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Biomedical subjects

K Okano

Publications and source records attributed to K Okano.

At least 55 records · Page 3Linked to original sources
PubMed2000

Practical asymmetric synthesis of (S)-MA20565, a wide-spectrum agricultural fungicide.

A practical asymmetric synthesis of a wide-spectrum agricultural fungicide, (S)-MA20565 (1), is described. The convergent synthesis was achieved starting from commercially available 3-(trifluoromethyl)aniline (7) in 44% overall yield through five steps and 2-bromobenzaldehyde (9) in 48% overall yield through four steps, respectively. (S)-O-[1-(3-Trifluoromethylphenyl)ethyl]hydroxylamine (2), a key intermediate of 1, was prepared via ruthenium(II)-catalyzed asymmetric transfer hydrogenation of 1-(3-trifluoromethylphenyl)ethanone (6) followed by chlorination using methanesulfonyl chloride and oxyamination using potassium acetohydroxamate with high level of stereocontrol.

Acetamides↗
PubMed2000

Calcaneus bone mineral density is lower among men and women with lower physical performance.

Fracture risk is influenced by both bone strength and by falls. Measures of physical function and performance are predictors of falls. However, the interrelationships among bone mineral density (BMD), regular physical activity, and measures of physical performance are not well known. We studied 447 community-dwelling Japanese people aged 40 years and over (96 men and 351 women) to examine the association of calcaneus BMD with measures of physical performance (grip strength, walking speed, chair stand, and functional reach) and regular physical activity. Calcaneus BMD decreased with age by approximately 25% in men and 42% in women. Measures of physical performance decreased with age by approximately 30% in both genders, however, performance on the chair stand test declined by approximately 60%. There were only minimal differences in performance measures and calcaneus BMD between people with and those without regular physical activity in both genders, and most differences were not significant. However, there were significant BMD increases of 3-6% per standard deviation (SD) increase in all performance measures for women and a 7% increase in BMD per SD increase in grip strength for men, after adjusting for age. These associations remained after additional adjustment for body mass index and regular physical activity. These findings suggest that bone density and physical function decline markedly in both men and women with age, and that low BMD and poor function tend to occur together, which would increase fracture risk more than either risk factor alone.

Absorptiometry, Photon↗
PubMed2000

Extent of pathologic invasion of the inferior vena cava in resected liver cancer compared with possible caval invasion diagnosed by preoperative images.

The extent of cancerous invasion of the inferior vena cava (IVC) determined from resected liver cancer was examined pathologically. Ten patients presenting with liver cancer (metastatic liver cancer, five patients; hepatocellular carcinoma, three; and cholangiocellular carcinoma, two) were diagnosed with positive IVC invasion using preoperative imaging techniques of extracorporeal ultrasonography, computed tomography, magnetic resonance imaging, and vena cavography. The diagnostic criterion for positive IVC invasion by preoperative imaging was longitudinal IVC compression measuring over 50 mm, or transverse IVC compression extending to more than half the circumference of the IVC, or the presence of lesions protruding into the IVC lumen, or the presence of developed collateral veins. All patients underwent combined resection of the IVC. However, pathology results revealed that four of the ten patients had no cancerous invasion of the IVC, and that the extent of invasion along both the longitudinal and transverse axes of the IVC was much smaller than the compression shown by imaging results. We believe that detailed preoperative assessment, using a more precise imaging technique, as well as further intraoperative examination, is required to predict the full pathological extent of cancerous invasion of the IVC.

Aged↗
PubMed2000

Structural and functional analysis of the Xestia c-nigrum granulovirus matrix metalloproteinase.

