Biodistribution of a radiolabelled monoclonal antibody NY3D11 recognizing the neural cell adhesion molecule in tumour xenografts and patients with small-cell lung cancer

In this study, we examined the acute anticonvulsant spectrum of (1) dizocilpine (0.03-3 mg/kg), CGS 19755 (1-10 mg/kg), and 7-chlorokynurenic acid (1-100 nmol) (NMDA receptor/ionophore complex antagonists); (2) muscimol (0.1-10 nmol; direct GABA(A) agonist); (3) YM90K (3-10 mg/kg; AMPA receptor antagonist); and (4) diazepam (2 and 5 mg/kg) and carbamazepine (5 and 20 mg/kg), two standard anticonvulsants, using the partially-kindled hippocampal model for epileptic seizures in freely moving rats. The anticonvulsant effect of these compounds were assessed by determining (1) the afterdischarge (AD), which is indicative of the severity of the seizure and related to seizure maintenance, and (2) the pulse number threshold (PNT), which is indicative of the seizure threshold or initiation. In addition, ataxia, a measure of CNS dysfunction, was assessed for each compound. Overall, our results indicated that the anticonvulsant compounds examined could be classified into three categories based on effects on the AD and PNT: (1) elevation of PNT (carbamazepine, dizocilpine, CGS 19755 and 7-chlorokynurenic acid); (2) reduction of AD (diazepam and muscimol); and (3) mixed action, i.e., increased PNT and decreased AD (YM90K). Behavioral data indicated that all compounds, except carbamazepine, produced a dose- or concentration-dependent ataxia. Overall, our results suggest that NMDA receptors play a role in seizure initiation, whereas the GABA(A) receptors appear to be involved in seizure maintenance and AMPA receptors may be involved in both phenomena.     

Impact of medical approach on the presentation form of AIDS defined by clinical episodes

BACKGROUND: In recent years there has been a change in the opportunistic diseases incidence in HIV-infected patients. The change could be related to the use antiviral therapy and chemoprophylaxis strategies. The aim of the present study was to evaluate if medical intervention is able to modificate the clinical presentation of AIDS and the CD4+ lymphocyte counts at time of AIDS diagnosis. PATIENTS AND METHODS: The first AIDS-defining condition and the CD4+ count at time of AIDS diagnosis were analyzed in 95 HIV-infected patients who developed an AIDS-defining disease since April 1989 until March 1996, retrospectively reviewed. Patients who had been previously followed at an AIDS Unit were compared with those who had not. RESULTS: The frequency of Pneumocystis carinii pneumonia as the first AIDS-defining condition was lower in medically followed patients. Among this group, AIDS cases who received chemoprophylaxis with isoniazide showed a decrease in the rate of tuberculosis. No differences were found in CD4+ lymphocyte counts between both groups. CONCLUSIONS: As a result of medical intervention significant changes have occurred in the spectrum of initial AIDS-defining conditions in relation to medical intervention; a decrease in the frequency of Pneumocystis carinii pneumonia and tuberculosis have been found; however, the CD4+ lymphocyte counts at time of AIDS diagnosis are not modificated by medical intervention.     

Hormonal and reproductive influences and risk of melanoma in women

Ratiometric images of cytoplasmic Ca2+ concentration ([Ca2+]c) in individual cells were recorded simultaneously with a confocal ultraviolet-laser microscope in the Indo-1-loaded islets isolated from mice. After changes in [Ca2+]c in response to glucose or amino acids were recorded, the islet was fixed, permeabilized, and stained by the indirect immunofluorescence method against insulin or glucagon in situ; the individual cells were then identified in the focal plain identical to that used for the [Ca2+]c imaging. Almost all cells identified as insulin-positive (beta-cells) by their distinct immunofluorescence responded to the increase in glucose concentration from 3 to 11 mmol/l with an increase in [Ca2+]c. Major populations of cells (approximately 65%) identified as glucagon-positive (alpha-cells) responded to the addition of arginine (5-10 mmol/l) to 3 mmol/l glucose solution with an increase in [Ca2+]c. About half of the alpha-cells (47.6%) responded to the addition of alanine (5-10 mmol/l) to 3 mmol/l glucose solution with an increase in [Ca2+]c. In contrast, <13% of beta-cells responded to the addition of alanine (5-10 mmol/l) or arginine (5-10 mmol/l) to 3 mol/l glucose with an increase in [Ca2+]c. More than one-fourth of alpha-cells responded with an increase in [Ca2+]c when glucose concentration in perifusion solution was reduced from 11 to 0 mmol/l. These results indicate that [Ca2+]c changes in islet cells stimulated by glucose or amino acid were characteristic of the cell species, at least in the alpha- and beta-cell. This technique provides a useful tool to investigate not only the intracellular signal transduction but also the intercellular signal transmission in the intact islet.     

