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Biomedical subjects

S Kawaguchi

Publications and source records attributed to S Kawaguchi.

At least 145 records · Page 8Linked to original sources

[Proton MR spectroscopy in patients with unilateral temporal lobe epilepsy].

The authors assessed proton magnetic resonance spectroscopy (1H-MRS) in patients with unilateral refractory temporal bole epilepsy. The subjects consisted of 20 patients (those with brain tumors, trauma, malformations or definite organic lesions were excluded) and 10 normal volunteers. 1H-MRS and MRI were performed using a 1.5 tesla machine. 1H-MRS was achieved using point-resolved spectroscopy (PRESS) or the stimulated echo acquisition mode (STEAM), and a 3 x 3 x 3 cm volume of interest was positioned at the hippocampus. N-Acetyl-aspartate (NAA) and choline-containing substance (Cho) signals were evaluated. The results showed decreased NAA and elevated Cho or asymmetry of both NAA and Cho in the epileptogenic focus in 19/20 cases. The reductions in NAA presumably reflect neuronal loss, while the elevation of Cho probably represents membrane break down within the lesion. These abnormalities were observed in 19/20 cases (95%), whereas abnormal magnetic resonance imaging was detected in only 6/20 (30%) of the patients. Thus, 1H-MRS appears to be a useful, non-invasive modality for evaluating metabolic changes in epileptogenic foci, and these metabolic changes can serve as a more sensitive indicator than magnetic resonance imaging.

Adolescent↗

[A comparative study of tazobactam/piperacillin and piperacillin in bacterial pneumonia].

The efficacy, safety and usefulness of tazobactam/piperacillin (TAZ/PIPC), in bacterial pneumonia and lung abscess were determined with PIPC as the control in a multi-institutional comparative study a penicillin antibiotic for injection prepared by combining a newly developed beta-lactamase inhibitor, tazobactam (TAZ), with a broad spectrum penicillin antibiotic, piperacillin (PIPC), at a ratio of 1:4. TAZ/PIPC was intravenously injected at a dose of 2.5 g (titer) twice a day, and PIPC at a dose of 2.0 g (titer) twice a day as a rule for 14 days. The following results were obtained: 1. The efficacy rates for bacterial pneumonia and lung abscess were 94% (80/85) in TAZ/PIPC group and 89% (70/79) in PIPC group, showing no significant difference between the two groups. 2. In a comparison of degrees of improvement in clinical symptoms, signs and laboratory findings, there were no significant differences between the two groups except for results on thoracic rales after three days of administration. 3. As for bacteriological effects, the elimination rates of causative organisms were 98% (40/41) in the TAZ/PIPC group and 80% (28/35) in the PIPC group. Thus, the TAZ/PIPC group was significantly superior to the PIPC group. The TAZ/PIPC group showed significantly better eradication of bacteria as well. Bacteria considered to be pyogenic were detected in 80 patients (43 administered TAZ/PIPC and 37 administered PIPC), but beta-lactamase production was confirmed in only 11 patients of each group. There were no significant differences in bacteriological effects among these patients. Minimum inhibitory concentrations of TAZ/PIPC against beta-lactamase producing organisms were distinctly superior to those of PIPC. 4. Side effects occurred in 10% (10/96) of the TAZ/PIPC group and 7% (7/95) of the PIPC group. Abnormal clinical laboratory test values were observed in 22% (20/92) of the TAZ/PIPC group and 18% (17/93) of the PIPC group. Thus, there were no significant differences between the two administration groups. 5. The usefulness rate in the TAZ/PIPC group was 87% (75/86) and it was 85% (67/79) in the PIPC group, showing no significant difference between them. The results suggest that TAZ/PIPC administered at a dose of 2.5 g (titer) twice a day is more useful than PIPC administered at a dose of 2.0 g (titer) twice a day in the treatment of bacterial pneumonia.

Adult↗

[A comparative study of tazobactam/piperacillin and piperacillin in chronic respiratory tract infections].

