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P Dominguez

Publications and source records attributed to P Dominguez.

16 recordsLinked to original sources

Sequence analysis and androgen regulation of MHG07 (Male harderian gland) mRNA in male hamster harderian gland.

The hamster Harderian gland (HG), a compound tubuloalveolar gland located in the orbital cavity, displays sex dimorphism. The present study focuses on the sequence analysis of a cDNA clone named MHG07 and on the regulation of its expression by steroid hormones. MHG07 mRNA (5.0 kb) is expressed in male HG only. The MHG07 cDNA (1.74 kb) shows an ORF of 94 amino acids and has no significant homologies with other polypeptides/genes. Castration leads to the disappearance of MHG07 mRNA after 4 days, whereas treatment with testosterone impairs the effect of castration. No MHG07 mRNA has been found in either rat or murine HGs. Androgen (A) administration to female hamsters induces the appearance of MHG07 mRNA. In primary culture of male hamster HG, androgens increase the MHG07 expression and this effect is blocked by both flutamide and cycloheximide. Dose-response experiments show that, at low A concentration (10(-12) M), the MHG07 was higher than that of the control (2-fold). This effect reaches its zenith at 10(-8) M (10-fold). This picture is paralleled by androgen receptor mRNA expression. It is argued that the expression of MHG07 is under androgenic control.

Amino Acid Sequence↗

Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice.

The resilience and strength of bone is due to the orderly mineralization of a specialized extracellular matrix (ECM) composed of type I collagen (90%) and a host of non-collagenous proteins that are, in general, also found in other tissues. Biglycan (encoded by the gene Bgn) is an ECM proteoglycan that is enriched in bone and other non-skeletal connective tissues. In vitro studies indicate that Bgn may function in connective tissue metabolism by binding to collagen fibrils and TGF-beta (refs 5,6), and may promote neuronal survival. To study the role of Bgn in vivo, we generated Bgn-deficient mice. Although apparently normal at birth, these mice display a phenotype characterized by a reduced growth rate and decreased bone mass due to the absence of Bgn. To our knowledge, this is the first report in which deficiency of a non-collagenous ECM protein leads to a skeletal phenotype that is marked by low bone mass that becomes more obvious with age. These mice may serve as an animal model to study the role of ECM proteins in osteoporosis.

Age Factors↗

Clinical, virological, and histologic evolution of hepatitis C virus infection in liver transplant recipients.

We designed a prospective study to assess the time course and evolution of hepatitis C virus (HCV) infection in 152 patients who underwent a liver transplantation (LT) in our institution. Forty-four recipients (29%) were infected by HCV after transplantation: 40 who developed recurrent infection after LT and four who acquired infection during or after LT. No differences were found in survival actuarial rates at 1, 2, and 4 years after transplantation for patients infected by HCV vs. noninfected ones. Graft hepatitis occurred in 66% of HCV-infected recipients: 18 developed chronic active hepatitis (10 of them with intense fibrosis) and 2 developed cirrhosis during the follow-up. Infection by the HCV-1b genotype was found in 79% of the infected recipients and in 100% of those in whom histologic evolution was worst. Fourteen grafts were lost in 44 HCV-infected recipients, in comparison with 12 in 108 HCV-negative patients (P = .007), mostly because of chronic rejection. HCV infection did not affect life expectancy in the midterm follow-up for LT patients. However, it was often associated with the occurrence of early and severe graft hepatitis and with a higher incidence of graft loss due to chronic rejection.

Adult↗

Antimitochondrial antibody-negative chronic nonsuppurative destructive cholangitis. Atypical primary biliary cirrhosis or autoimmune cholangitis?

We investigated whether autoimmune cholangitis (AC) has specific features that constitute an entity other than primary biliary cirrhosis (PBC). We compared clinical, laboratory, and liver biopsy features; response to treatment; and the follow-up of two groups of patients. The first group comprised seven patients with AC criteria-PBC with negative antimitochondrial antibodies (AMAs) and positive antinuclear antibodies (ANAs)-termed the PBC AMA-negative group; the second was made up of another seven PBC patients with positive AMA, labeled the PBC AMA-positive group. We found that the PBC AMA-negative group had, besides negative AMAs and positive ANAs, a significantly higher incidence of asthenia, a higher and earlier incidence of liver failure, and higher ANA titers and serum immunoglobulin G levels than the PBC AMA-positive group. There were no significant differences in the other laboratory tests, although the PBC AMA-negative group showed higher serum bilirubin and aminotransferase and lower serum alkaline phosphatase and immunoglobulin M levels. Liver histological data were similar in both groups. Patients in the PBC AMA-negative group, with more markedly abnormal liver tests, responded to immunosuppressive therapy. We concluded that patients with criteria for PBC but with negative AMAs and positive ANAs have a few specific features that fall between PBC and autoimmune chronic hepatitis. This finding suggests that these patients have a different disease, for which autoimmune cholangitis seems to be an appropriate name.

