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Biomedical subjects

S Kawaguchi

Publications and source records attributed to S Kawaguchi.

At least 109 records · Page 6Linked to original sources
PubMed1997

Cloning and characterization of the uvrD gene from an extremely thermophilic bacterium, Thermus thermophilus HB8.

The uvrD gene encodes a DNA helicase which plays an important role in prokaryotic nucleotide (nt) excision repair, mismatch repair and DNA replication. A cosmid-based genomic DNA library for Thermus thermophilus (Tt) HB8 was constructed, and this was screened by Southern hybridization using a uvrD fragment amplified by PCR as the probe. The nt sequence of cloned Tt uvrD was then determined. Characteristic helicase motifs, made up of seven elements, were all conserved in the amino acid (aa) sequence of Tt UvrD. The aa sequence showed 41% homology with that of Escherichia coli (Ec). In the aa composition of Tt UvrD, the number of Asn, Gln, Met and Cys residues was decreased, and the number of Pro residues was increased. The distribution of Pro residues and recent data on X-ray crystallographic structure suggested the importance of the structural dynamics of the protein. These changes are thought to stabilize the native protein conformation against heat denaturation. Tt uvrD complemented the UV sensitivity of a Ec uvrD mutant. Thus, the thermophilic bacterium has a UvrD helicase, whose function is common to Ec UvrD.

Adenosine Triphosphatases↗
PubMed1997

Stereoselective determination of a new antidepressant, E2011, and its diastereoisomer as a metabolite by high-performance liquid chromatography.

A stereoselective HPLC method has been developed for the determination of E2011 (compound I) and one of its metabolites and diastereoisomers, ER-20593 (compound II), in plasma. The two substances and the internal standard were extracted from plasma, followed by two purification steps. In the first step, a minicolumn, Bond Elut C18, was used and in the second step, another minicolumn, Bond Elut Si, was used for purification of the compounds. After the purification, the compounds were analyzed by HPLC with two Chiralpak AD columns. In this procedure, compounds I and II were stable and there was no chiral inversion. The within-day and the between-day assays were performed in rat plasma, where compounds I and II existed simultaneously. The within-day and the between-day precisions of compound I were 2.0 approximately 10.1% and 1.3 approximately 7.1%, and the within-day and the between-day accuracies were -8.2 approximately +3.0% and -6.6 approximately +4.0% in the concentration range 0.003-10 microg ml(-1). The within-day and the between-day precisions of compound II were 1.7 approximately 16.9% and 0.9 approximately 4.5% and the within-day and the between-day accuracies were -9.0 approximately +2.4% and -5.6 approximately +3.8% in the concentration range of 0.005-0.5 microg ml(-1). QC samples for compound I and II were stable for at least 3 months. The method was applied to measure the levels of compound I and II in the rat plasma after oral administration of compound I.

Animals↗
PubMed1997

B7-1-transfected tumor vaccine counteracts chemotherapy-induced immunosuppression and prolongs the survival of rats bearing highly metastatic osteosarcoma cells.

To investigate the therapeutic efficacy of B7-1-expressing tumor vaccine on metastatic osteosarcoma, we introduced mouse B7-1 cDNA into a rat osteosarcoma cell line, MSK-8G. Flow cytometric analysis confirmed that the transfectants designated as B7-1-8G 10-1 and B7-1-8G 15-5 stably expressed B7-1 molecules on the cell surface. B7-1 transfectants were not only rejected by immunocompetent F344 rats but also conferred systemic immunity that protected against challenge with B7-negative parental osteosarcoma cells. In contrast, T-cell-deficient nude rats failed to reject B7-1 transfectants, indicating that T cells play a major role in the development of systemic immunity. We then conducted experimental therapies using irradiated B7-1-transfected tumor vaccine and methotrexate in an orthotopic implantation model. B7-1-transfected tumor vaccine significantly reduced the number of pulmonary metastatic nodules. Moreover, the combination of methotrexate and tumor vaccine further decreased the number of pulmonary metastatic nodules. Most important, the combined therapy with methotrexate and tumor vaccine resulted in a tumor-free condition as judged by the histopathological absence of tumors and survival of rats for more than 180 days. Furthermore, B7-1-transfected tumor vaccine could counteract the immunosuppressive effect of methotrexate. These findings strongly suggest that the B7-1-transfected tumor vaccine may be of clinical value for patients with metastatic osteosarcoma who exhibit immunosuppression due to chemotherapy.