The efficacy, safety and usefulness were evaluated for a combined antibiotic tazobactam/piperacillin (TAZ/PIPC) consisting of a new beta-lactamase inhibitor, tazobactam (TAZ), and a broad spectrum penicillin antibiotic, piperacillin (PIPC), in chronic respiratory tract infections with PIPC as the control in a multi-institutional comparative study. The drugs used were a preparation containing 0.5 g of TAZ and 2.0 g of PIPC per vial (TAZ/PIPC group) and a preparation containing 2.0 g of (PIPC group). The drugs were intravenously injected one vial at a time twice a day for 14 days as a rule. The following results were obtained: 1. Clinical effect There was no significant difference between TAZ/PIPC (86% or 76/88) and PIPC (81% or 69/85). 2. Bacteriological effect There was no significant difference between TAZ/PIPC (93% or 42/45) and PIPC (88% or 36/41) in terms of bacterial eradication rates. In 34 patients with beta-lactamase-producing pyogenic bacteria, there was no significant difference between TAZ/PIPC (77% or 10/13) and PIPC (88% or 15/17). 3. Degrees of improvement in clinical symptoms, signs and laboratory findings The TAZ/PIPC group was likely to show reductions in fever and the amount of sputum soon after administration. 4. Side effects Incidences of side effects were 7% (7/96) in the TAZ/PIPC group and 3% (3/89) in the PIPC group, showing no significant difference between the two groups. The main symptoms were allergic reaction and gastrointestinal symptoms. 5. Abnormal clinical laboratory test values The incidence was 17% (15/89) in the TAZ/PIPC group and 21% (18/87) in the PIPC group. The main symptoms were eosinophilia and hepatic dysfunction, and most of these symptoms were mild. 6. Usefulness The usefulness rates in the TAZ/PIPC group were 80% (71/89) and 78% (66/85) in the PIPC group, showing no significant difference. Thus, TAZ/PIPC exhibited excellent clinical effects and presented no troubles with safety. When comprehensively evaluated, TAZ/PIPC appears to be a very useful drug for the treatment of chronic respiratory tract infections.

Adult↗

Minimum alpha chain cytoplasmic tail sequence needed to support integrin-mediated adhesion.

Previously, we found that deletion of the integrin alpha 4 and alpha 2 subunit cytoplasmic domains, just after the conserved GFFKR motif, causes a loss of adhesive activity mediated by VLA-4 or VLA-2, respectively (Kassner, P.D., and Hemler, M. E. (1993) J. Exp. Med. 178, 649-60; Kawaguchi, S., and Hemler, M. E. (1993) J. Biol. Chem. 268, 16279-12685). Here, we show for alpha 4 and alpha 2 chains (expressed in MIP101 and Chinese hamster ovary cells) that adding only 3-4 amino acids after the GFFKR motif restores substantial adhesive activity and that 5-7 amino acids confers maximal adhesive activity (to VCAM-1, CS1 peptide, or collagen, respectively). Point mutations within the most critical 5 alpha 4 residues had no effect on alpha 4 adhesive activity, nor did exchange of the alpha 4 tail with that of alpha 2. Thus, only a short and relatively nonspecific stretch of alpha chain cytoplasmic domain amino acids may be required to achieve maximal integrin adhesive activity. Also, comprehensive divalent cation titration assays revealed (i) that deletion of alpha chain cytoplasmic domains caused a marked decrease in the efficiency of divalent cation utilization during cell adhesion assays and (ii) that cytoplasmic domain deletion effects could be either suppressed or accentuated depending on the type and amount of divalent cation and the cellular environment utilized. Notably, integrin alpha chain tail deletions did not appear to alter the intrinsic ability to interact with ligand because deletion effects were minimal in the presence of metabolic energy inhibitors and were absent during cell-free ligand binding assays.

Amino Acid Sequence↗

Restoration of function by replacement of spinal cord segments in the rat.

Reconstruction of a severed mammalian spinal cord with restoration of function has so far not been achieved, although structural and functional restitution after spinal transection has been successful in some lower vertebrates. In quail-chick and chick-chick chimaeras, spinal cord segments were found to be functional after replacement by isotopic and isochronic grafting of the neural tube. Here we achieve such a replacement in neonatal rats under less restricted topological and temporal conditions than were necessary for the avian chimaeras. The replaced segments united with the host spinal cord and promoted robust growth and regrowth of axons across the graft, enabling neural connections to be reconstructed that were hardly distinguishable from normal. The animals with replaced segments could walk, run and climb with almost normal hind-forelimb coordination. This functional restoration in these animals appeared to be permanent, raising the possibility of therapeutic application in humans.