Sequence analysis of the Xestia c-nigrum granulovirus (XcGV) genome identified an open reading frame encoding a 469-amino-acid (54-kDa) protein with over 30% amino acid sequence identity to a region of about 150 amino acids that includes the catalytic domains of human stromelysin 1 (Str1)/matrix metalloproteinase 3 (MMP-3) (EC 3.4.24.17) and sea urchin hatching enzyme (HE). Stromelysin homologs have not been reported from baculoviruses or other viruses. Unlike human Str1 and sea urchin HE, the putative XcGV-MMP does not have a signal peptide and lacks the peptide motif involved in the cysteine switch that maintains other MMPs in an inactive form. The putative XcGV-MMP, however, possesses a conserved zinc-binding motif in its putative catalytic domain. The XcGV-MMP homolog was cloned, and a recombinant Bombyx mori nucleopolyhedrovirus (BmNPV) that expresses XcGV-MMP under the polyhedrin promoter was constructed. A distinct pattern of melanization was observed in B. mori larvae infected with MMP-expressing BmNPV. Fat body extracts from larvae overexpressing the 54-kDa recombinant MMP digested dye-impregnated collagen (Azocoll). The enzymatic activity was inhibited by two metalloproteinase inhibitors, EDTA and 1,10-phenanthroline. These results suggest that the XcGV MMP-3 gene homolog encodes a functional metalloproteinase.

Amino Acid Sequence↗
PubMed2000

Focal extraction of surface-bound DNA from a microchip using photo-thermal denaturation.

High-throughput, selective extraction of a particular DNA fragment from a mixture of DNA before PCR amplification is becoming increasingly important in the DNA analysis field. Although the latest microchip technology has enabled real-time DNA expression analysis using hybridization between surface-bound probe DNA and sample DNA, the potential of this technology in purification of a small amount of DNA has not been demonstrated. We report here a method for area-selective release and collection of specific DNA, in which an IR laser beam is focused onto surface-bound sample DNA at the target-spotted area to denature hybridized DNA. First, sample DNA labeled with a fluorescent dye was hybridized to a probe DNA immobilized on a chromium-coated chip. A 1053-nm IR laser beam with an intensity of 10-100 mW was then focused on the target area with a spatial resolution of 10 microns, causing the release of the fluorophore-labeled sample DNA as a result of photo-thermal denaturation. Confirmation of the amount of eluted DNA by PCR amplification after collection indicated that more than 10(-20) mol DNA/micron 2 area was eluted from the microchip, representing more than 70% of the chip-bound sample DNA. These results indicate that this method can be applied to the highly sensitive purification of DNA in microchip technology.

Chromium↗
PubMed2000

[Outcomes of home anti-cancer chemotherapy--estimation of hepatic arterial infusion chemotherapy for patients with multiple liver metastases].

A total of 18 patients (13: colon cancer, 5: gastric cancer) with multiple liver metastases (H3) underwent hepatic arterial infusion chemotherapy (HAI) using an implanted arterial port with portable syringe pumps in our outpatient clinic. Clinical perspective: overall response rate was 22.2% (CR: 1 case, PR: 3 cases (1 case: hepatectomy after HAI), NC: 12 cases, PD: 2 cases), however, 7 of 12 cases of NC were long NC (more than 6 months). No major complications with HAI were experienced. Patient Perspective: After HAI in our outpatient clinic, the 50% survival was 341 days, 50% hospital free days were 319 days and home stay rate was 92.9%. Societal Perspective: cost and hospital stay days were significantly reduced. Home anti-cancer chemotherapy using HAI for gastrointestinal cancer patients with multiple liver metastases was safe and efficient from the viewpoint of medical outcomes.

Aged↗
PubMed1999

Sequence analysis of the Xestia c-nigrum granulovirus genome.

The nucleotide sequence of the Xestia c-nigrum granulovirus (XcGV) genome was determined and found to comprise 178,733 bases with a G+C content of 40.7%. It contained 181 putative genes of 150 nucleotides or greater that showed minimal overlap. Eighty-four of these putative genes, which collectively accounted for 43% of the genome, are homologs of genes previously identified in the Autographa californica multinucleocapsid nucleopolyhedrovirus (AcMNPV) genome. These homologs showed on average 33% amino acid sequence identity to those from AcMNPV. Several genes reported to have major roles in AcMNPV biology including ie-2, gp64, and egt were not found in the XcGV genome. However, open reading frames with homology to DNA ligase, two DNA helicases (one similar to a yeast mitochondrial helicase and the other to a putative AcMNPV helicase), and four enhancins (virus enhancing factors) were found. In addition, several ORFs are repeated; there are 7 genes related to AcMNPV orf2, 4 genes related to AcMNPV orf145/150, and a number of repeated genes unique to XcGV. Eight major repeated sequences (XcGV hrs) that are similar to sequences found in the Trichoplusia ni GV genome (TnGV) were found.

