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Biomedical subjects

T Kohno

Publications and source records attributed to T Kohno.

At least 181 records · Page 10Linked to original sources
PubMed1998

Germline mutations of the PTEN/MMAC1 gene in Japanese patients with Cowden disease.

Cowden disease (CD) is an autosomal dominant disorder which confers a high susceptibility to diverse benign and malignant tumors. The PTEN/MMAC1 gene was identified as being responsible for CD, since its germline mutations have been identified in affected individuals in the United States and Europe. We identified three novel germline PTEN mutations, a 2-bp deletion, a 1-bp insertion and a missense mutation, in three of five Japanese patients with CD. The missense mutation resided outside of the region encoding a putative phosphatase domain of the predicted PTEN protein, where previously reported missense mutations in CD patients have been clustered. The present result suggests that a wide range of germline PTEN mutations may play a role in the pathogenesis of CD.

Female↗
PubMed1998

Pharmacokinetics, immunogenicity, and efficacy of dimeric TNFR binding proteins in healthy and bacteremic baboon.

Immunogenicity, pharmacokinetics, and therapeutic efficacy of three novel dimeric soluble tumor necrosis factor (TNF)-receptor I constructs [TNF-binding protein (bp)] were evaluated in 28 baboons, 12 of which were healthy and 16 were challenged with a lethal Escherichia coli bacteremia. The three constructs differed only in the number of extracellular domains of the TNF receptor I and were dimerized with polyethylene glycol. Although all three constructs had generally similar pharmacokinetics when administered to a naive animal, they differed quantitatively in their immunogenicity. Antibodies were detected more frequently, and titers were significantly higher (P < 0.05) in both healthy and septic baboons that received the 4.0-domain TNF-bp construct, compared with animals receiving the 2.6-domain construct. When the TNF-bp constructs were administered a second time (21 days later), the half-lives of the three constructs were significantly shorter in animals that had an antibody response after the first injection. In contrast, all three TNF-bp constructs were equally effective at improving outcome, blocking a systemic TNF-alpha response, and attenuating the cytokine responses when administered at a dose of 1.0 mg/kg body wt 1 h before a lethal E. coli infusion. The findings suggest that immunogenicity of TNF-bp constructs can be altered by changing the number of functional domains, without affecting their capacity to neutralize TNF-alpha and to abrogate TNF-mediated pathology.

Animals↗
PubMed1998

[Video-assisted mammary harvest technique with harmonic scalpel].

We have developed a video-assisted mammary harvest technique using the Harmonic Scalpel. The clinical method and results are reported here. Since Nov. 1995, 70 left and 5 right internal mammary arteries (L/RIMAs) were taken down thoracoscopically and utilized for minimally invasive coronary artery bypass grafting. Each of the IMAs was harvested up to the upper margin of the first rib or higher and down to the bifurcation. Coagulation and cutting of the branches were achieved with excellent hemostasis using only the Harmonic Scalpel with a hook dissector. A CO2 insufflation technique with 8-10 mmHg of intrathoracic pressure safely improved visualization of the IMA in each case. The mean operative time was 65 minutes (range 45-95) for the left and 35 minutes (range 25-45) for the right. All the pedicled IMAs but one which was lost due to intimal dissection had satisfactory free flows. Video-assisted mammary harvest can be accomplished with insufflation technique and facilitated by using the Harmonic Scalpel with a hook dissector.

Coronary Artery Bypass↗
PubMed1998

[A surgical case of cervical canal stenosis caused by atlas hypoplasia in an elderly patient].

We report an 81-year-old man with hypoplastic atlas resulting in a severe stiff feeling in the bilateral shoulders, spastic tetraparesis, and hypesthesia below the C2 segment level of the spinal cord. These symptoms are compatible with compression of the high cervical cord. Neuroimaging studies revealed a narrowing of the spinal cord by compression of the hypoplastic atlas. Laminoplasty of the atlas was performed under general anesthesia, and the patient's symptoms were resolved. Operated cases of older patient's with atlas hypoplasia have been rarely reported. Laminoplasty of the atlas is a safe and useful procedure for high cervical compression due to hypoplastic atlas.

