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Biomedical subjects

M Obata

Publications and source records attributed to M Obata.

71 records · Page 4Linked to original sources
PubMed1983

Acral melanoma in Japan.

Clinical records and histologic materials from 81 patients with malignant melanoma at the Department of Dermatology at Tohoku University School of Medicine were reviewed. In addition, a statistical study on 1597 cases of malignant melanoma collected from the Japanese literature from 1961 to 1982 was performed. The annual mortality rate has been increasing almost linearly over the past 20 years. The mortality rate per year for 1980 was 0.21 per 100,000. Five-year survival rate at Tohoku University was 35 percent. The most common site of melanoma was acral, especially the plantar surfaces. The clinical and histologic study of acral melanomas showed that clinicopathologic features are the same as those reported for acral lentiginous melanoma in the United States.

Extremities↗
PubMed1982

Structure of human immunoglobulin gamma genes: implications for evolution of a gene family.

We have cloned five human immunoglobulin gamma genes from a fetal liver gene library. Four of them encode the known human immunoglobulin gamma chains gamma 1, gamma 2, gamma 3 and gamma 4. A fifth gamma gene seems to be a pseudogene. Nucleotide sequence determination demonstrates that the gamma 3 gene contains four separate hinge exons. Comparison of these hinge exons with those of the other gamma genes indicates that the first hinge exon is homologous to that of the pseudogene, and that the other three hinge exons are homologous to that of the gamma 1 gene, suggesting that the gamma 3 gene ancestor is a hybrid gene created by unequal crossing-over between the ancestral gamma 1 and psi gamma genes. Amplification of the gamma 1-type hinge exon probably followed to complete the gamma 3 gene. This hypothesis inevitably postulates the gene order 5'-gamma 1-gamma 3-psi gamma-3'. Cloning of overlapping chromosomal segments demonstrates that the gamma 2 gene is located 19 kb 5' to the gamma 4 gene. These analyses indicate that the human gamma-gene family has evolved by several types of DNA rearrangemet, including duplication of a complete gene; duplication of a hinge exon; and reassortment of exons by unequal cross-over between two adjacent genes.

Animals↗
PubMed1981

Structure of a rearranged gamma 1 chain gene and its implication to immunoglobulin class-switch mechanism.

An expressed gene for gamma 1 chain of MC 101 myeloma was cloned from a phage library containing partial EcoRI digests of MC 101 DNA. The cloned DNA was analyzed by restriction enzyme cleavage, Southern blot hybridization, R-loop formation, and nucleotide sequence determination. The results indicate that the expressed gamma 1 chain gene comprises at least four germline DNA segments, namely a variable-region gene, a segment of the 5' flanking region of the mu chain gene (containing J regions), a segment of the 5' flanking region of the alpha chain gene, and the gamma 1 chain gene with its flanking regions. The presence of the alpha chain gene-flanking switch (S) region (S alpha region) at the 5' side of the gamma 1 chain gene-flanking region (S gamma 1 region) indicates that the heavy chain class switch may not be mediated by stepwise linear deletion along the order of the heavy chain constant-region genes (5'-mu-gamma 3-gamma 1-gamma 2b-gamma 2a-alpha-3'). We propose a siter-chromatid exchange model that explains class switch-associated deletion of heavy chain genes by unequal crossing-over events between sister chromatids.

Base Sequence↗
PubMed1981

Rearrangements of immunoglobulin genes during differentiation and evolution.

Immunoglobulin genes are shown to undergo dynamic rearrangements during differentiation as well as evolution. We have demonstrated that a complete immunoglobulin heavy chain gene is formed by at least two types of DNA rearrangement during B cell differentiation. The first type of rearrangement is V-D-J recombination to complete a variable region sequence and the second type is S-S recombination to switch a constant region sequence. Both types of recombination are accompanied by deletion of the intervening DNA segment. Structure and organization of CH genes are elucidated by molecular cloning and nucleotide sequence determination. Organization of H chain genes is summarized as VH-(unknown distance)-JH-(6.5 kb)-C mu-(4.5 kb)-C delta-(unknown distance)-C gamma 3-(34 kb)-C gamma 1-(21 kb)-C gamma 2b-(15 kb)-C gamma 2a-(14.5 kb)-C epsilon-(12.5 kb)-C alpha. The S-S recombination takes place at the S region which is located at the 5' side of each CH gene. Nucleotide sequence of the S region comprises tandem repetition of closely related sequences. The S-S recombination seems to be mediated by short common sequences shared among S regions. A sister chromatid exchange model was proposed as a mechanism for S-S recombination. Comparison of nucleotide sequences of CH genes indicates that immunoglobulin genes have scrambled by intervening sequence-mediated domain transfer during their evolution.

Animals↗
PubMed1981

Pharmacological properties of 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434).

Pharmacological properties of 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434) were investigated in vivo and in vitro experiments. M6434 showed a dose-dependent pressor effect in conscious rats at oral doses ranging from 1 to 5 mg/kg. The pressor effect of M6434 was 10 times as potent as those of phenylephrine and methoxamine. M6434 also showed a dose-dependent pressor effect in anesthetized dogs at i.v. doses ranging from 3 to 30 micrograms/kg. The effect of M6434 returned to control level 30 to 45 min after i.v. injection. M6434 caused a contraction of isolated guinea-pig aortic spiral strip at concentrations ranging from 10(-8) to 10(-4) mol/l. pD2 value of M6434 was larger than those of the other sympathomimetics, yet the maximal response of M6434 was 83.4% of the maximal response of noradrenaline. Pretreatment with phentolamine caused a parallel shift of the concentration-response curve of M6434 to the right. However, this effect of M6434 on an isolated aorta was not diminished even in reserpinized guinea-pigs. Therefore, the pressor effect of M6434 may be due to the direct adrenergic alpha-stimulation. M6434 is expected to be effective for the oral treatment of hypotensive disorders.

Adipose Tissue↗
PubMed1980

Immunoglobulin gamma 1 heavy chain gene: structural gene sequences cloned in a bacterial plasmid.

Immunoglobulin gamma 1 heavy chain cDNA was cloned into an Escherichia coli plasmid pCR1 and its nucleotide sequence was determined. The hybrid plasmid contained approx. 900-bases-long gamma 1 chain cDNA sequence, including the complete sequence of the CH2 and CH3 domains and the 3' untranslated region, and partial sequence of the CH1 domain. The nucleotide sequence predicts an extra lysine at the carboxyl-terminus of the gamma 1 chain. Comparison of the nucleotide sequence of 3' untranslated regions of the immunoglobulin gamma 1 chain and kappa light chain showed a significant homology although lengths are quite divergent.

Animals↗
PubMed1980

Nucleotide sequence divergence of mouse immunoglobulin gamma 1 and gamma 2b chain genes and the hypothesis of intervening sequence-mediated domain transfer.

The nucleotide sequences of the constant portions of mouse immunoglobulin gamma 1 and gamma 2b genes were compared. A remarkable homology was found in a long (about 500 nucleotides) continuous segment including the entire CH1 coding region and about the first half of the first intervening sequence. Furthermore, comparison of amino acid sequences of four gamma-class chains revealed that the CH1 domain shows limited divergence among gamma 1, gamma 2a, and gamma 2b. Interestingly, the homology region extends to the CH2 domain in gamma 2a and gamma 2b. These findings suggest that, during their evolution, a double unequal crossing-over event has taken place at different intervening sequences, resulting in the transfer of the DNA segment coding for the CH1 domain or CH1-CH2 domains. A possible evolutionary implication for such an "intervening sequence-mediated domain transfer" event is discussed.

Amino Acid Sequence↗