Biomedical subjects

R Delgado

Publications and source records attributed to R Delgado.

At least 19 recordsLinked to original sources

PubMed2000

[Estimate of HIV-1 infection prevalence in pregnant women and effectiveness of zidovudine administered during pregnancy in the prevention of vertical transmission].

BACKGROUND: Despite the proven efficacy of zidovudine (ZDV) for reducing perinatal transmission of HIV-1, questions remain about its implementation and effectiveness in routine practice. The aims of this study were to assess the impact of ZDV administered during pregnancy in preventing perinatal HIV-1 transmission, and to determine the proportion of early identification of maternal HIV-1 infection over time. PATIENTS AND METHODS: We prospectively followed from birth a cohort of children born between 1/1/1987 and 31/10/1997 to HIV-1-infected mothers. Infant infection status was assessed by follow-up beyond 18 months or HIV-PCR up to 3 months of age. RESULTS: 229 mothers and 248 infants were identified in the cohort. ZDV was administered during pregnancy as monotherapy to 34 mothers for a mean of 4.7 (3.1) months prior to delivery. There were no differences in baseline characteristics between the treated and untreated groups. Mean (SD) CD4 cell count was 465 (261) cells x 10(6)/l. Factors associated with transmission were a more prolonged time of rupture of obstetric membranes (median 6 vs 1.04 hours; p = 0.023) and ZDV treatment. Among the ZDV-treated mothers only one child was infected (2.9%), whereas 37 children born to 212 untreated women became infected. (OR: 0.14; 95% CI: 0.07-0.92). The estimated prevalence of HIV-1 in pregnant women in our area is about 0.39% (95% CI: 0.34-0.45). From 1987 to 1991, 9.7% of infected women were nor identified at the perinatal period, as compared to 2.5% in the last 5 years of the study period (p = 0.034). CONCLUSIONS: In this study, the estimated prevalence of HIV-1 infection is high. ZDV during pregnancy is significantly associated with a decrease in perinatal transmission in our setting. The awareness of an effective treatment might have contributed to the increased identification of HIV-infected mothers prior to delivery observed over time in our cohort of children born to HIV-infected mothers.

Adolescent↗

PubMed2000

Regulation of endothelial nitric oxide synthase expression by albumin-derived advanced glycosylation end products.

We examined whether albumin-derived advanced glycosylation end products (AGEs) downregulate the expression of endothelial nitric oxide synthase (NOS). Significant reductions in NOS activity and cGMP levels in bovine aortic endothelial cells were observed when exposed to different concentrations of albumin-derived AGEs. Western and Northern blot analyses showed significant decreases at the protein and transcript levels. Both reductions became evident after 24 hours of exposure. Nuclear run-on assays showed that AGE-BSA did not modify the transcription rate of the NOS III gene; however, AGE-BSA treatment markedly reduced the half-life of NOS III mRNA. In addition, AGE-treated endothelial cells displayed significant reduction on their antiplatelet properties. These results indicate that NOS expression is reduced by AGEs by increasing the rate of mRNA degradation and may be relevant to the impairment of some endothelial functions observed in diabetes and aging. The full text of this article is available at http://www.circresaha.org.

Animals↗

PubMed2000

Quantitative assessment of apolipoprotein E genotypes by image analysis of PCR-RFLP fragments.

Apolipoprotein E (APOE) genotyping usually involves polymerase chain reaction (PCR) and assessment of restriction fragment length polymorphism (RFLP) by gel electrophoresis. We made determination of HhaI restriction endonuclease digestive patterns more objective and improved diagnostic accuracy with a quantitative approach using sensitive DNA stain (SYBR Green) and image analysis of gel patterns. For distinguishing true and partially-digested restriction fragments, band ratios were calculated for the staining intensity of gel patterns from 116 sample runs of 63 human blood specimens. Each of these specimens was independently genotyped for APOE by at least two (and most of them by three) different PCR-RFLP methods. Based on the distribution of band ratios, decision levels were established and used for developing a program for computer-aided interpretation of APOE genotypes (Microsoft Excel software). Appropriateness of the decision levels for band ratios was validated by APOE genotyping of additional 61 specimens. The approach described here is applicable to a variety of other molecular diagnostic techniques that are based on PCR-RFLP or sequence-specific signal amplifications.

