Biomedical subjects

H Kojima

Publications and source records attributed to H Kojima.

At least 235 records · Page 13Linked to original sources

PubMed1998

Association study of a functional catechol-O-methyltransferase gene polymorphism in Japanese schizophrenics.

Catechol-O-methyltransferase (COMT) is an enzyme which inactivates catecholamine neurotransmitters by methylation, and is considered a candidate for involvement in schizophrenia. A functional COMT gene polymorphism influencing the enzyme activities, the high activity (val-108) and the low activity allele (met-108), was recently confirmed. We investigated a genetic association between schizophrenia and the COMT gene polymorphism in 150 Japanese schizophrenics and controls. We detected the low activity met-108 allele more frequently in schizophrenics than in the controls, and found that subjects sharing the met-108 allele (val/met and met/met) are significantly more common in the patients than in the controls. The results suggest that the low activity met-108 allele may be involved in susceptibility for schizophrenia.

Alleles↗

PubMed1998

Simultaneous observation of individual ATPase and mechanical events by a single myosin molecule during interaction with actin.

We have developed a technique that allows mechanical and ligand-binding events in a single myosin molecule to be monitored simultaneously. We describe how steps in the ATPase reaction are temporally related to mechanical events at the single molecule level. The results show that the force generation does not always coincide with the release of bound nucleotide, presumably ADP. Instead the myosin head produces force several hundreds of milliseconds after bound nucleotide is released. This finding does not support the widely accepted view that force generation is directly coupled to the release of bound ligands. It suggests that myosin has a hysteresis or memory state, which stores chemical energy from ATP hydrolysis.

Actin Cytoskeleton↗

PubMed1998

Cell proliferation and apoptosis in human middle ear cholesteatoma.

OBJECTIVE: To compare the pattern of proliferation and apoptotic cell death in cholesteatoma tissues with that in normal skin. PARTICIPANTS: The cholesteatoma tissue samples were excised from 10 patients during surgery. Normal skin specimens collected from the external ear canal of 6 of the 10 patients were used as controls. RESULTS: In all cholesteatoma tissue samples, apoptotic cells were not seen in the basal cell layer, but they were observed in the suprabasal, prickle, and granular cell layers. In skin specimens obtained from normal external ear canal skin, in which the suprabasal cell layer was comparatively small, similar kinetics of apoptotic cell death were observed. Immunohistochemical analysis using a monoclonal antibody to proliferation cell nuclear antigen demonstrated the presence of proliferating cells in the basal and suprabasal cell layers of the normal external ear canal skin, whereas in the cholesteatoma tissue samples, large numbers of proliferation cell nuclear antigen-positive cells were also observed in the prickle and granular cell layers. CONCLUSIONS: Proliferation in cholesteatoma epidermal cells is not uncontrolled, as it is in malignant tumors. Our results demonstrate an increase in the rate of proliferation and apoptotic cell death in cholesteatoma epidermis.

Adult↗

PubMed1998

Brain tumors in surgical neuropathology of intractable epilepsies, with special reference to cerebral dysplasias.

Surgical specimens from 30 patients (13 males and 17 females) with intractable epilepsy with brain tumors and allied lesions were histopathologically examined: 4 of nonneurogenic origin (1 angiolipoma with cortical dysplasia and 3 cavernous hemangiomas), 2 low-grade fibrillary astrocytomas, 1 pleomorphic xanthoastrocytoma, 3 pilocytic astrocytomas with nuclear polymorphism, 1 oligoastrocytoma, 9 gangliogliomas, 3 gangliogliomatous lesions combined with tuberous sclerosis-like dysplastic changes, and 7 undetermined lesions suspected of being mixed glioma, dysembryoplastic neuroectodermal tumor (DNT), or dysplasia. They were all located supratentorially: in the temporal lobe in 21, frontal lobe in 6, and parietooccipital lobe in 3. The age of onset was under 20 years in most patients. Some kinds of dysplasias, such as focal cortical dysplasia, glioneuronal heterotopia, and clustered neurons in the hippocampus and amygdaloid nucleus, were combined in 11 cases, especially those with age of onset under 10 years. Pilocytic astrocytoma-like features were seen in 5 of the gangliogliomas and 3 of the undetermined lesions, and DNT-like features in 2 of the former and 3 of the latter. Gangliogliomas, pilocytic astrocytomas, mixed gliomas, DNTs, and dysplasias may be closely inter-related in the development of intractable epilepsies of young patients.

