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Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 847 records · Page 47Linked to original sources
PubMed1995

Comparison of carboplatin/etoposide/vincristine with cisplatin/etoposide as combination chemotherapy for small cell lung cancer.

We compared the efficacy and toxicity of the CEV regimen (carboplatin at 300 mg/m2 on day 1, etoposide at 100 mg/body on days 1 to 3, and vincristine at 1 mg/m2 on days 1 and 8) with the PVP regimen (cisplatin at 80 mg/m2 on day 1 and etoposide at 100 mg/body on days 1 to 3) in patients with untreated small cell lung cancer (SCLC). Of the 13 patients treated with the PVP regimen, two achieved complete response (CR, 15.4%) and eight partial response (RP, 61.5%). Of the 15 evaluable patients treated with the CEV regimen, one achieved CR (6.7%) and 13 PR (86.7%). Thus, there was no significant difference in response rate between the PVP (76.9%) and CEV (93.3%) regimens. There was also no significant difference in response duration [PVP, 756 +/- 903 (mean +/- SD) days vs. CEV, 318 +/- 159 days] and median survival time (PVP, 472 days, vs. CEV, 471 days). The number of days hospitalized divided by the duration of chemotherapy was shorter with the CEV regimen, but this difference was not statistically significant. Severe leukopenia (< 2,000/microliter) occurred in 15.4% of PVP patients and 31.3% of CEV patients. Severe thrombocytopenia (< 50,000/microliter) occurred in only one patient in this study. In conclusion, the CEV regimen demonstrated a response rate and median survival time comparable to the PVP regimen, although the response time was short. The CEV regimen had the advantage of lower toxicity and ease of outpatient administration. Thus, the CEV regimen is a useful outpatient induction chemotherapy for SCLC.

Antineoplastic Agents↗
PubMed1994

Participation of diacylglycerol kinase in mitogenic signal transduction induced by platelet-derived growth factor in vascular smooth muscle cells.

In rat vascular smooth muscle cells, platelet-derived growth factor (PDGF), stimulated phosphatidic acid synthesis by activating both of the two alternative pathways, diacyglycerol kinase (DGK) and phospholipase D (PLD). Genistein, a tyrosine kinase inhibitor, inhibited PLD activation but not DGK activation, the latter was inhibited selectively by R 59022. PDGF-induced DNA synthesis was partially inhibited by genistein or R 59022, but these inhibitors had no effect on phorbol ester-induced DNA synthesis. Further, the specific effects of these inhibitors on PDGF-induced DNA synthesis were additive.

Alkaloids↗
PubMed1994

Differences in signal transduction between platelet-derived growth factor (PDGF) alpha and beta receptors in vascular smooth muscle cells. PDGF-BB is a potent mitogen, but PDGF-AA promotes only protein synthesis without activation of DNA synthesis.

Cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats express both alpha and beta isoforms of the platelet-derived growth factor (PDGF) receptors at high levels (100,000 and 240,000 sites/cell, respectively). In this cell type, PDGF-BB elicited a mitogenic response; however, PDGF-AA increased only protein synthesis without activating DNA synthesis. Protein kinase C (PKC) was activated by PDGF-AA as well as PDGF-BB with concomitant translocation from cytosol to membrane fractions. However, the hypertrophic effect of PDGF-AA was not affected by depletion of cellular PKC, whereas the mitogenic action of PDGF-BB was partially attenuated by the depletion. Following incubation with PDGF-AA or -BB, phospholipase C-gamma 1 (PLC-gamma 1) and phosphatidylinositol 3-kinase were tyrosine phosphorylated; however, the phosphorylation of Ras-GTPase-activating protein was induced only by PDGF-BB. Both PDGF isoforms resulted in a prompt and transient increase in the level of 1,2-diacylglycerol (DAG), presumably through the action of PLC-gamma 1. After returning to basal levels, the rate of DAG synthesis steadily increased for at least 15 min due to activation of phosphatidylcholine-hydrolyzing phospholipase C (PC-PLC). Incubation with PDGF-BB-activated phospholipase D (PLD) in a PKC-dependent manner resulting in the formation of phosphatidic acid (PA). PA was also formed by the sequential reactions of PC-PLC and DAG kinase in the PDGF-BB-stimulated VSMC, and these sequential reactions were not affected by PKC depletion. In contrast, PDGF-AA stimulation did not result in increased PA synthesis as neither PLD nor DAG kinase activities were affected. PA may be a significant second messenger in the activation of DNA synthesis by PDGF-BB. These results indicate that signaling mechanisms of the PDGF-alpha and -beta receptors in VSMC are distinctly different in signal transduction in VSMC and that the alpha receptor promotes cellular hypertrophy (but not hyperplasia), whereas a mitogenic response is mediated only through the beta receptor.

