Biomedical subjects
Publications and source records attributed to A Shimamoto.
The wide variety of calls received by the Hawaii Poison Center are described. These include the typical, humorous and calls unique to the islands. Methods include descriptive anecdotal recall and review of Hawaii Poison Center call statistics. A brief description of staff, resources and call taking procedures are also provided.
We reviewed pT3 lung cancer for 86 cases (13.1%) out of 659 cases treated surgically for primary lung cancer between 1985 and march 1998. Five-year and ten-year survival rates for all pT3 cases were 48% and 40% respectively and those for pT3N0M0 cases were 67.2%. The operative mortality between 1990 and 1998 (2.4%) was better than that between 1985 and 1989 (6.7%). The extensive resection for pT3 lung cancer was evaluated to be appropriate. However, the prognosis of the patients who underwent combined resection of mediastinal pleura, pericardium or diaphragm was very poor. Five-year survival rate was significantly worse in patients with N2 disease (17.3%) than in patients with N0 disease (65.8%) (p < 0.05). Although the surgical indication for the patients with mediastinal pleura, pericardium or diaphragm disease and N2 disease is still controversial, there is not the extensive surgical indication.
Bloom syndrome (BS) is a rare genetic disorder characterized by small body size, sun sensitivity, immunodeficiency and a high predisposition to various types of cancer. BLM was identified as the causative gene for BS, and BLM protein is homologous to DNA helicase. There are two putative nuclear localization signals (NLSs) within amino acid residues 1334-1349 in the C-terminus of the BLM protein, which has the distinctive structure of two basic residue arms separated by a spacer. The entire coding or deleted BLM sequences of various sizes were ligated into an enhanced green fluorescent protein (EGFP) vector and transfected into HeLa cells. The EGFP vector harboring the entire BLM coding sequence was transported to the nucleus. The BLM protein truncated at 1341 amino acid, containing an intact helicase domain and only one proximal arm, was not transported to the nucleus. The BLM protein truncated at 1357 amino acid, containing an intact helicase domain and two arms, was transported to the nucleus. The EGFP vector harboring DNA fragments encoding a protein having only the distal arms of basic amino acids in the C-terminus was also transported to the nucleus. The truncated BLM proteins corresponding to previously reported mutated BLM proteins were retained in the cytoplasm or both the cytoplasm and the nucleus as was the EGFP vector with no insert. These results show that the BLM protein translocates into the nucleus and that the distal arm of the bipartite basic residues in the C-terminus of the BLM protein is essential for targeting the nucleus.
The gene responsible for Werner's syndrome (WRN) contains a region homologous to the Escherichia coli RecQ type DNA helicase and was thought to code for a DNA helicase belonging to this helicase family. However, no evidence has been shown before to substantiate this prediction. Here, we show data that the product of the WRN gene is indeed a DNA helicase. The gene product, a polypeptide with a relative molecular mass of 170 kDa, expressed in the insect Spodoptera frugiperda (Sf21) cell and purified by affinity column chromatography contained both the ATPase and DNA unwinding activities characteristic of DNA helicase. Expressions in Sf21, as well as in HeLa cells, showed that the WRN DNA helicase is exclusively transported to the nucleoplasm, which is consistent with its function in DNA metabolism. Our studies on strand displacement suggest that WRN helicase can unwind not only a duplex DNA, but also an RNA-DNA heteroduplex, while the latter reaction seems less efficient. Enzymological features learned from the purified WRN helicase are discussed with respect to the biological function, which remains to be clarified.
A novel human gene referred to as the WS-3 gene, in the short arm of human chromosome 8, was cloned by a combination of exon trapping, thermal asymmetric interlaced-PCR (TAIL-PCR) and the Marathon-Ready cDNA amplification method. The gene consists of 7 exons separated by 6 introns, and is at the telomere side of the STS marker, D8S1055. The full-length WS-3 gene contains 1052 nucleotides and codes for a protein of 190 amino acids with a calculated mol. wt. of 20,747. Southern blot experiments showed that the WS-3 gene exists as a single copy in the human genome. A protein encoded by the WS-3 gene has an R-G-D (Arg-Gly-Asp) motif in the N-terminal region, which seems to confer adhesive properties to macromolecular proteins like fibronectin. Although WS-3 is a small gene with unknown biological function, its ubiquitous expression in various tissues and organs suggests that the encoded protein is one of the essential components of all organs and tissues.
