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Biomedical subjects

G Garcia

Publications and source records attributed to G Garcia.

At least 109 records · Page 6Linked to original sources

Purification and characterization of a cofactor that controls the oxidative phase of the pentose phosphate cycle in liver and other tissues of rat.

We have recently reported the presence, in rat liver, of a cofactor characterized as a protein of Mr 10(5), which cooperates with GSSG to prevent the inhibition of glucose-6-phosphate dehydrogenase by NADPH. The inhibition that this coenzyme also exerts on 6-phosphogluconate dehydrogenase is similarly prevented by a cofactor-GSSG system. The activity of the cofactor increases in the livers of rats fed on carbohydrate-rich diets. Purification of the components in rat liver homogenate by ion-exchange chromatography and preparative polyacrylamide gel electrophoresis showed that the deinhibitory effect on both dehydrogenases is exerted by the same cofactor. The purified cofactor appeared as a unique protein of Mr 37.10(3) in SDS-polyacrylamide gel electrophoresis. Rat kidney and adipose tissue were the only nonhepatic tissues showing a cofactor-GSSG deinhibitory effect on both dehydrogenases of the oxidative phase of the pentose phosphate cycle. The deinhibitory activity, also corresponding with a cellular component of Mr 10(5), was only diet-inducible in adipose tissue. The neutralization of the kidney and adipose tissue deinhibitory activity by rat liver cofactor antibodies suggested that there was a structural relationship between the cofactors prepared from these tissues.

Adipose Tissue↗

Chronic viral hepatitis.

Chronic viral hepatitis is a common clinical problem; it must be differentiated from other forms of chronic liver disease by history, laboratory data, and liver biopsy. This article reviews the treatment of chronic hepatitis B, delta hepatitis, and nonA and nonB viral hepatitis and emphasizes the controlled trials when available.

Adrenal Cortex Hormones↗

Functional affinity of antibody to the Haemophilus influenzae type b polysaccharide.

The functional affinity, or avidity, of antibody to the capsular polysaccharide of Haemophilus influenzae (Hib-PS) was measured in serum samples from 12 adult male subjects before and after immunization with Hib-PS vaccine. Mean avidity increased from 0.74 nM-1 to 1.5 nM-1 after immunization (P less than .05, paired Student's t test). The Bureau of Biologics reference antiserum had an avidity constant of 12 nM-1, which was the highest of all 25 serum samples studied.

Antibodies, Bacterial↗

Priming for rotavirus neutralizing antibodies by a VP4 protein-derived synthetic peptide.

In the rotavirus SA11 surface protein VP4, the trypsin cleavage sites associated with the enhancement of infectivity are flanked by two amino acid regions that are highly conserved among different rotaviruses. We have tested the ability of synthetic peptides that mimic these two regions to induce and prime for a rotavirus neutralizing antibody response in mice. After the peptide immunization schedule, both peptides induced peptide antibodies, but neither was able to induce virus antibodies, as measured by an enzyme-linked immunosorbent assay or a neutralization assay. However, when the peptide-inoculated mice were subsequently injected with intact SA11 virus, a rapid and high neutralizing antibody response was observed in mice that had previously received the peptide comprising amino acids 220 to 233 of the VP4 protein. This neutralizing activity was serotype specific; however, this peptide was also able to efficiently prime the immune system of mice for a neutralizing antibody response to the heterotypic rotavirus ST3 when the ST3 virus was used for the secondary inoculation.

Amino Acid Sequence↗

Determination of tissue type plasminogen activator in the glomeruli of patients with IgA nephropathy.

The detection, by immunofluorescence, of tissue type plasminogen activator (t-PA) in the glomeruli of 50 patients with IgA nephropathy was described. Patients with t-PA deposits revealed a higher frequency in the glomerular deposition of fibrin and/or fibrinogen than did patients without t-PA deposits. There also was a distinct relationship between the level of serum t-PA and the degree of renal tissue injury in patients with glomerular t-PA deposits. It was concluded that the deposition of t-PA along with fibrin and/or fibrinogen might reduce the effectiveness of fibrinolysis in the glomeruli of patients with IgA nephropathy.

Adult↗

Metabolic and biochemical abnormalities of articular cartilage induced by implantation of a sterile sheet of polyethylene in the rabbit patellofemoral joint.