Animals↗
PubMed1997

Path and target finding of afferents in cerebellar anlagen grafted in the cerebellum of adult rats: a Phaseolus vulgaris leucoagglutinin study.

Cerebellar anlagen from rat embryos were grafted into the cerebellum of intact adult rats. Most of the grafts survived and formed 'minicerebella'. The location of the grafts were varied, which provided various types of host/graft interface in laminar configuration: Hw/Gg, Hw/Gp, Hw/Gm, Hg/Gw, Hg/Gg, Hm/Gw, Hm/Gg, Hm/Gp, and Hm/Gm that comprised of the granule cell layer (g), the Purkinje cell layer (p), the molecular layer (m), or the white matter (w) of the host (H) or graft (G). The manner of entrance of mossy and climbing fibers through the host/graft interface and their outgrowth in the graft which has various subset of laminar organization of the cerebellum were examined 28-158 days after grafting by means of anterograde Phaseolus vulgaris leucoagglutinin (PHA-L) labeling. Each cerebellar afferent entered the graft through specific types of interface and grew in specific layers. Mossy fibers passed through Hg/Gg and Hw/Gg, grew in Gg, and mostly terminated there like normal fibers. Fibers in Gg, though rarely, grew further outside Gg like in development. Climbing fibers passed through Hm/Gg, Hw/Gg, and Hw/Gm, proceeded in cortical layers, and terminated in Gm. The outgrowth of climbing fibers in Gm showed selectivity for the direction of Gm with respect to the polarity of Purkinje cells; they permeated Gm to form terminal arbors similar to normal in the direction from the side of Purkinje cell somata to dendrites but not in the reverse direction. Occasionally a single fiber innervated neighboring multiple Purkinje cells. These results indicate that mature cerebellar afferents have potential to regrow and innervate the extraneous cerebellar anlage by finding paths and targets in a manner similar to normal ontogenesis.

Animals↗
PubMed1997

Absorption, distribution, metabolism and excretion of a new, 14C-labelled oxazolidinone MAO-A inhibitor in rat and dog.

1. After oral administration of 14C-labelled (5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5-metho xymethyl -2-oxazolidinone (E2011) at a dose of 1 mg/kg, the blood level of radioactivity reached a maximum concentration (Cmax) of 0.545 microgram eq./ml after 0.25 h in the rat and of 0.900 microgram eq./ml after 0.5 h in the dog. In dog plasma, Cmax for radioactivity and unchanged E2011 were 0.862 microgram eq./ml and 0.650 microgram/ml respectively with corresponding Tmax (time at Cmax) of 0.75 and 0.25 h. The unchanged drug in dog plasma was below the detection limit (5 ng/ml plasma) after 24 h. 2. The tissue levels of radioactivity were measured at 0.25 (Tmax), 6, 24, and 168 h after administration to the rat and at 0.5 (Tmax), 24, and 168 h in the dog. The radioactivity was distributed in all tissues examined at Tmax in the rat and dog. The radioactivity levels of the cerebral cortex in the rat and dog were 26 and 36% of the plasma level at Tmax. The radioactivity in tissues decreased at almost the same rate as that in plasma. Plasma protein binding of the unchanged drug in the rat in vitro were about 70% in the range of 0.1-10 micrograms/ml, and those in the dog were about 45% in the same concentration range. 3. Cumulative excretion of radioactivity in the rat was 74.5% in urine and 22.5% in faeces after 7 days. In the dog, 55.5 and 36.5% of the radioactivity administered were excreted in urine and faeces respectively after 7 days. The biliary excretion of radioactivity in the cannulated rat was 23.0% within 48 h. 4. In tlc analysis of plasma and tissues of the rat and dog, the radioactivity for the unchanged drug was much higher than metabolites. In tlc analysis of urine, the same metabolites were detected in the rat and dog, and the radioactivity of a metabolite, IM1, was the highest in the both animals. Eight metabolites were detected in the plasma, tissues and excreta of the rat, and four metabolites in the dog. 5. In conclusion, the absorption, distribution, metabolism and excretion of 14C-labelled E2011 in the rat and dog have been established, and only minor differences were observed between these species.