Adolescent↗

PubMed1998

Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty rats.

Otsuka Long-Evans Tokushima Fatty (OLETF) rats are reported to be obese Type II (non-insulin-dependent) diabetic rats with insulin resistance and impaired insulin secretion. To investigate the contribution of intestinal glucose absorption to postprandial hyperglycaemia, we determined the plasma xylose concentrations after an 0.8 g/kg oral xylose load which was used as a test of small intestinal glucose absorption in 6-week-old OLETF rats and weight-matched Long-Evans Tokushima Otsuka (LETO) rats. An oral glucose tolerance test showed that OLETF rats developed hyperglycaemia at 60 and 90 min after the glucose load, though the fasting plasma glucose concentration, insulin concentration and insulin-induced in vivo glucose utilization rate were similar. Consistently, in an oral D-xylose loading test, the peak concentration of plasma xylose in OLETF rats was increased by 58.7% compared with that of LETO rats (p < 0.005). The disappearance rate of plasma xylose concentrations after intravenous xylose loading did not differ between the two strains. Co-treatment with 0.4 g/kg phlorizin, a specific inhibitor of sodium-dependent glucose transporter 1 (SGLT1), abolished both plasma glucose and xylose concentrations after the loads. Morphological studies showed that both the small intestinal wet weight and surface area were 30% larger in the OLETF rats than in the LETO rats. Furthermore, the SGLT1 mRNA content of OLETF rats also increased compared with LETO rats. These results suggest that an increased SGLT1 expression concomitant with intestinal hypertrophy in OLETF rats is partly associated with postprandial hyperglycaemia before the onset of insulin resistance and hyperinsulinaemia.

Animals↗

PubMed1998

Anaplastic large-cell lymphoma of null-cell type with multiple bone involvement.

A 21-year-old man who had anaplastic large cell lymphoma (ALCL) of the null-cell type with multiple bone involvement is reported. On admission, he had symptoms of incomplete paraplegia and urinary and rectal incontinence. Workup studies for staging revealed para-aortic lymph node swellings and multiple bone involvement including skull, ribs, left iliac bone, and thoracic/lumbar spine. Because paraplegia was rapidly progressive, a decompression operation was performed. The biopsy specimen obtained from the lumbar spine revealed sheetlike proliferation of anaplastic large cells. These cells were positive for CD30 (Ki-1), EMA, vimentin, and p80NPM/ALK, and negative for CD3, CD20 (L26), and CD45 (LCA). Epstein-Barr virus-encoded small RNAs were not detectable in these cells. Thus, the patient was diagnosed as having ALCL of the null-cell type. He was treated with several courses of combination chemotherapy, and finally with total body irradiation plus high-dose chemotherapy supported by peripheral blood stem cell transplantation. However, soon after the treatment, the lymphoma cells massively infiltrated his bone marrow. He died of lymphoma 8 months after admission.

Adult↗

PubMed1998

News & notes. Efficient library construction with a TA vector and its application to cloning of the phytoene synthase gene from the cyanobacterium Spirulina platensis.

An efficient and simple method for constructing a genomic DNA library is presented by use of a TA cloning vector. It is based on sonicative cleavage of genomic DNA and modification of the fragment ends with Taq DNA polymerase, followed by ligation with a TA vector. This method was successfully applied to cloning of the phytoene synthase gene crtB from Spirulina platensis. The method is useful when the genomic DNA is not well digested with restriction enzymes owing to methylation or other reasons.

Alkyl and Aryl Transferases↗

PubMed1998

Neuropathological and molecular studies of spinocerebellar ataxia type 6 (SCA6).

SCA6 is an autosomal dominant spinocerebellar ataxia (SCA) caused by a small CAG repeat expansion of the gene encoding an alpha-1A-voltage-dependent Ca channel gene subunit on chromosome 19p13. A Japanese woman with SCA6, with a 7-year history of progressive pure cerebellar ataxia, died of malignant lymphoma. Systematic neuropathological examination showed that neuronal degeneration was confined to the cerebellar Purkinje cells and, to a lesser degree, the granular cells, without any involvement of other central nervous system structures. Such pathological selectivity correlates with the localized expression of the responsible gene, and coincides with the neurological manifestation. These findings might contribute to establishing the phenotype of the SCA6 via comparison with other dominant ataxias.

Age of Onset↗

PubMed1998

Figure/ground segregation from temporal delay is best at high spatial frequencies.

