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Biomedical subjects

H Kondo

Publications and source records attributed to H Kondo.

At least 415 records · Page 23Linked to original sources
PubMed1997

[Glutathione levels in human colon cancer cell line M7609 following culture in a low sulfur amino acid medium and its sensitivity to various anticancer drugs].

Glutathione levels in human colon cancer cell line M7609 and its sensitivity to anticancer drugs were investigated in a complete medium RPMI-1640 (medium A) and an incomplete medium (medium B), which was prepared by removing glutathione and sulfur amino acids from medium A. Four different medium conditions were prepared by combining a medium A and a medium B; a medium of 100% medium A (Control), a 50:50 mixture medium of medium A and medium B (Condition 2), a 20:80 mixture medium of medium A and medium B (Condition 3), and a 10:90 mixture medium of medium A and medium B (Condition 4). The cells were cultured in each medium for 14 days, and intracellular levels of glutathione were determined to estimate the cell sensitivity to anticancer drugs. There were no significant differences in glutathione levels among the cancer agents in condition 2, as compared to those in the control. In condition 3, the reduced glutathione levels were decreased to 23.1%, where CDDP, ADM, MMC and melphalane showed 2.5, 2.2, 1.8 and 1.5 times greater antitumor activity than in the control, respectively. In condition 4, cell proliferation was too low to collect adequate cells for glutathione determination. These results demonstrated that the decrease in cellular glutathione concentration with this method might enhance the cytotoxic effects of anticancer drugs.

Amino Acids, Sulfur↗
PubMed1997

[A new approach to assessing rheumatoid arthritis (RA) disease activity using the American College of Rheumatology core set of disease activity measures for RA trials--a multi-center study].

To characterize the American College of Rheumatology core set of disease activity measures for rheumatoid arthritis (RA) clinical trials (ACR core set measures) and the ACR definition of improvement of RA (ACR improvement definition), we studied 42 Japanese patients with active RA who were treated with DMARDs including mizoribine. Each patient's disease activity was assessed at the time of enrollment to the study and after 24 weeks using the ACR core set measures as well as the physical global assessment through the conventional measures. Twenty-five (60%) patients were discerned as showing improved by physicians through the conventional measures. This decision appeared to be based on improvement in Lansbury activity index (LAI) and C-reactive protein (CRP) value. Twelve of the 25 "improved" patients satisfied the ACR improvement definition. The 12 patients showed significant improvement in "outcome" measures including patients assessments of pain, disease activity, and physical function, compared to the 30 patients not satisfying the ACR definition. However, no significant differences were observed between these two groups in "process" measures including LAI, tender joint count, swallen joint count, or CRP value. In conclusion, the ACR core set measures including both process and outcome measures have potential to reflect clinical important changes on "real life" of patients with RA.

Activities of Daily Living↗
PubMed1997

[Malignant lymphoma complicating myelodysplastic syndrome with autoantibody for the thyroid gland].

A 68 year old woman was hospitalized because of cervical lymphadenopathy. Hematological data on admission showed anemia, leukopenia with a normal platelet count. Serum serological studies revealed polyclonal hypergammaglobulinemia, a positive microsome and thyroid test, and positive reaction to antithyroglobulin antibody. Microscopic examination of a cervical lymph node revealed malignant lymphoma, diffuse large cells of B cell phenotype. The bone marrow smears revealed hypercellularity with dysplastic features including pseudo-Pelger and other nuclear abnormalities of neutrophils, micromegakaryocytes, dyserythropoiesis with megalobastic changes, 60% ring sideroblast and with no increase in proportion of blast cells (3.6%). A diagnosis of myelodysplastic syndrome (MDS, refractory anemia with ring sideroblast (RARS)) was made. Remission of ML obtained with radiation and subsequent systemic chemotherapy with CHOP-Bleo regimen, although she died 2.5 yr after the diagnosis due to relapse of ML without leukemic transformation of MDS. Although basic disturbances in these three conditions are not clear, it is evident that treatment was not concerned with the pathogenesis in this case, because the three conditions existed without treatment. It may be hypothesized that an initial event which selects a clone of stem cells that retains the capacity to differentiate into myeloid and lymphoid line would manifest with the features of RARS in the myeloid line and with the sort of immunological abnormalities reported in this case. Subsequent events select subclones and these progressively lose terminal differentiation, culminating as B-cell lymphoma.

Aged↗
PubMed1997

[Overlap syndrome].

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Connective Tissue Diseases↗
PubMed1997

[Non-uremic neuropathy in hemodialysis patients].

We have reviewed 20 clinical records of hemodialysis patients with neuropathy admitted to the Department of Neurology during 1978 april through 1995 march. The clinical diagnosis was made based on clinical findings, neurophysiological examinations, and histopathological findings of sural nerve and peroneal muscle biopsies. Four out of twenty hemodialysis patients with neuropathy were non-uremic neuropathy. The diagnosis of neuropathy of four patients were chronic inflammatory demyelinating polyneuropathy, neuropathy with graft versus host disease, Guillain-Barré syndrome, and subacute combined degeneration of the spinal cord. All patients improved after the treatment. It is important to consider the possibility of association of non-uremic neuropathy in hemodialysis patients.