Adult↗

Effects of human chorionic gonadotropin and progesterone administration on porphyrin biosynthesis and histology of the Harderian glands in male and female Syrian hamsters.

We investigated the influence of hCG and progesterone on the control of porphyrin biosynthesis and histology in the Syrian hamster Harderian glands. Castration of male hamsters caused a marked elevation in porphyrin biosynthesis as revealed by the concentrations of porphyrins and the mRNA levels of the porphyrin pathway rate-limiting enzyme, 5-aminolevulinate synthase (ALV-S). Injection of hCG into castrated male hamsters also resulted in a significant increase in both porphyrin concentrations and levels of ALV-S mRNA compared with those in saline-injected castrated hamsters. Type II cells, which are filled with large lipid vacuoles and are characteristic of male phenotype, disappeared after castration, but administration of hCG partially prevented this change. On the other hand, neither administration of hCG nor progesterone implants could increase the very high porphyrin concentrations and ALV-S mRNA levels characteristic of female Syrian hamsters. As in the case of castrated male hamsters, injections of 20 IU hCG to female Syrian hamsters increased the relative number of Type II cells per square millimeter, whereas progesterone administration did not modify the relative number of Type II cells. These results indicate that hCG can modify Harderian gland morphology in both male and female hamsters and can exert a positive control in the expression of ALV-S gene in castrated male hamsters.

5-Aminolevulinate Synthetase↗

Expression of the osteonectin gene potentially controlled by multiple cis- and trans-acting factors in cultured bone cells.

The cis-acting regulatory elements of the osteonectin gene have been studied using a chloramphenicol acetyltransferase (CAT) promoter assay in osteonectin-expressing and nonexpressing cultured cells. When various stretches of the promoter were transiently transfected into fetal bovine bone cells, a positive element was detected in the DNA located between bases -504 and 11 (1 being the start of transcription) and a negative element between bases -900 and -504. The positive element of the promoter also conferred preferential expression of the gene, showing more activity in cells with higher levels of osteonectin mRNA expression. A 1.2 kb fragment of intron 1 displayed a negative effect on CAT expression when inserted 5' to the promoter. An additional regulatory element was found in DNA encoding exon 1, which significantly influenced expression of the gene in fetal bovine bone cells. Gel shift analysis using positive genomic elements located 5' to the start of transcription indicated that one of the nuclear proteins that interacts with the osteonectin promoter may be related to the transcription factor AP2.

Animals↗

5-aminolevulinate synthase mRNA levels in the Harderian gland of Syrian hamsters: correlation with porphyrin concentrations and regulation by androgens and melatonin.

The levels of 5-aminolevulinate synthase mRNA were investigated in the Harderian glands of male and female Syrian hamsters by using a cDNA clone from rat liver. Female hamsters showed higher levels of mRNA than those in males, while the administration of testosterone to female hamsters led to a reduction in mRNA levels. Castration of male hamsters caused a marked elevation of mRNA levels, whereas both the exposure to constant darkness or melatonin injections to castrated males partially prevented the effects of castration. Porphyrin concentration of Harderian glands showed a strong correlation with the mRNA levels of 5-aminolevulinate synthase in all the animals studied. These results lead to the conclusion that in this system, porphyrin metabolism is controlled through hormonal regulation of 5-aminolevulinate synthase gene expression.

5-Aminolevulinate Synthetase↗

Sonographic diagnosis of adrenal hemorrhage in patients with fulminant meningococcal septicemia.

We report two patients with fulminant meningococcal septicemia, in whom massive bilateral adrenal hemorrhages were diagnosed by ultrasound. Low plasma cortisol levels were found in one patient who eventually died. The other patient survived and has remained asymptomatic for the last three years. His adrenal function is normal. We suggest that routine ultrasound examination should be performed in patients with meningococcal sepsis and shock in order to clarify the prevalence of a renal hemorrhage. Determination of plasma cortisol levels in patients with adrenal hemorrhage, would allow identification of those with adrenal insufficiency who may benefit from steroid replacement.

Adrenal Gland Diseases↗

Osteonectin promoter. DNA sequence analysis and S1 endonuclease site potentially associated with transcriptional control in bone cells.