Animals↗
PubMed1994

Biochemical evidence for the long-tail form (A beta 1-42/43) of amyloid beta protein as a seed molecule in cerebral deposits of Alzheimer's disease.

We measured the amounts of total A beta, A beta 1-40 and A beta 1-42/43 in brain tissues using a newly developed ELISA assay and found that the amounts of insoluble A beta 1-42/43 and insoluble A beta 1-40 were linearly related to the amount of A beta deposits or total insoluble A beta at their lower and higher concentrations, respectively. In an experiment to characterize the A beta species in brain homogenates with buffered saline, we unexpectedly detected soluble A beta which was derived from the insoluble amyloid deposits in brain tissue, indicating reversible depolymerization of A beta from insoluble amyloid deposits. To confirm this finding, we performed 5 consecutive washes of insoluble precipitates of AD brains with buffered saline. Both species of A beta were found in all 5 supernatant fractions and their amounts were gradually decreased. The ratio of A beta 1-42/43 to A beta 1-40 was increased with the numbers of washes, indicating that A beta 1-40 existed in an exposed manner as compared to A beta 1-42/43. Thus the present finding is the first biochemical evidence that A beta 1-40 was the predominant species involved in the reversible exchanging reaction on seeding A beta 1-42/43 between the soluble and the insoluble forms (amyloid fibrils).

Alzheimer Disease↗
PubMed1994

Circadian clock mutants of cyanobacteria.

A diverse set of circadian clock mutants was isolated in a cyanobacterial strain that carries a bacterial luciferase reporter gene attached to a clock-controlled promoter. Among 150,000 clones of chemically mutagenized bioluminescent cells, 12 mutants were isolated that exhibit a broad spectrum of periods (between 16 and 60 hours), and 5 mutants were found that show a variety of unusual patterns, including arrhythmia. These mutations appear to be clock-specific. Moreover, it was demonstrated that in this cyanobacterium it is possible to clone mutant genes by complementation, which provides a means to genetically dissect the circadian mechanism.

Circadian Rhythm↗
PubMed1994

Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients.

Interleukin (IL)-1 beta, IL-6, epidermal growth factor (EGF), and transforming growth factor-alpha (TGF-alpha) were measured for the first time in the brain (caudate nucleus, putamen and cerebral cortex) from control and parkinsonian patients by highly sensitive sandwich enzyme immunoassays. The concentrations of IL-1 beta, IL-6, EGF, and TGF-alpha in the dopaminergic, striatal regions were significantly higher in parkinsonian patients than those in controls, whereas those in the cerebral cortex did not show significant differences between parkinsonian and control subjects. Since these cytokines and growth factors may play important roles as neurotrophic factors in the brain, the present results suggest that they may be produced as compensatory responses in the nigrostriatal dopaminergic regions in Parkinson's disease, and may be related, at least in part, to the process of neurodegeneration in Parkinson's disease.

Aged↗
PubMed1994

Cloning and expression of a novel form of leukotriene B4 omega-hydroxylase from human liver.

