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Biomedical subjects

I Garcia

Publications and source records attributed to I Garcia.

At least 163 records · Page 9Linked to original sources

[Serum lipids in diabetes mellitus. Relation to equilibration and microangiopathy].

We have determined in 128 diabetic (57 non insulin-dependent (NIDDM) and 71 insulin-dependent (IDDM) patients) and in control subjects, serum total cholesterol, HDL cholesterol, triglycerides and Hb Alc levels. Presence of macroangiopathy was assessed by clinical findings. In IDDM increasingly poor control of diabetes was associated with significant increases in total cholesterol (p less than 0.001) and triglycerides (p less than 0.01). HDL cholesterol (1.19 +/- 0.39 mM/l) did not differ from control subjects (1.30 +/- 0.35 mM/l) and was not related to Hb Alc levels. NIDDM had increased total cholesterol (5.91 +/- 1.45 vs 5.38 +/- 0.93 mM/l, p less than 0.05) and triglycerides (2.06 - 0.32 to 8.80- vs 1.03 - 0.22 à 2.20 mM/l, p less than 0.01) and decreased HDL cholesterol (1.08 +/- 0.44 vs 1.31 +/- 0.36 mM/l, p less than 0.01). These differences could be explained only in part by the overweight of the NIDDM patients. There was no significant correlation in NIDDM between Hb Alc and serum lipids levels but overweight and triglycerides were positively correlated (p less than 0.02) and triglycerides and HDL cholesterol negatively correlated (p less than 0.05). IDDM with macroangiopathy had higher total cholesterol levels than those without (6.44 +/- 1.60 vs 5.29 +/- 1.22 mM/l, p less than 0.01). IDDM and NIDDM with macroangiopathy had slightly decreased HDL cholesterol; however, the diabetic subjects with macroangiopathy were older and had a longer duration of diabetes than subjects without macroangiopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Allotypes in Basilea rabbits.

Basilea rabbits produce immunoglobulin molecules, practically all of which have lambda light chains rather than kappa chains. This variant strain was derived form a homozygous (b9/b9) male. Sensitive serological methods revealed that at least some homozygous bas/bas individuals possess traces (about 100 ng/ml) of b9 molecules. This level usually increases to almost 1 microgram/ml upon hyperimmunization with pneumococcal or streptococcal vaccines. One exceptional rabbit, with 50 micrograms/ml of b9 molecules, was found. In spite of the presence of b9 molecules in early pre-immune bleeds, homozygous bas/bas rabbits produce strong anti-b9 antibodies; i.e., they are capable of making autoantibodies. These anti-b9 allotypic antisera were not distinguishable by our methods from routinely produced anti-b9.

Animals↗

BASILEA rabbits express two types of immunoglobulin light chains: lambda and kappa-like.

In the variant rabbit strain BASILEA, immunoglobulin G were shown to contain two distinct populations of IgG molecules whose light (L) chains belonged to the known lambda isotype and to a new kappa-like type. These two L chains differed from each other by electrophoretic, chemical, and antigenic properties. The kappa-like L chain fraction showed (i) an acid-labile Asp-Pro bond at the end of the joining region and (ii) a tryptic peptide, whose amino acid sequence of the NH2-terminal 15 residues was identical to the homologous constant (C) region sequence of b9 kappa chain with the exception of the residue in position 70, which is asparagine in the kappa-like chain instead of the characteristic half-cystine residue in all L chains of kappa B type expressing b4, b5, b6, or b9 allotypes. The data suggest that the kappa-like L chain component does not contain the C region half-cystine residue involved in the formation of the extra variable (V) region-C region disulfide bridge in L chains of the kappa B [Rejnek, J., Appella, E., Mage, R. G. & Reisfeld, R. A. (1969) Biochemistry 8, 2712-2718]. The partial NH2-terminal amino acid sequence of the C region of the kappa-like L chain was shown to be markedly different from b4, b6, or b9 region sequences and from rabbit lambda C region sequence. Taken together, the chemical data suggest that the kappa bas component represents a new subtype of kappa chain. A rabbit alloantiserum made against bas IgG and adsorbed with IgG fractions showing b4, b5, b6, b95, and b96 L chain allotypes appeared to be directed against the kappa-like L chain component of BASILEA IgG exclusively. All BASILEA animals expressed IgG molecules containing kappa-like chains; in contrast, IgG molecules derived from the standard domestic rabbit did not react with this antiserum.

Amino Acid Sequence↗

The primary structure of the constant region of Basilea-rabbit immunoglobulin lambda-chains.

The amino acid sequence of the constant region of the immunoglobulin lambda-chain of the rabbit (C lambda) has been determined. This chain was obtained from a homogeneous anti-(type II pneumococcal polysaccharide) antibody fraction raised in Basilea rabbit 4548. The C lambda-region sequence was established by the analysis of tryptic and some overlapping chymotryptic peptides and partly by homology with known C lambda-region sequences of lambda-chains from other species. Peptides were isolated by a combination of methods including high-voltage paper electrophoresis, gel filtration and high-pressure liquid chromatography. The peptides were subjected to automated Edman degradation in the presence of Polybrene. The sequence showed no evidence of heterogeneity. Large interspecies similarities, as well as amino acid interchanges, are apparent among various C lambda regions; the degrees of homology between rabbit C lambda region and the C lambda region from human, porcine and murine chains are 72.6, 71 and 72% respectively. The similarity of lambda-chains of different species is much greater than that found between rabbit kappa- and lambda-chains (about 34% homology). Genetic implications of these results are discussed.