Two experiments investigated the role of spatial frequency in performance of a figure/ground segregation task based on temporal cues. Figure orientation was much easier to judge when figure and ground portions of the target were defined exclusively by random texture composed entirely of high spatial frequencies. When target components were defined by low spatial frequencies only, the task was nearly impossible except with long temporal delay between figure and ground. These results are inconsistent with the hypothesis that M-cell activity is primarily responsible for figure/ground segregation from temporal delay. Instead, these results point to a distinction between temporal integration and temporal differentiation. Additionally, the present results can be related to recent work on the binding of spatial features over time.

Adult↗

PubMed1998

Significance of increased plasma adrenomedullin concentration in patients with cirrhosis.

BACKGROUND/AIMS: Adrenomedullin recently discovered in human pheochromocytoma is a potent vasodilatory peptide mainly derived from vascular endothelial and smooth muscle cells. Hyperdynamic circulation, ultimately leading to ascites formation, has been attributed to peripheral vasodilatation in liver cirrhosis. However, little is known about the role of adrenomedullin in this condition. METHODS: Plasma adrenomedullin concentrations were measured by radioimmunoassay after extraction and purification in 28 cirrhotic patients without ascites, 12 cirrhotic patients with ascites and 10 healthy subjects. RESULTS: Plasma adrenomedullin concentrations in cirrhotic patients with ascites (12.7+/-4.5 fmol/ml) were significantly higher than those in cirrhotic patients without ascites (8.2+/-2.3 fmol/ml, p<0.005) and healthy subjects (5.8+/-0.8 fmol/ml, p<0.005). Interestingly, plasma adrenomedullin concentrations were highest in patients with refractory ascites (n=5, 15.8+/-3.0 fmol/ml) and were positively correlated with the Child-Pugh score (r=0.44, p<0.01). Moreover, plasma adrenomedullin concentrations were positively correlated with plasma renin activity (r=0.63, p<0.0001), plasma aldosterone (r=0.60, p<0.0001) and plasma norepinephrine concentrations (r=0.60, p<0.0001), and negatively correlated with creatinine clearance (r=-0.61, p<0.0005) and urinary sodium excretion (r=-0.44, p<0.02). Stepwise multiple regression analysis using certain independent variables, including Pugh's score, vasoactive substances, renal function and hemodynamic parameters, showed that the adjusted R square was highest when plasma renin activity and creatinine clearance (standard coefficient=0.53, -0.49, respectively) were considered (adjusted R square=0.61, p<0.0001). CONCLUSIONS: Plasma adrenomedullin concentrations increased with the progression of liver cirrhosis and were highest in cirrhotic patients with refractory ascites. In addition, elevated adrenomedullin was associated with activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, and with functional renal impairment in cirrhosis. Considering the potent vasodilatory action of adrenomedullin, increased adrenomedullin may participate in the hyperdynamic circulation, ultimately leading to ascites formation, in patients with liver cirrhosis.

Adrenomedullin↗

PubMed1998

Expression of transforming growth factor-alpha (TGF-alpha) in cholesteatoma.

This study aims at elucidating the role of cytokines in the mechanism of proliferation of cholesteatoma epithelium by investigating the mode of expression of epidermal growth factors, such as TGF-alpha. The subjects of this study were patients who had undergone operation for middle ear cholesteatoma. Skins of the bone region of the external ear canal (normal skin) of the same patients were used as the negative control. The mode of expression of TGF-alpha was studied by immunohistochemistry and in situ hybridization. In the immunohistochemical study, there were no conspicuous differences observed between cholesteatoma tissues and normal skin. After in situ hybridization, expression of TGF-alpha mRNA was mainly observed in the epidermal basal cell layer in the normal skin, while in the cholesteatoma epidermis with severe inflammatory cell infiltration, expression of TGF-alpha mRNA was observed up to layers superior to the basal cell layer. The expression of TGF-alpha mRNA is greatly affected by subepithelial connective tissue, strongly suggesting involvement of paracrine regulation in proliferation of cholesteatoma epithelium.

Adolescent↗

PubMed1998

Differential induction by methyl jasmonate of genes encoding ornithine decarboxylase and other enzymes involved in nicotine biosynthesis in tobacco cell cultures.

