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Biomedical subjects

H Kawano

Publications and source records attributed to H Kawano.

At least 145 records · Page 8Linked to original sources
PubMed1998

The expressions of epidermal growth factor receptor mRNA and protein gene product 9.5 in developing rat brain.

To clarify the role of epidermal growth factor receptor (EGFR) in brain development, especially with regard to neuron differentiation, EGFR mRNA expression was studied by in situ hybridization in embryonic day (E)12, E16, postnatal day (P)1, P4, P15, P29 and adult rat, using protein gene product (PGP) 9.5 as a neuron marker. The primary germinal zone (neuroepithelium) expressed neither PGP 9.5 immunoreactivity (IR) nor EGFR mRNA. In the developing brain, cells expressing EGFR mRNA but not PGP 9.5 IR were found in the secondary germinal zone such as the subventricular zone and cerebellar external germinal layer, the cortical plate and, in later stage animals, the fiber tracts. Cells expressing both EGFR mRNA and PGP 9.5 IR appeared in a differentiating field. In the adult brain, strong EGFR mRNA expression was observed in Purkinje cells, Golgi cells, some hippocampal cells and neurons of the diencephalon, pontine and medullary nuclei, and weak expression was seen in neurons of the cerebral cortex. These results suggest that EGFR is related to the process of differentiation and maturation of neurons and the maintenance of some types of adult neurons.

Aging↗
PubMed1998

Deficiency in protein L-isoaspartyl methyltransferase results in a fatal progressive epilepsy.

Protein L-isoaspartyl methyltransferase (PIMT) is suggested to play a role in the repair of aged protein spontaneously incorporated with isoaspartyl residues. We generated PIMT-deficient mice by targeted disruption of the PIMT gene to elucidate the biological role of the gene in vivo. PIMT-deficient mice died from progressive epileptic seizures with grand mal and myoclonus between 4 and 12 weeks of age. An anticonvulsive drug, dipropylacetic acid (DPA), improved their survival but failed to cure the fatal outcome. L-Isoaspartatate, the putative substrate for PIMT, was increased ninefold in the brains of PIMT-deficient mice. The brains of PIMT-deficient mice started to enlarge after 4 weeks of age when the apical dendrites of pyramidal neurons in cerebral cortices showed aberrant arborizations with disorganized microtubules. We conclude that methylation of modified proteins with isoaspartyl residues is essential for the maintenance of a mature CNS and that a deficiency in PIMT results in fatal progressive epilepsy in mice.

Animals↗
PubMed1998

Comparative analysis of expression of hepatocyte growth factor and its receptor, c-met, in gliomas, meningiomas and schwannomas in humans.

Expression of hepatocyte growth factor (HGF) and c-met, a proto-oncogene that encodes a receptor for HGF, was examined in 45 cases of human primary intracranial tumors by means of RT-PCR. In gliomas, HGF and c-met mRNAs were preferentially expressed in high-grade tumors. Co-expression of both genes was observed in glioblastomas (6/15) and in one anaplastic astrocytoma (1/5) but not in low-grade astrocytomas (0/3). By contrast, the c-met gene was consistently expressed in meningiomas (12/14) and schwannomas (8/8). The presence of c-Met protein was confirmed in the tumor cells of glioblastoma, meningioma and schwannoma by immunohistochemical staining. Moreover, all of the schwannoma cases co-expressed the HGF gene. These observations suggest that HGF/c-met expression is somehow related to the disease progression in gliomas, whereas c-Met protein might have an important fundamental biological role in meningioma and schwannoma. Moreover, since all of the schwannoma cases concomitantly expressed the ligand (HGF) and the receptor (c-met) genes, HGF may act in an autocrine fashion in schwannoma.

Astrocytoma↗
PubMed1998

Regional differences in hippocampal excitability manifested by paired-pulse stimulation of genetically epileptic El mice.

