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Biomedical subjects

M A Castro

Publications and source records attributed to M A Castro.

At least 37 records · Page 2Linked to original sources
PubMed1999

Phenotype modulation of cellular UV-sensitivity.

Mammalian cell shape is critically important to cell differentiation, apoptosis, cell division, and growth arrest. In the present study we examined the relationship among cell density, cell phenotype (which include shape and coupling) and cell survival using the human A549, H596 and H520 non-small cell lung carcinoma lines. Thus, cells from monolayers, aggregated and suspended cultures at different densities were exposed to UV-radiation and both the density and the phenotype of the cells induce shifts in cellular growth rate. Except in suspended cultures, we observed a UV-sensitivity closely related to the proliferative status of the cells. The variability of the cellular response to UV were investigated taking into account the shape and the coupling potential of the cell lines, suggesting that an intercellular-contact mechanism provides further protection against UV-radiation damage.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

CD2 and CD3 associate independently with CD5 and differentially regulate signaling through CD5 in Jurkat T cells.

In T lymphocytes, the CD2 and CD5 glycoproteins are believed to be involved in the regulation of signals elicited by the TCR/CD3 complex. Here we show that CD2 and CD3 independently associate with CD5 in human PBMC and Jurkat cells. CD5 coprecipitates with CD2 in CD3-deficient cells and, conversely, coprecipitates with CD3 in cells devoid of CD2. In unstimulated CD2+ CD3+ Jurkat cells, CD5 associates equivalently with CD2 and CD3 and is as efficiently phosphorylated in CD2 as in CD3 immune complexes. However, upon activation the involvement of CD5 is the opposite in the CD2 and CD3 pathways. CD5 becomes rapidly tyrosine phosphorylated after CD3 stimulation, but is dephosphorylated upon CD2 cross-linking. These opposing effects correlate with the decrease in the activity of the SH2 domain-containing protein phosphatase 1 (SHP-1) following CD3 activation vs an enhanced activity of the phosphatase after CD2 triggering. The failure of CD5 to become phosphorylated on tyrosine residues in the CD2 pathway has no parallel with the lack of use of zeta-chains in CD2 signaling; contrasting with comparable levels of association of CD2 or CD3 with CD5, zeta associates with CD2 only residually and is nevertheless slightly phosphorylated after CD2 stimulation. The modulation of CD5 phosphorylation may thus represent a level of regulation controlled by CD2 in signal transduction mechanisms in human T lymphocytes.

Antibodies, Monoclonal↗
PubMed1999

Reversible peripartum liver failure: a new perspective on the diagnosis, treatment, and cause of acute fatty liver of pregnancy, based on 28 consecutive cases.

OBJECTIVE: We sought to describe our experience with the clinical diagnosis, management, and course of patients with acute fatty liver of pregnancy. STUDY DESIGN: Twenty-eight cases of acute fatty liver of pregnancy at the Los Angeles County and University of Southern California Medical Center from 1982 to June 1997 were identified, and presenting symptoms, clinical course, laboratory values, maternal complications, and neonatal outcomes were studied. RESULTS: The incidence of acute fatty liver of pregnancy was 1 in 6659 births. There were no maternal deaths. Initial presentation was at an average of 37 weeks of gestation with a characteristic prodrome of malaise, nausea, vomiting, and abdominal pain. No patient was admitted with the diagnosis of acute fatty liver of pregnancy. The condition was diagnosed most commonly on the second hospital day after laboratory results indicated coagulopathy, renal insufficiency, and liver function abnormalities. One patient underwent liver biopsy at cesarean delivery. Radiologic studies did not aid with the diagnosis. Twenty-one patients were admitted in spontaneous labor, and 16 labors were complicated by abnormal fetal heart rate patterns or meconium. There was 1 stillbirth and 1 neonatal death as a result of perinatal asphyxia. Maternal morbidity consisted of hypoglycemia, infection, renal insufficiency, coagulopathy, encephalopathy, and wound complications. All patients had evidence of disseminated intravascular coagulopathy with profoundly decreased antithrombin levels. All patients recovered normal liver function post partum. CONCLUSIONS: Reversible peripartum liver failure may be diagnosed and managed on the basis of clinical and laboratory criteria. With adequate support, these patients may have full recovery of hepatic function.