Adult↗
PubMed1997

[Neuronal apoptosis in the central and peripheral nervous system in HIV infection].

Apart from the unique changes characteristic of "HIV encephalitis", the productive infection of central nervous system by HIV, which predominantly involves the white matter and basal ganglia, evidence is accumulating that the cerebral cortex may also be affected in AIDS patients. Neuronal loss, suspected at microscopic examination, has been demonstrated by a number of morphometric studies. However, the cause and mechanism of neuronal damage in HIV infection, are still unclear. In an attempt to look for an apoptotic process at the origin of neuronal loss in AIDS, we examined samples of frontal cortex, temporal cortex and basal ganglia from 12 patients who died from AIDS and 4 asymptomatic HIV-positive cases using in situ end labelling to demonstrate characteristic DNA fragmentation. These were compared with 5 asymptomatic seronegative controls, and 2 seronegative patients with Alzheimer's disease. We demonstrated neuronal apoptosis in all AIDS cases and in the Alzheimer's cases. Positive in situ end labelling was usually associated with morphological changes suggestive of neuronal apoptosis. Semiquantitative assessment of the density of apoptotic neurons showed that neuronal apoptosis was more severe in atrophic brains. In contrast, no correlation was found between the density of apoptotic neurons and the presence of HIV-encephalitis or a history of cognitive disorder. Only occasional apoptotic neurons were found in one asymptomatic, HIV-positive case. Apoptosis was never observed in asymptomatic seronegative cases. We also looked for apoptotic neurons in spinal ganglia of 20 AIDS cases, 5 of whom had a terminal sensory distal neuropathy, and 10 seronegative controls devoid of neuropathy. Apoptotic neurons were found in 6 of the AIDS patients and in none of the seronegative controls. However, no correlation was found between the severity of neuronal apoptosis in the spinal root ganglia and the presence of absence of a terminal distal sensory neuropathy. Experimental studies tend to support our in vivo findings. HIV-infection of primary cultures of human embryonic central nervous system induced frequent apoptosis of neurons. No apoptotic cell was identified in non infected control cultures.

AIDS Dementia Complex↗
PubMed1997

[Myelodysplastic syndrome associated with gastric cancer and colon polyp].

A 62-year-old man was found to have myelodysplastic syndrome (MDS) and gastric cancer. Serum studies revealed hypogammaglobulinemia, and positive reactions to rheumatoid test and anti-nuclear antibody. Chromosomal analysis of the bone marrow revealed deletions of No. 5 and 7 chromosomes and that of the stomach showed complex abnormalities. It may be hypothesized that an initial event which selects a clone of stem cells could manifest with this sort of immunological abnormalities. Subsequent deranged immunosurveillance may be responsible for the increased risk of cancer. Alternatively an increased chromosomal instability which seems to be associated with immunodeficiencies might be responsible for cancer development.

Anemia, Refractory, with Excess of Blasts↗
PubMed1997

Hydrophobic effect of alkyl substituents on DNA intercalation of a dye.

Naphthalene imides carrying alkyl chains of different length were synthesized to evaluate the hydrophobic effect on DNA interaction with small molecules. These dyes bind to DNA with moderately high affinity of 10(4)-10(5) M-1 and raise the melting temperature of the DNA duplex by 8-18 degrees C at a 0.2 molar ratio of dye to DNA-p (phosphate unit). However, both the DNA binding affinity and DNA duplex stability decrease with an increase in the hydrophobicity (logP) of the dye. These results demonstrate that the interaction of the hydrophobic alkyl chain of the dye with the DNA groove destabilizes the DNA structure, presumably by removing the structure-stabilizing water from the DNA groove.

Alkylation↗
PubMed1997

DNA sequence dependent binding modes of bis(vinylpyridinium)benzene derivatives.

The DNA binding selectivity of new dicationic ligands based on the bis(vinylpyridinium)benzene unit has been investigated by means of UV-Vis absorption spectroscopy. From the experimental results it is concluded that these extended pi-electron bridged viologens have relatively high affinity to AT base pair sequences whereas the binding to GC pairs is about 10 times lower, and binding affinity depends on minor variation in the ligand structure. Linear type ligand exhibits two binding mode interaction, intercalation at high dye concentration which undergoes switching to groove binding at low ligand concentration.

Base Composition↗
PubMed1996

Cloning and expression localization of cDNA for rat homolog of TRP protein, a possible store-operated calcium (Ca2+) channel.