Hippocampal excitability in El mice was studied by analyzing paired-pulse responses of population excitatory postsynaptic potentials (EPSPs) and population spikes (PSs). In vitro slice preparations from seizure-susceptible adult (15 weeks old) and non-seizure susceptible young (5 weeks old) El mice were compared with age-matched mother strain ddY mice. In CA1 area, paired-pulse inhibition of PSs was reduced by about 50% at 10 ms interpulse interval (IPI) in both 5 and 15 weeks old El mice when compared to ddY mice. Phenobarbital (200 microM) decreased paired-pulse ratio (PPR) by 30% in El mice, and bicuculline (1 microM) increased PPR by 80% in ddY mice at 10 ms IPI. These results suggest an intrinsic existence of decreased GABA(A) receptor-mediated inhibition in CA1 of El mice. In dentate gyrus (DG), an increase in paired-pulse facilitation of PSs was observed at intermediate IPIs (50-200 ms) in El mice at both ages, especially at 15 weeks of age, when 52%-increased PPR was recorded. The facilitation was not due to GABA(A) receptor-mediated inhibition and was not age-dependent. In CA3 area, increased paired-pulse facilitation of PSs and EPSPs over the range of 10-1000 ms IPIs was observed only in the 15-week-old El mice. The age-dependent appearance of seizure susceptibility was associated with the increase in excitatory synaptic transmission in CA3. Our results show that El mice possess excitatory/inhibitory synaptic transmission abnormalities in the hippocampus that could contribute to seizure predisposition.

Action Potentials↗
PubMed1998

Concurrent enchondroma and periosteal chondroma of the humerus mimicking chondrosarcoma.

A case of concurrent enchondroma and periosteal chondroma of the right proximal humerus in a 19-year-old woman is reported. Radiographs and CT scans showed a periosteal lesion with saucerization and spicula-like mineralization of the lateral aspect of the right proximal humerus and an ill-defined irregular lucency with stippled calcifications of the medullary cavity adjacent to it. MRI showed a long intramedullary lesion in addition to the surface lesion. There was no cortical disruption by imaging and gross examination. Histologically, both lesions showed benign cartilaginous tumors; concurrent enchondroma and periosteal chondroma of the humerus was therefore diagnosed. This combination in the same bone in a patient without enchondromatosis is exceedingly rare. Radiographic features may be confused with chondrosarcoma.

Adult↗
PubMed1998

Application of SPET using technetium-99m sestamibi in brain tumours and comparison with expression of the MDR-1 gene: is it possible to predict the response to chemotherapy in patients with gliomas by means of 99mTc-sestamibi SPET?

Technetium-99m sestamibi (MIBI) is thought to be passively taken up by metabolically active tumour cells and effluxed from them by P-glycoprotein (Pgp). This 170-kDa membrane-bound protein, encoded by the MDR-1 gene, acts as an energy-dependent efflux pump for several antineoplastic agents, resulting in multidrug resistance. For this reason, it is of interest whether the tumour's response to chemotherapy can be predicted by MIBI single-photon emission tomography (SPET). In this study, MIBI SPET was compared with thallium-201 (Tl) SPET using magnetic resonance imaging as a guide in 16 patients with untreated brain tumours [ten glioblastomas (GBs), two anaplastic astrocytomas (AAs), two low-grade gliomas (LGASs) and two metastatic brain tumours) and in four patients who had received treatment for with brain tumours (two GBs, two AAs). In addition, we investigated the expression of the MDR-1 gene and its product Pgp in the same patients, and compared the results with MIBI SPET findings. MIBI, as well as Tl, was highly accumulated and retained in the enhanced region of malignant gliomas. In addition, MIBI SPET yielded sharp and well-contrasted images, and the margin of the tumour was more clearly defined than with Tl SPET due to a good signal-to-noise ratio. Follow-up MIBI SPET in patients who had received therapy showed marked uptake in a patient with malignant transformation, who deteriorated clinically. Patients with no uptake on MIBI SPET showed no sign of recurrence. Semiquantitative analysis of untreated patients showed a relationship between the early uptake index (UI, ratio of average count/pixel in the lesion to that in the contralateral area on early images) and the degree of malignancy (early UI = 1.08+/-0.06 in LGASs, 4.10+/-0.84 in AAs, 5.71+/-3.47 in GBs, and 7.52+/-1.52 in metastatic brain tumours). The retention index (RI, ratio of delayed to early UI) of MIBI was significantly lower than that of Tl in metastatic brain tumours (P<0.05), but not in malignant gliomas. Histological and biological investigation of gliomas showed that the MDR-1 gene and its product Pgp were expressed only in normal endothelial cells and not in tumour cells or proliferating endothelial cells; Pgp tended to decrease as the degree of malignancy rose. Hence, the presence of Pgp and the grade of malignancy were inversely related in gliomas. By contrast, immunohistochemical study showed strong accumulation of Pgp in metastatic brain tumour cells. These histopathological findings and MIBI SPET findings are compatible with experimental data; MIBI was washed out by Pgp. The main cause of chemoresistance is probably not an increasing drug efflux by Pgp in gliomas. Thus, MIBI SPET is useful for detecting the active lesions, but may not be useful for predicting the response to chemotherapy in gliomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Vitamin C attenuates abnormal vasomotor reactivity in spasm coronary arteries in patients with coronary spastic angina.