A novel human gene referred to as the Rep-8 gene (D8S2298E) was cloned by a combination of exon trapping, thermal asymmetric interlaced-PCR, and screening of a cDNA library. It is located in human chromosome 8p11.2-p12. The gene consists of eight exons and spans about 20 kb between the glutathione S-reductase and the protein phosphatase 2A beta subunit genes. The full-length Rep-8 gene contains 1483 nucleotides and codes for a protein of 270 amino acids. Southern blot experiments showed that the Rep-8 gene exists as a single copy per haploid. With a zoo blot analysis, human Rep-8 DNA hybridized strongly with the monkey DNA, but only weakly with the DNAs of species other than Homo sapiens. Northern blot analysis showed that it is expressed abundantly in the testis and ovary, suggesting that the Rep-8 gene product may play a role in reproduction.
The correlation between mutations in the Werner's syndrome (WRN) gene and the haplotypes of surrounding markers was studied in Japanese patients. We have elucidated the genomic structure of WRN helicase, and found five additional mutations, designated mutations 6-10. Mutations 4 and 6 were found to be the two major mutations in this population; these mutations comprised 50.8% and 17.5%, respectively, of the total in a sample of 126 apparently unrelated chromosomes. Almost all the patients homozygous for mutation 4 shared a haplotype around the WRN gene, consistent with the view that they are derived from a single ancestor. This important advantage demonstrated in the identification of the WRN gene suggests that the Japanese present a unique population for the cloning of other disease genes. The conserved haplotype was observed across 19 loci, extending a distance estimated to be more than 1.4 Mbp around the WRN gene. This haplotype is rare among random Japanese individuals. Unexpectedly, all the nine patients homozygous for mutation 6 shared a haplotype that was identical to this haplotype at 18 of these 19 markers. These results suggest that mutations 4 and 6 arose independently in almost identical rare haplotypes. The remaining mutations (1, 5, 7, 8, 9, and 10) occurred rarely, and were each associated with different haplotypes.
BACKGROUND: A membrane oxygenator consisting of a microporous polypropylene hollow fiber with a 0.2-microm ultrathin silicone layer (cyclosiloxane) was developed. Animal experimental and preliminary clinical studies evaluated its reliability in bypass procedures. METHODS: Five 24-hour venoarterial bypass periods were conducted on dogs using the oxygenator (group A). In 5 controls, bypass periods were conducted using the same oxygenator without silicone coating (group B). As a preliminary clinical study, 14 patients underwent cardiopulmonary bypass with the silicone-coated oxygenator. RESULTS: Eight to 16 hours (mean, 12.2 hours) after initiation of bypass, plasma leakage occurred in all group B animals, but none in group A. The O2 and CO2 transfer rates after 24 hours in group A were significantly higher than at termination of bypass in group B (p < 0.005 and p < 0.03, respectively). Scanning electron microscopy of silicone-coated fibers after 24 hours of bypass revealed no damage to the silicone coating of the polypropylene hollow fibers. In the clinical study, the oxygenator showed good gas transfer, acceptable pressure loss, low hemolysis, and good durability. CONCLUSIONS: This oxygenator is more durable and offers greater gas transfer capabilities than the previous generation of oxygenators.
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We discussed on the treatments for T4 lung cancer with invasion to the superior vena cava, whose prognosis has been poor. However, surgical resection may improve the prognosis compared with radiation therapy. The prosthetic replacement of superior vena cava can be done safely, and its patency is good in cases of ring-enforced ePTFE graft. Although superior vena caval obstruction syndrome had been a hard issue in the advanced cases, stenting in superior vena using the interventional radiological technique is a safe and reliable method. We should consider the stenting as the first choice for superior vena cava obstruction syndrome, because it makes the QOL improve so much.
A unique gene, RBP-MS, spanning over 230 kb in the human chromosome 8p11-12 near the Werner syndrome gene locus is described. The single-copy RBP-MS gene is alternatively spliced, resulting in a family of at least 12 transcripts (average length of 1.5 kb). Nine different types of cDNAs that encode an RNa-binding motif at the N terminus and helix-rich sequences at the C terminus have been identified thus far. Among the 16 exons identified, four 5'-proximal exons contained sequences homologous to the RNA-binding domain of Drosophila couch potato gene. Northern blot analysis showed that the RBP-MS gene was expressed strongly in the heart, prostate, intestine, and ovary, and poorly in the skeletal muscle, spleen, thymus, brain, and peripheral leukocytes. The possible role of this gene in RNA metabolism is discussed.