A polyethylene sheet was implanted in the patellofemoral joint of the right knee of the rabbit and the biochemical and metabolic changes in the articular cartilage from femoral trochleas (in contact with the implant) and femoral condyles (free of direct contact) were compared with those in their sham-operated counterparts 7, 15, and 30 days after joint implantation. The results showed that there was an increase in the water content; the extraction yields of uronic acid--, 35SO4-, and [3H]glycine-containing compounds; and the incorporation of [3H]thymidine, [3H]glycine, and 35SO4. Concomitantly, the contents of uronic acid--, hexosamine-, neutral sugars-, and hydroxyproline-containing substances decreased in the femoral trochlear cartilage and, to a much lesser extent, in the femoral condylar cartilage from implanted joints. The increased capacity of viable chondrocytes to incorporate metabolic radiolabeled precursors into newly synthesized macromolecules may represent a reparative cell response to the tissue injury induced by the implant. This is therefore a useful model for studying the response of chondrocytes to mechanical injury and tissue tolerance to intraarticularly implanted prosthetic materials.

Animals↗

Antibodies to extractable cellular antigens in Spanish systemic lupus erythematosus (SLE) patients.

We studied the frequency of antibodies to extractable cellular antigens in 90 Spanish SLE patients. Antibodies to Sm, nRNP, Ro and La were found, respectively, in 6 (6.6%), 18 (20%), 30 (33.3%) and 6 (6.6%) patients. In spite of HLA differences, these results are similar to those found by other authors in Caucasian SLE patients. Our only relevant association was the finding of severe renal disease and high frequency of anti-DNA and hypocomplementemia in patients with antibodies to Ro. Based on these and earlier findings, we discuss the possibility that the immune response to Ro in Spanish patients might be located in a unique extended HLA-complement haplotype.

Adult↗

Adenine arabinoside monophosphate (vidarabine phosphate) in combination with human leukocyte interferon in the treatment of chronic hepatitis B. A randomized, double-blinded, placebo-controlled trial.

STUDY OBJECTIVE: To determine the efficacy of adenine arabinoside monophosphate (Ara-AMP vidarabine phosphate) with or without human leukocyte interferon in chronic hepatitis B. STUDY DESIGN: Randomized, double-blinded, placebo-controlled trial with 6-month treatment and an 18-month follow-up. SETTING: Referral-based liver-disease clinics at three university medical centers. PATIENTS: Twenty-five patients with chronic active hepatitis or cirrhosis and 39 with chronic persistent hepatitis. INTERVENTIONS: Thirteen patients received intramuscular Ara-AMP, 2.5 mg/kg body weight, twice daily, alternated monthly for 6 months with subcutaneous human leukocyte interferon, 5 million units, twice daily. Painful paresthesia of the legs necessitated dosage reduction and early discontinuation of enrollment. Twenty-four patients received intramuscular Ara-AMP, 2.5 mg/kg, twice daily, alternated monthly for 6 months with a matching placebo given subcutaneously twice daily. Twenty-seven patients received placebo by intramuscular and subcutaneous injections twice daily for 6 months. MEASUREMENTS AND MAIN RESULTS: Of the 64 patients, 95% had symptomatic and virologic data available and 64% had biopsies at 12 months; at 24 months, 77% had data available and 56% had repeat biopsies. The highest dropout rate was seen in the group receiving Ara-AMP. The group receiving the placebo was less symptomatic (Karnofsky score of 96% compared with 91% in the group receiving Ara-AMP/placebo and 92% in the group receiving Ara-AMP/human leukocyte interferon, p = 0.02) at 12 but not at 24 months. Loss of DNA polymerase, the hepatitis B e antigen, and the serum hepatitis B virus DNA was similar in all three groups. Histologically, erosion of the limiting plate and lobular activity favored Ara-AMP at 12 but not at 24 months and these differences did not result in differences in the histologic diagnosis. CONCLUSION: These results do not support the use of Ara-AMP and human leukocyte interferon in chronic persistent or chronic active hepatitis B.

Adult↗

Biochemical and morphometric analysis of the effect of spironolactone on the livers from immature and adult rats.

Biochemical and morphometric studies were carried out to characterize the effect of spironolactone (SP) on liver tissue from immature and adult young rats: 1. The SP produced an increase in total protein in all the groups. 2. Hypertrophy in 24 days-old rats. 3. Hypertrophy and hyperplasia in 48 days-old rats. 4. The morphometric studies were correlated to the biochemical parameters.

Aging↗

Regulation of the pentose phosphate cycle. Cofactor that controls the inhibition of glucose-6-phosphate dehydrogenase by NADPH in rat liver.

