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Biomedical subjects

H Kondo

Publications and source records attributed to H Kondo.

At least 577 records · Page 32Linked to original sources

Abnormal cytoskeletal pathology peculiar to corticobasal degeneration is different from that of Alzheimer's disease or progressive supranuclear palsy.

An autopsy case of clinically diagnosed "corticobasal degeneration (CBD)" was investigated. In addition to status spongiosus and neuronal achormasia around the central sulcus, cortical pyramidal neurons and thread-like structures were densely stained by Gallyas stain and tau immunohistochemistry, but apparent fibrillary structures like Alzheimer's disease neurofibrillary tangle were absent. Bodian, methenamine-Bodian, Congo red, thioflavin S, or Bielshowsky stains failed to visualize these structures. They were not stained by immunohistochemical stain with anti-ubiquitin antibody. The widespread cytoskeletal pathology, which is distinct from that in Alzheimer's disease or progressive supranuclear palsy, is suggestive of CBD.

Alzheimer Disease↗

Malignant germ cell tumor of the mediastinum: a multimodality therapeutic approach.

Twenty-five patients with a malignant germ cell tumor of the mediastinum were treated at the National Cancer Center Hospital, Tokyo. Three patients had pure seminomas while 22 had a nonseminomatous histology. The treatment modalities consisted of surgery alone in 7 patients, surgery with chemotherapy and/or radiation in 14, and chemotherapy and/or radiation without surgery in 4. Cisplatin-based chemotherapy was administered in nine patients, one of whom successfully underwent high-dose chemotherapy with autologous bone marrow transplantation after resection of the tumor. A complete response was achieved in only five patients. The overall survival rate at 5 years was 33.5% and the median survival time was 51 weeks. Eight patients (32%), all of whom underwent surgery either with or without chemotherapy and/or radiation, were free of disease with a mean follow-up period of 439 weeks (72-1,120 weeks). The median survival times for 14 patients undergoing combined modality treatment, 7 patients undergoing surgery alone, and 4 patients undergoing chemotherapy and/or radiation were 83, 16, and 18 weeks, respectively.

Adolescent↗

Extended resection of the left atrium, great vessels, or both for lung cancer.

One hundred one patients with locally advanced lung cancer underwent combined resection of the lung and the left atrium with or without the great vessels. A single additional organ was resected in 92 patients, two organs in 8 patients, and three organs in 1 patient. The left atrium was resected in 44 patients, the superior vena cava in 32, the adventitia of the aorta in 21, the aorta in 7, and the pulmonary artery in 7. The most important factors affecting survival defined by multivariate analysis were postoperative pneumonia, complete resection, postoperative bleeding, and lymph node metastasis (p < 0.05). Thirteen patients survived 3 years or more and 10 of the 13 survived 5 years or more. The 5-year survival rate for all patients, including 8 with operative death, was 13%, and the median survival time was 9.2 months. The 5-year survival and median survival time were 19% and 13.8 months after complete resection and 0% and 6.5 months after incomplete resection (p < 0.01). The 5-year survival and median survival time for patients with pathologic stage IIIA, IIIB, and IV were 16.8% and 16.8 months; 18.3% and 9.8 months; and 0% and 5.4 months, respectively. There was a significant difference between stages IIIA plus IIIB and stage IV (p < 0.05). The 5-year survival after left atrium resection was 22%. Extended resection was worthwhile for the patients undergoing complete resection and without postoperative complications.

Adenocarcinoma↗

Computed tomography-guided coil injection and thoracoscopic pulmonary resection under roentgenographic fluoroscopy.

To remove a small, chest roentgenogram-negative, computed tomogram-positive nodule, we developed a novel technique of thoracoscopic pulmonary resection. This technique consists of the computed tomography-guided coil injection of a metallic coil and subsequent thoracoscopic resection under roentgenographic fluoroscopy. During the thoracoscopic resection, the fluoroscopic image was a valuable aid in determining the location of the nodule and in ensuring that the stapler was applied with a sufficient distance from the coil. Because this technique helps to determine the exact location of the nodule regardless of its depth from the pleural surface, even a minithoracotomy for direct palpation can be avoided.

Adenocarcinoma↗

Localization of mRNA for protein phosphatase 2A in the brain of adult rats.