OBJECTIVES: This study sought to examine effect of vitamin C, an antioxidant, on the abnormal vasomotor reactivity in spasm coronary arteries. BACKGROUND: Oxygen free radicals generated in the arterial walls have been shown to cause endothelial vasomotor dysfunction. METHODS: Responses of the epicardial arterial diameters of the left coronary arteries to the intracoronary infusion of acetylcholine (ACh) (10 and 50 microg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of vitamin C (10 mg/min) or saline as a placebo in 32 patients with coronary spastic angina and in 34 control subjects. RESULTS: Vitamin C infusion suppressed the constrictor response of the epicardial diameter to ACh in spasm coronary arteries but had no significant effect in the control coronary arteries (percent change in distal diameter in response to 10 microg/min of ACh [constriction (-), dilation (+), mean +/- SEM] before vitamin C: -8.2 +/- 2.9% in spasm arteries, +8.4 +/- 2.9%* in control arteries; during vitamin C: +0.2 +/- 3.8%* in spasm arteries, +7.2 +/- 1.3%* in control arteries [*p < 0.01 vs. spasm arteries before vitamin CI). The coronary sinus-arterial difference in plasma thiobarbituric acid reactive substances during ACh infusion, an indicator of lipid peroxidation in coronary circulation, was higher in patients with coronary spastic angina than in control subjects (p < 0.01) but was suppressed in patients with coronary spastic angina to comparable levels in control subjects by combined infusion of vitamin C. Saline infusion had no effect. CONCLUSIONS: The results indicate that vitamin C attenuates vasomotor dysfunction in epicardial coronary arteries in patients with coronary spastic angina. Oxygen free radicals may at least in part play a role in the abnormal coronary vasomotor reactivity in response to ACh in spasm coronary arteries.

Acetylcholine↗
PubMed1998

Antenatal diagnosis of velamentous umbilical cord insertion and vasa previa with color Doppler imaging.

OBJECTIVE: To determine whether cord insertion can be consistently visualized and whether velamentous cord insertion and vasa previa can be consistently identified with color Doppler imaging during routine sonography in the mid-trimester. DESIGN: A prospective study. SUBJECTS: A total of 587 fetuses at 18-20 weeks' gestation. METHODS: During routine ultrasound examinations, the sonographer was instructed to take additional time and to image the placental cord insertion with color Doppler imaging and classify this as normal, velamentous or 'not seen'. When the insertion was velamentous, the sonographer was instructed to indicate whether or not it was vasa previa. The sonogram obtained at 18-20 weeks' gestation was used for comparison with outcome data. RESULTS: Cord insertion was visualized by color Doppler imaging in 99.8% (586/587) of the fetuses in our study. The mean time required for examination was 20 s and, in 95% of the cases, cord insertion was visualized within 1 min. The sonographic identification of velamentous cord insertion had a sensitivity of 100% (5/5), a specificity of 99.8% (580/581), a positive predictive value of 83% (5/6) and a negative predictive value of 100% (580/580). In our study, vasa previa was diagnosed at 18 gestational weeks in two cases and, in one of the cases, vasa previa was confirmed at delivery. CONCLUSIONS: We could consistently identify cord insertion and velamentous cord insertion with color Doppler imaging during routine sonography in the mid-trimester. Transvaginal color Doppler imaging and serial scans were needed to identify vasa previa.

Female↗
PubMed1998

Results of a qualitative and field study using the WHOQOL instrument for cancer patients.

The main purpose of the study was to evaluate quality of life (QOL) among cancer patients using the WHOQOL-100 instrument and to see if any significant differences were seen in cancer stages, treatment status and prognosis. This study consisted of two parts; qualitative and quantitative. For the qualitative study, two focus groups were conducted by medical professionals to establish the applicability of the WHOQOL instrument in evaluating the QOL of cancer patients, but most participants were negative about using a generic instrument such as WHOQOL. For the quantitative study, 197 cancer patients (average age 55.86) from eight medical centers using the WHOQOL instrument, in addition to each patient's information sheet filled in by their own physicians, were analyzed. The average overall QOL score was 3.39. There was high reliability (Cronbach's alpha = 0.9685) and a high correlation between the psychological and the environmental domains (r = 0.7021), the physical domain and the level of independence (r = 0.6031) and social relations and the environment (r = 0.6856) and between health conditions perceived by patients and QOL scores. In addition, differences by gender, treatments and cancer sites were also found to be significantly different at the 5% significance level. The results indicated that the WHOQOL core instrument was sensitive enough to evaluate the QOL of cancer patients.

