Biomedical subjects

T Baba

Publications and source records attributed to T Baba.

At least 199 records · Page 11Linked to original sources

PubMed1997

Ubiquitously expressed dynamin-II has a higher intrinsic GTPase activity and a greater propensity for self-assembly than neuronal dynamin-I.

To begin to understand mechanistic differences in endocytosis in neurons and nonneuronal cells, we have compared the biochemical properties of the ubiquitously expressed dynamin-II isoform with those of neuron-specific dynamin-I. Like dynamin-I, dynamin-II is specifically localized to and highly concentrated in coated pits on the plasma membrane and can assemble in vitro into rings and helical arrays. As expected, the two closely related isoforms share a similar mechanism for GTP hydrolysis: both are stimulated in vitro by self-assembly and by interaction with microtubules or the SH3 domain-containing protein, grb2. Deletion of the C-terminal proline/arginine-rich domain from either isoform abrogates self-assembly and assembly-dependent increases in GTP hydrolysis. However, dynamin-II exhibits a approximately threefold higher rate of intrinsic GTP hydrolysis and higher affinity for GTP than dynamin-I. Strikingly, the stimulated GTPase activity of dynamin-II can be >40-fold higher than dynamin-I, due principally to its greater propensity for self-assembly and the increased resistance of assembled dynamin-II to GTP-triggered disassembly. These results are consistent with the hypothesis that self-assembly is a major regulator of dynamin GTPase activity and that the intrinsic rate of GTP hydrolysis reflects a dynamic, GTP-dependent equilibrium of assembly and disassembly.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Cerebral ischemic disorders and cerebral oxygen balance during cardiopulmonary bypass surgery: preoperative evaluation using magnetic resonance imaging and angiography.

We compared the preoperative prevalence of small cerebral infarctions and carotid stenosis to jugular venous oxygen saturation (Sjvo2) during coronary artery bypass grafting (CABG). Sjvo2 served as an indicator of whether cerebral oxygen supply meets demand in patients on cardiopulmonary bypass (CPB). The study population consisted of 121 patients who were either older than 65 yr or had a history of cerebrovascular disease. The patients underwent preoperative cerebral magnetic resonance imaging (MRI) and cervical magnetic resonance angiography (MRA) to detect small cerebral infarctions and carotid artery stenosis. Patients with atherosclerosis of the ascending aorta were identified by intraoperative epiaortic ultrasonography. Liberation of emboli from the aorta in these patients was prevented by modification of the standard operation. From preoperative MRI and MRA, 65 patients (54%) had small cerebral infarctions in the white matter or basal ganglia and nine patients (7%) demonstrated moderate or severe stenosis in the carotid arteries. Thirteen patients (11%) had moderate or severe atheromatous disease of the ascending aorta. The severity of aortic atherosclerosis was significantly correlated with the grade of carotid stenosis (P < 0.05). In patients with small infarctions, Sjvo2 was significantly lower than in patients without infarctions (controls) at initiation of CPB, 30 min after aortic cross-clamping, and during the rewarming period of CPB (P < 0.05). Thus, small cerebral infarctions were not uncommon in elderly patients undergoing CABG. Patients with small cerebral infarctions may be at risk for an imbalance in cerebral oxygen supply and demand during the rewarming period because they are unable to deliver the necessary compensatory blood flow.

Aged↗

PubMed1997

Radial artery diameter decreases with increased femoral to radial arterial pressure gradient during cardiopulmonary bypass.

UNLABELLED: A clinically significant femoral to radial artery pressure gradient sometimes develops during cardiopulmonary bypass (CPB), but the mechanism responsible is not clear. We investigated when the pressure gradient developed and what mechanism could be responsible by comparing mean femoral to mean radial artery pressure and radial artery diameter in 75 male patients undergoing coronary artery bypass grafting. A pressure gradient > or =5 mm Hg (High-P) occurred in 38 patients, and the remaining 37 patients had pressure gradients <5 mm Hg (Low-P) at sternal closure. In High-P group, the pressure gradient was significantly greater (4.8 +/- 3.1 vs 1.0 +/- 3.1 mm Hg; P < 0.001) than in Low-P group, and the ratio of radial artery diameter to the diameter after induction of anesthesia was significantly decreased (0.79 +/- 0.12 vs 0.87 +/- 0.14; P = 0.006) at 5 min after aortic clamping. The pressure gradient and the arterial diameter changes persisted until sternal closure. There was a negative linear correlation between the pressure gradient (deltaP) and the radial artery diameter ratio (D) at sternal closure (D = -15.0deltaP + 16.6, r = 0.39, P < 0.001). In a subgroup of 11 High-P patients, palm temperature was significantly lower (P < 0.05) than that of 11 Low-P patients during and after CPB. We conclude that the femoral to radial artery pressure gradient develops by 5 min after aortic clamping during CPB and persists until sternal closure, and that radial artery constriction could be responsible for the pressure gradient. IMPLICATIONS: A femoral to radial pressure gradient has been observed after cardiopulmonary bypass. Arterial vasodilation and vasoconstriction have been considered as causes for this gradient. We measured radial artery diameter using pulsed Doppler ultrasound and examined radial artery vasodilation versus vasoconstriction as possible mechanisms for the pressure gradient.

