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Biomedical subjects

K Gotoh

Publications and source records attributed to K Gotoh.

At least 19 recordsLinked to original sources
PubMed2002

Electric and magnetic phenomena observed before the volcano-seismic activity in 2000 in the Izu Island Region, Japan.

Significant anomalous changes in the ultra low frequency range (approximately 0.01 Hz) were observed in both geoelectric and geomagnetic fields before the major volcano-seismic activity in the Izu Island region, Japan. The spectral intensity of the geoelectric potential difference between some electrodes on Niijima Island and the third principal component of geomagnetic field variations at an array network in Izu Peninsula started to increase from a few months before the onset of the volcano-seismic activity, culminating immediately before nearby magnitude 6 class earthquakes. Appearance of similar changes in two different measurements conducted at two far apart sites seems to provide information supporting the reality of preseismic electromagnetic signals.

Electricity↗
PubMed2001

Separation and characterization of the molecular species of thrombomodulin in the plasma of diabetic patients.

Thrombomodulin (TM) and its molecular species have been identified as markers of vascular endothelial cells (EC). In the present study, using high-performance liquid chromatography (HPLC) in 7 normal subjects, 5 chronic glomerulonephritis (GN) patients, and 25 diabetes mellitus (DM) patients, the TM molecular species separated from plasma showed seven heterogeneous fragments of 94, 74, 48, 36, 27, 14, and 12 kDa. Comparing the diabetic patients and healthy subjects, it was found that plasma TM generally, and its 74-kDa molecular species particularly, were increased in diabetic patients and the increase became more apparent as the disease progressed in severity. Comparing the patients with diabetic nephropathy and those with nephritis of the same degree of renal dysfunction, both groups had increased levels of TM, but the distribution of the molecular species differed; that is, the 74-kDa form increased in the diabetic patients and the 12-kDa species increased markedly in the nephritis patients. Glycation of the various TM molecular species increased more in the diabetic patients than in healthy subjects. There was a significantly positive correlation between the HbA(1c) and the 74-kDa TM molecular species in diabetic patients. These findings suggest that a fluctuation in the blood glucose level is significantly related to vascular EC damage in DM.

Adult↗
PubMed2001

Development of specific CXCR4 inhibitors possessing high selectivity indexes as well as complete stability in serum based on an anti-HIV peptide T140.

We previously reported a truncated polyphemusin peptide analogue, T140, which efficiently inhibits infection of target cells by T-cell line-tropic strains of HIV-1 (X4-HIV-1) through its specific binding to a chemokine receptor, CXCR4. We have found that T140 is not stable in feline serum due to the cleavage of the C-terminal Arg,(14) indispensable for anti-HIV activity. On the other hand, a C-terminally amidated analogue of T140, TZ14004, has been found to be completely stable in incubation in the serum for 2 days. The C-terminal amide is thought to be needed for stability in serum. However, TZ14004 does not have fairly strong anti-HIV activity, but has relatively strong cytotoxicity, probably due to an increase by +1 charge from total +7 charges of T140. In our previous study, the number of total +6 charges seemed to be a suitable balance between activity and cytotoxicity. In this study, we have conducted a double-L-citrulline (Cit)-scanning study on TZ14004 based on the C-terminally amidated form in due consideration of the total net charges in the whole molecule to find novel effective CXCR4 inhibitors, TN14003 ([Cit(6)]-T140 with the C-terminal amide) and TC14012 ([Cit(6), D-Cit(8)]-T140 with the C-terminal amide), which possess high selectivity indexes (SIs) and complete stability in feline serum.

Animals↗
PubMed2001

Biological and genetic characterization of a human immunodeficiency virus strain resistant to CXCR4 antagonist T134.