Apolipoproteins E↗

PubMed2000

Precipitation of carbonates by Nesterenkonia halobia in liquid media.

We investigated the precipitation of carbonates by Nesterenkonia halobia in a liquid medium at different concentrations of salts and incubation times. N. halobia only produced crystals at salt concentrations of 2.5%, 7.5% and 15%. At 20% salt concentration no crystal formation was observed. Calcite, aragonite and dolomite were precipitated in different quantities, depending on the salinity of the medium and incubation time. Scanning and transmission electron microscopy, microanalysis and electron diffraction were all used to study in detail the morphology, composition and internal structure of the bioliths. We propose a mechanism for biolith formation involving both biological and inorganic processes.

Carbonates↗

PubMed2000

Malignant neoplasms of the nasal cavity and paranasal sinuses: a series of 256 patients in Mexico City and Monterrey. Is air pollution the missing link?

Air pollution is a serious health problem in major cities in Mexico. The concentrations of monitored criteria pollutants have been above the US National Ambient Air Quality Standards for the last decade. To determine whether the number of primary malignant nasal and paranasal neoplasms has increased, we surveyed 256 such cases admitted to a major adult oncology hospital located in metropolitan Mexico City (MMC) for the period from 1976-1997 and to a tertiary hospital in Monterrey, an industrial city, for the period from 1993-1998. The clinical histories and histopathologic material were reviewed, and a brief clinical summary was written for each case. In the MMC hospital the number of newly diagnosed nasal and paranasal neoplasms per year for the period from 1976-1986 averaged 5.1, whereas for the next 11 years it increased to 12.5. The maximal increase was observed in 1995-1997, with an average of 20.3 new cases per year (P = 0.0006). The predominant neoplasms in these series were non-Hodgkin's lymphoma, squamous cell carcinoma, melanoma, adenocarcinoma, Schneiderian carcinoma, and nasopharyngeal carcinoma. In the Monterrey hospital a 2-fold increase in the numbers of newly diagnosed nasal and paranasal neoplasms was recorded between 1993 and 1998. The predominant MMC neoplasm in this series, namely nasal T-cell/natural killer cell non-Hodgkin's lymphoma, is potentially Epstein-Barr virus related. Nasal and paranasal malignant neoplasms are generally rare. Environmental causative factors include exposure in industries such as nickel refining, leather, and wood furniture manufacturing. Although epidemiologic studies have not addressed the relationship between outdoor air pollution and sinonasal malignant neoplasms, there is strong evidence for the nasal and paranasal carcinogenic effect of occupational aerosol complex chemical mixtures. General practitioners and ear, nose, and throat physicians working in highly polluted cities should be aware of the clinical presentations of these patients. Identification of this apparent increase in sinonasal malignant neoplasms in two urban Mexican polluted cities warrants further mechanistic and epidemiologic studies.

Adenocarcinoma↗

PubMed2000

Plasma concentrations of alpha-melanocyte-stimulating hormone are elevated in patients on chronic haemodialysis.