Adult↗
PubMed1998

Multihormone-producing islet cell tumor of the pancreas associated with somatostatin-immunoreactive amyloid: immunohistochemical and immunoelectron microscopic studies.

Pancreatic islet cell tumors, especially insulinomas, are often associated with amyloid deposition in the tumor tissue. Biochemical analysis has demonstrated that the amyloid protein from insulinoma is derived from islet amyloid polypeptide (or amylin) that is produced by tumor cells originating from beta cells of the islet of Langerhans. We examined a case of malignant pancreatic islet cell tumor with amyloid deposition in the tumor tissue using immunohistochemistry and double-labeling immunogold electron microscopy. The tumors were composed of cells producing multiple hormones, including somatostatin, gastrin, amylin, insulin, calcitonin gene-related polypeptide, and calcitonin. Amyloid deposits reacted with antisomatostatin antiserum but not with other antisera, including antiamylin. The present study demonstrated for the first time that amyloid associated with islet cell tumors is not always derived from amylin and can come from somatostatin.

Aged↗
PubMed1998

An immunohistochemical study of amyloid P component, apolipoprotein E and ubiquitin in human and murine amyloidoses.

Amyloid P component (AP) and apolipoprotein E (Apo E), which are known to be minor constituents of amyloid deposits, commonly are associated with almost all types of amyloid deposits. In this study, the distribution of AP-, Apo E- and ubiquitin (Ub)-immunoreactivity (IR) in amyloid deposits in the liver and spleen of human systemic amyloidosis (34 autopsy cases: 17 immunoglobulin light chain derived, 17 amyloid A protein derived) and experimental murine amyloidosis is examined using an immuno-histochemical technique. In human cases, all of the amyloid deposits examined showed colocalization of AP- and Apo E-IR with individual amyloid proteins. In experimental amyloidosis, AP-IR of amyloid deposits in the liver and spleen and Apo E-IR in the liver were seen uniformly throughout this experiment. In contrast, Apo E-IR in the spleen was not uniform at the phase of amyloid deposition. At 4 weeks and at 16 weeks after casein injection, Apo E-IR was unevenly distributed in amyloid deposits in the perifollicular area; however, from 6 to 12 weeks it was seen to be uniform. Ubiquitin-IR of amyloid deposits in human cases was seen in 22 of 34 livers and in 22 of 33 spleens. In experimental amyloidosis, Ub-IR of amyloid deposits was demonstrated in the space of Disse in all mice examined, and there appeared to be a gradual increase in intensity with the amount of amyloid deposition. However, in the spleen, amyloid deposits did not react with anti-Ub antibody in any phase of amyloid induction. These results suggest that Apo E and Ub are not always associated with the process of amyloid deposition and may appear in a deposit after the deposition.

Adult↗
PubMed1998

Inhibitory effects of pentamethine trinuclear cyanine dyes on ADP/Fe2+-induced lipid peroxidation in rat liver mitochondria: changes in the mode of action with the hydrophobic nature of the dyes.

The effects of various pentamethine trinuclear cyanine dyes, each of which has three alkyl chains, on ADP/Fe2+-induced lipid peroxidation in rat liver mitochondria were examined. Although the dye having the shortest -C2H5 chains (tri-S-C2(5)) did not show any appreciable effect, the dyes having -C4H9 (tri-S-C4(5)), -C7H15 (tri-S-C7(5)), and -C12H25 (tri-S-C12(5)) chains significantly inhibited lipid peroxidation, the most potent inhibitory effect being observed with tri-S-C7(5). The mode of antiperoxidation effect of the dyes was dependent on the length of the alkyl chains. The relatively hydrophilic dye tri-S-C4(5) was suggested to scavenge radicals more efficiently at or near the membrane surface rather than in the interior of the lipid membrane, whereas the more hydrophobic dye tri-S-C7(5) was suggested to scavenge radicals efficiently in the membrane rather than at or near the membrane surface. The hydrophilic/hydrophobic balance of the dye was found to regulate the site of action of the dyes.

Adenosine Diphosphate↗
PubMed1998

Aortic valve replacement with a small mechanical valve prosthesis--a clinical and echocardiographic study of a St Jude Medical valve prosthesis.