Amino Acid Sequence↗
PubMed1999

Spermiogenesis is impaired in mice bearing a targeted mutation in the protein phosphatase 1cgamma gene.

Type 1 protein phosphatases (PP1) are involved in diverse cellular activities, ranging from glycogen metabolism to chromatin structure modification, mitosis, and meiosis. The holoenzymes are composed of two or more subunits, including a catalytic subunit (PP1c) and one or more regulatory subunits. Many eukaryotes possess several catalytic subunit genes which encode highly conserved isoforms. In rodents, one of these isoforms, PP1cgamma2, appears to be expressed predominantly in testes. Whether PP1cgamma2 performs a testis-specific function is unclear. To address this and other questions, the PP1cgamma gene was disrupted by targeted insertion in murine embryonic stem cells. Mice derived from these cells were viable, and homozygous females were fertile. However, males homozygous for the targeted insertion were infertile. Histological examination revealed severe impairment of spermiogenesis beginning at the round spermatid stage. In addition, defects in meiosis were inferred from the presence of polyploid spermatids. Immunohistochemistry revealed the presence of PP1calpha protein on condensing spermatids in both wild-type and mutant testes, suggesting that this closely related isoform is unable to compensate for the loss of PP1cgamma. These defects are discussed in the light of known functions of protein phosphatase 1.

Animals↗
PubMed1999

Prospective study of interferon therapy for compensated cirrhotic patients with chronic hepatitis C by monitoring serum hepatitis C RNA.

Because interferon therapy exhibits low efficacy for cirrhotic patients infected with hepatitis C virus, this prospective study was conducted to determine effective interferon regimens tailored to treatment response by monitoring HCV RNA status. A total of 157 cirrhotic patients were enrolled to receive 9 million units (MU) of interferon three times a week. The HCV RNA values were drawn 8 weeks apart and the patients were randomized to a further 16 or 32 weeks of treatment after two sequential findings of negativity for HCV RNA. A total of 73 out of 157 patients (46%) proceeded to randomization to different durations of treatment, 37 short-course and 36 long-course (duration: 38 +/- 8 and 49 +/- 13 weeks; total amount of interferon: 940 +/- 240 and 1130 +/- 390 MU, respectively). The remaining 84 patients without two sequential negative serum HCV RNA determinations received 44.8 +/- 27.4 weeks of interferon (IFN) therapy with total amount of 993 +/- 633 MU. Of these 157 patients, sustained virological and biochemical response was shown in 32 (20%) and 37 patients (24%), respectively. Sustained virological and biochemical response rate in the randomized patients was significantly higher than in nonrandomized patients (41% vs. 2%, and 38% vs. 11%; each P <.01). Of the 73 randomized patients, the rate of sustained virological response in patients with long-course treatment (50%) was significantly higher than that of patients with short-course treatment (32%) (P =.026: log-rank test), and in patients with early disappearance of HCV RNA especially within 8 weeks, in patients with low virus load (</=10(6.3) copies/mL) and with HCV 2a. Multivariate analysis revealed that HCV RNA level and subtypes were the most important factors contributing to sustained virological response. Interferon is effective even in cirrhotic patients with low viral load and HCV 2a, but requires a longer course of administration.

Adult↗
PubMed1999

Clinicopathologic and immunohistochemical study of early colorectal cancer with liver metastases.