A cofactor of Mr 10(4), characterized as a polypeptide, was found to co-operate with GSSG to prevent the inhibition of glucose-6-phosphate dehydrogenase by NADPH, in order to ensure the operation of the oxidative phase of the pentose phosphate pathway, in rat liver [Eggleston & Krebs (1974) Biochem. J. 138, 425-435; Rodriguez-Segade, Carrion & Freire (1979) Biochem. Biophys. Res. Commun. 89, 148-154]. This cofactor has now been partially purified by ion-exchange chromatography and molecular gel filtration, and characterized as a protein of Mr 10(5). The lighter cofactor reported previously was apparently the result of proteolytic activity generated during the tissue homogenization. The heavier cofactor was unstable, and its amount increased in livers of rats fed on carbohydrate-rich diet. Since the purified cofactor contained no glutathione reductase activity, the involvement of this enzyme in the deinhibitory mechanism of glucose-6-phosphate dehydrogenase by NADPH should be ruled out.

Animals↗

Hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus.

Although persistent infection with hepatitis B virus and woodchuck hepatitis virus has been associated with development of hepatocellular carcinoma in the host, little has been known of such an association with ground squirrel hepatitis virus (GSHV), which is closely related to the woodchuck virus. Colonies of GSHV-infected and -uninfected Beechey ground squirrels were observed for tumors for a period of 5 years. Tumors developed in seven squirrels after a minimum of 2.4 years of observation per animal; each of the seven animals was over 4 years old when the tumor was detected. The predominant type of tumor was hepatocellular carcinoma, which appeared in 2 of 28 GSHV-bearing animals studied and in 1 of 23 squirrels with antibody to the virus. No hepatocellular carcinoma appeared in 24 GSHV marker-free squirrels. Integrated GSHV DNA was found in the hepatocellular carcinoma tissue of the one carrier animal examined, paralleling the frequent findings of integrated hepatitis B and woodchuck hepatitis viral DNA in human and woodchuck hepatocellular carcinoma. Although the incidence of liver carcinoma reported here in carrier ground squirrels is neither as great as that in carrier woodchucks nor statistically different from the incidence in noncarrier squirrels, the data presented suggest that persistent infection with GSHV may also be associated with hepatocellular carcinoma.

Animals↗

Preliminary trial of recombinant fibroblast interferon in chronic hepatitis B virus infection.

Five patients with chronic hepatitis B were treated with 8-day courses of leukocyte (alpha) interferon (5 X 10(6) U/day) and with 8-day courses of recombinant fibroblast (betaser) interferon at dosages of 5 X 10(6), 35 X 10(6), and 105 X 10(6) U/day. Inhibition of hepatitis B virus replication as evidenced by a decrease in DNA polymerase (DNAP) activity was seen during all treatment courses. Equivalent reduction in DNAP was seen from the low-dose alpha and beta ser regimens, but beta ser interferon at 35 X 10(6) U/day achieved a significantly greater decrease in DNAP activity than did the low-dose regimens. In no patient, however, was permanent loss of DNAP noted. Because of dose-limiting toxicity, only two patients were escalated to the 105 X 10(6)-U/day dosage level. Transient proteinuria was noted in two patients while they were receiving interferon. This has not been noted in other patients receiving this preparation and could not be explained by the development of anti-interferon antibodies. This study has defined an appropriate dosage for future longer-term trials of this agent alone and in combination with other antivirals for the treatment of chronic hepatitis B.

Adult↗

[Principle and practice of in vitro fertilization. Role in the treatment of female sterility].

In vitro fertilization (IVF) and embryo transfer (ET) appear to constitute a revolution in the reproductive sciences rather than merely a new technique in the treatment of sterility. Principle of IVF: IVF accomplishes in vitro the process than normally occurs in the oviduct between the ovulation of oocyte II and embryo implantation in the endometrium. This 4 day period (under normal conditions in the woman) involves 4 steps: recovery, fertilization, segmentation and transport. Performance of IVF: Recovery of the oocytes: The oocytes are recovered under celioscopic or echographic observation when they have completed cytoplasmic maturation and their first meiosis. A precise monitoring of ovulation (spontaneous or induced) should be performed using estrogen and LH assays. IVF provides an opportunity for evaluating the methods of ovulation induction and monitoring, as a function of the maturation of the oocytes recovered. Fertilization: When the oocyte has achieved maturing after several hours of incubation, fertilization is obtained 15 h contact with washed and capacitated spermatozoa (100 000/ml). This step is highly dependent on gametocyte quality: oocyte maturity and fecundity of spermatozoa, which can be estimated from the percentage of survival in the insemination medium. Segmentation occurs in culture at pH 7.28 in the presence of 5 per cent CO2 at 37 degrees C (pronucleus 15th, 2 blastomeres 26 h, 4-8 blastomeres 52 h). Embryo transfer is carried out when an embryo is present at 52 h. Only 1/10 of the embryo transfers result in successful implantation, which depends on the quality of the embryo; the quality can only be indirect criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