The chemokine receptors CXCR4 and CCR5 are considered to be potential targets for the inhibition of HIV-1 replication. We have reported that T134 and T140 inhibited X4 HIV-1 infection specifically because they acted as CXCR4 antagonists. In the present study, we have generated a T134-resistant virus (trHIV-1(NL4-3)) in a cell culture with gradually increasing concentrations of the compound. The EC(50) of T134 against trHIV-1(NL4-3) recovered after 145 passages was 15 times greater than that against wild-type HIV-1(NL4-3). This adapted virus was resistant to other CXCR4 antagonists, T140, AMD3100, and ALX40-4C, and SDF-1; from 10 to 145 times greater than that against wild-type HIV-1(NL4-3). On the other hand, T134, T140, and ALX40-4C were still active against AMD3100-resistant viruses (arHIV-1(018A)). The trHIV-1(NL4-3) contained the following mutations in the V3 loop of gp120: N269K, Q278T, R279K, A284V, F285L, V286Y, I288T, K290E, N293D, M294I, and Q296K; an insertion of T at 290; and Delta274-275 (SI). In addition, many other mutations were recognized in the V1, V2, and V4 domains. Thus, resistance to T134 may be the consequence of amino acid substitutions in the envelope glycoprotein of X4 HIV-1. The trHIV-1(NL4-3) could not utilize CCR5 as an HIV infection coreceptor, although many amino acid substitutions were recognized. The trHIV-1(NL4-3) acquired resistance to vMIP II, which could inhibit both X4 and R5 HIV-1 infection. However, neither the ligands of CCR5, RANTES, and MIP-1alpha, nor a CCR5 low molecular antagonist, TAK-779, were able to influence the infection of trHIV-1(NL4-3). Those results indicated that alternation of coreceptor usage of trHIV-1(NL4-3) was not induced.

Amino Acid Sequence↗
PubMed2001

Relationship between thallium-201 myocardial SPECT and findings of endomyocardial biopsy specimens in dilated cardiomyopathy.

The purpose of this study was to clarify which myocardial histological findings associated with dilated cardiomyopathy (DCM) are reflected in quantitative 201Tl myocardial SPECT. We obtained studied SPECT images from 21 patients with DCM 10 minutes and 2 hours after they received an injection of 111 MBq 201Tl at rest. We calculated the percent coefficient of variation of myocardial 201Tl counts [%CV(TI)], the washout rate (WR), standard deviation of WR [SD(WR)], extent score (ES) and severity score (SS). We used image analysis to measure % fibrosis, % myocytes, the ratio of fibrous tissue to myocyte tissue (F/My), myocyte size and standard deviation of myocyte size [SD(My)] in left ventricular endomyocardial biopsy specimens. The %CV(Tl) was correlated with % fibrosis and F/My. The ES and SS also correlated with F/My. The correlation between SD(WR) and SD(My) was significant. The present findings suggest that %CV(Tl), ES and SS of rest 201Tl SPECT reflect myocardial fibrosis and that the standard deviation of washout reflects the distribution of myocyte size.

Biopsy↗
PubMed2001

Increase of R5 HIV-1 infection and CCR5 expression in T cells treated with high concentrations of CXCR4 antagonists and SDF-1.

The chemokine receptors CXCR4 and CCR5 are considered to be potential targets for the inhibition of HIV-1 replication. We found that the synthetic peptides T134 and T140 (see text for full names) inhibited X4 HIV-1 infection with selectivity and low toxicity because they acted as CXCR4 antagonists. However, high concentrations of T134, T140, and ALX40-4C (see text for full name) increased the expression of CCR5 and R5 HIV-1 infection, as did stromal cell-derived factor 1 (SDF-1). In contrast to CXCR4 antagonists and SDF-1, viral monocyte inflammatory protein (vMIP) II inhibited not only anti-CXCR4 monoclonal antibody (MAb) but also inhibited anti-CCR5 MAb binding to human peripheral blood mononuclear cells, and inhibited both X4 and R5 HIV-1 strains. T134, T140, ALX40-4C, and SDF-1 increased viral transcription in the treated cells. In addition, ALX40-4C and SDF-1 also increased nuclear transcription factor (NF)-kappaB. However, the mechanisms of action of T134 and T140 are different from those of clinically used anti-HIV drugs. Thus, synergistic activities were observed in the concomitant treatment with T134 and reverse transcriptase inhibitors or protease inhibitors. Our findings, presented here, are noteworthy in regard to the potential clinical use of these agents as drugs for the treatment of AIDS.