Acute Disease↗
PubMed1998

Mapping of MCP-1 functional domains by peptide analysis and site-directed mutagenesis.

Monocyte chemoattractant protein-1 (MCP-1) is a member of the beta chemokine family which acts through specific seven transmembrane receptors to recruit monocytes, basophils, and T lymphocytes to sites of inflammation. To identify regions of the human MCP-1 protein which are important for its biological activity, we have synthesized domain-specific peptides and tested their ability to antagonize MCP-1 binding and chemotaxis in THP-1 cells. We have found that an intercysteine first loop peptide encompassing amino acids 13-35 inhibits MCP-1 binding and chemotactic activity, while peptides representing the amino-terminus (amino acids 1-10), second loop (amino acids 37-51), and carboxy-terminus (amino acids 56-71) of MCP-1 have no effect. In addition, we have found that cyclization of the first loop peptide by disulfide linkage and blocking the C-terminus of the peptide by amidation increases the activity of this peptide to block MCP-1 binding and chemotaxis. In order to specifically identify amino acid residues within the first loop that are crucial for MCP-1 functional activity, we have substituted alanine for tyrosine (Y13A) or arginine (R18A) in MCP-1 recombinant proteins. While baculovirus produced wild type and R18A MCP-1 proteins are indistinguishable in their ability to induce THP-1 chemotaxis and show modest effects in binding activity compared to commercially available recombinant MCP-1 protein, the Y13A point mutation causes a dramatic loss in function. The identification of functional domains of MCP-1 will assist in the design of MCP-1 receptor antagonists which may be clinically beneficial in a number of inflammatory diseases.

Amino Acid Sequence↗
PubMed1998

Deficient proliferation of myeloid, erythroid, and multipotent progenitor cells in long-term marrow cultures from patients with aplastic anemia treated with immunosuppressive therapy.

By using Dexter-type long-term marrow cultures (D-LTMC), it has been shown previously that hematopoietic progenitor cells (HPC) from patients with aplastic anemia (AA) have a deficient proliferation in vitro. The studies reported to date, however, have focused exclusively on granulomonocytic progenitors and no information exists on erythroid or multipotent progenitor cells. On the other hand, in such studies, the input progenitor cell numbers were significantly below normal levels, thus suggesting that the rapid disappearance of myeloid progenitor cells from AA D-LTMC could also be due, at least in part, to their reduced number at culture onset. In the present study, we have followed the kinetics of myeloid, erythroid, and multipotent progenitors, from 24 AA patients subjected to immunosuppressive therapy (including patients that achieved complete, partial, or no remission at all), throughout a seven-week culture period. For analysis, we grouped all the patients based on their initial content of all three types of progenitors. Thus, we were able to evaluate separately the kinetics of these cells in D-LTMC from patients with normal and subnormal levels of progenitor cells. At the time of marrow sampling, most patients showed decreased levels of HPC; in fact, only 21%, 8%, and 16% of them showed normal levels of myeloid, erythroid, and multipotent progenitors, respectively. When cultured in D-LTMC, HPC from all AA patients analyzed showed a relatively fast disappearance from the cultures. Indeed, myeloid progenitors could be detected for only six weeks, whereas erythroid and multipotent progenitors disappeared from the cultures after two and one weeks of culture, respectively. In contrast, in normal marrow D-LTMC, myeloid, erythroid, and multipotent progenitors were detected for at least seven, five, and three weeks, respectively. Such a deficient proliferation was observed even in cultures of AA patients that contained normal levels of HPC at culture onset. Interestingly, no correlation was found between HPC proliferation in D-LTMC and response to treatment. Thus, the results of this study indicate the presence of a functional in vitro deficiency in the hematopoietic system of patients with AA, including those that achieved partial or complete remission after immunosuppressive treatment. Furthermore, this work suggests that such a proliferation deficiency is more pronounced in erythroid and multipotent progenitors than in their myeloid counterparts.