Aged↗

PubMed1997

Possible migration of harderian gland immunoglobulin A bearing lymphocytes into the caecal tonsil in chickens.

This study was designed to evaluate the significance of the Harderian gland (HG) in the chicken IgA-production system by investigating the influence of HG on the increase of surface IgA (sIgA)-positive cells in other lymphoid organs and also the possibility of migration of HG lymphocytes into other organs. Non-contact culture of splenic or caecal tonsil (CT) lymphocytes with HG whole cells did not enhance the expression of sIgA. The experiment of HG lymphocyte transfer showed that the transferred HG lymphocytes migrated mainly into the CT in the 3-week-old recipient, and mainly into the CT and bursa of Fabricius (BF) in the 6-week-old recipient. It was also found that the transferred sIgA-positive HG lymphocytes migrated selectively into CT in both 3-week-old and 6-week-old recipients. These results indicated that chicken HG plays a central role not only in governing the local immunity in the eyes and respiratory tract but also as an organ which supplies precursory IgA-producing cells involved in local immunity in the intestine.

Animals↗

PubMed1997

Immunopotentiating activities of polysaccharide fraction from pine seed shell extract.

The function of polysaccharide (PSE) extracted from pine seed shells as a immunopotentiator was investigated. The phagocytosis and chemotaxis of mouse peritoneal macrophages (MP) were augmented by oral administration of PSE. The incorporation of 3H-thymidine by Con A-stimulated mouse splenic cells was significantly intensified by administration of PSE but the adherent-cells (MP)-eliminated splenic lymphocytes was not increased. It is shown that the existence of activated MP is needed for the activation (proliferation) of T lymphocytes. The responsiveness of mouse T cells to alloantigen was also augmented by administration of PSE. The number of anti-SRBC plaque-forming cells in the spleen of mouse and chicken was also significantly increased. The results indicate that MP are first activated by oral administration of PSE and that the activation of T cells is then initiated indirectly by humoral factors (cytokines) produced by activated MP.

Adjuvants, Immunologic↗

PubMed1997

The method for keeping low perfusion flow weaning from centrifugal pumps: an evaluation of hemolysis in the circulator units.

Currently, the clinical application of extracorporeal and assisted circulation using centrifugal pumps is becoming popular. However, a problem in the use of centrifugal pumps is the difficulty in controlling the flow rate when it is a low range. Although we have been controlling the flow rate with a control unit that simply squeezes the blood outlet tube from the outside, hemolysis resulting from turbulent flow in the tube was discovered. Therefore, this control procedure was evaluated experimentally. Two groups were tested as follows: in Group A (n = 10), the tube was squeezed from the outside using the control unit, and in Group B (n = 10), no control unit was used. Blood in each circuit was circulated at 1,500 rpm, and the flow rate was controlled to 250 ml/min using the control unit for Group A. Time-course changes of lactate dehydrogenase (LDH) and free hemoglobin in the blood were measured during 8 h of circulation. There were no significant differences between the 2 groups in the mean values of LDH and free hemoglobin. Therefore, the present low flow rate control provided by the control unit makes it appear to be a simple and useful apparatus for controlling blood circulation using centrifugal pumps.

Analysis of Variance↗

PubMed1997

Experimental studies on three types of heparin-coated cardiopulmonary bypass circuits.

In cardiovascular operations, we have usually used heparin-coated cardiopulmonary bypass circuits with low systemic heparinization. Three types of heparin-coated cardiopulmonary bypass circuits are available in Japan: 2 of the 3 have covalent heparin bonding, and the other has ionic heparin bonding. We studied these circuits in ex vivo experiments to explore which were the best in terms of biocompatibility. In this study we compared the Carmeda system (Medtronic) and the Capiox system (Terumo) with covalent heparin bonding, and the Duraflo-II (Baxter) with ionic heparin bonding, evaluating them in ex vivo experiments. They were primed with fresh human blood, and we studied and compared the platelet counts, fibrinogen, D-dimmer, beta-thioguanine (TG), thrombin-antithrombin complex (TAT), and C3a and C4a of each of them. Additional research will be presented in the future.