Action Potentials↗

Signals through membrane Ig of peritoneal CD5 B cells to suppress LPS-induced Ig secretion.

Murine peritoneal CD5 B cells include many B cells reactive with bromelain-treated mouse RBC (BrMRBC). Anti-BrMRBC B cells are through to expand after selection by self-antigens, but little is known about signals through their membrane Ig (mIg). Most anti-BrMRBC antibodies use VH11 and V kappa 9 genes, and VH11/V kappa 9-type antibodies are detectable specifically with rabbit anti-idiotype antibodies (here referred to as RAIa). Preincubation of peritoneal cells with RAIa at 37 degrees C before LPS stimulation reduced LPS-induced secretion of RAIa-detectable Ig. To render RAIa-reactive B cells hyporesponsive, a continuous reaction of their mIg with RAIa was necessary. Binding of BrMRBC to RAIa-reactive B cells hardly affected their LPS reactivity. It appears that fresh mIg deliver the suppressive signals after reacted with RAIa, and the degree of hyporesponsiveness of a RAIa-reactive B cell depends on the amount of mIg-RAIa complexes. RAIa-suppressed B cells could regenerate mIg in the absence of RAIa and could respond to LPS to enlarge. It is suggested that binding of RAIa to mIg renders RAIa-reactive B cells without proliferation in an anergy state, where synthesis of secretory Ig is rather specifically suppressed.

Animals↗

Management of dissecting aneurysms of the posterior circulation.

We analysed the clinical presentation, treatment and outcome of our own 36 cases of posterior circulation dissecting aneurysms (DA) and discussed the surgical indications and procedures regarding posterior fossa DA. Twenty one cases were male, 15 cases were female. Their mean age was 54 +/- 14 years. Clinical manifestations were subarachnoid haemorrhage (SAH) in 14 cases (39%) and ischaemic attacks in 22 cases (61%). Three of 14 SAH cases had rebleeding in the acute stage. Angiographic findings were aneurysmal dilatation in 16 cases, retention of contrast medium in 12 cases, string sign in 9 cases, double lumen in 4 cases, pearl and string sign in 3 cases, and occlusion of parent artery in 2 cases. Surgical treatment was performed on nineteen cases (53%). The operation was carried out in the acute stage on the SAH group; in the subacute or chronic stage on the ischaemic group. The surgical procedure was the proximal ligation, trapping and removal of DA with or without revascularization of the parent artery. 84% of the surgically managed patients and 71% of the nonsurgical cases had a favourable outcome (good recovery or moderate disability). Poor prognosis was revealed from the rebleeding and primary neurological stage. We recommend surgical treatment in the acute stage on the SAH group. On the ischaemic group surgical treatment in the subacute or chronic stage is recommended, if the DA has the risk of rupture or progression of the dissection.

Adolescent↗

Effects of superficial temporal to middle cerebral artery bypass for ischaemic retinopathy due to internal carotid artery occlusion/stenosis.

The effects of superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis for retinopathy is discussed and analysed in 19 cases of occlusive internal carotid artery disease (4 with stenosis and 15 with occlusion) according to Doppler sonography (DS) of the retinal artery, optic fundi and visual impairment symptoms. Preoperatively, all cases showed abnormal DS findings (stenosis patterns in 2 cases and the reversed flow patterns in 17 cases). All cases showed ischaemic changes of the optic fundi. Visual symptoms were amaurosis fugax in 2 cases, decline of visual acuity in 13 cases and both in 4 cases. At one month after the bypass, two stenosis pattern cases showed almost normal DS findings. In the 17 reversed flow pattern cases, 13 cases had a marked improvement of the reversed flow. The ischaemic changes of the optic fundi were ameliorated in 12 cases. In the follow-up stage, greater improvement in the DS findings and the optic fundi could be seen in all cases. In all cases worsening of the visual acuity was prevented, and in some cases the decreased visual acuity improved. The above improvements correlated well with the improvement of DS findings. It is believed that this procedure should be performed to prevent and improve ischaemic retinopathy caused by ischaemic ICA lesion.