Aged↗
PubMed1998

[Thoracoscopic decortication for chronic empyema thoracis: report of a case].

Thoracoscopic surgery for empyema thoracis treatment is still uncommon in Japan. We report a case of chronic empyema thoracis which was successfully treated with decortication through thoracoscopy. A 63-year-old man presented with respiratory distress, appetite loss and hoarseness. He had been suffering from diabetes mellitus for 13 months. His chest X-ray film revealed that he had suffered from the left chronic empyema. As the decortication procedure was feasible at the preliminary exploration, it was then performed through the thoracoscopy. The lung re-expanded well after the pleural peel was removed. His chest drainage tube was drawn out on 19th postoperative day.

Chronic Disease↗
PubMed1998

[Late results of acute aortic dissection: analysis of the patients longer than five years after the operation].

Between 1985 and 1992, 28 patients of acute type A aortic dissection were operated on at our department. Our surgical strategy for this disease is "limited aortic resection", that is to avoid replacement of the entire arch except for the patients with arch tear that cannot be resected without total arch replacement. There were one operative mortality due to post transfusion GVHD, and ten late mortality (rupture of the residual dissecting aneurysm 3; complication of the late reoperation 3; cerebrovascular disease 2; pulmonary infection 2). Actuarial survival rate of all cases is 92.9%, 62.9%, and 58.4% at 1, 5, and 10 years, respectively. Comparing the patients whose primary tear was resected or not resected, there was no difference in the rate of residual dissection (12/16, 75% vs 5/6, 83.3%; primary tear resected vs not resected), the rate of late reoperation (3/16, 18.8% vs 1/6, 16.7%), nor actuarial survival rate (90.5% vs 100%, 66.7% vs %, 53.6% vs 71.4%, at 1, 5, 10 years, respectively). There were three cases with Marfan's syndrome, and all three cases died of the rupture of the residual dissection. We will follow the policy of the "limited aortic resection" unless the operative mortality of the entire arch replacement is proved as good as that of the ascending or hemiarch replacement. Because of the poor late results of the patients with Marfan's syndrome, entire arch replacement at the initial surgery and aggressive reoperation for the residual dissection is necessary.

Acute Disease↗
PubMed1998

[Snare injury in coronary artery bypass grafting on the beating heart: report of 2 cases].

From June to November 1997, 8 patients underwent coronary artery bypass grafting on the beating heart. The first 2 patients had snare injury. Postoperative angiography showed coronary stenosis distal to the LITA-LAD anastomosis in the first case and a pseudo-aneurysm at the septal branch of the LAD in the second case, most likely due to snaring maneuver with 3-0 prolene or 3-0 GORE-TEX suture with a sharp needle. Since then, we have been satisfactorily utilizing the RETRACT-O-TAPE (a silicone tape with blunt needle, QUEST Medical, Inc.) for coronary occlusion to avoid injury to the native vessels and their branches.

Angina Pectoris↗
PubMed1997

Determination of tumor necrosis factor binding protein disulfide structure: deviation of the fourth domain structure from the TNFR/NGFR family cysteine-rich region signature.

Tumor necrosis factor binding protein is a soluble molecule derived from the extracellular domain of the 55 kDa human tumor necrosis factor receptor, which can block the biological function of tumor necrosis factor by binding to the growth factor. This cysteine-rich molecule is subdivided into four domains, each containing six conserved cysteines that form three intrachain disulfide linkages known as the tumor necrosis factor receptor/nerve growth factor receptor family cysteine-rich region signature structure. In an effort to elucidate the molecular integrity of the molecule, we performed detailed analysis and searched for strategies to elucidate the complete disulfide structure of the E. coli-derived tumor necrosis factor binding protein and to determine the disulfide arrangement in the fourth domain of Chinese hamster ovary cell-derived molecule. The methods employed included various proteolytic digestions, peptide mapping, partial reduction, and assignment of disulfides by N-terminal sequencing and matrix-assisted laser desorption ionization mass spectrometry with post-source decay. The first three domains of the molecule were confirmed to have disulfide structures identical to the cysteine-rich region signature structure found in the above-mentioned receptor superfamily. The fourth domain has a different structure from the first three domains where the last four cysteines form two disulfide bonds in opposite positions.