We have isolated and sequenced a cDNA for human liver LTB4 omega-hydroxylase. The cDNA encoded a protein of 520 amino acids with a molecular weight of 59,853 Da. The cDNA-deduced amino acid sequence showed 87.3% homology to that of human polymorphonuclear leukocytes (PMN) LTB4 omega-hydroxylase (CYP4F3). Northern blot analysis revealed that the mRNA hybridized to the specific cDNA fragment is expressed in human liver, but not in human PMN. The microsomes from yeast cells transfected with the cDNA catalyzed the omega-hydroxylation of LTB4 with a Km of 44.8 microM. These results clearly show that a new form of the CYP4F LTB4 omega-hydroxylase exists in human liver.

Amino Acid Sequence↗
PubMed1994

Thermosensitization and modification of cytosolic calcium concentration by verapamil and diltiazem in mouse mammary carcinoma cells.

PURPOSE: The cardinal role of Ca2+ signaling in the development of heat damage at 42 degrees C and 44 degrees C and the effect of verapamil and diltiazem on the change of cytosolic Ca2+ concentration, [Ca2+]c, were investigated. METHODS AND MATERIALS: Hyperthermic treatment was performed by immersing the tubes containing the mouse mammary carcinoma FM3A cells in a water-bath set at 42.0 degrees C or 44.0 degrees C. The [Ca2+]c of a single cell after hyperthermia was monitored by a digital image analyzing technique using Fura-2. Influx of Ca2+ was examined by the measurement of the radioactivity of 45Ca2+ incorporated into the cells for 60 min during or after hyperthermia. RESULTS: While the [Ca2+]c of the cells treated at 37 degrees C for 60 min was less than 230 nM, the percentage of the cells showing more than 230 nM increased after 42 degrees C hyperthermia and that of the cells showing more than 300 nM increased after 44 degrees C hyperthermia. When cellular uptake of 45Ca2+ during and after hyperthermia was examined, the increase in 45Ca2+ uptake was observed only for 44 degrees C hyperthermia. Verapamil or diltiazem (100 microM) enhanced a delay of cell growth, an increase in [Ca2+]c and an increase in 45Ca2+ influx for 42 degrees C and 44 degrees C hyperthermia. CONCLUSION: These results are compatible with the view that the increase in [Ca2+]c after 42 degrees C hyperthermia results from intracellular release from calcium store sites whereas the rise in [Ca2+]c after 44 degrees C hyperthermia is mainly due to entry of extracellular Ca2+. Verapamil or diltiazem combined with hyperthermia increased [Ca2+]c, which may play a cardinal role in thermosensitization by these agents.

Animals↗
PubMed1994

Epidural herniation of the cerebral tissue in a burned body: a case report.

A case in which herniation of the cerebral tissue was seen in the epidural space of a burned body is reported. The dead, burned body of an 8-year-old female was found in her burnt-out house. Externally, the body (except the back) was burned to the third or fourth degree, although there was no injury, specifically no skull fracture due to a mechanical force. Internally, much soot deposit was observed in the trachea, main bronchi and peripheral bronchioles. A 9.5 cm x 6.0 cm, thermo-coagulated, yellowish-white mass was unexpectedly found lying on the dura mater of the left temporal lobe. Histologically, H&E stain showed that the mass was thermo-coagulated cerebral tissue, although neither intra-cerebral haemorrhage nor cerebral contusion was found. The carboxyhaemoglobin (CO-Hb) concentration in the intracardiac blood was 83%. The cause of her death was diagnosed as death due to fire, based on the autopsy findings described above and the high CO-Hb concentration value. Therefore, the unexpected entry of the cerebral tissue into the epidural space was considered to be one of the morphological changes due to the local action of heat; the authors propose that such a postmortem change should be called 'heat brain herniation'.

Brain Injuries↗
PubMed1994

Frequency dependence of electric-field-induced orientation of myelin tubes.