Seven (3.3%) of 213 patients who underwent surgery for early colorectal cancer (invasion limited to no deeper than the submucosa) at the National Cancer Center Hospital, Tokyo, between 1986 and 1995 had synchronous (2 patients) or metachronous (5 patients) liver metastases. The average period from surgical resection of the primary colorectal cancer to the diagnosis of liver metastases was 25 months (range, 0-52 months). The clinicopathologic and immunohistochemical features of the primary lesions in these patients were compared with these features in the lesions in consecutive patients with early colorectal cancer who had no evidence of liver metastases within at least 5 years after colorectal resection. Venous invasion was more frequent in the primary lesions with liver metastases than in those without liver metastases (57% vs 0%; P = 0.0035). Expression of p53 and CD44v9 was more frequent in the primary lesions with liver metastases (71% and 100%) than in those without metastases (56% and 72%). In contrast, MUC2 expression was more frequent in the primary lesions without liver metastases (72%) than in those with metastases (43%). Venous invasion is considered to be closely related to liver metastasis, and the immunohistochemical expression of p53 and CD44v9 provides useful information for identifying those patients with early colorectal cancer who have a high risk of developing liver metastases.

Adenocarcinoma↗
PubMed1999

Presence of alpha-fetoprotein mRNA in blood correlates with outcome in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Since hematogenous spread of tumor cells may adversely affect the prognosis of patients with hepatocellular carcinoma, we prospectively analyzed whether the presence of alpha-fetoprotein (AFP) messenger RNA (mRNA) in blood, used as a marker of circulating hepatocellular carcinoma cells, correlates with outcome. METHODS: Eighty-eight patients were enrolled between December 1993 and August 1995, and 81 were followed until the end of 1997. All patients were treated with percutaneous ethanol injection therapy and/or transarterial embolization during follow-up. The status of AFP mRNA in blood was serially determined. Cumulative metastasis-free survival and overall survival were analyzed in relation to AFP mRNA and other clinical and laboratory variables. RESULTS: Among 81 patients followed, 54 were positive for AFP mRNA at entry and 27 were negative. Extrahepatic metastasis developed more frequently among the AFP mRNA-positive patients (13 of 54) than among the AFP mRNA-negative patients (2 of 27) (p=0.0296). After treatment, AFP mRNA became negative in 24 of 54 patients (44%). Cumulative metastasis-free survival and overall survival were significantly better in the 24 patients whose AFP mRNA became negative after treatment than in the 30 patients with persistently positive AFP mRNA (p= 0.0001 and p<0.0001, respectively). CONCLUSIONS: The presence or absence of AFP mRNA in blood is a predictor of outcome in patients with hepatocellular carcinoma.

Administration, Cutaneous↗
PubMed1999

Involvement of calcineurin in the signal transduction of PBAN in the silkworm, Bombyx mori (Lepidoptera).

In several moth species sex pheromone production in the pheromone gland is regulated by a neurohormone, pheromone biosynthesis activating neuropeptide (PBAN). In Bombyx mori it is suggested that PBAN, after binding to the cell-surface receptor, primarily activates a plasma membrane receptor-activated Ca2+ channel to increase cytosolic levels of Ca2+, and Ca2+/calmodulin complex directly or indirectly activates a phosphoprotein phosphatase, which in turn elicits activation of acyl CoA reductase (the key enzyme under PBAN control) through dephosphorylation, resulting in pheromone (bombykol) production. The effect of cyclosporin A (CsA) and FK 506, specific inhibitors of calcineurin (phosphoprotein phosphatase 2B) was studied on the sex pheromone production, in B. mori. The in vitro experiments showed that both chemicals exerted a dose-dependent inhibitory action when they were co-incubated with TKYFSPRL amide (Hez-PBAN fragment peptide). Practically, no difference was detected between the two chemicals in the tested doses (0.025-1250 microM). When effects of CsA or FK 506 were studied on cell-free production of bombykol by using microsomal fraction no inhibition was detected. Since microsomal fraction contains the acyl CoA synthetase, the rate-limiting acyl CoA reductase and the precursor, bombykol is produced if supplied with CoA, ATP and NADPH. Thus, the inhibitory action of CsA and FK506 under in vitro conditions should occur before the step of acyl group reduction and the effect is likely to be attributable to the inhibition of calcineurin in the signal transduction cascade mechanism of PBAN, in B. mori. The existence of calcineurin in the pheromone gland by using Western blot analysis is also demonstrated.