BACKGROUND: Clinical and/or laboratory signs of systemic inflammation occur frequently in patients undergoing long-term haemodialysis. It is likely, therefore, that a compensatory release of endogenous anti-inflammatory molecules occurs to limit host reactions. The aim of the present research was to determine if the potent anti-inflammatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH), a pro-opiomelanocortin derivative, is increased in plasma of haemodialysis patients. Because endotoxin and cytokines induce alpha-MSH in vivo and in vitro, we also measured plasma concentrations of endotoxin, interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), and the two circulating products of activated monocytes, nitric oxide (NO) and neopterin. METHODS: Thirty-five chronic haemodialysis patients, 20 patients with chronic renal failure not yet on dialysis, and 35 normal controls were included in the study. In the haemodialysis group, blood samples were obtained before and at the end of a dialysis session. Plasma alpha-MSH was measured using a double antibody radioimmunoassay, and IL-6, TNF-alpha, and neopterin using specific enzyme-linked immunosorbent assays. Plasma nitrites were determined by a colorimetric method, and endotoxin with the quantitative chromogenic LAL (limulus amoebocyte lysate) method. RESULTS: Mean plasma alpha-MSH was higher in haemodialysis patients than in control subjects, with the peptide concentrations being particularly elevated in dialysed patients with detectable endotoxin. High alpha-MSH concentrations were observed in the pre-dialysis samples, with no substantial change at the end of the dialysis session. Plasma concentrations of IL-6, TNF-alpha, neopterin, and NO were generally elevated in chronic haemodialysis patients and there was a negative correlation between circulating alpha-MSH and IL-6. In patients with renal failure not yet on dialysis, mean plasma alpha-MSH was similar to that of normal subjects. CONCLUSIONS: alpha-MSH is increased in the circulation of chronic haemodialysis patients and particularly so in case of detectable endotoxaemia. Reduction of renal clearance is unlikely to contribute to the observed rise of the peptide because alpha-MSH concentration is not increased in patients with chronic renal failure who are not yet on dialysis. It is likely that dialysis-associated endotoxaemia, directly and/or through cytokine release, enhances the production of the anti-inflammatory mediator alpha-MSH that limits host reactions.

Adult↗

PubMed2000

[Control of inhaled triggering factors decreases prolonged drug therapy requirements in patients with asthma].

The past decade of research has led to a greater understanding of the pathogenesis of asthma and, in particular, the pivotal role of the underlying inflammatory process. Along with inheritance in atopic patients, the presence of inhaled triggering allergens are considered the predominant predisposing factors in the development of the disease. We have conducted a longitudinal clinical therapeutic study, which included 45 pediatrics patients with asthma, in order to evaluate whether the removal of any potential inhaled triggering factor, could decrease the requirement of drug based anti-inflammatory therapy. Patients admitted in this study presented at least, two monthly asthma attacks during the last four months. A single treatment with theophylline (group A), beclomethasone (group B) or salbutamol (group C), was prescribed during the first 2 weeks, along with specific instructions to avoid inhaled allergens. Regardless of the drug used, patients showed impressive and prolonged clinical improvement during 6 months, reduction of total IgE serum levels in the three groups (p < 0.02; 0.005 and 0.02 respectively) and favorable modification of force expiratory volume at the first second, forced vital capacity and flow expiratory peak. During the observation period a constant monitoring of mites allergens concentrations was performed, showing a decrease of these antigens, associated with clinical improvement, and only in those patients who remained symptomatic (group A 31%, group B 29% and group C 9%), failures performing the measures designed to reduce their exposure to environmental allergens, was demonstrated. These results suggest that reduction of inhaled triggering factors may decrease the requirement of anti-inflammatory drug therapy to control the symptoms in patients with asthma.

Adolescent↗

PubMed1999

Expression of the RNA component of human telomerase in adult testicular germ cell neoplasia.