Aged↗

Integrin alpha 2 cytoplasmic domain deletion effects: loss of adhesive activity parallels ligand-independent recruitment into focal adhesions.

Chinese hamster ovary (CHO) cells transfected with the integrin alpha 2 subunit formed a stable VLA-2 heterodimer that mediated cell adhesion to collagen. Within CHO cells spread on collagen, but not fibronectin, wild-type alpha 2 subunit localized into focal adhesion complexes (FACs). In contrast, alpha 2 with a deleted cytoplasmic domain was recruited into FACs whether CHO cells were spread on collagen or fibronectin. Thus, as previously seen for other integrins, the alpha 2 cytoplasmic domain acts as a negative regulator, preventing indiscriminate integrin recruitment into FACs. Notably, ligand-independent localization of the VLA-2 alpha 2 subunit into FACs was partially prevented if only one or two amino acids were present in the alpha 2 cytoplasmic domain (beyond the conserved GFFKR motif) and was completely prevented by four to seven amino acids. The addition of two alanine residues (added to GFFKR) also partially prevented ligand-independent localization. In a striking inverse correlation, the same mutants showing increased ligand-independent recruitment into FACs exhibited diminished alpha 2-dependent adhesion to collagen. Thus, control of VLA-2 localization may be closely related to the suppression of cell adhesion to collagen. In contrast to FAC localization and collagen adhesion results, VLA-2-dependent binding and infection by echovirus were unaffected by either alpha 2 cytoplasmic domain deletion or exchange with other cytoplasmic domains.

Amino Acid Sequence↗

Construction of aminotransferase chimeras and analysis of their substrate specificity.

Escherichia coli aspartate aminotransferase (AspAT) and E. coli aromatic amino acid aminotransferase (AroAT) have almost identical and high activities toward acidic amino acid substrates. AroAT also has high activity toward aromatic amino acid substrates. The two proteins have 44% amino acid sequence homology. In order to study the mechanism responsible for the different substrate specificities of these aminotransferases, chimeric enzymes of AspAT and AroAT were constructed using homologous recombination in E. coli cells. Five chimeric enzymes were obtained, even though the nucleotide sequence homology between the two parent enzymes was as low as about 50%. The yields of the legitimate chimeric genes were related to the lengths of the homologous region between the two parent genes. Homologous recombination occurred in the region where more than eight nucleotides out of ten were identical. The substrate specificity of the chimeric enzymes suggest that not only the amino acid residues in the active site but also those distant from the active site contribute to the substrate specificity of the parental aminotransferases.

Amino Acid Sequence↗

Nasal mast cells in experimentally induced allergic rhinitis in guinea-pigs.

The kinetics of mast cell accumulation in the nasal mucosa during allergen exposure were investigated in the animal model of experimentally induced allergic rhinitis. Guinea-pigs were divided into an unsensitized control group and five sensitized groups each containing five animals. Five sensitized groups were immunized intraperitoneally with ovalbumin, followed by intranasal administration of ovalbumin in each of four groups for 1, 2, 3 and 4 weeks, respectively. There were significant increases in the number of mast cells in the epithelium after 2 and 3 weeks in the groups receiving intranasal ovalbumin. No significant changes were detected in the lamina propria and the total number of mast cells. In the lamina propria, the distance between a mast cell and the basement membrane was significantly decreased in the groups after 2, 3 and 4 weeks of intranasal administration. These findings suggest that an infiltration of mast cells from the lamina propria to the epithelium occurred after 2 weeks of intranasal administration of allergen. An electron microscopic study showed no mast cells at the luminal surface of the epithelium and the majority of mast cells lying around the basal cells. This finding suggests that the allergen must penetrate into the epithelium in order to interact with mast cells in guinea-pig nose.

Animals↗

Immunocytochemical characterization and identification of SGE1, a rat glomerular epithelial cell line.