The use of small aortic valve prostheses raises concerns about harmful effects of residual obstruction to left ventricular outflow. The present study was undertaken to examine long-term clinical and echocardiographic results in 193 patients who underwent isolated aortic valve replacement (AVR) with a St Jude Medical (SJM) valve of 25 mm or smaller. The study subjects comprised 128 male and 65 female patients with a mean age of 54.1 years. The patients were divided into 2 groups according to the size of the valve prosthesis used for AVR. Small valves (19 or 21 mm) were implanted in 49 patients (group S) and large valves (23 or 25 mm) were used in 144 patients (group L). The group S patients were mainly female, older, and had smaller body surface areas. There were no significant differences in early and late mortality in group S as compared with group L. Furthermore, there was no difference in the incidence of valve-related or cardiac, non-valve-related death, including the incidence of sudden death, between the 2 groups, and they enjoy a similar level of daily routine activity regardless of the valve size used. Left ventricular (LV) function (ejection fraction, fractional shortening, LV mass index, LV end-systolic volume index, and LV end-diastolic volume index) measured by echocardiography improved significantly and returned to normal values after AVR in both groups. Moreover, no significant differences were observed in the postoperative variables of the LV function. These results suggest that 19-mm and 21-mm SJM valves can be safely used for AVR in the majority of Japanese patients.

Aged↗
PubMed1998

Ultrastructural evidence for the formation of amyloid fibrils within cardiomyocytes in isolated atrial amyloid.

Isolated atrial amyloid (IAA) frequently affects elderly human hearts in which only the atria are involved by the deposits. Biochemical analysis has indicated that the major subunit protein of IAA is alpha-human atrial natriuretic peptide (alpha-ANP), which is synthesized by the atrial muscle cells. To define the exact location of the formation of IAA fibrils, right atria from 25 patients undergoing cardiac surgery have been examined by an immunohistochemistry and immunoelectron microscopy with anti-alpha-ANP, apolipoprotein E, amyloid P component, transthyretin, and cathepsin B antisera. Of 25 patients, 19 were involved with IAA deposits which reacted with anti-alpha-ANP, apolipoprotein E, amyloid P component antisera but not with anti-transthyretin antiserum. In 8 of them, amyloid fibrils were seen not only in the interstitium of the atrial myocardium but also in the dilated transverse tubules of the cardiomyocytes. In some cardiomyocytes, amyloid fibrils were also demonstrated within the organelles such as coated and uncoated secretory vesicles or lysosomes. These findings lead to the inescapable conclusion that the polymerization of amyloid fibrils in IAA occurs within the cytoplasm of cardiomyocytes under some conditions.

Adult↗
PubMed1998

Diagnosis of the level of depth in superficial depressed-type colorectal tumors in terms of stereomicroscopic pit patterns.

We investigated the relationship between stereomicroscopic pit patterns and histological structures in 93 lesions of superficial depressed-type colorectal tumors to assess the possibility of diagnosing the level of invasion by the pit patterns. All 9 lesions with Va (amorphous)-type pit pattern showed massive invasion into the submucosal layer (sm2, sm3). Massive invasion into sm was observed in 66.7% (6/9) of lesions with Vi (irregular)-type pit pattern, whereas 22.2% (2/9) of the lesions invaded the shallow layer of the submucosa (sm1) and 11.1% (1/9) were limited to the mucosa. Among the lesions with pit patterns other than Va and Vi, 93. 3% (70/75) were limited to the mucosa, whereas 6.7% (5/70) invaded the submucosal layer, but all were limited to sm1. These findings show that stereomicroscopic analysis of the pit patterns of the superficial depressed-type colorectal tumors is useful for diagnosing the level of invasion.

Adult↗
PubMed1998

Usefulness of the high-frequency ultrasound probe in pretherapeutic staging of superficial-type colorectal tumors.

We evaluated the usefulness of the high-frequency ultrasound probe (HFUP, 20 MHz) to determine the depth of tumor invasion in 45 patients with superficial colorectal tumors. The correct diagnostic rate was 66% (30/45) when the depth of tumor invasion was classified into the following 6 layers: mucosa (m), upper 1/3 (sm1), middle 1/3 (sm2), and lower 1/3 (sm3) areas of the submucosa, muscularis propria (mp), and the subserosa or deeper areas (s). However, when the depth of tumor invasion was evaluated in 3 layers (m-sm1, sm2-sm3, and mp-deeper layer), which is the classification used to select cases for endoscopic mucosal resection, the correct diagnostic rate was 88.9% (40/45). These results suggest that the HFUP is useful to determine the depth of invasion to select treatment for superficial colorectal tumors.

Aged↗