BACKGROUND: During human development, telomerase is repressed in most somatic cells, whereas it is maintained in male germline cells. Reactivation of telomerase has been associated with somatic cancers. To the authors' knowledge, the role of telomerase in germ cell derived malignancies has not previously been evaluated. METHODS: A radioactive in situ hybridization method was used to study the expression of the RNA component of human telomerase (hTR) in 22 cases of adult testicular germ cell neoplasia encompassing all major histomorphologic types. For precise cell identification, hTR in situ hybridization was combined with immunohistochemistry in select cases. RESULTS: Testicular germ cell tumors showed differential expression of hTR. The highest level of expression was seen in embryonal carcinoma. Seminoma and unclassified intratubular germ cell neoplasia exhibited moderate levels of expression. Yolk sac tumor was characterized by a range of expression, which mirrored its morphologic variation. Immature teratoma recapitulated the down-regulation of telomerase manifested during human embryogenesis. Mature teratoma represented the adult pattern of somatic repression. Notably, choriocarcinoma showed modest expression. The expression of spermatocytic seminoma was intermediate between that of classic seminoma and embryonal carcinoma. No difference in expression was evident between matching intratubular and invasive components. In nonneoplastic testis, hTR expression was down-regulated during spermatogenesis and was absent in spermatozoa. Expression was negligible in rete testis and interstitial Leydig cells, and low in epididymis. Unexpectedly, Sertoli cells, which are testicular accessory somatic cells, displayed the most intense expression observed in this study. CONCLUSIONS: In testicular germ cell tumors of young adults (and during spermatogenesis), hTR expression is down-regulated with differentiation, irrespective of the aggressiveness of the tumors. Spermatocytic seminoma, regarded as a low grade malignancy, shows moderately intense expression.

Adult↗

PubMed1999

alpha-MSH in systemic inflammation. Central and peripheral actions.

Until recently, inflammation was believed to arise from events taking place exclusively in the periphery. However, it is now clear that central neurogenic influences can either enhance or modulate peripheral inflammation. Therefore, it should be possible to improve treatment of inflammation by use of antiinflammatory agents that reduce peripheral host responses and inhibit proinflammatory signals in the central nervous system (CNS). One such strategy could be based on alpha-melanocyte stimulating hormone (alpha-MSH). Increases in circulating TNF-alpha and nitric oxide (NO), induced by intraperitoneal administration of endotoxin in mice, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Increase in lung myeloperoxidase (MPO) activity was significantly less in lungs of mice treated with central alpha-MSH. Proinflammatory agents induced by endotoxin were significantly greater after blockade of central alpha-MSH. The results suggest that antiinflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation. In addition to its central influences, alpha-MSH has inhibitory effects on peripheral host cells, in which it reduces release of proinflammatory mediators. alpha-MSH reduces chemotaxis of human neutrophils and production of TNF-alpha, neopterin, and NO by monocytes. In research on septic patients, alpha-MSH inhibited release of TNF-alpha, interleukin-1 beta (IL-1 beta), and interleukin-8 (IL-8) in whole blood samples in vitro. Combined central and peripheral influences can be beneficial in treatment of sepsis.

Animals↗

PubMed1999

Alpha-MSH peptides inhibit production of nitric oxide and tumor necrosis factor-alpha by microglial cells activated with beta-amyloid and interferon gamma.

Alpha-melanocyte stimulating hormone (alpha-MSH) is an ancient tridecapeptide with potent inhibitory activity in all major forms of inflammation. The anti-inflammatory message sequence of alpha-MSH resides in the COOH-terminal tripeptide alpha-MSH[11-13]. We tested the influence of alpha-MSH[1-13] and of alpha-MSH[11-13] in a cultured murine microglia cell line known to produce nitric oxide (NO(-)(2)) and tumor necrosis factor (TNFalpha) when stimulated with beta-amyloid protein (Abeta). Melanocortin peptides significantly inhibited release of both NO(-)(2) and TNFalpha into cell-free supernatants from microglia stimulated with Abeta[1-42] or Abeta[25-35] peptides and interferon gamma (IFNgamma). Northern blot analysis demonstrated that alpha-MSH[1-13] and alpha-MSH[11-13] inhibited accumulation of inducible nitric oxide synthase (iNOS) and TNFalpha mRNA was triggered by Abeta stimulation. Abeta/microglial interaction is believed to promote the progression of inflammatory and neurodegenerative changes in senile plaques in Alzheimer's disease. Our data indicate that alpha-MSH peptides might be used to modulate the local response of the brain to Abeta deposition in this neurodegenerative disease.