The gene expression for alpha and beta isoforms of type 2A protein phosphatase (PP2A-alpha and -beta) in the adult rat brain was examined by in situ hybridization analysis. No marked difference in the gene expression was discerned between the two isoforms in large portions of brain, except for the thalami in which the expression level for the alpha isoform was similar to that in the cerebral neocortex whereas that for the beta was lower than that in the neocortex. The gene expression was observed intensely in the piriform cortex, the cerebellar Purkinje and granule cell layers, and the hippocampal pyramidal and dentate granule cell layers, and the locus ceruleus, whereas the moderate levels of its expression were observed in the olfactory mitral cells and the pontine nuclei. The cerebral neocortex expressed the mRNA moderately to weakly without any laminar patterns, whereas the expression level in the caudate-putamen was very low. This expression pattern is basically similar to that of PP2C reported previously, except for the plexus choroideus and ependyma having no significant expression for PP2A.

Animals↗

Molecular cloning of rat cDNA for cytosolic phospholipase A2 and the increased gene expression in the dentate gyrus following transient forebrain ischemia.

Rat cytosolic phospholipase A2 (cPLA2) cDNA was cloned from rat brain. The cDNA showed a high homology of 90% in the nucleotide sequence of the coding region with the human counterpart. By in situ hybridization, the gene expression for cPLA2 was detected in the hippocampus, olfactory bulb, and cerebellar granular cells at very low level of normal rats. The expression was markedly increased in the dentate granule cells of postischemic rat brain. This alteration of the gene expression was discussed in relation to the free fatty acid-mediated neurotoxicity.

Amino Acid Sequence↗

Localization of mRNAs for calpain and calpastatin in the adult rat brain by in situ hybridization histochemistry.

The detailed localization of mRNAs for calpain II and calpastatin was examined in adult rat brain by in situ hybridization histochemistry. The expression patterns of the two mRNAs were similar to each other throughout the brain in terms of relative expression intensity, and almost all neurons expressed both mRNAs more or less. Among them, neurons in cranial nerve nuclei and some others in the brain stem expressed at relatively high levels, suggesting the high involvement of the non-lysosomal proteolytic system in the function of these neurons. On the other hand, the expression levels of the two mRNAs in non-neuronal cells including glia were basically low with the choroid plexuses expressing calpastatin mRNA relatively highly.

Animals↗

Localization of phosphatase inhibitor-1 mRNA in the developing and adult rat brain in comparison with that of protein phosphatase-1 mRNAs.

The localization and ontogenic changes in the gene expression for phosphatase inhibitor-1 (I-1) were analyzed by in situ hybridization histochemistry, and they were compared with those for three catalytic subunits of protein phosphatase type 1 (PP-1). At the adult stage, intense expression signals for I-1 were detected in the hippocampal formation, piriform cortex, claustrum, dorsal endopiriform cortex, suprachiasmatic nucleus, choroid plexus, arachnoid membrane, and pineal body. Moderate expression signals for I-1 were observed in the olfactory neuronal layers, caudate putamen, layers II-IV, and VI of the neocortex, and cerebellar granule cells, whereas the expression levels were low in the thalamus, cerebellar Purkinje cells, and brain stem nuclei. Although the expression levels for the three PP-1 mRNAs varied notably in various brain regions, a relatively high and parallel expression of I-1 and PP-1 mRNAs was found in most regions of the forebrain. However, the dissociation in the expression levels between I-1 and PP-1 mRNAs was found in several loci: the laminar expression of I-1 mRNA versus the homogeneous expression of PP-1 mRNAs in the cerebral cortex; low levels of expression of I-1 mRNA versus relatively high expression of PP-1 mRNAs in the brain stem nuclei; high expression of I-1 mRNA in the arachnoid membrane versus low expression of PP-1 mRNAs in it. The unparallel expression was also seen in embryonic brain: No significant expression of I-1 mRNA versus substantial expression of PP-1 mRNAs in the ventricular zone and cerebellar external granular layer; transiently high expression of I-1 mRNA in developing thalamus versus constantly moderate to low expression of PP-1 mRNAs there. These findings suggest that I-1 may play some discrete roles independent of the regulation of PP-1 in certain regions and developing stages of the brain.

Animals↗

Re-examination of the ontogeny in the gene expression of DARPP-32 in the rat brain.