Animals↗
PubMed2001

Synthesis and evaluation of bifunctional anti-HIV agents based on specific CXCR4 antagonists-AZT conjugation.

We have previously found that T140, a 14-amino acid residue peptide, inhibits infection of target cells by T cell-line-tropic strains of HIV-1 (X4-HIV-1) through its specific binding to a chemokine receptor, CXCR4. Here, we report synthesis and evaluation of bifunctional anti-HIV compounds, which are composed of T140 analogues and a reverse transcriptase inhibitor, 3'-azido-3'-deoxythymidine (AZT). Novel conjugated analogues have been proved to have the ability for controlled release of AZT in neutral aqueous media as well as mouse and feline sera, and high selectivity indexes (SIs, 50% cytotoxic concentration/50% effective concentration) caused by a synergistic effect of two different regenerating agents. Thus, these bifunctional compounds have several potential advantages. T140 analogues can possibly work as a carrier of AZT targeting T cells due to their specific affinity for CXCR4 on T cells. A synergistic effect by two types of regenerating agents may enable drug dosage to be reduced, and thus it may effectively suppress toxic side effects and the appearance of drug-resistant virus.

Animals↗
PubMed2001

Anti-tumor effect of gallic acid on LL-2 lung cancer cells transplanted in mice.

We previously reported that gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plant phenol, can induce apoptosis in four kinds of human lung cancer cell lines in vitro. The present study further investigated the in vivo anti-tumor effects of orally administered gallic acid. Gallic acid reduced cell viability of LL-2 mouse lung cancer cells in vitro dose dependently, with a 50% inhibitory concentration (IC50) value of around 200 microM. C57Black mice were transplanted with LL-2 cells, and administered gallic acid (1 mg/ml in drinking water, ad libitum) and/or cisplatin (4 mg/kg i.p. injection, once a week). The average weight of the transplanted tumors, obtained at 29 days after transplantation, in the mice of control, gallic acid-treated cisplatin-treated and cisplatin plus gallic acid-treated groups was 4.02, 3.65, 3.19 and 1.72 g, respectively. The average tumor weight of the mice treated with cisplatin combined with gallic acid was significantly smaller than that of the control group (p<0.05). The amount of apoptotic cells in the tumor tissues of mice treated with gallic acid and/or cisplatin was significantly higher than those of the control mice. Combination of gallic acid and cisplatin increased the tumor cell apoptosis compared with the treatment with cisplatin alone. The present findings suggest that the combination of gallic acid with an anti-cancer drug, including cisplatin, may be an effective protocol for lung cancer therapy.

Animals↗
PubMed2001

Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation.

Betulinic acid, a triterpenoid isolated from the methyl alcohol extract of the leaves of Syzigium claviflorum, was found to have a potent inhibitory activity against human immunodeficiency virus type 1 (HIV-1). Betulinic acid derivatives were synthesized to enhance the anti-HIV activity. Among the derivatives, 3-O-(3',3'-dimethylsuccinyl) betulinic acid, designated YK-FH312, showed the highest activity against HIV-induced cytopathic effects in HIV-1-infected MT-4 cells. To determine the step(s) of HIV replication affected by YK-FH312, a syncytium formation inhibition assay in MOLT-4/HIV-1(IIIB) and MOLT-4 coculture, a multinuclear-activation-of-galactosidase-indicator (MAGI) assay in MAGI-CCR5 cells, electron microscopic observation, and a time-of-addition assay were performed. In the syncytium formation inhibition assay or in the MAGI assay for de novo infection, the compound did not show inhibitory effects against HIV replication. Conversely, no virions were detected in HIV-1-infected cell cultures treated with YK-FH312 either by electron microscopic observation or by viral yield in the supernatant. In accordance with a p24 enzyme-linked immunosorbent assay of culture supernatant in the time-of-addition assay, YK-FH312 inhibited virus expression in the supernatant when it was added 18 h postinfection. However, Western blot analysis of the cells in the time-of-addition assay revealed that the production of viral proteins in the cells was not inhibited completely by YK-FH312. These results suggest that YK-FH312 might affect the step(s) of virion assembly and/or budding of virions, and this is a novel mechanism of action of an anti-HIV compound.