Amino Acid Sequence↗
PubMed1997

The stiffness of lymph nodes containing lung carcinoma metastases: a new diagnostic parameter measured by a tactile sensor.

BACKGROUND: It is believed that the stiffness or hardness of a lymph node containing a metastasis differs from that of lymph node without a metastasis because of the difference in tissue density, which is derived from the lymph node's histopathologic features. Prior to this study, however, there had been no attempts to quantify the hardness or stiffness of lymph nodes. The authors developed a new tactile sensor and system for measuring the stiffness (g/cm) of lymph nodes accurately, and they studied its utility as a tool for diagnosing lymph node metastases. METHODS: Clinical specimens were obtained from 14 patients who underwent lobectomy or pneumonectomy with hilar and mediastinal lymph node dissection for nonsmall cell lung carcinoma at the University of Tokyo between January and July 1996. With the tactile sensor developed by the authors, 212 resected lymph nodes were measured for their stiffness. RESULTS: Among these 212 resected lymph nodes, 57 were diagnosed as containing metastases (38 from adenocarcinomas and 19 from squamous cell carcinomas). The mean stiffness of the lymph nodes that contained metastases was 3.35 +/- 1.57 g/cm, and that of lymph nodes without metastases was 1.23 +/- 0.50 g/cm (P < 0.001). Receiver operating characteristic analysis revealed that the area under the curve was 0.93, indicating excellent accuracy of the method. When the cutoff was 1.5 g/cm, the sensitivity was 91.2% and the specificity was 78.1% for detection of lymph node metastases. CONCLUSIONS: Measurement of the stiffness of resected lymph nodes was confirmed as an accurate approach to diagnosing lymph node metastases without knowledge of other factors, such as lymph node size or color.

Aged↗
PubMed1997

Identification and characterization of a pro-tumor necrosis factor-alpha-processing enzyme from the ADAM family of zinc metalloproteases.

Tumor necrosis factor-alpha (TNF) is initially expressed as a 26-kDa membrane-bound precusor protein (pro-TNF) that is shed proteolytically from the cell surface, releasing soluble 17-kDa TNF. We have identified human ADAM 10 (HuAD10) from THP-1 membrane extracts as a metalloprotease that specifically clips a peptide substrate spanning the authentic cleavage site between Ala76 and Val77 in pro-TNF. To confirm that HuAD10 has TNF processing activity, we cloned, expressed, and purified an active, truncated form of HuAD10. Characterization of recombinant HuAD10 (rHuAD10) suggests that this enzyme has many of the properties (i.e. substrate specificity, metalloprotease activity, cellular location) expected for a physiologically relevant TNF-processing enzyme.

ADAM Proteins↗
PubMed1997

Binding of chimeric analogs of omega-conotoxin MVIIA and MVIIC to the N- and P/Q-type calcium channels.

Despite their high sequence homology, the peptide neurotoxins omega-conotoxin MVIIA and MVIIC selectively block N- and P/Q-type calcium channels, respectively. To study the recognition mechanism of calcium channel subtypes, two chimeric analogs of omega-conotoxin MVIIA and MVIIC were synthesized by exchanging their N- and C-terminal halves. Binding assay for both N- and P/Q-type calcium channels showed that amino acid residues restricted to the N-terminal half are important for the recognition of N-type channels, whereas essential residues for P/Q-type channel recognition are widely spread over the whole omega-conotoxin molecule.

Amino Acid Sequence↗
PubMed1997

Real-time monitoring of the effects of normothermia and hypothermia on extracellular glutamate re-uptake in the rat following global brain ischemia.