By in situ hybridization histochemistry, we have re-examined the ontogeny of the gene expression of mRNA encoding the dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32,000, termed DARPP-32. On E13 and E15, weak expression signals were detected in the mantle zones and ventricular germinal zones of the fore-, mid-, hind-brain, and spinal cord. In the caudate putamen, the expression signals were first visible at its lateral margin on E15. The ventrolateral region of the caudate putamen expressed the gene intensely, while its ventricular germinal zone expressed it weakly on E18-20. Thereafter, the mRNA for DARPP-32 were expressed over the entire caudate putamen in patchy patterns. After birth, the expression levels in the caudate putamen increased markedly, with the majority of the neurons in the caudate putamen expressing the gene intensely on P7 and thereafter. In addition to the caudate putamen, expression signals were detected, albeit faintly, in the olfactory bulb, cortical plate, hippocampal pyramidal cell layer, and their ventricular zones on E18-20. The olfactory tubercle and medial habenular nucleus expressed the gene at slightly higher levels. In the cerebellum, the Purkinje cells showed progressively increasing gene expression from E20 to P7, whereas the external granule cell layer expressed the gene weakly. The ontogeny of the gene expression is largely consistent with previous immunohistochemical findings by other authors. Furthermore, the present finding suggests that DARPP-32 is involved in the regulation of the mitosis-related dephosphorylation by protein phosphatase 1 in the neuroepithelium.

Animals↗

Molecular cloning of rat cDNAs for the zeta and theta subtypes of 14-3-3 protein and differential distributions of their mRNAs in the brain.

We isolated from the rat brain two cDNA clones encoding the zeta and theta subtypes of the 14-3-3 protein. Both clones encoded 245 amino acid sequences, which share a high sequence homology with each other and also with other subtypes of the 14-3-3 protein. The distribution of their mRNAs was determined in the developing brain, by in situ hybridization with subtype-specific oligonucleotide probes. At embryonic day 18, the zeta and theta subtype mRNAs were expressed at high levels throughout the brain and the spinal cord. Distribution patterns of the two mRNAs were distinct in the brain at postnatal day 21. The zeta subtype mRNA was distributed widely in the brain gray matter, and high levels of the transcripts were detected in various brain regions, including the neocortex, hippocampus, caudate-putamen, thalamus, cerebellar cortex, and several brainstem nuclei. On the other hand, high signal levels of the theta subtype mRNA in the gray matter were restricted to the cerebellar cortex and the hippocampus. In addition, significant signals for the theta subtype mRNA were found over the white matter, where cell bodies of glial cells are populated. The wide gene expression of the zeta and theta subtypes suggests their fundamental and essential role in the brain function, but the degrees of functional involvement by the respective subtypes would be heterogeneous between neuron and glia, and also among neuron types.

14-3-3 Proteins↗

Abnormal coronary flow dynamics at rest and during tachycardia associated with impaired left ventricular relaxation in humans: implication for tachycardia-induced myocardial ischemia.

OBJECTIVES: This study attempted to clarify the effect of ventricular relaxation abnormalities on coronary flow dynamics at rest and during tachycardia in humans. BACKGROUND: Ventricular relaxation abnormality has been demonstrated in animals to have an adverse impact on early diastolic coronary flow dynamics. However, this relation has not been established in humans. Even if the adverse effect were latent at rest, it might become evident during tachycardia because tachycardia reduces coronary flow reserve and facilitates the production of myocardial ischemia. METHODS: Doppler phasic left coronary flow velocity pattern was obtained at rest and during tachycardia in 23 patients without coronary stenosis. The time constant of left ventricular isovolumic pressure (tau) was used to assess ventricular relaxation. RESULTS: The time to peak flow velocity of the diastolic coronary flow wave was longer, and the fraction of the first third of diastolic coronary flow was smaller, in patients with a longer tau (r = 0.58, p < 0.01; r = -0.44, p < 0.05), indicating a close relation between early diastolic coronary flow dynamics and ventricular relaxation. Although rapid atrial pacing yielded an increase in the coronary flow velocity integral per minute in all patients, diastolic coronary flow velocity integral per minute increased in 9 patients with a normal (< or = 40 ms) tau at rest but decreased in 14 patients with a longer (> 40 ms) tau at rest. CONCLUSIONS: Impaired left ventricular relaxation was associated with decreased coronary flow in early diastole at rest and decreased coronary flow throughout diastole during tachycardia in patients without coronary stenosis. These findings may provide more insight into the mechanism of tachycardia-induced subendocardial ischemia in patients with impaired ventricular relaxation but without concomitant coronary stenosis.

Adult↗

Analysis of transmural trend of myocardial integrated ultrasound backscatter for differentiation of hypertrophic cardiomyopathy and ventricular hypertrophy due to hypertension.