Anticoagulants↗

PubMed1997

Our distal aortic perfusion system in descending thoracic and thoracoabdominal aortic aneurysm repairs.

We have used heparin-bonded partial cardiopulmonary bypass to support distal aortic circulation during aortic cross-clamping. However, there were no cardiotomy reservoirs with fully reliable thromboresistance. To resolve this problem, a short-acting anticoagulant (nafamostat mesilate) was added into a cardiotomy reservoir. The present study was designed to evaluate the efficacy of our distal perfusion system. From May 1995 through the end of May 1996, 27 patients underwent descending thoracic and thoracoabdominal aortic aneurysm repairs with this adjunct, 4 being excluded from the experiment. Twenty patients who had undergone conventional partial cardiopulmonary bypass were defined as the control group. There were no significant differences between the 2 groups in the morbidity, mortality, gas transfer, or transfusion requirements despite the fact that more complicated surgical procedures (shown by a two-fold increase in the prevalence of reoperation) were required in the group that had received the current distal perfusion adjunct the heparin-bonded group. In conclusion, our perfusion system is very effective for descending thoracic and thoracoabdominal aortic aneurysm repairs.

Analysis of Variance↗

PubMed1997

Clinical, pathological, and etiologic aspects of acquired dermal melanocytosis.

To study the pathogenesis of acquired dermal melanocytosis (ADM), we reviewed the clinical, immunohistochemical, and ultrastructural features of 34 cases (female, 33, and male, 1) of ADM. The patients' ages at onset ranged from 8 to 51 years and averaged 26.8 +/- 12.7 years. There was a positive family history. Gray-brown macules were mostly recognized on the face. Not only active dermal melanocytes but also non-pigmented c-KIT- and TRP-2-positive immature melanocytes were detected in the dermis. Taken together those clinical and histological findings, activation of pre-existing immature melanocytes by sunlight, estrogen, and/or progesterone, and some other factors, may be the most likely mode of the development of ADM. Moreover, using cultured murine neural crest cells as a model of c-KIT-positive immature melanocytes, we confirmed that endothelin-1, which is produced and secreted by keratinocytes after UV-irradiation, affects melanocytes and accelerated melanogenesis.

Adult↗

PubMed1997

DAX-1 gene mutations and deletions in Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism.

Abnormality of the DAX-1 gene accounts for many instances of congenital adrenal hypoplasia. In the present study, we performed molecular genetic analysis of DAX-1 in 4 unrelated Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. A double-point mutation for V126M and W171X was identified in 1 family and a complex de novo insertion-deletion mutation was identified in a second. The DAX-1 gene was entirely deleted in a 3rd patient as well as in a 4th with the additional feature of glycerol kinase deficiency.

Adolescent↗

PubMed1997

Pubertal changes in testicular 3 beta-hydroxysteroid dehydrogenase activity in a male with classical 3 beta-hydroxysteroid dehydrogenase deficiency showing spontaneous secondary sexual maturation.

Males with classical 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency manifest appropriate secondary sexual maturation with an elevation in serum testosterone levels at pubertal age. To define the origin of serum testosterone, we evaluated a male patient with classical 3 beta-HSD who showed pubertal development. High values of testosterone and a ratio of delta(5) to delta(4) steroids in the spermatic vein indicated direct production of considerable amounts of testosterone and a persistent defect of 3 beta-HSD activity in the gonad. Immunohistochemical analysis showed distinct immunoreactivity in the Leydig cells of the patient. The patient was homozygous for a nonsense mutation in the type-II 3 beta-HSD gene. We propose that gonadal type-I 3 beta-HSD could be expressed by gonadotropin stimulation at pubertal age, and delta(4)-steroid precursors would convert to testosterone.

3-Hydroxysteroid Dehydrogenases↗

PubMed1997

Effects of adenosine triphosphate on ventriculoatrial conduction--usefulness and problems in assessment of catheter ablation of accessory pathways.

The effects of adenosine triphosphate (ATP) on ventriculoatrial (VA) conduction were examined before and after accessory pathway (AP) ablation, with emphasis on assessment of the complication of dual atrioventricular (AV) node pathway. By evaluating the differences in the response to ATP of APs and other pathways, we assessed the usefulness and problems of this method. Of 59 patients who underwent AP ablation, 31 showed pre-excitation and 28 had concealed APs. A dual AV node pathway was found in 9 patients (15.3%) before ablation. After ablation, a dual AV node pathway was newly found in 9 patients. Thus, the total number of patients with a dual AV node pathway was 18 (30.5%). VA conduction over APs was not blocked in 26 of 29 patients, but the remaining 3 APs were blocked transiently by ATP. ATP caused VA block over the AV node in 15 of 16 patients and a dual AV node pathway in all 11 patients. In contrast, VA conduction over the retrograde fast pathway was blocked in 9 of 14 patients with AV node re-entrant tachycardia. ATP has little effect on APs, so observation of the response to ATP provides a more reliable and useful means of evaluating successful ablation. With this method, however, it is important to consider the possibility of the presence of ATP-sensitive APs and ATP-resistant retrograde fast pathways. The influence of ablation-induced injury has not been fully clarified. It is therefore essential to take into account various data, including the comparison between data obtained before and after ablation.