Brain hypothermia during ischemia may have a neuroprotective effect on pathological and functional outcomes in vivo. Although a microdialysis study demonstrated that hypothermia decreases glutamate release into the extracellular space, the issue of whether this suppression of the glutamate elevation normally accompanying ischemia is attributable to inhibition of intra-ischemic release or acceleration of post-ischemic re-uptake was not addressed. Recently, we established a real-time method for monitoring glutamate levels in extracellular space, utilizing a dialysis electrode. This method allows detailed analysis of the in vivo dynamics of biphasic glutamate elevation in the extracellular space during the intra-ischemic period and post-ischemic re-uptake. The present results show that post-ischemic hypothermia has little effect on the initial glutamate release, but remarkably enhances post-ischemic glutamate re-uptake.

Animals↗
PubMed1997

Cloning of a human homolog of the yeast OGG1 gene that is involved in the repair of oxidative DNA damage.

We report the cloning of a human homolog of the yeast OGGC1 gene, which encodes a DNA glycosylase that excises an oxidatively damaged form of guanine, 8-hydroxyguanine (also known as 7,8-dihydro-8-oxoguanine). Since the deduced amino acid sequence (68 amino acids) of a human expressed sequence tag, N55394, matched a short stretch of yeast OGG1 protein with greater than 40% amino acid identity, a full length cDNA clone was isolated from a HeLa cell cDNA library with the N55394 clone as a probe. The cDNA clone encodes a predicted protein of 345 amino acids which is homologous to yeast OGG1 protein throughout the entire polypeptide sequence and shares 38% amino acid identity with yeast OGG1 protein. Moreover, we found that both a human homolog and yeast OGG1 protein possess two distinct DNA binding motifs, a helix-hairpin-helix (HhH) motif and a C2H2 zinc finger like motif, and a domain homologous to human and E. coli MutY proteins. Expression of a human homolog suppressed spontaneous mutagenesis of an E. coli (mutM mutY) mutant as in the case of yeast OGG1 protein. The gene was ubiquitously expressed in a variety of human organs and mapped to chromosome 3p26.2. These results strongly suggest that the gene isolated here is a human counterpart of the yeast OGGI gene and is involved in the repair of oxidative DNA damage in human cells.

Amino Acid Sequence↗
PubMed1997

The cloning and characterization of a murine secretory leukocyte protease inhibitor cDNA.

Human secretory leukocyte protease inhibitor (hSLPI) is produced by epithelial cells at mucosal surfaces, where it regulates both the neutrophil-mediated inflammation that characterizes inflammatory diseases, and pathogens themselves via both antiprotease and "defensin-like" activities. Additionally, hSLPI may regulate other processes such as cutaneous desquamation and placental invasiveness. To better understand the primary physiologic roles of SLPI, it will be important to establish a genetically tractable animal model, the most attractive candidate being the mouse. In this report, the cloning and characterization of murine (m) SLPI is described. mSLPI is encoded by a single copy gene, and appears structurally highly similar to hSLPI. At the same time, significant differences between mSLPI and hSLPI are presented, notably a difference in expression pattern, and a structural difference in the protease binding site that correlates with a difference in the spectrum of protease inhibiton. Such species-specific evolution of this protease inhibitor is notable given that species-specific structure-function differences have previously been reported for the alpha-1 antitrypsin family.

Amino Acid Sequence↗
PubMed1997

Deletion map of chromosome 9 and p16 (CDKN2A) gene alterations in neuroblastoma.