Orientation induced by an alternating electric field was studied for myelin tubes of egg phosphatidylcholine (egg-PC) in water and in KCl electrolyte solution. The orientation was also studied for myelin tubes of egg-PC/cholesterol mixtures in water. The orientation effect was measured by the bending curvature of myelin tubes with hairpin-like deformation at frequencies between 10 kHz and 20 MHz. The bending deformation of egg-PC myelin tubes in water decreased abruptly with a decreasing frequency within the low-frequency range below 100 kHz, and shrinkage of myelin tubes was often observed. The bending deformation decreased as the frequency was increased in a higher frequency range. The profile of the frequency dependence for egg-PC in KCl solution was similar to that in water but shifted towards a higher frequency. At low KCl concentrations below 3 mM, the relaxation frequency increased proportionally with increasing an KCl concentration, which was due to a proportional increase in the conductivity of the surrounding medium. Similar profiles of the frequency dependence were observed for egg-PC/cholesterol mixtures but with no shift in the relaxation frequency. These data in the high-frequency range fitted well with calculations based on theoretical equations for the electric-field-induced orientation of nonspherical particles. The conductivity of myelin tubes was estimated to be in the order of 10(-4) S/m in water and of 10(-3) S/m at the low KCl concentrations. The bending modulus of a bilayer membrane was estimated to be (1.0 +/- 0.5) x 10(-19) J for egg-PC in water. No change in the bending modulus was observed for egg-PC in KCl solution. However, for egg-PC/cholesterol mixtures in water, the bending modulus abruptly increased to (1.8 +/- 0.5) x 10(-19) J at a cholesterol concentration of 40 mol%.

Egg Yolk↗
PubMed1994

Digital nerve conduction velocity as a sensitive indication of peripheral neuropathy in vibration syndrome.

Digital nerve conduction velocities in the median and ulnar nerves were measured in order to obtain a more accurate indication of peripheral nerve impairment induced by hand-arm vibration. The subjects were 26 patients with vibration syndrome and 28 healthy controls, both groups of about the same age. Two pairs of surface electrodes were attached to the finger and one pair was positioned on the palm, while electrical stimulation was applied to the nerve at the wrist and elbow. Then sensory nerve conduction velocities were antidromically measured within the finger, and also from the wrist to the palm and from the elbow to the wrist. Slowed conduction within the finger was mostly found among the patients. The slowing was also encountered from the wrist to the palm across the carpal tunnel. Abnormalities were observed in the digital nerve segment in about 50-70% of the patients, and in the wrist-to-palm segment in about 10-25% of them. The present study indicates that digital nerve impairment predominantly occurs in the vibration-exposed patients, and that measurement of digital nerve conduction velocity can be a useful objective means to detect peripheral neuropathy in vibration syndrome.

Aged↗
PubMed1994

Analysis of dog and rat plasma for metabolites of a new isoindoline anxiolytic, DN-2327, by liquid chromatography/thermospray mass spectrometry and tandem mass spectrometry.

Combined liquid chromatography/thermospray mass spectrometry (full scan) and its tandem mass spectrometry (precursor ion, product ion and neutral loss scan) were used to characterize rat and dog plasma metabolites of an anxiolytic candidate (DN-2327; (+-)-2-(7-chloro-1,8-naphthyridin-2-yl)-3-[(1,4-dioxa-8- azaspiro[4.5]dec-8-yl)carbonylmethyl]isoindolin-1-one) . The results indicated that DN-2327 was metabolized to M-I by hydrolysis of the dioxolane ring which was subsequently reduced at the carbonyl moiety to form M-II. M-II was further metabolized to diol isomers, M-III and M-IV, by hydroxylation on the hydroxypiperidine moiety. M-V was an acyclic diol resulting from cleavage of the piperidine ring followed by reduction of the aldehyde. By the methodology used here, detailed structural information could be obtained without recourse to individual metabolite isolation and this provided a great saving in time and effort.

Animals↗
PubMed1994

Molecular epidemiological studies of human herpesvirus 6 in families.

The mode of transmission of human herpesvirus 6 (HHV-6) was investigated by molecular epidemiological techniques in four families. HHV-6 was isolated from the peripheral blood of seven infants with exanthem subitum, including siblings, and from the saliva of two mothers. These isolates were examined for genetic relatedness by means of restriction enzymes analysis of purified DNA. While the profiles of the digestion patterns differed among families, they were very similar in a particular family. These results may suggest that HHV-6 is transmitted primarily from mother to child.

Adult↗