Although the hepatocyte growth factor-like protein (HLP) shares a 50% homology with the hepatocyte growth factor, the biological function of HLP has remained unknown. Addition of conditioned medium of COS-7 cells transfected with the expression plasmid for HLP cDNA to cultures of resident peritoneal macrophages induced specific activation of macrophages, and the factor which stimulates macrophages was purified from the conditioned medium. The purified protein showed M(r) of 85 kDa on SDS-PAGE, and this M(r) is in agreement with that of macrophage-stimulating protein (MSP) previously purified from human serum, as well as with the predicted M(r) of HLP. Amino acid composition of the purified protein coincided with the compositions of human HLP and MSP. Together with the finding that the partial amino acid sequences of MSP are highly homologous to that of HLP, we conclude that the biological function of HLP is to activate macrophages and that HLP and MSP are identical molecules.
The narrow-band action potentials (NAP) and the ordinary electrocochleograms were recorded from the guinea-pig cochlea under normal and pathological conditions in order to study whether the NAP could be a useful measure to detect cochlear dysfunctions. The cochlea damaged either by the administration of kanamycin or by a mechanical lesion of the round window served as pathological materials. Recordings showed that the threshold and amplitude measured for the N1 potential of NAPs ran in parallel with those of the cochlear microphonic potentials (CM), under both normal and pathological conditions of the cochlea. This implies that the CM could be replaced by the NAP when difficulties were present in recording CMs. It may be inferred that the NAP reflects responses of the inner hair-cells and cochlear nerves, while the CM would mainly be derived from responses of the outer hair-cells to the frequency-specific movements of the basilar membrane. If so, the NAP should offer a good means for the objective audiometry. Recording NAPs is also superior to the ordinary electrocochleography in that the method makes it possible to obtain responses generated near the apex of the cochlea, i.e., responses to low-pitch sound stimuli.
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In pediatric cardiac surgery, the initial priming solutions of the extracorporeal circulation include preserved blood. In an effort to eliminate unfavorable effects of preserved blood on the circulation, the authors introduced the preserved blood to ultrafiltration (UF). Seventeen infants with congenital heart defects were included in this study. UF was performed with a polysulfone ultrafiltrator before extracorporeal circulation. The 1600 ml of fluid, consisting of saline, 5% glucose, and maltose, were added to 400 ml of preserved blood, and the same amount of fluid was removed by UF. The concentrations of potassium, NH3, and bradykinin in the priming blood decreased significantly after UF. In the UF group, water balance during extracorporeal circulation and max. Creatinine-phosphokinase levels after surgery were better than controls. These data suggest that UF is able to remove some substances and result in reduction of an unfavorable effect on the circulation.
In this article, the clinical experience with a cardiopulmonary bypass (CPB) using a newly developed hollow fiber oxygenator with an ultra-thin layer of silicone is reported. A comparative study of biocompatibility between the new oxygenator and a heparin coated oxygenator is also described. The CPB was performed with a silicone coated oxygenator, Mera Excelung Binding Prim HPO 15 H-C (Group I, n = 6) or Binding Prim HPO 25 H-C (Group II, n = 10) (Senko Medical Instrument Mfg., Tokyo, Japan). Air could be vented through the silicone coated hollow fibers, and it was easy to prime the circuits. The CPB duration was 101 +/- 37 min and 170 +/- 64 min for Groups I and II, respectively. There were no deaths and no complications from CPB. Partial arterial pressure of O2 levels 60 minutes after the start of CPB were 529 +/- 28 mm Hg and 529 +/- 28 mmHg for Group I and II, respectively. Partial arterial pressure of CO2 levels 60 min after the start of CPB were 36.4 +/- 4.6 mmHg and 39.4 +/- 4.4 mmHg, respectively. Plasma free hemoglobin at 60 min was 33.5 +/- 17.2 mg/ dL and 46.7 +/- 26.1 mg/dL for Groups I and II, respectively. As an evaluation of biocompatibility, the effects of the new oxygenator on platelet activation (GP Ib, IIb/IIIa), coagulation (TAT), fibrinolysis (PIC), and inflammatory response (C3a, granulocyte elastase) were investigated during CPB and comparing to those of the heparin coated oxygenator. There were no significant differences in GP Ib, GP IIb/IIa, TAT, PIC, and granulocyte elastase between the two oxygenators. However, 60 min after the start of CPB, the C3a was significantly lower for the new oxygenator group than for the heparin coated oxygenator group (p < 0.03). The new oxygenator showed good gas transfer, low hemolysis, and good biocompatibility. Because of its durability and good biocompatibility, the new oxygenator was determined to be suitable for prolonged extra corporeal circulation.