The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency

Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301-302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301-302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301-302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301-302delAG deletion suggests that rather than being inherited from a common founder, the 301-302delAG may be a recurring mutation.     

Ureteral stricture formation after removal of impacted calculi

PURPOSE: We retrospectively evaluated the records of 21 patients a mean of 46.1 years old with ureteral stones that had been impacted for greater than 2 months to determine predisposing factors for stricture formation. MATERIALS AND METHODS: Between January 1993 and September 1996, 21 patients were referred for ureteral stones that had remained unchanged in location for at least 2 months. In 11 patients previous attempts at stone removal had failed. Each patient underwent successful stone extraction by retrograde or percutaneous antegrade ureteroscopy, or laparoscopic or open ureterolithotomy. Outcome was determined by reviewing the clinical records and radiographic studies, including excretory urography and nephrostography. RESULTS: Average duration of stone impaction before definitive treatment was 8.8 months (range 2 to 48) and mean stone size was 10.3 mm. (range 1 to 30). All stones were calcium based. There were 3 proximal, 8 mid and 10 distal ureteral calculi. At a mean followup of 7 months ureteral strictures developed in 5 patients (24%) at the previous stone site. Mean duration of stone impaction was 11 months (range 5 to 17) in patients with stricture versus 8.2 months (range 2 to 48) in those with no stricture. Four of the 5 strictures occurred in patients who had had iatrogenic ureteral perforation during previous unsuccessful attempts at stone removal. CONCLUSIONS: Ureteral stone impaction more than 2 months in duration is associated with a 24% incidence of stricture formation. Ureteral perforation at the site of the stone was identified as the primary risk factor for stricture formation in these cases.     

Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade

Caveolin-1 is a principal component of caveolae membranes in vivo. Caveolin-1 mRNA and protein expression are lost or reduced during cell transformation by activated oncogenes. Interestingly, the human caveolin-1 gene is localized to a suspected tumor suppressor locus (7q31.1). However, it remains unknown whether downregulation of caveolin-1 is sufficient to mediate cell transformation or tumorigenicity. Here, we employ an antisense approach to derive stable NIH 3T3 cell lines that express dramatically reduced levels of caveolin-1 but contain normal amounts of caveolin-2. NIH 3T3 cells harboring antisense caveolin-1 exhibit anchorage-independent growth, form tumors in immunodeficient mice and show hyperactivation of the p42/44 MAP kinase cascade. Importantly, transformation induced by caveolin-1 downregulation is reversed when caveolin-1 protein levels are restored to normal by loss of the caveolin-1 antisense vector. In addition, we show that in normal NIH 3T3 cells, caveolin-1 expression levels are tightly regulated by specific growth factor stimuli and cell density. Our results suggest that upregulation of caveolin-1 may be important in mediating contact inhibition and negatively regulating the activation state of the p42/44 MAP kinase cascade.     

Valsalva minimal leak point pressure: a useful approximation to type III female urinary incontinence

Aging is associated with changes in physical characteristics and decline of many physiological functions. The aging process have been described by various theories, in particular the free radical theory of aging has received widespread attention. It has been accepted that the oxidative stress or damage induced by free radicals is related to aging. In this study, we determined the serum concentration of lipid peroxide and antioxidant as biomarker for aging. Healthy subjects were classified into 3 groups, elderly (65-), middle-aged (40-64) and young group (20-39). Findings in the elderly were as follows: 1. Lipid peroxides in the elderly group were significantly higher than those in the young group. 2. Preventive antioxidant concentrations of superoxide dismutase, glutathione peroxidase and albumin were lower than those in the young group, but ceruloplasmin values increased and catalase activity was unchanged. 3. The total antioxidant capacity of serum was slightly decreased. 4. Superoxide generation by neutrophils while resting was significantly higher in the young group.