Absorption↗
PubMed1997

Enzyme flexibility: a new concept in recognition of hydrophobic substrates.

The mechanism of recognition of hydrophobic substrates was investigated using Escherichia coli aspartate aminotransferase (AspAT), E. coli aromatic amino acid aminotransferase (AroAT), and their chimeric enzyme (DY18). Surprisingly, broad substrate specificity was observed in the reaction of aminotransferases with hydrophobic substrates. The catalytic efficiency increased with an increase in the side chain length of straight or branched-terminal aliphatic substrates. The straight-chain substrates catalysed with maximal efficiency were the 7-carbon substrate in the case of AspAT and the 8-carbon substrate for AroAT and DY18. Consecutive addition of single methylene groups to the substrate had a constant effect on the stabilization energy of the transition state relative to the unbound state. The dependency of binding energy on each methylene group is usually interpreted as indicating hydrophobicity of the active site. However, we observed that AroAT and DY18 had different dependencies although both enzymes have the same residues in the substrate-binding pocket. For substrates with more than 7 carbons, the aminotransferases did not strictly distinguish between substrates with straight and branched side chains. These results suggest that the recognition of manifold hydrophobic substrates of different shapes might require not only the hydrophobicity of the active site but also enzyme flexibility.

Amino Acid Sequence↗
PubMed1997

Evaluating the effect of superficial temporal artery to middle cerebral artery bypass on pure motor function using motor activation single photon emission computed tomography.

OBJECTIVE: We evaluated and analyzed the effect of superficial temporal artery to middle cerebral artery bypass for internal carotid artery occlusion on pure motor function using motor activation single photon emission computed tomography. METHODS: Motor activation single photon emission computed tomographic (SPECT) images were obtained for nine patients who had undergone superficial temporal artery to middle cerebral artery anastomosis for symptomatic internal carotid artery occlusion. All motor activation SPECT images using the finger opposition task on the affected side were obtained before bypass surgery and at 1 week, 1 month, and 3 months after bypass surgery. The results of motor activation single photon emission computed tomography were expressed as negative or positive. RESULTS: Before bypass surgery, the resting SPECT images revealed reduction of cerebral blood flow (CBF) on the affected side in all nine patients. The results of motor activation single photon emission computed tomography in three patients were positive. One week after bypass surgery, the results of the resting and motor activation CBF studies did not demonstrate any marked changes. One month after bypass surgery, the resting CBF increased in four patients. The results obtained for two of the patients revealed preoperative positive motor activation. The results of motor activation single photon emission computed tomography obtained for five patients were positive. Three months after bypass surgery, eight patients experienced improvement in the resting CBF, and the results of motor activation single photon emission computed tomography obtained for seven patients were positive. Among these, the results of preoperative motor activation single photon emission tomography obtained for four patients were negative. CONCLUSION: Superficial temporal artery to middle cerebral artery bypass is useful not only for resting CBF but also for pure motor function based on motor activation SPECT images. From the preoperative motor activation study, it was concluded that patients with preoperative positive motor activation could attain the effect of bypass earlier than patients with preoperative negative motor activation.

Aged↗
PubMed1997

Comparison of bactericidal effects of commonly used antiseptics against pathogens causing nosocomial infections. Part 2.