Amino Acid Sequence↗

Human metabolism of 7-substituted theophyllines: N3-demethylation and lack of oxidation of proxyphylline.

Proxyphylline metabolism after oral administration to humans was studied. The only metabolic process detected was N3-demethylation, and 1-methyl-7-(2-hydroxypropyl)xanthine was isolated and identified. Proxyphylline was excreted in urine both an unchanged compound (12.7% of dose) and as its metabolic product (30.2% of dose). The latter substance was not found (detection limit = 1 microgram/ml) in the systemic circulation. Thus, it probably does not participate in the pharmacological activity of proxyphylline in vivo, although it was as active as the parent drug in relaxing the guinea pig tracheal chain. Lack of metabolism to uric acid derivatives is explained by the low affinity of both substances toward the enzymes the oxidize xanthine (xanthine oxidase) and methylxanthine derivatives. The presence of the metabolite in urine interferes with some analytical methods developed for estimation of unchanged proxyphylline. Published data on the urinary excretion of this drug need reevaluation.

Aminophylline↗

Reactions between polyribonucleotides and low density lipoproteins in sera of patients with progressive systemic sclerosis.

A high percentage (58%) of sera from patients with progressive systemic sclerosis reacted with synthetic polyribonucleotides to give precipitin lines. This was demonstrated by counterimmunoelectrophoresis. The synthetic polyribonucleotides included polyuridylic acid (poly U), polyadenylic acid (poly A), and co-polymers of poly A-poly U. The reactive factor in serum was not immunoglobulin but was associated with low density lipoprotein.

Antibodies↗

Diversity of antinuclear antibodies in progressive systemic sclerosis. Anti-centromere antibody and its relationship to CREST syndrome.

Antinuclear antibodies were demonstrated in the sera of 43 of 45 (96%) patients with progressive systemic sclerosis (22 of 24 with diffuse scleroderma and 21 of 21 with the CREST syndrome variant). This high percentage of positive reactions resulted from the use of a tissue culture substrate (HEp-2) to detect antinuclear antibodies by the indirect immunofluorescent method. Patterns of nuclear staining included diffuse fine speckles, large coarse speckles, nucleolar and centromere staining. When organ sections such as mouse kidney were used as substrate for the detection of antinuclear antibodies, nucleolar staining and centromere staining were the two patterns most frequently overlooked. Three types of antibodies appeared to be highly specific for scleroderma: antibody to Scl-70 antigen, antibody to centromere, and antinucleolar antibody. The anti-centromere antibody appeared to be highly selective for the CREST variant of progressive systemic sclerosis.

Antibodies, Antinuclear↗

[Spermatogenic dysfunction and gonadotrophins (author's transl)].

The authors try to demonstrate a relation between the number of immature cells of germinal origin in sterile men's sperm and plasmatic gonadotrophin levels of the same patients. Plasma FSH, LH, testosterone and 17 beta-estradiol were assayed in two groups of male patients with teratospermia. Results were compared with those obtained in a control group of normal men. Hypophyseal gonadotrophins level is higher in men whose spermatogenesis is defective than in normal men. It is suggested that these results might support the hypothesis that a defect in inhibin synthesis would be responsible for raised gonadotrophins.

Estradiol↗

Pulmonary cell response patterns after exposure to airborne bacteria.

The free lung cells obtained with a lavage technique were studied in guinea-pigs exposed to an aerosol of E.coli, K. pneumoniae or B.subtilis. An increase in the number of polymorphonuclear leucocytes was found 5-48 hours after exposure to E.coli and B.subtilis. The clearance of a mixture of viable and radioactively labelled E.coli was studied in animals with a naturally present or artificially induced high leucocyte level in the lungs. It was found that animals with the higher leucocyte number cleared the inhaled bacteria faster.

Aerosols↗

Monoclonal anti-EGFreceptor antibody (ior-R3) pharmacokinetic study in tumor bearing nude mice: role of the receptor-mediated endocytosis on drug clearance.

With the purpose of describing the MAb ior-R3's kinetic behavior in disease state, this paper is focused on the study of this response using a human cancer (lung carcinoma cell line, H125) bearing nude mice animal model. This MAb was administered by a single 16 mg/Kg intravenous bolus dose and the blood samples were collected at several times ranging from 0 to 72 hours for serum drug quantification. The experimental data set was best fitted using a classical two-compartment mammilary pharmacokinetic (PK) model and the corresponding PK parameters were determined. Comparatively, the analysis of the more relevant physiologically-based PK parameters showed a significant enhancing of clearance as compound with the earlier reported study on healthy mice, increasing from 0.09 to 0.19 mL/h (p<0.01). However, the corresponding distribution volumes don't seem to be altered by the tumor xenograft. We conclude that all of these evidences suggest a possible mechanism of receptor-mediated endocytosis (RME) as a major cause of this increased drug clearance which also contributed to the faster decrease of the drug disposition.

Animals↗