Adult↗
PubMed1998

Ex vivo proliferation of mesothelial cells directly obtained from peritoneal effluent: its relationship with peritoneal antecedents and functional parameters.

The peritoneal membrane requires anatomico-functional integrity to guarantee long-term stability for peritoneal dialysis (PD). Since mesothelial cells (MC) are active cells and the first part of the membrane to contact the dialysate, they are important in maintaining this stability. Mesothelial cells released daily into peritoneal effluent are able to grow in culture. This growth capacity may be related to some of the anatomicofunctional characteristics of each peritoneum. Our aim was to culture mesothelial cells taken from peritoneal effluents drained by 32 PD-stable patients, and relate this growth capacity to individual peritoneal data. Cells were taken from a residual fluid after sedimentation, washed twice with phosphate-buffered saline (PBS), and seeded into 25-cm2 tissue-culture flasks. These flasks were incubated in a humidified 5%-CO2 atmosphere. After MC confluence, cells were detached by trypsinization, passaged into 24-well plates, and finally counted. Cells were identified by morphology and immuno-histochemical characteristics. Cells from 28 out of 32 patients showed an appropriate growth in culture. Mesothelial cell confluence was reached in a mean of 18.2 +/- 8 days. After 7 days of seeding in plate wells, the cell growth showed a significant and progressive increase until day 16. Mesothelial cell growth rate was inversely related to PD duration. Neither peritonitis incidence nor other demographic characteristic were related to MC growth. Creatinine and urea mass transfer coefficients (MTC), but not ultrafiltration (UF) capacity, were significantly related to MC growth rate. In conclusion, the growth in culture of MC taken directly from PD bags is certainly possible. This growth is influenced by some of the intrinsic peritoneal characteristics derived from the peritoneal dialysis process. This tool could be useful in evaluating individual peritoneal conditions and, probably, as a method for peritoneal viability follow-up, although further research is required.

Ascitic Fluid↗
PubMed1997

An HIV/AIDS prevention project for Mexican homosexual men: an empowerment approach.

In this intervention, participants design and implement an HIV/AIDS prevention project for Mexican homosexual men. The intervention is consistent with, and contributes to, empowerment theory because it enhances collective action, provides opportunities to develop knowledge and skills, creates needed resources, and includes shared control with professional and among participants. The intervention described provides an illustration of an empowering process and distinguishes itself from empowerment outcomes. An evaluation of the project is also described, but the outcomes were HIV/AIDS-related behaviors rather than psychological empowerment of the participants. The results suggest that the participants' HIV/AIDS knowledge and preventive behavior improved when compared to individuals who did not participate in the intervention. In addition, the intervention generated community change initiated by participants. Implications for designing interventions using an empowerment approach are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Epidemiology of the osteoporotic fracture of the hip in the province of Palencia].

BACKGROUND: Hip fracture is the most severe consequence of osteoporosis. The aim of the present study was to know the incidence of osteoporotic hip fracture in the Palencia province, its direct economical consequences and characteristics associated with the origin episode. PATIENTS AND METHODS: All patients aged over 49 years who had a nontraumatic hip fracture during the second semester of 1994 and the first semester of 1995 were included in the study. An analysis of costs was performed and each patient received a questionnaire to know the circumstances associated with the episode. RESULTS: During the study period the overall incidence of hip fracture was 83/100,000 inhabitants/year, which corresponds to an adjusted incidence of 240.9/100,000 inhabitants older than 49 years (336.8 women and 120.7 men). There was an exponential growth, with peak values starting at 80 years. The female/male ratio was 2.8 and the mean age 80.8 years. Twenty-four percent of fractures occurred in institutionalized persons, with an adjusted incidence of 1,107/100,000 inhabitants/year, which corresponds to a relative risk of 13.57 (95% CI: 10.06-18.28). No significant differences were observed between trochanteric and neck fractures. Ninety-seven percent of fractures occurred after a fall, usually in the morning or afternoon (86%), with lateral direction and impact on the greater trochanter (89%). The mortality rate during admission was 5.9%. The mean cost of care during admission was 1,170,000 pesetas. CONCLUSIONS: The incidence of hip fracture in Palencia is slightly higher than the national mean, probably due to populational ageing. The risk of fracture reaches alarming proportions in the institutionalized population. The implementation of efficient preventive measures, particularly among the exposed populations, is necessary.

