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Biomedical subjects

M Komatsu

Publications and source records attributed to M Komatsu.

At least 289 records · Page 16Linked to original sources

Hereditary C3 hypocomplementemia in the rabbit.

Hereditary hypocomplementemia of the third component of complement (C3) was found in a strain of rabbits in which hereditary C8 alpha-gamma deficiency was also found. The serum C3 concentration, haemolytic C3 activity and total complement haemolytic activity (CH50) of these animals were, respectively, 6-12%, 8-13% and 27-37% of the normal levels. The haemolytic complement activity in the C3 hypocomplementemic (C3-hypo) rabbit serum was restored in a dose-dependent manner by the addition of purified rabbit C3. The levels of factor H and properdin and components C2 and C6 were in the normal range, and the levels of factors B and D and component C8 were higher than normal. The low level of serum C3 in C3-hypo rabbits was not due to C3 conversion, partial C3 antigenicity, presence of a C3 inhibitor or hypercatabolism of normal C3. Furthermore, no change in the ratio of C3 protein levels was observed between C3-hypo and normal rabbits, even after turpentine injection. In addition, the C8 alpha-gamma deficiency condition does not affect C3 activity and C3 catabolism in vivo. Mating tests showed that the C3 hypocomplementemia is transmitted as a simple autosomal co-dominant trait. C3-hypo rabbits have a lower survival at 3 months than normal rabbits. C3-hypo rabbit serum also has a lower bactericidal activity than normal rabbit serum. The PAGE under reducing conditions showed no difference in the molecular weights of C3 alpha and C3 beta chains between C3-hypo, heterozygous and normal animals.

Aging↗

Genomic DNA encoding rabbit T cell receptor beta-chains: isotypes and allotypes of C beta.

We have discovered sequence differences in DNA encoding the first exon of rabbit T cell receptor beta-chains from unrelated rabbits that probably reflect allelic C beta 1 allotypes. Rabbit I was from a colony bred to maintain the K1-expression mutation Basilea, and rabbit II was from a colony bred to maintain the K1b9 allotype. Genomic DNA from rabbits I and II also exhibit restriction fragment length polymorphism of C beta on Southern blots. In addition, several different restriction enzyme digests of DNA from rabbit I give three bands, whereas DNA from rabbit II gives two when probed with C beta. An approximately 14-kb cloned genomic DNA fragment from rabbit I has two copies of C beta exon 1 and a 6-kb fragment has a third copy, suggesting that rabbit I has three different C beta genes. The DNA sequence of a germ-line genomic DNA fragment encoding the first exon of the beta-chain constant region from rabbit I also has an open reading frame encoding 140 amino acids immediately 5' of the C beta sequence. A corresponding sequence had previously been found in a cDNA clone from the second rabbit (rabbit II).

Alleles↗

Evolution of genes for allelic and isotypic forms of immunoglobulin kappa chains and of the genes for T-cell receptor beta chains in rabbits.

New insights into the evolution of the families of genes encoding immunoglobulins and T-cell receptors of rabbits (Oryctolagus cuniculus) have come from molecular genetic studies. In contrast to human and mouse, rabbits were shown to have two genes for the constant region of immunoglobulin light chains (C kappa 1 and C kappa 2 isotypes) and complex allelic variants of K1 (allotypes). Although K1 allotype protein sequences differed at up to 41% of the amino acid positions, 3' untranslated, 5', and 3' flanking regions were conserved, and in the coding regions 78-80% of the codons with differences had replacement changes. Proportions of silent changes and changes in noncoding regions were comparable. Thus, in spite of their markedly different protein sequences, the K1b4, b5, and b9 allotypes appeared to be products of allelic genes. Molecular genetic analyses suggested that they may have undergone rapid divergence after an ancestral K2-like gene duplicated. Some rabbits were found to have two similar T-cell receptor C beta genes as do humans and many strains of mice, but others appeared to have three different C beta. In addition, we found allotypic forms of C beta. Some of the C beta allotypic differences occurred at positions where analogous C kappa allotypic differences were found. We also found V beta in mouse and human that were more similar to rabbit V beta than closely linked rabbit genes were to each other. This contrasts with rabbit immunoglobulin VH gene sequences that reflect concerted evolution. The data suggested that T-cell receptor V beta genes duplicated prior to mammalian radiation.

Alleles↗

Thyroid function in children with long-term anticonvulsant treatment.

Thyroid functions were studied in 287 children given long-term treatment with anticonvulsants. Of these 287 patients, 26 were treated with carbamazepine (CBZ) alone, 63 with phenobarbital (PB) alone, 66 with sodium valproate (VPA) alone and 132 with combination therapy. Serum triiodothyronine (T3) and thyroxine (T4) concentrations were decreased after more than 3 years of treatment with CBZ. The regression line of serum T4 concentrations against serum CBZ concentrations indicated a negative correlation. Serum T3 and T4 concentrations were decreased after more than 6 years of treatment with PB, although there was no statistical significance in the relationship between serum T4 and PB concentrations. There was no significant decrease in serum T3 or T4 concentration in patients treated with VPA. Serum-free T4 and thyroxine-binding globulin were decreased and serum thyrotropic hormone concentration was increased in patients with low serum T4 concentrations. We conclude that thyroid functions should be examined in children given long-term treatment with anticonvulsants.