We reported previously that loss of heterozygosity (LOH) on chromosomes 2q, 9p and 18q frequently occurs in neuroblastoma and that patients with 9p LOH in the tumors showed statistically significant association with an advanced stage of the disease and poor prognosis. To determine the role of chromosome 9 loss in neuroblastoma, we performed deletion mapping of chromosome 9 in 80 cases of neuroblastoma using 11 polymorphic microsatellite markers and a restriction fragment length porymorphism marker. LOH at one or more loci on chromosome 9 was detected in 33 of 80 cases (41%). Chromosome 9p was lost in 24 of 80 cases (32%), whereas chromosome 9q was lost in 18 of 80 cases (23%). There were two commonly deleted regions mapped to 9p21 between the D9S171 marker and the IFNB1 marker and 9q34-qter distal to the D9S176 marker. In addition, patients with LOH at 9p21 but not at 9q34-qter in the tumors showed statistically significant association with poor prognosis (P = 0.023). Because the commonly deleted regions at 9p21 includes the p16 (CDKN2A) gene, the status of the p16 gene was further examined in 80 fresh tumors and 19 cell lines of neuroblastoma. A missense mutation was detected at codon 52 in a fresh tumor. The p16 gene was not expressed in 13 of 19 cell lines (72%), and 5 of the 13 cell lines displayed methylation of the CpG island surrounding the first exon of the p16 gene. These results suggest that the p16 gene is a candidate tumor suppressor gene for neuroblastoma, and its inactivation may contribute to the progression of neuroblastoma.

Carrier Proteins↗
PubMed1997

Behçet's disease associated with myelodysplastic syndromes. A case report and a review of the literature.

BACKGROUND: Behçet's disease has rarely been reported in association with myelodysplastic syndromes (MDS). Increased production of reactive oxygen species (ROS) by neutrophils has a primary role in the pathogenesis of Behçet's disease. However, decreased production of ROS by neutrophils has frequently been reported in patients with MDS. The current study was undertaken to determine the role of ROS production in a patient with Behçet's disease and MDS. METHODS: A patient with MDS with trisomy 8 who developed Behçet's disease is described and a review of the literature of patients with Behçet's disease in MDS is presented. The production of ROS by neutrophils was investigated by luminol-enhanced chemiluminescence (CL) assay. RESULTS: Based on a review of the literature, 10 cases of Behçet's disease associated with MDS have been reported to date. Nine patients had undergone cytogenetic analysis of bone marrow cells, 7 of whom (78%) had trisomy 8. Neutrophils taken from the authors' patient during the active phase of Behçet's disease demonstrated an increased CL response. Moreover, serum from this patient increased the CL emission of neutrophils from healthy volunteers. CONCLUSIONS: These data suggest that trisomy 8 predisposes to Behçet's disease in patients with MDS. Furthermore, an increased ROS production by neutrophils may be associated with the diverse clinical findings in this disease. In this study, neutrophils were activated directly by serum factors.

Adult↗
PubMed1997

Plasma level monitoring of nasal salmon calcitonin in the rat by a heterogeneous two-site enzyme immunoassay.

The experimental and clinical effectiveness of nasal salmon calcitonin (SCT) for treatment of osteoporosis in humans has been well established, but none is known yet about the pharmacokinetic property in relation to therapeutic efficacy, especially when used in a therapeutic dose range. This preclinical study was designed to evaluate such a property, first of all in rats, using a novel heterogeneous two-site enzyme immunoassay that has allowed us to evaluate the pharmacokinetic property of parenteral SCT in rats due to the high sensitivity (the detection limit = 2 pg of SCT/ml of plasma). It was found that as early as 10 min after the nasal dosing of 1.25, 5, or 20 U/rat, the SCT immunoactivity became detectable in plasma and thereafter it waned rapidly with time. Hypocalcemia developed in a dose-dependent manner, but with a delay of approximately 20 min from the peak of the immunoactivity and lasted hours. The pharmacokinetic parameters measured for the doses (1.25, 5, and 20 U/rat) were as follows; the AUCs (pg.hr/ml) = 20.8, 89.0, and 189, and the MRTs (min) = 52, 54, and 45, respectively. The results appear to suggest: (1) the unexpected quick transfer of nasal SCT into and from the circulation, (2) a delayed onset of hypocalcemia and possibly its anti-osteopenic action, both of which may last longer, (3) that keeping the plasma SCT above the in vitro anti-osteoclastic level (approximately 1 pM) only for a few hours per 2 days would be enough for inducing the distinct anti-osteopenic effect in rats, and (4) the feasibility of designing the clinical study as to the pharmacokinetics and pharmacodynamics of nasal SCT on humans.

Administration, Intranasal↗