Accidental Falls↗
PubMed1996

Immunosuppressive cyclolignans.

The immunosuppressive activity of several lactonic, nonlactonic, and heterocycle-fused cyclolignans has been demonstrated for the first time by use of a T-cell-mediated immune response. Of the compounds tested, 4'-demethyldeoxypodophyllotoxin (8), beta-apopicropodophyllin (6), and the isoxazoline-fused cyclolignan 15 are the most potent with respect to their suppression of activated splenocytes.

Animals↗
PubMed1996

Preeclampsia and liver infarction in early pregnancy associated with the antiphospholipid syndrome.

BACKGROUND: Usually, preeclampsia is a disease of the second half of pregnancy (i.e., beyond 20 weeks' gestation). Early-onset preeclampsia has been reported in association with the antiphospholipid syndrome, however, the cases reported have been at 25-30 weeks' gestation. CASES: Three pregnant women presented with clinical and laboratory features of severe preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) before 20 weeks' gestation. On evaluation, they were found to have antiphospholipid antibodies (anticardiolipin and/or lupus anticoagulant). Two of the patients had abdominal computed tomography scans that showed a low-density area along the hepatic periphery, compatible with hepatic infarction. Spontaneous resolution of all clinical and laboratory manifestations of preeclampsia and HELLP syndrome was observed after fetal death and pregnancy termination. CONCLUSION: Preeclampsia and HELLP syndrome can present before 20 weeks' gestation in association with the antiphospholipid syndrome and may be associated with hepatic infarction.

Adult↗
PubMed1996

Disseminated intravascular coagulation and antithrombin III depression in acute fatty liver of pregnancy.

OBJECTIVE: Acute fatty liver of pregnancy has been associated with a syndrome of marked depression of antithrombin III and disseminated intravascular coagulation. We sought to identify the clinical importance of this accelerated coagulation. STUDY DESIGN: The medical records of patients with acute fatty liver of pregnancy identified during the period of 1982 to 1994 were retrospectively reviewed. RESULTS: Twenty-eight patients with acute fatty liver of pregnancy were identified for an incidence of 1:6692 births. Laboratory evidence of persistent disseminated intravascular coagulation was found in all patients tested. Six patients had clinical bleeding, all associated with genital tract injury. Twenty-three of twenty-three patients tested had markedly decreased antithrombin III levels (average 11%, normal range 80% to 100%). Seven patients received antithrombin III transfusions, which was associated with a significant transient rise in the plasma level. Compared with patients not transfused, however, there was a similar clinical outcome. CONCLUSION: Profoundly depressed antithrombin III levels and laboratory evidence of disseminated intravascular coagulation were present in all cases of acute fatty liver of pregnancy but rarely influenced clinical outcome unless there was concomitant genital tract injury. Antithrombin III transfusions increased plasma levels, but no definite clinical benefit was established in this series because of the small number of cases.

Acute Disease↗
PubMed1996

Prognostic significance of antenatally detected fetal pyelectasis.

In order to evaluate the prognostic significance of ultrasonographically detected fetal pyelectasis, a retrospective review was performed of patients evaluated for fetal pyelectasis over a 24-month period. From 84 patients a total of 98 fetal kidneys with pyelectasis were identified. Fetal pyelectasis was more common in the left kidney and in males. Postpartum evaluation revealed 48 (57.1%) neonates with hydronephrosis. Among these, mean (SD; range) values of antenatal fetal pyelectasis were 17.0 mm (8.4; 5-26) before 33 weeks and 16.9 mm (8.5; 5-34) after 33 weeks in the left kidney and 15.4 mm (3.3; 10-24) and 17.1 mm (5.1; 5-36), respectively, in the right kidney. Thirteen infants (15.4%) with hydronephrosis required surgical pyeloplasties (mean age 6 months; range 3-18 months). It was found, from a receiver-operating characteristic curve, that fetal pyelectasis of 8 mm was 91% sensitive and 72% specific in predicting subsequent hydronephrosis. Use of a threshold of 5 mm yielded a sensitivity of 100% and a specificity of 24%. On the basis of these findings, we recommend that women with ultrasonographically detected antenatal fetal pyelectasis of > or = 5 mm at any gestational age have follow-up ultrasound examinations and detailed postnatal evaluation.