To understand the basis of osteonectin (SPARC) transcriptional regulation, we have isolated a bovine genomic clone (lambda Og15) encoding exon 1 and 15 kilobase pairs (kb) of flanking DNA. Direct RNA sequencing of the 5' end of the osteonectin message showed it contained a sequence identical to that of a 2.4-kb EcoRI-BamHI fragment located midway in the clone lambda Og15. The results indicate exon 1 is located 10 kb away from exon 2 in the bovine genome. The DNA sequence unit CCTG is repeated five times in exon 1 which is composed exclusively of untranslated sequence. Sequence analysis of the 5'-flanking DNA revealed the presence of many regulatory motifs including a "GC" box with four overlapping SP1 consensus sequences. Immediately downstream from the GC box is a 72-base pair purine-rich stretch composed primarily of direct repeats of the sequence motifs GGGGA and GGA (GAGA box). Digestion of the flanking DNA in vitro with S1 endonuclease showed a site for the enzyme at position -55 which is just 3' to the GAGA box. Chimeric chloramphenicol acetyltransferase constructs were prepared containing the S1-sensitive site and showed substantial transcriptional activity in UMR-106 and fetal and adult human bone cells which are known to be high producers of the protein. The results indicate a potential regulatory activity of the S1 site in osteonectin gene activation.

Animals↗

Treatment of small cell lung cancer with a combination of VP16-213 and cyclophosphamide with cisplatin or radiotherapy.

Fifty five patients with small cell lung cancer with treated with VP16-213 combination chemotherapy regimen in two consecutive series. The first series included 24 patients; 10 with limited and 14 with extensive disease were treated with VP16-213, 120 mg/m2 p.o. daily for 5 consecutive days, Cyclophosphamide 600 mg/m2 i.v. and Cisplatin 80 mg/m2 i.v. with hydratation and manitol induced diuresis. The cycle was repeated every 3 weeks. The second series included 31 similar patients, 16 limited, and 15 extensive disease, treated with VP16-213 at the same dose and Cyclophosphamide at 1,200 mg/m2 i.v. also repeated every 3 weeks; after three cycles the patients were treated with radiotherapy to the primary tumor and regional lymph nodes with 4,000 rads in a split course of three weeks interval, followed by the same combination chemotherapy. Response rate was 75% for the first series with 6 of 24 (25%) of complete responses in four limited and two extensive disease and a median survival time of 24 weeks. In the second series of patients there were 26 of 31 (83.8%) responses with 10 of 31 (32%) complete responses in nine limited and one extensive disease and a median survival time of 33 weeks for responders. Duration of response for complete responders was 36.8 weeks for the first series and 51 weeks for the second. Toxicity was mild and includes nausea and vomiting, myelosupression, alopecia in both series, with one toxic death in the second series. Both regimens are active with a low complete response rate, which was increased in the second series by the addition of radiotherapy, which did not increase overall survival.

Adult↗

Preoperative estimation of risk in cardiac surgery.

In order to determine the usefulness of the preoperative subjective estimation of risk and compare it with preoperative estimation of risk based upon objective data, two groups of patients subjected to open heart surgery at the Catholic University of Chile Hospital were studied prospectively. Group I comprised 227 consecutive patients operated on in 1975 and group II comprised 181 consecutive patients operated on in 1979. There were several important differences in management and techniques between the two groups, which resulted in different factors perioperative mortality. Mortality in group I was related to extreme age subsets (p less than 0.01) and to duration an anoxic arrest (p less than 0.001); mortality in group II correlated only to preoperative functional class (NYHA) (p less than 0.02). Despite these differences, subjective risk estimation as preoperatively recorded by the anesthesiologist was accurate in both groups (r = 0.969, p less than 0.05 in group I and r = 0.998, p less than 0.01 in group II). It was concluded that in the absence of a universally valid objective risk index, subjective risk estimation provides a clinical index as useful as reliance upon presently available objective data.

Adolescent↗

Sidelining conflict.

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Admitting Department, Hospital↗

Histopathologic prognostic score in colorectal adenocarcinomas.

OBJECTIVE: To analyze the prognostic value of a set of pathological variables after curative resection for large bowel adenocarcinoma and to test a prognostic score derived from factors with independent effect. PATIENTS AND METHODS: The study is based on data from 292 consecutive unselected patients (B-C Astler-Coller stages). Histopathological features were evaluated prospectively on the resected primary tumors. Relationship between these factors and risk of recurrence was assessed by a Cox's proportional regression analysis. RESULTS: Four variables retained independent prognostic significance: extent of bowel wall invasion, peritumoral lymphocytic infiltration, number of positive nodes and vascular invasion. A prognostic score based on the regression coefficients attained by such variables was developed. This system revealed four prognostic groups. Group I included 14% of patients, with 94% 5-year disease-free survival. These figures were: 35% and 60% in group II; 43% and 46% in group III; and 7% and 24.4% in group IV. Histopathologic score applied to bearers of Astler-Coller B2 tumors permitted the identification of two populations, one characterized by a low risk of relapse and another with high risk (p = 0.002). CONCLUSION: A prognostic score based in the evaluation of four histopathologic parameters concerning the tumor phenotype enables the identification of groups of patients at risk of relapse after curative resection for colorectal adenocarcinoma.

Adenocarcinoma↗