N-acetyl-D-glucosamine induces germination in Candida albicans through a mechanism sensitive to inhibitors of cAMP-dependent protein kinase

PURPOSE: Carcinomas of unknown primary site are frequent neoplasms which raise diagnostic and therapeutic problems in clinical practice. METHODS: Clinical records of 100 patients with carcinoma of unknown primary site whose clinical management took place at the Centre Regional de Lutte Contre le Cancer de Montpellier were retrospectively reviewed. Initial clinical and biological characteristics, pre-treatment evaluation, therapies and outcome were recorded. RESULTS: Three main histological types were observed: adenocarcinoma (66 patients), poorly differentiated carcinoma (19 patients), epidermoid carcinoma (11 patients). Bone, lung, lymph nodes and liver were the most frequently involved metastatic sites. Analysis of the investigations aimed at identifying the primary site (none of which being positive) showed 68 different combinations in 100 patients. Anemia (< 100 g/L) was observed in 10 patients, while serum alkaline phosphatase was increased in 42 patients. Seven patients died before any therapy. Chemotherapy or radiotherapy was advocated in 70 and 59 patients, respectively. Thirty-six patients had concomitant chemoradiotherapy. Chemotherapy included a platinum derivative in 53 patients. The median number of cycles was four. Nine objective responses were observed, six of which occurred in patients who were receiving platinum-based chemotherapy. Ninety-six deaths were encountered, 95 due to the disease progress and one due to an intercurrent cause. The median survival was 9 months. Univariate analysis identified two prognostic factors: the number of metastatic sites and the serum alkaline phosphatase. CONCLUSIONS: This retrospective study confirms the difficulties in the management of patients with carcinomas of unknown primary site. A literature review suggests limited diagnostic investigations in clinical practice with the aim of identifying tumors of potential prognostic (breast and ovary) or therapeutic (prostate) value. Apart from specific subgroups of patients for whom specific therapy is recommended, there is no current standard chemotherapy.     

Expression of the c-erbB-3 gene product in gastric cancer

The pattern of c-erbB-3 gene product was studied in 91 advanced gastric carcinomas, adjacent hyperplastic mucosa, intestinal metaplasia and dysplasia and in normal controls, using immunohistochemistry in archival material. All tumours showed positive c-erbB-3 staining in both cytoplasm and membrane. No significant differences of expression were observed between intestinal and diffuse-type carcinomas or any other clinical parameters. Of interest is the expression in the adjacent mucosa, which is extensive, cytoplasmic, and of lower intensity than in the tumours. Further studies are currently being carried out to clarify the role of this protein in tumour behaviour and gastric carcinogenesis.     

On the metabolism of prostaglandins by rat brain homogenate

Using radio-immuno assays for prostaglandins and prostaglandin metabolites, three prostaglandin metabolizing enzymes were found in the 100,000 X g supernatant of rat brain, 15-hydroxy-prostaglandin-dehydrogenase, delta13-reductase and prostaglandin E-9-keto-reductase. Specific activity of the latter enzyme was highest in striatum and midbrain and lowest in cortex, cerebellum and spinal cord.     

Design, synthesis, and conformational analysis of a novel series of HIV protease inhibitors

A combination of structure-based design and both solution, and solid-phase synthesis were utilized to derive a potent (nM) series of HIV-1 protease inhibitors bearing a structurally novel backbone. Detailed structural analysis of several inhibitors prepared in this series has suggested that rigidification of the P1/P2 region of this class of molecules may result in compounds with improved potency.     

Effects of amperozide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol

Ventilatory acclimatization to sustained hypoxia (VASH) is the time-dependent increase in ventilation that occurs during prolonged exposure to hypoxia. We tested the hypothesis that carotid body (CB) dopaminergic mechanisms are down-regulated during VASH, which would allow CB afferent discharge and ventilation to increase beyond the initial response to hypoxia. Domperidone (DOM; 1.0 mg.kg-1) was administered intravenously to block CB dopamine (DA) receptors after VASH was complete in awake goats. DOM caused a significant augmentation of the ventilatory response to hypoxia in acclimatized goats, failing to support the hypothesis. We conclude that inhibitory CB dopaminergic function is not significantly reduced following prolonged hypoxia, and that down-regulation of CB dopaminergic mechanisms may not be involved in VASH in the goat.     

Estimation of AIDS morbidity and mortality in Spain

BACKGROUND: To obtain corrected estimates of the cumulative incidence and mortality, as well as prevalence of AIDS in Spain on June 1992. METHODS: The number of cases in the National Register of AIDS by December 1992 was adjusted for reporting delays to estimate the cumulative incidence by June 1992. The prevalence and mortality in this date were obtained using this figure and the probabilities of survival after diagnosis from the AIDS Register of Madrid. This methodology was used for Spain as all, and for each Autonomous Community. RESULTS: The estimated cumulative incidence of AIDS in Spain by June 1992 was 16,486 cases, 13.4% greater than that reported by the same date. The prevalent cases were 6,351 (95% CI, 5,996-6,708) and the remaining 10,135 (61.5%) would have died. This number of deaths is 69.6% greater than the reported figure. There were considerable differences among Autonomous Communities. Some of them exhibited rates more than six times greater than others. CONCLUSIONS: The adjusted estimations provide a view of the actual situation more accurate than the raw figures from the register. These great differences should be taken into account for appropriate allocation of health care resources.