Glomerular epithelial cells (GEC) in culture facilitate the study of glomerular physiology and pathology. However, characterization and identification of GECs in culture have been difficult due to the absence of markers specific to them. We compared the immunocytochemical characteristics of a rat normal GEC line (SGE1) and glomerular cells from rat kidney sections using a lectin and commercially available and newly raised monoclonal and polyclonal antibodies. Antivimentin, anti-dipeptidyl-peptidase-IV (gp 108) and monoclonal antibody 5-1-6 antibodies and Limax flavus lectin bound to visceral GECs, anticytokeratin antibody and antibody against common acute lymphocytic leukemia antigen bound to parietal GECs, and anti-SGE1 cell membrane and monoclonal antibody PHM 5 antibodies bound to both visceral GECs and parietal GECs in normal rat kidney sections, and all of these antibodies and L. flavus lectin consistently bound to SGE1 cells in culture. The pattern of antigenic expression on SGE1 cells indicates that SGE1 cells possess phenotypic characteristics of visceral GECs and parietal GECs, and it further suggests that SGE1 cells may be stem cells or cells undergoing differentiation.

Animals↗

Retinoic acid enhances the number of epidermal growth factor receptors in rat glomerular epithelial cells in vitro.

The renal epithelium appears to be an important target tissue for retinoic acid and epidermal growth factor (EGF). We report here that retinoic acid enhances the proliferative effect of EGF on glomerular epithelial cells (GEC) in vitro and also increases EGF binding to GEC. When GEC were exposed to EGF (> or = 1 ng/ml), cellular DNA synthesis was markedly increased. Moreover, the stimulating effect of EGF was synergistically increased by retinoic acid at 5 micrograms/ml. 125I-EGF binding to cultured GEC was increased approximately 3-fold after addition of retinoic acid to cultures for 48 h. Analysis of 125I-EGF binding revealed 8.1 x 10(4) receptors per control (untreated) cell, while retinoic acid-treated cells demonstrated an increase to 14.3 x 10(4) receptors per cell with no detectable change in receptor affinity. These findings suggest that interactions between retinoic acid and EGF may play an important role in the regulation of GEC growth.

Animals↗

Expression of phenotypic markers during regeneration of rat tracheal epithelium following mechanical injury.

We examined epithelial regeneration in mechanically injured rat trachea using phenotypic markers that identify unique differentiated stages of epithelial cells. Following a focal denuding wound, the cells from the adjacent nonwounded epithelium flattened and migrated into the wounded site during the first 12 h. At 24 h, these cells dedifferentiated into poorly differentiated (PD) cells that did not precisely resemble any of the mature tracheal cells. Proliferation of PD cells produced a multilayered epithelium by 48 h. Mitotic activity, measured as mitotic rate (MR) following a 6-h colchicine metaphase blockade, was high at 24 h (MR 23.4%) and 48 h (MR 24.0%). These PD cells expressed keratin 14 and Griffonia simplicifolia I-isolectin B4 (GSI-B4) lectin binding sites, which are specific for basal cells in normal epithelium but did not react with secretory or ciliated cell markers. At 72 h, MR fell to 1.8% (control MR 0.38%). The wound was covered with a pseudostratified epithelium; secretory cell markers were present at the apex of differentiating columnar cells, and a few preciliated cells expressing ciliated cell markers appeared. Basal cells also became distinctly recognizable and expressed keratin 14 and GSI-B4 binding sites. Newly appearing secretory or ciliated cells also expressed these markers but lost them gradually as they acquired new sets of specific markers. During epithelial regeneration after mechanical injury, "dedifferentiation," "proliferation," and "redifferentiation" of epithelial cells occurred, and the PD cell was pivotal in this process.

Animals↗

Medulloblastoma associated with cysts and calcifications--case report.

An 11-year-old boy presented with medulloblastoma occurring in the cerebellar vermis. Computed tomography and magnetic resonance imaging revealed numerous cysts and calcifications in the tumor. The tumor was subtotally removed and cellular synchronization radiation therapy given. He was discharged without neurological deficits. Histological examination showed the cysts represented necrotic foci. Macrophages, which appeared around the necrotic foci, were important in the development of the calcifications via proliferation of collagen fibers.

Brain↗