Amyloid beta-Peptides↗

PubMed1999

Generation of retroviral vector for clinical studies using transient transfection.

Transient transfection of 293T cells was utilized to produce high-titer murine recombinant retroviral vectors for clinical studies. This system was initially optimized by gene transfer using different retroviral envelope proteins into activated human CD4+ T lymphocytes in vitro. Higher titer and infectivity were obtained than with stable murine producer lines; titers of 0.3-1 x 10(7) infectious units per milliliter for vectors encoding the green fluorescent protein (GFP) were achieved. Virions pseudotyped with envelope proteins from gibbon ape leukemia virus or amphotropic murine leukemia virus resulted in gene transfer of > or = 50% in CD4+ human T lymphocytes with this marker. Gene transfer of Rev M10 with this vector conferred resistance to HIV infection compared with negative controls in the absence of drug selection. Thus, the efficiency of transduction achieved under these conditions obviated the need to include selection to detect biologic effects in T cells. Finally, a protocol for the production of large-scale supernatants using transient transfection was optimized up to titers of 1.9 x 10(7) IU/ml. These packaging cells can be used to generate high-titer virus in sufficient quantities for clinical studies and will facilitate the rapid, cost-effective generation of improved retroviral, lentiviral, or other viral vectors for human gene therapy.

Animals↗

PubMed1999

Biomineralization of carbonates by Marinococcus albus and Marinococcus halophilus isolated from the Salar de Atacama (Chile).

We studied the precipitation of carbonates in 17 strains of moderately halophilic, Gram-positive cocci belonging to two species: Marinococcus halophilus and Marinococcus albus, isolated from the Salar de Atacama (Chile). They were cultivated in solid and liquid laboratory media for 42 days at salt concentrations (wt/vol) of 3%, 7.5%, 15%, and 20%. The bioliths precipitated were studied by X-ray diffraction and scanning electron microscopy. M. halophilus formed crystals at each of the salt concentrations, with a maximum number of strains capable of precipitating carbonates at 7.5% and 15% salt concentrations. M. albus did not precipitate at 20% and showed a maximum at 7.5%. This behavior is similar to that of other gram-positive bacteria and differs from that found in gram-negative bacteria. The bioliths precipitated were spherical, generally isolated, with a size of 10-100 microm, varying with salinity. They were of magnesium calcite (CO3 Ca1-x Mgx) with Mg content increasing with increasing salinity and Mg/Ca molar ratio of the culture medium. These results demonstrate the active role played by M. halophilus and M. albus in the precipitation of carbonates.

Carbonates↗

PubMed1999

Well-differentiated adenocarcinoma, gastric foveolar type, of the extrahepatic bile ducts: A previously unrecognized and distinctive morphologic variant of bile duct carcinoma.

Two examples of a rare but distinctive morphologic variant of extremely well-differentiated adenocarcinoma of the extrahepatic bile ducts are reported. One tumor arose in the common bile duct of a 51-year-old man; the other arose in the common hepatic duct of a 27-year-old man. Both tumors were composed predominantly (>95%) of gastric foveolar-type epithelium. Because of their bland nuclear features, low mitotic index, and focal polypoid and lobular architecture, they were initially confused with adenomas. Foci of less-differentiated adenocarcinoma and perineural invasion present in the deep portions of the tumors facilitated recognition. The neoplastic cells and extracellular mucin were periodic acid-Schiff- and alcian blue-positive. By immunohistochemistry, the tumor cells expressed cytokeratins 8 and 20 as well as cathepsin D, as reported in normal foveolar cells. Likewise, p53 overexpression was documented immunohistochemically in both adenocarcinomas, which also stained with the Ki-67 antibody. Despite the well-differentiated nature of the neoplasms and their deceptively benign microscopic appearance, one patient developed recurrence and liver metastasis 5 years after surgery. The other patient is disease-free 2 years following a segmental resection of the common hepatic duct, cystic duct, and gallbladder. The cell phenotype of these tumors can be explained by the ability of the bile duct epithelium to differentiate along gastric cell lines.