Dilatation, Pathologic↗
PubMed1996

Circulating burst-forming unit-erythroid (BFU-E) colonies as an early marker to measure the recombinant human erythropoietin response in peritoneal dialysis patients.

To evaluate circulating burst-forming unit-erythroid (BFU-E) cells after erythropoietin (EPO) treatment, 7 female continuous ambulatory peritoneal dialysis patients were studied [baseline hemoglobin (HB): 7-10.5 g/dL)]. EPO (4000 U subcutaneously) was administered twice weekly for two months. The control group consisted of 7 healthy women with similar demographic characteristics. Mononuclear cells (MC) (5 x 10(5)) were added to 1 mL of culture medium, supplemented with 30% fetal bovine serum, 2 U/mL of EPO, 1% bovine serum albumin, and 0.3% agar. To enumerate colonies derived from each circulating BFU-E, plates were examined by inverse light microscopy, identifying BFU-E as large aggregates with more than 100 hemoglobinized cells (HC). A remarkable individual response was observed, with Hb values ranging 8.4-13.6 g/dL at week 4 and 8.8-16.5 g/dL at week 8. Baseline levels of BFU-E in patients ranged 0-100/5 x 10(5) MC (0-358 mL of whole blood), and in controls they ranged 6-24/5 x 10(5) MC (29.6-101.3/mL) (NS). Hemoglobin levels after four and eight weeks of EPO showed a significant relationship with circulating BFU-E at baseline (r = -0.873, r = -0.928, respectively). The increment in Hb after eight weeks showed a significant relationship with baseline BFU-E (r = 0.812). Hemoglobin levels at the fourth to eighth week, and the increment in Hb after eight weeks, showed a significant, direct relationship with the increments in circulating BFU-E registered after one to two weeks of treatment. We conclude that, after the first week of EPO treatment, its effect on hemoglobin may be predieted by the increment in circulating BFU-E. Thus; a new tool to measure the earliest EPO effects has become available.

Adult↗
PubMed1996

Radiologic studies in acute fatty liver of pregnancy. A review of the literature and 19 new cases.

OBJECTIVE: Radiologic findings thought to be characteristic of acute fatty liver of pregnancy have been described in a limited number of cases. We describe wide experience with liver imaging of this disease. STUDY DESIGN: A retrospective review was performed on charts from 1982 to 1994 to identify those patients with acute fatty liver of pregnancy who had radiologic studies. RESULTS: Twenty-eight patients with acute fatty liver of pregnancy were identified, for an incidence of 1/6,692 births. Nineteen patients underwent at least one imaging study, and seven had more than one. Findings consistent with fatty infiltration of the liver are found in 3/11 patients with ultrasound, 5/10 with computed tomography (CT) and 0/5 with magnetic resonance imaging (MRI). Three patients with normal ultrasound scans subsequently had evidence of fatty filtration on CT scan. CONCLUSION: Detection of fat in the liver of patients with acute fatty liver of pregnancy with current imaging techniques is limited and did not contribute to the management of patients in this series. Further studies are necessary to define to role of MRI--in particular, spectroscopy.

Adult↗
PubMed1995

Synthesis and evaluation of pyrazolignans. A new class of cytotoxic agents.

A series of fused pyrazole derivatives of cyclolignans have been prepared through simple chemical routes and evaluated for their cytotoxic activities in culture cells of P-388 murine leukemia, A-549 lung carcinoma and HT-29 colon carcinoma. Despite the lack of the lactone moiety in their structures, they show IC50 values at microM levels.

Animals↗