A cDNA of tobacco BY-2 cells corresponding to an mRNA species which was rapidly induced by methyl jasmonate (MeJA) in the presence of cycloheximide (CHX) was found to encode ornithine decarboxylase (ODC). Another cDNA from a MeJA-inducible mRNA encoded S-adenosylmethionine synthase (SAMS). Although these enzymes could be involved in the biosynthesis of polyamines, the level of putrescine, a reaction product of ODC, increased slowly and while the levels of spermidine and spermine did not change following treatment of cells with MeJA. However, N-methylputrescine, which is a precursor of pyrrolidine ring of nicotine, started to increase shortly after MeJA-treatment of cells and the production of nicotine occured thereafter. The levels of mRNA for arginine decarboxylase (ADC), an alternative enzyme for putrescine synthesis, and that for S-adenosylmethionine decarboxylase (SAMDC), required for polyamine synthesis, were not affected by MeJA. In addition to mRNAs for ODC and SAMS, mRNA for putrescine N-methyltransferase (PMT) was also induced by MeJA. Unlike the MeJA-induction of ODC mRNA, MeJA-induction of SAMS and PMT mRNAs were blocked by CHX. The level of ODC mRNA declined after 1 to 4 h following MeJA treatment, while the levels of mRNAs for SAMS and PMT continued to increase. Auxin significantly reduced the MeJA-inducible accumulation of mRNAs for ODC, SAMS and PMT. These results indicate that MeJA sequentially induces expression of a series of genes involved in nicotine biosynthesis by multiple regulatory mechanisms.

Acetates↗

PubMed1998

Three-dimensional structure of a glycosphingolipid having a novel carbohydrate linkage, Galbeta1-4(Fucalpha1-3)Glcbeta1-3Galbeta, determined by theoretical calculations.

The novel glycosphingolipid, SEGLx (Galbeta1-4(Fucalpha1-3)Glcbeta1-3GalbetaCer), which was identified by us (Kawakami Y, et al. (1993) J Biochem 114: 677-83), shows a characteristic spectrum on 1H-NMR analysis, in which the anomeric proton resonances of a reducing end galactose and a glucose are split. To elucidate the structural characteristics of SEGLx, we determined its three-dimensional (3D) structure by means of computer simulation, involving such techniques as molecular mechanics (MM2), the semiempirical molecular orbital method (AM1), molecular dynamics (Amber), and computer 3D modelling. With the hypothesis that all OH group(s) of a ceramide participate in intramolecular hydrogen bonds, two kinds of stable conformers, horizontal and right-angled ones, were formed, depending on the ceramide species. The present findings suggest that the chemical species of both the long chain base and fatty acid moieties, mainly the occurrence of OH group(s), affect the chemical shifts of the anomeric proton resonances not only of the reducing terminal galactose but also the penultimate glucose through the formation of intramolecular hydrogen bonds. Computer simulation through theoretical calculation and 3D modelling was shown to be the best means of confirming the results obtained by experimental analysis.

Algorithms↗

PubMed1998

Serum thrombopoietin level is mainly regulated by megakaryocyte mass rather than platelet mass in human subjects.

A patient with idiopathic thrombocytopenic purpura (ITP) developed T-cell lymphoma while undergoing steroid therapy. We examined the relationship between the patient's serum thrombopoietin (Tpo) level, platelet count, megakaryocyte number and CFU-Meg number during the second 5 d course of chemotherapy for lymphoma in which megakaryopoiesis switched from ITP phase to amegakaryocytic phase. The patient's platelet count was temporarily elevated but CFU-Meg numbers were markedly suppressed, and megakaryocyte numbers were decreased in this period, whereas serum Tpo level was not suppressed despite an increased platelet count, indicating that serum Tpo level is mainly regulated by megakaryocyte mass.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Role of spatial and temporal coincidence in depth organization.

The linking of spatial information is essential for coherent space perception. A study is reported of the contribution of temporal and spatial alignment for the linkage of spatial elements in terms of depth perception. Stereo half-images were generated on the left and right halves of a large-screen video monitor and viewed through a mirror stereoscope. The half-images portrayed a black vertically oriented bar with two brackets immediately flanking this bar and placed in crossed or uncrossed disparity relative to the bar. A pair of thin white 'bridging lines' could appear on the black bar, always at zero disparity. Brackets and bridging lines could be flickered either in phase or out of phase. Observers judged whether the brackets appeared in front of or behind the black bar, with disparity varied. Compared to conditions when the bridging lines were absent, depth judgments were markedly biased toward "in front" when bridging lines and brackets flashed in temporal phase; this bias was much reduced when the bridging lines and brackets flashed out of phase. This biasing effect also depended on spatial offset of lines and brackets. However, perception was uninfluenced by the lateral separation between object and brackets.