Adenocarcinoma↗

PubMed1999

Intrasellar adenoid cystic carcinoma and papillary mucinous adenocarcinoma: two previously undescribed primary neoplasms at this site.

Most carcinomas involving the sella turcica are metastases. We report two previously undescribed carcinomas that appear to be primary at this site. The first occurred in a 44-year-old woman who presented with hemianopsia. A mass was noted by computed tomography to occupy the sella turcica, from which it appeared to originate. Transphenoidal biopsy showed the tumor to be an adenoid cystic carcinoma with a typical cribriform pattern. The patient died shortly after a subsequent attempt at tumor resection. The second tumor arose in a 55-year-old man who presented with diplopia. Computed tomography showed a mass in the sella turcica that was presumed to be a pituitary adenoma. However, transphenoidal resection revealed a mucinous adenocarcinoma composed of small papillae and glands lined by columnar epithelium. The tumor cells exhibited varying degrees of stratification with prominent interspersed mucin vacuoles. Focal solid areas showed a component of signet ring-type cells. In contrast to the apparent aggressive behavior of the adenoid cystic carcinoma, the papillary mucinous adenocarcinoma appeared much less aggressive, as the second patient was alive and without evidence of disease 5 years later. Both tumors may be derived from epithelial rests within the pituitary gland, either minor salivary gland rests or Rathke's cleft remnants.

Adenocarcinoma, Mucinous↗

PubMed1999

Prognostic factors in metastatic neuroblastoma in patients over 1 year of age treated with high-dose chemotherapy and stem cell transplantation: a multivariate analysis in 218 patients treated in a single institution.

The purpose of this paper is to study prognostic factors in neuroblastoma patients treated with high-dose chemotherapy and hematopoietic stem cell transplantation. Two hundred and eighteen children over 1 year of age and treated for stage 4 neuroblastoma were enrolled in this study. The median age at diagnosis was 39 months, the sex ratio 1.5 and 84% of patients had an abdominal primary tumor. Skeletal disease was detected in 79% of cases and bone marrow involvement in 93%. N-myc oncogene amplification was present in 27% of the patients studied. The probability of event-free survival at 5 years post-diagnosis was 29% in this series. Three major favorable prognostic factors were significant and independent in the multivariate analysis: age under 2 years at diagnosis (P<0.01), absence of bone marrow metastases at diagnosis (P<0.04) and the high-dose conditioning regimen containing busulfanmelphalan combination (P = 0.001). The quality of response to conventional primary chemotherapy was close to significance (P = 0.053). We conclude that factors related to the patient (age) and extent of disease are predictive of outcome in patients with neuroblastoma treated with conventional chemotherapy followed by surgical excision of the primary and consolidation with high-dose chemotherapy. They should be taken into account in future prospective studies. Moreover, the type of conditioning regimen appears to be the most important prognostic factor. This should encourage new investigations into innovative drug combinations.

Adolescent↗

PubMed1999

HIV infection of placental macrophages: effect on the secretion of HIV stimulatory cytokines.

Vertical transmission of HIV-1 can occur at three different stages: during gestation, delivery and breast feeding. To determine the role of cytokines in vertical transmission of HIV during gestation, we studied the secretion of IL-1beta, TNF-alpha and IL-6 from in vitro infected and Mock-infected placental macrophages (Hofbauer cells) in comparison to blood monocyte derived macrophages (MDM). Hofbauer cells stimulated with lipopolysaccharide (LPS) secreted lower levels of HIV stimulatory cytokines (6-8 ng/ml) in the supernatants than MDM (26 ng/ml, p<0.005). Cytokine levels in MDM decreased upon HIV infection to 7 ng/ml. IL-6 was the major cytokine produced after LPS stimulation by the two cell populations (p<0.005), being MDM the major cytokine producer. In vitro infection studies with a M-tropic virus (HIV-BaL) indicated that MDM were 10x more susceptible to HIV than placental macrophages (p=0.001). Our results indicate that although macrophages from term placenta secrete lower amount of HIV stimulatory cytokines than MDM, there was no correlation between the levels of cytokines and HIV production by both cells.

