 0.57. An attempt to use a two grade system gave a Kappa figure of 0.52. CONCLUSIONS: Our group had a satisfactory agreement on the distinction of mild from severe dysplasia and on microinvasive carcinoma without any discussion as to histopathological criteria to be used. Clinical management--review endoscopy, repeat cord stripping, radiotherapy and laryngectomy--is in general dependent on histological assessment. Thus the agreement on categories which underpin clinical management is reassuring. However, assessment of moderate dysplasia remains problematic. An attempt to utilize a two grade system--low grade from high grade dysplasia/CIS--may have merit. The implications of the terminology used must be agreed among pathologists and clinicians working closely within clinicopathological cancer groups.

Adenocarcinoma↗
PubMed2000

[Adenomatoid tumor of the pleura. Case report].

We report a case of an adenomatoid tumor of particular location within the pleura, incidentally discovered on a pulmonary lobectomy specimen after surgical resection of a pulmonary squamous cell carcinoma. This adenomatoid tumor appeared as a unique pleural mass located away from the primary carcinoma and consisted of a cellular proliferation organised in tubes and sheets. Adenomatoid tumors are considered as benign tumors of mesothelial nature. Their morphological and immunohistochemical features in association with their location to the pleura, warrant a precise analysis to eliminate malignant tumours such as malignant mesothelioma or metastatic adenocarcinoma.

Epithelium↗
PubMed1999

In vitro measurement of muscle volume with 3-dimensional ultrasound.

The aim was to test the accuracy of muscle volume measurements with a new 3-dimensional (3-D) ultrasound system, which allows a freehand scanning of the transducer with an improved quality of the ultrasound images and therefore the outlines of the muscles. Five resected cadaveric hand muscles were insonated and the muscle volumes calculated by 3-D reconstructions of the acquired 2-D ultrasound sections. Intra-reader, inter-reader and follow-up variability were calculated, as well as the volume of the muscle tissue measured by water displacement. In the results, 3-D ultrasound and water displacement measurements showed an average deviation of 10.1%; Data of 3-D ultrasound measurements were: intra-reader variability 2.8%; inter-reader variability 2.4% and follow-up variability 2.3%. 3-D measurements of muscle volume are valid and reliable. Serial sonographic measurements of muscle may be able to quantitate changes in muscle volume that occur in disease and recovery.

Cadaver↗
PubMed1999

Reduced number of Langerhans cells in oesophageal mucosa from AIDS patients.

AIMS: The oesophageal mucosa is a frequent target of opportunistic infections in human immunodeficiency virus (HIV) infection. Langerhans cells (LC) are known as a target and reservoir of HIV in the skin. The aim of this study was to characterize oesophageal LC in HIV-infected patients. METHODS AND RESULTS: Thirty oesophageal biopsies were obtained from 29 patients (median age 35.5), all in stage IV of the HIV Center of Disease Control Classification. We performed histological assessment of the oesophageal mucosa and immunohistochemical detection of oesophageal LC using an anti-CD1a antibody, followed by morphometric analysis. Biopsies from 17 noninfected patients were studied using the same procedure. LC in oesophageal mucosa of the HIV positive patients showed a significantly and dramatically decreased number (LC(N) median = 5.85/mm2) and surface/epithelial surface (LC (S) ratio = 0.09) when compared with HIV-negative controls (LC(N) median = 29.7/mm2, LC(S) ratio = 1.83) with P = 0.003 for LC(N) and P < 0.0001 for LC(S). CONCLUSION: These data suggest that oesophageal LC are, like their epidermal counterparts, a preferential target for HIV infection. Their alterations may provide a clue to the pathogenesis of the decreased local oesophageal immunity and to the occurrence of opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMed1999

Ebola virus outbreak among wild chimpanzees living in a rain forest of Côte d'Ivoire.

An outbreak of Ebola in nature is described for the first time. During a few weeks in November 1994, approximately 25% of 43 members of a wild chimpanzee community disappeared or were found dead in the Taï National Park, Côte d'Ivoire. A retrospective cohort study was done on the chimpanzee community. Laboratory procedures included histology, immunohistochemistry, bacteriology, and serology. Ebola-specific immunohistochemical staining was positive for autopsy tissue sections from 1 chimpanzee. Demographic, epidemiologic, and ecologic investigations were compatible with a point-source epidemic. Contact activities associated with a case (e.g., touching dead bodies or grooming) did not constitute significant risk factors, whereas consumption of meat did. The relative risk of meat consumption was 5.2 (95% confidence interval, 1.3-21.1). A similar outbreak occurred in November 1992 among the same community. A high mortality rate among apes tends to indicate that they are not the reservoir for the disease causing the illness. These points will have to be investigated by additional studies.

Animals↗