Anti-HIV Agents↗
PubMed2001

Effect of supplementation of dry cat food with D,L-methionine and ammonium chloride on struvite activity product and sediment in urine.

Feeding dry foods supplemented with urine acidifier (D,L-methionine (Met) or ammonium chloride) decreased urinary pH and struvite activity product in clinically normal cats. As a result, the number of struvite crystals in urine was greatly reduced. Supplementation with 3% Met but not 1% Met caused decrease in the urinary concentration of sediment, which resulted from a reduction in the HCl-soluble fraction. The concentration of HCl-insoluble sediment was not affected by supplementation with the urine acidifier.

Ammonium Chloride↗
PubMed2001

Comparison of bacteriological, genetic and pathological characters between Escherichia coli O115a,c:K(B) and Citrobacter rodentium.

Murine pathogenic Escherichia coli O115a,c:K(B) (MPEC) is the causative agent of mouse megaenteron, the pathology of which resembles that of transmissible murine colonic hyperplasia caused by Citrobacter rodentium. We compared their genetic and pathological features to reveal the relationship between these two bacteria. To evaluate the genetic distances, 16S rDNA genes were sequenced and biochemical reactions were tested. Mouse strain susceptibility tests, using CF1 MPEC-susceptible germfree mice and BALB/cA(Jic) resistant mice were performed. MPEC strains and C. rodentium showed more than 99.6% identity by comparison of 16S rDNA gene sequences. All results from biochemical reactions and the mouse strain susceptibility tests were identical. It is proposed that MPEC should be reclassified as C. rodentium.

Animals↗
PubMed2001

[Multiple cerebral tuberculomas presenting with paradoxical expansion: a case report].

A 24-year-old male presented with headache. He had been treated with antituberculous drugs for 19 months. MRI revealed 4 intracranial Gd-DTPA enhanced lesions surrounded by massive edema in the right frontal, both occipital and left basal ganglionic regions. Digital subtraction angiography showed no tumor stain. Two procedures for tumor resection were performed for the right frontal and left occipital regions, the latter of which definitively diagnosed by the polymerase chain reaction method. The tumors were well demarcated, showed a rough surface, and were elastically hard. The two residual lesions responded differently to chemotherapy. The lesion in the right occipital region decreased in size, while the other in the left basal ganglionic region continued to grow gradually 26 months after the antituberculous chemotherapy was started. According to previous reports, treatment should be continued for as long as 12-30 months in cases showing paradoxical expansion. In this case, the left basal ganglionic lesion began to decrease in size after 28 months of administration of anti-tuberculous drugs. We report successful treatment of a case of multiple tuberculomas presenting with paradoxical expansion managed by a combination of surgery and continuous chemotherapy.

Adult↗
PubMed2000

Genome-wide detection of unknown subtle mutations in bacteria by combination of MutS and RDA.

We propose a procedure for detecting unknown, subtle DNA changes throughout the entire bacterial genome by a combination of MutS and RDA. Current techniques detect subtle mutations after PCR amplification of the target regions, so the mutation detection is done between amplified PCR fragments. In this paper, genome-wide subtle mutation scanning in bacteria was performed by combining the MutS and RDA techniques. Our strategy for cloning a small mutation region is composed of two steps: an enrichment of fragments containing subtle mutations using MutS, followed by an RDA subtraction procedure for further enrichment. We successfully identified small mutations such as a four-base insertion, a two-base insertion, and transition mutations in bacteria.