Animals↗
PubMed1999

How soon can a virological sustained response be determined after withdrawal of interferon therapy in chronic hepatitis C? Tokyo-Chiba Hepatitis Research Group.

Hepatitis C virus (HCV)-RNA status and alanine aminotransferase (ALT) levels determined shortly after interferon (IFN) therapy in patients with chronic hepatitis C do not predict long-term response. To determine the virological sustained response after the completion of IFN therapy, HCV-RNA was measured at the end of treatment and at 3-4 months and 12 months after the completion of therapy in 537 patients with chronic hepatitis C. In 347 patients, HCV-RNA was not detected by polymerase chain reaction (PCR) at the completion of therapy and 175 of these patients (50%) were still PCR negative 12 months later. In contrast, of the 180 patients who were HCV-RNA negative at 3-4 months after completion of therapy, 99% remained negative at 12 months. Normal ALT levels were found in 80, 93 and 95% of patients who were negative for HCV-RNA either at the end of treatment or at 3-4 months and 12 months after the completion of therapy, respectively. Of patients who were HCV-RNA positive, 30, 15 and 20% were found to have normal ALT levels at the same respective time points. To determine a sustained virological response shortly after the completion of therapy, serum HCV-RNA was serially examined in 66 patients negative for HCV-RNA at the end of therapy. Of 31 patients who relapsed, HCV-RNA reappeared in 33, 80, 97 and 100% of patients by 1, 2, 4 and 8 weeks after the completion of therapy. In conclusion, a sustained virological response could be determined with 97 and 99% certainty at 4 weeks and at 3-4 months after the completion of therapy, respectively.

Adult↗
PubMed1999

Spinal epidural abscess associated with epidural catheterization: report of a case and a review of the literature.

We describe a 53-year-old man who developed a catheter-related epidural abscess 8 days after left upper lobectomy for lung cancer. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in a culture of the epidural pus. Magnetic resonance imaging was essential for the diagnosis of epidural abscess and for determining the extent of spread. The patient was treated by laminectomy and administration of appropriate antibiotics, with almost complete recovery, except for urinary retention. A literature search yielded 29 additional cases of catheter-related epidural abscess. The median duration of catheterization was 4 days and the median time to onset of the clinical symptoms after catheter placement was 8 days. Eleven of the 30 patients had some underlying disorders, including malignancy or herpes zoster, or were receiving steroids. Nine of the 10 patients with thoracic epidural abscess had persistent neurological deficits, whereas 12 of the 15 patients with lumbar epidural abscess showed a full recovery after treatment. Surgical decompression was not required in six patients without significant neurological deficits, who recovered following antibiotic treatment (four patients) or percutaneous drainage (two patients). Thoracic catheters are associated with a disproportionately high incidence of epidural abscess and persistent neurological sequelae following treatment.

Abscess↗
PubMed1999

Bovine milk antibodies against cell surface protein antigen PAc-glucosyltransferase fusion protein suppress cell adhesion and alter glucan synthesis of Streptococcus mutans.

Cell surface protein antigen (PAc) and glucosyltransferases (GTF) produced by Streptococcus mutans are considered major colonization factors of the organism, and the inhibition of these factors is thought to prevent dental caries. In this study, 8-mo-old pregnant Holstein cows were immunized with fusion protein PAcA-GB, a fusion of the saliva-binding alanine-rich region (PAcA) of PAc with the glucan binding (GB) domain of GTF-I, an enzyme catalyzing the synthesis of water-insoluble glucan from sucrose. High titers of immunoglobulin antibodies specific for the fusion protein were found in normal milk after reimmunization, and they persisted for approximately 3 mo. The immunoglobulin G (IgG) antibodies against PAcA-GB were purified from immunized milk. The antibodies significantly inhibited the adhesion of S. mutans cells to saliva-coated hydroxyapatite beads. IgG antibodies purified from immunized milk also inhibited total glucan synthesis by cell-associated GTF preparation and GTF-I from S. mutans. The immunized milk may be useful as a means of passive immunization for the prevention of dental caries in humans.

Animals↗