Adolescent↗

Alteration in dipeptidyl peptidase activities in cultured human carcinoma cells.

For the investigation of the possibility of its being a marker enzyme for tumor cells, the activity of dipeptidyl peptidase (DPP) IV (EC 3.4.14.5), a membrane-bound enzyme, in cultured human carcinoma cells was examined. The homogenates of three carcinoma cell lines (HeLa, KB, and K-44) contained lower glycylprolyl methylcoumarinamide (Gly-Pro-MCA) hydrolase activities at pH 8.7 (assumed to be DPP IV) and higher activities of alkaline phosphatase and gamma-glutamyl transpeptidase, which are also membrane-bound enzymes, than those of normal human fibroblasts (HF). Examination of carcinoma cells for the subcellular localization and pH optimum of Gly-Pro-MCA hydrolase activity revealed that the activity of a lysosomal enzyme that hydrolyzes Gly-Pro-MCA at pH 6.4 was markedly increased in carcinoma cells, but not in normal cells. The separation and characterization of Gly-Pro-MCA hydrolases by gel filtration, affinity chromatography, and substrate specificity demonstrated that HF have three peaks indicating DPP IV, DPP II, and an unknown enzyme, whereas the three carcinoma cell lines gave a prominent peak indicating DPP II and a trace of DPP IV. The DPP II activity was 6- to 24-fold higher in carcinoma cell lines than in HF, and it also was 2.85- to 4.13-fold higher than the DPP IV activity in carcinoma cell lines but was 10-fold lower in HF. These clear enzymatic differences between carcinoma cells and normal HF may be useful as a marker of malignancy.

Alkaline Phosphatase↗

Effects of an LHRH agonist on endocrine function, LHRH receptor and LH/hCG receptor in the pituitary-gonadal axis of male rats.

The effects of an LHRH agonist (LHRHa), [D-Ser (tBu)]6 des-Gly-NH210) ethylamide, on endocrine function and the LHRH and LH/hCG receptors in the pituitary-gonadal axis were examined. The LHRHa was injected at 100 ng/100 g body weight into male rats once a day for 4 weeks and its effects were observed until 2 weeks after the end of treatment. Due to LHRHa treatment, the plasma LH concentration began to increase on day 3, reached a peak on day 7, and then decreased, although it remained above the control level during the treatment. The pituitary LH content decreased on day 1, reached a minimum (about 40% of the control) between days 3 and 7, and then was maintained at 60% of the control level until week 4. In contrast, the pituitary LHRH receptor concentration increased only on day 3, and the association constant (Ka) remained unchanged during the observation period. The testis weight and plasma testosterone concentration began to decrease on day 3, reached the minimum on day 7 and remained at this level until week 4, and their levels were not completely restored to normal 2 weeks after cessation of treatment. The testicular LH/hCG receptor concentration was decreased on day 1, and markedly decreased to 10-15% of the control value between day 7 and week 4, but the Ka value was slightly increased during the treatment. However, these values had completely recovered 2 weeks after the cessation of treatment. The testicular LHRH receptor concentration increased between days 1 and 7, returned to the control level in weeks 2 and 4, and then decreased 2 weeks after cessation of treatment. Its Ka value was reduced in weeks 2 and 4. These data suggest that the inhibitory effect of LHRHa on the gonad in male rats is not due to reduced pituitary LH release, but to changes in the number and Ka values of gonadal receptors for LH/hCG and LHRH.

Animals↗

The treatment of chronic myelogenous leukemia in blastic crisis with the chemotherapy incorporating vindesine-prednisolone.

Twenty-three patients with chronic myelogenous leukemia (CML) in terminal transformation were treated with regimen incorporating vindesine and prednisolone with or without cytosine arabinoside. Twenty-one patients in blastic crisis (BC) were classified into subgroups on the blast cell morphology. Of these 21 patients, 5 (23.8%) had lymphoid morphology, 12 (57.2%) had myeloid morphology, and 4 (19.0%) had monocytoid morphology. All of five patients with lymphoid morphology and ten of twelve patients with myeloid morphology achieved complete remission (83.3%), while none of four patients with monocytoid morphology achieved complete remission. Two patients in accelerated phase also attained complete remission. Our results indicate that the regimens incorporating vindesine and prednisolone with or without cytosine arabinoside should be the treatment of choice in CML-BC both lymphoid and myeloid morphology and accelerated phase of CML as well.

Adult↗

Studies on monocyclic beta-lactam antibiotics. IV. Synthesis and antibacterial activity of (3S,4R)-3-[2-(2-aminothiazol-4-yl)-(Z)-2-(O-substituted oxyimino)acetamido]-4-methyl-1- (1H-tetrazol-5-yl)-2-azetidinones.

The synthesis and in vitro activity of the 3-(O-substituted oxyiminoacetamido)-2-azetidinones (IV) possessing a tetrazole moiety at N-1 position are described. The introduction of lipophilic functions into the oxyimino moiety gave in some good activity against staphylococci, but decreased activity against Gram-negative bacteria. In contrast, the introduction of hydrophilic functions such as carboxycyclobutane resulted in strong activity against Gram-negative bacteria including Pseudomonas aeruginosa, and no or very small activity against the staphylococci.

Anti-Bacterial Agents↗