A 3.2 kbp cDNA clone encoding a possible candidate for the store-operated Ca2+ channel was isolated from a rat brain cDNA library. The deduced amino acid sequence was 51.8% identical to TRP encoded by a Drosophila trp (transient receptor potential) gene and contained ankyrin motifs, a coiled-coil structure and six transmembrane segments similar to the previously identified TRP family and named as TRP-R (rat TRP). By in situ hybridization histochemistry of rat body on embryonic day 15, no significant expression signal for TRP-R was detected. On embryonic day 20 and postnatal day 1, the expression signals were most evident in the septum, cerebral cortical plate and hippocampal neuronal layers. On postnatal day 7 and thereafter the expression in the cerebral cortex and the septum decreased progressively, and weak expression remained only in the CA1 and CA2 neuronal layers of the hippocampus in the brain on postnatal day 21 and 49. This limited spatiotemporal expression of this novel molecule. TRP-R, suggests that it is involved in some specific functions related to the neuronal differentiation.

Amino Acid Sequence↗
PubMed1996

Enhancement of glucose-induced insulin secretion in transgenic mice overexpressing human VIP gene in pancreatic beta cells.

Using transgenic mice technology, it has now become possible to test directly whether VIP and PHM-27 can enhance glucose-induced insulin secretion and reduce blood glucose in vivo. By microinjecting the entire human VIP gene ligated to the rat insulin II promoter, we have established a mouse model that overproduces VIP and PHM-27 in pancreatic beta cells. VIP was secreted from transgenic islets in a glucose-dependent manner. Analyses of these VIP-transgenic mice indicated that the transgene efficiently enhances glucose-induced insulin secretion and significantly reduces blood glucose as compared with control mice. The transgene also ameliorated glucose intolerance of 70% depancreatized mice. The present results suggest that somatic cell gene therapy directed to diabetic islets by human VIP/PHM-27 gene introduction may provide a means to improve the secretory function of the diabetic islets.

Animals↗
PubMed1996

Cloning and characterization of a 92 kDa soluble phosphatidylinositol 4-kinase.

A phosphatidylinositol (PtdIns) 4-kinase cDNA cloned from a rat brain cDNA library encoded a protein of 816 amino acids with a calculated molecular mass of 91654 Da. This molecule contained a lipid-kinase-unique domain and a presumed lipid/ protein kinase homology domain that are found in other PtdIns 4-kinases and PtdIns 3-kinases. Furthermore, this kinase molecule had 43.3% shared identity with the presumed catalytic domain of yeast PtdIns 4-kinase, PtdInsK1, and the two molecules had a region of similarity that is not conserved in other lipid kinases. By examining PtdIns kinase activity in transfected COS-7 cells using epitope tag immunoprecipitation as well as conventional methods, the product PtdIns phosphate was identified as phosphatidylinositol 4-phosphate (PtdIns4P), but not phosphatidylinositol 3-phosphate (PtdIns3P). The PtdIns 4-kinase activity was recovered predominantly from the soluble fraction and the activity was markedly enhanced in the presence of Triton X-100 and was relatively insensitive to inhibition by adenosine. In addition, the PtdIns 4-kinase activity was completely inhibited in the presence of 10 microM wortmannin. When examined by epitope tag immunocytochemistry, the immunoreactivity for the PtdIns 4-kinase molecule was dominantly aggregated in a cytoplasmic region juxtaposed to the nuclei and was faintly but widely dispersed in the cytoplasm. By in situ hybridization analysis, the mRNA for PtdIns 4-kinase was expressed ubiquitously and was detected in most neurons throughout the grey matter of the brain, with higher expression intensity found in fetal than in adult brain.

1-Phosphatidylinositol 4-Kinase↗
PubMed1996

The amino-terminally truncated forms of amyloid beta-protein in brain macrophages in the ischemic lesions of Alzheimer's disease patients.

We have investigated the cerebral cortex of Alzheimer's disease in which small infarcts are found on postmortem neuropathological examination. In areas that have been subjected to recent ischemia, immunohistochemical staining for amyloid beta-protein (A beta) is much less intense than in the non-ischemic surround. However, the infiltrating brain macrophages contain granules immunopositive for C-terminal fragments of A beta. The immunohistochemical profile indicates that A beta in these granules lacks epitopes in the N-terminal fragments. These data suggest that appropriately stimulated macrophages can phagocytose A beta deposits and that digestion of the N-terminal region is an early consequence of this phagocytosis.

Aged↗
PubMed1996

Studies on selectin blocker. 3. Investigation of the carbohydrate ligand sialyl Lewis X recognition site of P-selectin.

We have previously found that a 1-deoxy sialyl Lewis X (3), which lacks only the C-1 hydroxyl group of sialyl Lewis X (sLeX), exhibited up to 20 times more potency than the sLeX toward P-selectin binding. In order to explain the structure-activity relationship, we constructed structural models of the complexes of P-selectin and compounds 1-3 and sLeX. From the modeling analysis, we found that the carbonyl oxygen of the N-acetyl group of GlcNAc in 3 formed a hydrogen bond with the amide group of Asn 82 in P-selectin. We also supposed that there was a hydrophobic interaction between the pyranose of GlcNAc in compound 3 and the imidazole ring of His 108 in P-selectin. However, it is considered that those interactions would not be appreciable in the case of sLeX or other 1-deoxy sLeX analogs (1,2). Accordingly, our results could be helpful in obtaining a new concept to design a potent inhibitor toward P-selectin binding.

Amino Acid Sequence↗