Adenosine Triphosphatases↗
PubMed2000

Expression of human telomerase subunit genes in primary lung cancer and its clinical significance.

BACKGROUND: Three major components of human telomerase, RNA component (hTERC), telomerase-associated protein (TEP1), and catalytic subunit (hTERT) have been cloned recently. The aim of this study was to examine the expression of these genes and to search for clinical usefulness. METHODS: Expression of these genes was evaluated by reverse transcription-polymerase chain reaction in 92 human lung cancers and in 32 non-neoplastic lung tissues. In 15 patients, both telomerase activity by telomeric repeat amplification protocol assay and expression were evaluated. RESULTS: hTERT expression was best associated with telomerase activity with a concordance of 77%. In 92 lung cancer tissues, hTERC, TEP1, and hTERT were expressed in 100%, 93%, and 89%, respectively. Whereas most adjacent non-neoplastic lung tissues expressed hTERC and TEP1 (94% and 100%, respectively), hTERT was detected in only 1 of 32 normal lungs. However, there was no relationship between hTERT expression and clinicopathologic features. CONCLUSIONS: hTERT expression can be a surrogate for telomerase activity that may serve as a novel biomarker of lung cancer with high specificity and sensitivity.

Adenocarcinoma↗
PubMed2000

BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation.

Tyrosine phosphorylation of adaptor proteins permits the B cell antigen receptor (BCR)-associated protein tyrosine kinases to regulate downstream effector molecules. Here, we report the identification of a novel B cell adaptor for phosphoinositide 3-kinase (PI3K), termed BCAP. Tyrosine phosphorylation of BCAP is mediated by Syk and Btk, thereby providing binding site(s) for the p85 subunit of PI3K. Disruption of the BCAP gene in the DT40 B cell line inhibits BCR-mediated phosphatidylinositol 3,4,5-trisphosphate generation, leading to impaired Akt response. Moreover, recruitment of PI3K to glycolipid-enriched microdomains (GEMs) is significantly attenuated in the absence of BCAP. Hence, these data suggest that BCAP bridges BCR-associated kinases to the PI3K pathway by regulating PI3K localization.

Adaptor Proteins, Signal Transducing↗
PubMed2000

A case of eosinophilic cystitis in a 5-year-old boy.

Eosinophilic cystitis (EC) is rather an uncommon disease in childhood. A case of EC in a 5-year-old boy, in which open biopsy was needed for final diagnosis, is reported. After diagnosis, he was treated with pemirolast potassium followed-up with eosinophil cationic protein (ECP) in serum and urine. Eosinophil cationic protein is an appropriate marker of EC.

Child, Preschool↗
PubMed2000

Sulfated fibroin, a novel sulfated peptide derived from silk, inhibits human immunodeficiency virus replication in vitro.

We prepared two kinds of sulfated silk fibroins, SclFib30 and SclFib31, which contain different amounts of sulfate. These sulfated silk fibroins have anti-HIV-1 activity in vitro, apparently due to interference with the adsorption of virus particles to CD4+ cells, and completely blocked virus binding to the cells at a concentration of 100 microg/ml. Sulfated fibroins also abolished cell-to-cell infection-induced syncytium formation upon cocultivation of MOLT-4 and MOLT-4/HIV-IIIB cells, suggesting that they would interfere with gp120 and prevent the formation of gp120/CD4 complex. Silk is used in biomaterials such as surgical sutures and is believed to be a safe material for humans. In accordance with low anticoagulant activity and high anti-HIV-1 activity against both X4 HIV-1 and R5 HIV-1 strains, sulfated silk fibroins have potential as antiviral material such for a vaginal anti-HIV formulation.

Animals↗