Opportunistic infections caused by gram-negative rods (GNR), conventionally regarded as organisms with low or no pathogenicity, and intractable infections caused by various resistant organisms pose a great problem now. In view of this, we determined the bactericidal effects of 5 commonly used disinfectants using as the test strains Xanthomonas maltophilia and Serratia marcescens, chosen among other GNR since they often cause nosocomial infections. Regarding the bactericidal activities against X. maltophilia and S. marcescens, both sensitive strains and resistant strains were killed within 20 s of exposure to povidone-iodine and sodium hypochlorite. With chlorhexidine, 1 strain each of both species was not killed within 10 min of exposure at a concentration of 0.2%. Both sensitive strains and resistant strains of X. maltophilia were killed within 20 s of exposure to benzalkonium at 0.02%, while a concentration of 0.1% was required for benzalkonium to kill S. marcescens within 20 s. With Tego-51, both sensitive strains and resistant strains of X. maltophilia were killed within 20 s at 0.02%, while 1 strain of S. marcescens was not killed within 20 s at a concentration of 0.1%. In the use of disinfectants, comparative bactericidal effects of various disinfectants against clinical isolates should be taken into consideration.

Anti-Infective Agents, Local↗
PubMed1997

Orbital varix diagnosed by color Doppler flow imaging--case report.

A 66-year-old male presented with an angiographically occult orbital varix. Angiography and phlebography failed to demonstrate the lesion. Computed tomography angiography showed the varix, but not the vascular flow. Color Doppler flow imaging clearly demonstrated the well-defined varix with slow flow velocity, as well as the precise anatomical location. We recommend color Doppler flow imaging as one of the differential diagnostic tools for intraorbital vascular lesions.

Aged↗
PubMed1997

Development of anterior cranial fossa dural arteriovenous malformation following head trauma. Case report.

Dural arteriovenous malformations (AVMs) are considered to be acquired lesions that develop secondary to venous obstruction, which sometimes happens in head trauma. However, there has been a report of an anterior cranial fossa dural AVM that occurred independently of a history of head trauma, and there has been speculation that these malformations are congenital. The authors recount their experience with a patient who had an anterior cranial fossa dural AVM that was discovered incidentally. The lesion was fed by the bilateral anterior ethmoidal arteries and drained into the superior sagittal sinus via frontal cortical veins. The patient had a history of severe head trauma that had occurred 30 years earlier. This is the first case report in which a previous head trauma is strongly believed to be the cause of an anterior cranial fossa dural AVM. The authors postulate that anterior cranial fossa dural AVMs can develop secondary to a head trauma.

Aged↗
PubMed1997

[Tuberculosis in the crew of a submarine].

We report the apparent spread of mycobacterial tuberculosis among a submarine crew from a crew member with a low grade of infectivity. The air-conditioning system of submarines requires completely closed recirculation of ambient air. If a person with pulmonary tuberculosis were in a submarine, one would expect to find a high incidence of tuberculosis among others on the ship. The index patient was a 35-year-old member of a submarine crew. An abnormal shadow was found on a chest roentgenogram during an annual medical checkup, and he was hospitalized for examination. Acid-fast bacilli were found in his gastric secretions, but he did not complain of coughing and no tuberculosis bacilli were found in his sputum. All members of the submarine crew were examined, and some who were on board with the index patient reacted strongly. Because those who were also suspected to be infected were usually not close to the index patient's living quarters and had little contact with the patient in the submarine, we strongly suspect that the closed ventilation system contributed to the spread of the infection. Control of tuberculosis in a sealed environment requires detailed investigation of the environment and completion of chemoprophylaxis. Adequate ventilation and ultraviolet radiation are more effective than decontamination with disinfectants for the control of infectious droplet nuclei. Ships should be equipped with those systems.

Adult↗
PubMed1997

[Stent graft treatment for two cases of DeBakey IIIb dissecting aortic aneurysm].