Computer Graphics↗

PubMed1998

Influence of speech-coding strategy on cortical activity in cochlear implant users: a positron emission tomographic study.

The effects of a speech-coding strategy of cochlear implant (CI) on cortical activity were evaluated using positron emission tomography. The CIs used in the present study were those of a 22-channel system using the Multipeak speech-coding strategy (MPEAK) and the spectral peak strategy (SPEAK). On comparing the 2 groups, it was found that the speech-tracking performance was significantly higher in the SPEAK group than in the MPEAK group. Regional cerebral blood flow (rCBF) was measured during the silent resting, noise stimulus and speech stimulus periods. The increase in rCBF was localized mainly in the primary auditory area during the noise stimulus period. The increase in rCBF in the auditory association area during the speech stimulus period was stronger in the SPEAK group than in the MPEAK group. This finding suggests that the SPEAK strategy activates more speech processing neuronal networks in the auditory association area than the MPEAK strategy.

Acoustic Stimulation↗

PubMed1998

Increased plasma levels of substance P and disturbed water excretion in patients with liver cirrhosis.

BACKGROUND: The pathogenesis of impaired water excretion in liver cirrhosis has not been fully elucidated. METHODS: We induced an intravenous water overload of 20 ml/kg body weight in 10 cirrhotics without ascites (CLC), 11 cirrhotics with ascites (DLC), and 10 normal subjects (N) and investigated the relationship of plasma levels of substance P (SP), norepinephrine (NE), and antidiuretic hormone (ADH) to impaired water excretion. RESULTS: Free water clearance (CH2O) was lower in DLC (mean, 2.7 ml/min) than in N (8.3 ml/min; P < 0.001) and CLC (6.9 ml/min; P < 0.001). In DLC the creatinine clearance (CCr), maximal urine flow rate/CCr, (CH2O + CNa)/CCr, and mean arterial pressure (MAP) were significantly lower than in N and CLC. There was a progressive increase in basal SP, from lowest in N to CLC, to highest in DLC. Basal NE increased in CLC and DLC. Basal ADH did not differ among N, CLC, and DLC. In cirrhotics CH2O was correlated positively with serum albumin and cholinesterase and negatively with the retention rate of indocyanine green at 15 min. Basal SP was negatively correlated with CH2O (r= -0.71: P < 0.001) and MAP (r= -0.56; P < 0.005). Basal NE was correlated positively with basal SP (r= 0.67, P < 0.01 ). CONCLUSIONS: Decreased CH2O is closely related to the severity of the liver disturbance. Decreased CCr and reduced delivery of filtrate to the ascending limb of the loop of Henle secondary to an increased sodium reabsorption in the proximal tubule may play an important role in the impairment of water excretion. The increase in SP, which has a potent vasodilatory action, and the associated enhanced activity of the sympathetic nervous system may be responsible for the mild or moderate impairment of water excretion in the absence of nonosmotic hypersecretion of ADH in cirrhotics with ascites.

Adult↗

PubMed1998

Characterization of a calcium-dependent protein kinase of tobacco leaves that is associated with the plasma membrane and is inducible by sucrose.

The plasma membrane fraction from leaves of tobacco contains a 54-kDa protein with autophosphorylation activity, and the level of this protein increases after feeding of leaves with sucrose [Ohto and Nakamura (1995) Plant Physiol. 109: 973]. The 54-kDa autophosphorylation protein could not be released from the plasma membrane by treatment with salt or alkali but could be efficiently solubilized by 1% sodium deoxycholate (NaDOC). Ion-exchange chromatography of the NaDOC-solubilized proteins in the presence of octylglucoside separated the 54-kDa autophosphorylation protein into three peaks. The autophosphorylation activity of the 54-kDa protein in peaks I and II increased after feeding of leaves with sucrose. The 54-kDa protein in the peak II fraction was enriched about 125-fold starting from the microsomal membrane fraction. The 54-kDa protein in this fraction phosphorylated histone IIIS in a calcium-dependent manner and cross-reacted with an antibody against a calcium-dependent protein kinase (CDPK) of Arabidopsis thaliana. These results suggest that the 54-kDa protein in the peak II fraction is a novel isoform of CDPK which is associated with the plasma membrane and is inducible by sucrose.

Arabidopsis↗