Cells, Cultured↗

PubMed1998

Atypical angiomyolipoma of the kidney: a distinct morphologic variant that is easily confused with a variety of malignant neoplasms.

BACKGROUND: The purpose of this study was to fully characterize and emphasize the salient features of an unusual variant of angiomyolipoma that the authors believe has been underrecognized. METHODS: Five cases of atypical angiomyolipoma (AAML) of the kidney, two of which were reported previously, were retrieved from the consultation files of one of the authors. In one patient a small extrarenal tumor was examined in addition to the primary renal tumor. The histopathologic features of all six tumors, the immunohistochemical findings of five tumors (including the extrarenal tumor), and the ultrastructure of three tumors were analyzed. Clinical follow-up was obtained for all patients. RESULTS: Two tumors occurred in children and presented as large masses (> or = 15 cm), and 2 tumors were small (< 5 cm) and affected middle-aged adults; the remaining tumor, of intermediate size (6 cm), occurred in an adolescent. One child with tuberous sclerosis also had a small (2 cm) extrarenal lesion. All tumors were circumscribed and had a red-brown cut surface. The largest tumors showed areas of hemorrhage and necrosis. The tumors were highly cellular and composed of various types of multinucleated and mononuclear cells. The most distinguishing of these, and virtually pathognomonic of this entity, were huge cells with abnormal strap-like and ameboid configurations having copious eosinophilic hyaline cytoplasm and myriad nuclei disposed peripherally in a ring-like fashion. Ganglion-like cells, polygonal cells, and spindle cells also were observed. For the most part, all cell types shared the same nuclear features, and except for one tumor, mitoses were negligible. The cells displayed a perivascular arrangement, and grew as loosely organized sheets oriented around abnormally dilated vascular channels or in a hemangiopericytic pattern; glomeruloid vessels were variably present. Notably, adipose tissue was inconspicuous. The tumors stained positive for HMB-45 protein, smooth muscle specific actin, and muscle specific actin antibodies, with a tendency for immunoreactivity to segregate along with individual cell phenotypes. Immunoperoxidase stains also disclosed a prominent and consistent intratumoral histiocytic component and a T-cell lymphoid infiltrate. Ultrastructurally, the tumor cells were replete with organelles showing highly electron-dense granules. All patients underwent radical nephrectomy; three patients with significant follow-up remain free of disease. CONCLUSIONS: AAML exhibits unusual but distinctive "pseudomalignant" histomorphologic features that facilitate its recognition, and a singular immunohistochemical profile that allows diagnostic confirmation. It occurs both sporadically and in association with tuberous sclerosis, affects both the adult and pediatric populations, and has shown an indolent behavior. AAML attests to the biologic and morphologic diversity that characterizes tuberous sclerosis hamartomata in general, and to the plasticity of the yet unclarified precursor of angiomyolipoma in particular.

Actins↗

PubMed1998

Mouse sperm patch-clamp recordings reveal single Cl- channels sensitive to niflumic acid, a blocker of the sperm acrosome reaction.

Ion channels lie at the heart of gamete signaling. Understanding their regulation will improve our knowledge of sperm physiology, and may lead to novel contraceptive strategies. Sperm are tiny (approximately 3 microm diameter) and, until now, direct evidence of ion channel activity in these cells was lacking. Using patch-clamp recording we document here, for the first time, the presence of cationic and anionic channels in mouse sperm. Anion selective channels were blocked by niflumic acid (NA) (IC50 = 11 microM). The blocker was effective also in inhibiting the acrosome reaction induced by the zona pellucida, GABA or progesterone. These observations suggest that Cl- channels participate in the sperm acrosome reaction in mammals.

Acrosome↗