Two patients with DeBakey IIIb dissecting aortic aneurysms were treated with transluminally placed endovascular stent grafts. Surgery was required for both patients because the false lumens were not thrombosed for several months. Stent graft devices composed of several units of self-expandable Z stents covered with ultra-thin woven Dacron were inserted through 18 Fr sheathes via femoral arteries. The stent grafts were deployed successfully and blood flow into the false lumens was reduced immediately and finally thrombosed without blood leakage from the entries. The endoluminal stent graft treatment is minimally invasive operation in comparison with former surgical operations, and is useful for aortic aneurysms especially in high risk patients. However, improvement of the stent graft devices, including the delivery systems such as the dilator, sheath and pushing rod, which are incomplete, and developing better devices, is required to reduce delivery failure and to make the stent graft treatment more reliable.

Aged↗
PubMed1996

Quantitative age-related changes in apical dendrites and dendritic spines of CA1 pyramidal neurons among senescence accelerated mice (SAMP1TA/Ngs).

SAMP1TA/Ngs, a substrain of senescence accelerated mouse, is a useful animal model for research on brain dysfunction due to senescence. In a previous study it was reported that the age-related changes in basal dendrites and spines of CA1 pyramidal neurons coincide with the behavioral characteristics found in SAMP1TA/Ngs. The goal of the present study was to investigate morphological changes in apical dendrites and dendritic spines of CA1 pyramidal neurons among 3-, 5-, 7-month-old SAMP1TA/Ngs. Pyramidal neurons of the hippocampus were stained by the rapid Golgi method, and the number of apical dendrites, the number of their spines and the density of the dendritic spines were evaluated. The number and density of the spines of apical dendrites were significantly higher at 5 months than at 3 or 7 months of age. We propose that the low number of dendritic spines in 3-month-old animals was caused by immaturity, while the changes in the density and number of dendritic spines in 7-month-old mice were due to accelerated aging. The data on the morphology of apical dendrites are a useful complement to the results reported previously. The findings of the present study also support the hypothesis that this model mouse demonstrates changes in respective developmental stages, i.e. immaturity, adulthood and senescence. This pattern of postnatal growth has special meaning because it indicates the usefulness of the strain in the study of geriatric disorders in humans.

Aging↗
PubMed1996

Characteristics of intracranial aneurysms associated with moyamoya disease. A review of 111 cases.

A retrospective analysis of 111 patients with aneurysms associated with Moyamoya disease is presented. The subjects comprised of our 12 cases and 99 other well-documented cases. These 111 cases had 131 aneurysms. There were 48 males and 63 females. The average age was 40.3 years. The clinical manifestations were intracranial haemorrhage in 99 cases (89%), and ischaemic events in 9 cases (8%), but no mention was made of these in the last three cases (2%). The Hunt and Kosnik grades were grade 1 in 8%, grade 2 in 23%, grade 3 in 31%, grade 4 in 35%, and grade 5 in 3%. Of the 131 aneurysms, 73 (56%) were found distributed around the circle of Willis, 24 (18%) in the basal ganglia, 29 (22%) on collateral vessels, and 5 (4%) on other vessels. Forty-six percent of the cases were treated surgically, 51% conservatively, and 3% by endovascular procedures. The surgical procedures for the aneurysms were; neck clipping in 49%, aneurysmectomy in 18%, wrapping of the aneurysm in 11%, coating or cautery of the aneurysm in 7%, and revascularization only in 11%. The outcomes were Glasgow Outcome Scale 1 in 30%, 2 in 22%, 3 in 11%, 4 in 1%, and 5 in 25%. The main reasons for the unfavourable outcome were initial poor clinical grade and rebleeding. Follow-up angiography of 25 aneurysms demonstrated that all aneurysms in the basal ganglia or on the collateral vessels disappeared. We recommend surgical intervention for aneurysms associated with Moyamoya disease to prevent rupture or rebleeding, especially for aneurysms around the circle of Willis. However, direct surgery is not recommended for aneurysms found in the basal ganglia or on the collateral vessels.