OBJECTIVES: This study was undertaken to differentiate hypertrophic cardiomyopathy from hypertensive hypertrophy using a newly developed M-mode format integrated backscatter imaging system capable of calibrating myocardial integrated backscatter with the power of Doppler signals from the blood. BACKGROUND: Myocardial integrated ultrasound backscatter changes in patients with hypertrophic cardiomyopathy; however, it is unknown whether ultrasound myocardial tissue characterization may be useful in differentiating hypertrophic cardiomyopathy from hypertensive hypertrophy. METHODS: Calibrated myocardial integrated backscatter and its transmural gradient were measured in the septum and posterior wall in 31 normal subjects, 13 patients with hypertensive hypertrophy and 22 patients with hypertrophic cardiomyopathy. The gradient in integrated backscatter was determined as the ratio of calibrated integrated backscatter in the endocardial half to that in the epicardial half of the myocardium. RESULTS: Cyclic variation of integrated backscatter was smaller and calibrated myocardial integrated backscatter higher in patients with hypertrophied hearts than in normal subjects, but there were no significant differences in either integrated backscatter measure between patients with hypertensive hypertrophy and those with hypertrophic cardiomyopathy. Transmural gradient in myocardial integrated backscatter was present only in patients with hypertrophic cardiomyopathy (5.0 +/- 1.8 dB [mean +/- SD] for the septum; 1.2 +/- 1.6 dB for the posterior wall). CONCLUSIONS: Hypertrophic cardiomyopathy and ventricular hypertrophy due to hypertension can be differentiated on the basis of quantitative analysis of the transmural gradient in integrated backscatter.

Acoustics↗

Expression of DNA methyltransferase gene in mature and immature neurons as well as proliferating cells in mice.

A major role of DNA-methyltransferase (MTase) is thought to be maintaining the DNA methylation profile through DNA replication. However, previous surveys of mRNA distribution in different tissues by Northern-blot analysis have shown unexpectedly high levels of expression of DNA-MTase mRNA in adult mouse brain, which consists mostly of slowly proliferating glial and nonproliferating neuronal cells. In order to identify cells expressing the gene in the brain, we performed an in situ hybridization analysis of mature brain as well as whole embryos of different ages. In addition to various embryonic tissues with active cell proliferation such as the ventricular neurogenic layer, hair follicle epithelia, thymus and epithelia of the base of intestinal villi, almost all mature neurons in brain of adult and even aged mice expressed DNA-MTase mRNA at substantial levels. No significant expression of the gene was detected in the white matter. These findings suggest some neuron-specific biological function of DNA methylation, unrelated to DNA replication.

Animals↗

Early mortality rate of atomic bomb survivors based on House Reconstruction Survey.

This paper studies the mortality rate experienced by over 23,000 A-bomb survivors in Nagasaki between September 1945 and 1950 when the RERF-ABCC initiated the follow-up of the large LSS cohort. The study is based on the data of the 10-year House Reconstruction Survey. As expected, these data show an increasing mortality rate with increasing proximity to the hypocenter of the bomb. What was not anticipated was a higher mortality rate in the 1400-1699 m band than in the closer distance interval of 1200-1399 m. This suggests a possible selective survival among A-bomb survivors. Whether this affects the cancer risk estimates has not as yet been determined.

Dose-Response Relationship, Radiation↗

In vitro and in vivo effects of cisplatin and etoposide in combination on small cell lung cancer cell lines.

The effects of cisplatin (CDDP) and etoposide (ETP) in combination were evaluated in vitro and in vivo using small cell lung cancer cell lines. The combination effects in vitro were investigated using isobologram analysis. Used together, CDDP and ETP showed a synergistic effect against cell growth on only 1 cell line (SBC-3), additive effects on 6 (SBC-2, SBC-5, Lu130, Lu134AH, Lu135T and H69) and an antagonistic effect on 1 (SBC-1). In the in vivo experiment, nude mice were inoculated with SBC-1, SBC-3 and SBC-5 cells. Two or 5 mg/kg CDDP and 10 or 30 mg/kg ETP were administered intraperitoneally alone and simultaneously in combination to nude mice. The in vivo effects of the combination were determined by comparing the observed growth ratio in mice treated with the combination with the expected value of this ratio calculated based on the assumption that the effects of the drugs were simply additive. According to this definition, synergistic effects were observed against all 3 tumors. Thus, the in vivo and in vitro effects differed. The toxicity of the combination therapy, which was analyzed by estimating the body weight change of mice, was no higher than that of CDDP or ETP alone. These results suggest that the excellent clinical effects of CDDP and ETP combination therapy may be attributable not to drug interaction at the cellular level but to the feasibility of combined use of them at full doses without overlapping side effects.

Animals↗