Adolescent↗
PubMed1996

Expanding laminoplasty for cervical myelopathy-spinous process roofing technique.

We have carried out expanding laminoplasty using spinous process roofing technique for patients presenting with cervical myelopathy. The technique is a modified Kurokawa's method. The result shows that laminoplasty with this technique provides better postoperative neck movement with a simpler surgical procedure. The clinical material consists of 54 cases with more than 3 years follow-up. Long-term investigation was performed focusing on the following three points, (1) bony fusion rates, (2) radiographic neck movement, (3) neurological improvement. The results indicate good postoperative bony fusion in all cases. Postoperative neck movement was also well preserved in the majority of cases.

Adult↗
PubMed1996

Clinical features of the haemorrhage type moyamoya disease based on 31 cases.

We evaluated and analysed our own 31 cases of the haemorrhagic type of moyamoya disease to clarify the clinical features of this disease. The cases were divided into three groups. Group A consisted of 12 cases with aneurysms. Aneurysms on the circle of Willis were treated as ordinary saccular aneurysms. Group B consisted of 14 cases with intracerebral haemorrhage (ICH) without aneurysms. These were managed almost as spontaneous ICH. Group C consisted of 5 cases with intraventricular haemorrhage (IVH) without aneurysms or ICH. Twenty-two surgical procedures for aneurysms, ICH and IVH were done in 19 cases (62%). Nineteen procedures for preventing future strokes were undertaken in 11 cases (35%). The overall initial outcome was excellent in 12 cases (39%), good in 7 cases (23%), poor in 7 cases (23%), and death in 5 cases (15%). During the follow-up period (mean: 6.5 years), rebleeding occurred in two cases (8%), and ischaemic attacks in two cases (8%). The rate of rebleeding or ischaemic attacks was 1.19% per patient-year during the follow-up period. There was no ischaemic or rebleeding episode in cases treated by STA-MCA bypass with encephalomyosynagiosis (EMS) during the follow-up period. Management of the primary haemorrhage should be according to the clinical condition, type of haemorrhage, and source of haemorrhage. When the patient needs to undergo revascularization surgery to prevent future strokes, we recommend STA-MCA bypass with EMS instead of encephaloduro-arteriosynangiosis (EDAS).

Adult↗
PubMed1996

Spontaneous antibody-secreting cells in the stomach of gastric cancer patients.

The gastric mucosa has been regarded as an active site of humoral immunity since the discovery of Helicobacter pylori. The present study was conducted to determine the in vivo activity of gastric B cells in 53 gastric cancer patients. B-cell activity was measured by protein-A plaque assay, in which IgA-, IgM-, and IgG-plaque-forming cells (PFC) were counted. The number of PFC was associated with the stage of cancer, but the response of lymphocytes in a non-tumorous area (NML) and tumor-infiltrating lymphocytes (TIL) differed. PFC in both sites were decreased compared to n0 cancer in n1 lymph node metastasis-positive cancer, while only NML showed raised PFC in n2 + (P < 0.05, vs TIL). Cancer cells penetrating the submucosa caused the PFC of TIL (but not of NML) to decrease. Invasion of the intratumor capillary (V) or lymphatic (Ly) vessels also caused PFC to change, showing differences of Ig class; there was a decrease of PFC in V2 (IgG- and IgM-PFC) and in Ly2 (all Ig-PFC). IgA-PFC in Ly1 differed in TIL (decrease of PFC) and NML (increase). PFC also differed in TIL and NML in cancer cells, as follows: TIL < NML in tubular and poorly differentiated adenocarcinoma and TIL > NML in papillary and signet ring cell adenocarcinoma. Changes in lymph node (LNL) and blood lymphocytes were similar to those in gastric PFC whose IgA value was 10 times as much as that of LNL. The 5-year survival rate was significantly better in patients with lower rather than higher PFC such as 89% vs 68%. Gastric B cells thus appear to be active and to reflect gastric mucosal immunity.

Adult↗