Adenosine Triphosphate↗

PubMed1997

Diabetic nephropathy. Its relationship to hypertension and means of pharmacological intervention.

Hypertension and diabetes mellitus are common chronic conditions which frequently coexist. Diabetic nephropathy is a major cause of elevated blood pressure in patients with insulin-dependent diabetes mellitus (IDDM). Diabetic nephropathy, arterial sclerosis, obesity and association of essential hypertension can be the causes of hypertension in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ambulatory blood pressure monitoring has revealed that the nocturnal fall of blood pressure is blunted in patients with diabetic nephropathy. A blunted diurnal blood pressure variation is seen in microalbuminuric diabetic patients and even in some normoalbuminuric patients. Accumulating data suggest that normalisation of blood pressure in hypertensive IDDM patients is most important to minimise the loss of kidney function. Angiotensin converting enzyme (ACE) inhibitors have been reported to be effective in postponing the development of nephropathy and in slowing its progression. Whether only ACE inhibitors have such beneficial renal effects on diabetic nephropathy is under discussion. While many studies have suggested that insulin resistance and hyperinsulinaemia are related to an elevated blood pressure in hypertensive patients, there does not seem to be enough evidence to prove that insulin per se can raise blood pressure in humans. Neither an insulin infusion within a physiological range nor sustained hyperinsulinaemia and insulin resistance (e.g. patients with insulinoma, cystic ovary syndrome) have been associated with an elevated blood pressure. Insulin resistance in some hypertensive patients may be a consequence of a decreased blood flow due to an increased peripheral resistance. Preliminary evidence suggests that low birth weight or impaired fetal growth is related to hypertension and NIDDM. Familial clustering of diabetic nephropathy suggests the contribution of genetic susceptibility and/or environmental inheritance. The frequent association of nephropathy with hypertension has led to research on the genes related to hypertension (ACE, angiotensinogen). Nevertheless, to date no reliable and clinically useful genetic marker has been found. Attempts to correct the metabolic abnormalities derived from diabetes are a new topic in the treatment of diabetic nephropathy. The effects of HMG CoA reductase inhibitors (antihypercholesterolaemic drugs), aldose reductase inhibitors (inhibitors of the polyol pathway) and glycation inhibitors (inhibitors of formation of advanced glycosylation end-products) on diabetic nephropathy have been evaluated in animal studies and in some clinical trials. Thus far, results with HMG CoA reductase and aldose reductase inhibitors have been somewhat conflicting. The potential therapeutic role of glycation inhibition in the treatment of diabetes deserves further study.

Adrenergic beta-Agonists↗

PubMed1997

Erythromycin derivative improves gastric emptying and insulin requirement in diabetic patients with gastroparesis.

OBJECTIVE: To evaluate the effect of the erythromycin derivative EM523L on gastric emptying and postprandial insulin requirement in insulin-dependent diabetic patients with severe gastroparesis. RESEARCH DESIGN AND METHODS: In six IDDM patients with severe gastroparesis (two men and four women, mean age 44.5 years [range 36-53]), the insulin infusion pattern during feedback control with an artificial endocrine pancreas device (Biostator) after intake of a test meal, the retention rate of residual isotope ([99m]Tc-labelled Sn-colloid) in the stomach, and the time-concentration curve of plasma acetaminophen as the marker for liquid emptying were studied with EM523L or a control placebo RESULTS: Time courses of insulin infusion rates peaked within 120 min after intake of the test meal in the EM523L phase, whereas no apparent peak rates were observed in the control phase. The total amount of insulin required in the first 90 min postprandial was significantly greater in the EM523L phase than in the control phase. EM523L significantly decreased the residual isotope ratio in the stomach at > or =50 min postprandial and increased the plasma acetaminophen concentrations at 30-120 min postprandial, compared with respective values in the control phase. CONCLUSIONS: Preliminary results obtained from a small number of patients suggest that EM523L or erythromycin analogs, which have agonistic activity to motilin receptors as well as no antibacterial effect, may be useful to accelerate gastric emptying and improve insulin requirement patterns, thereby establishing more stable glycemic control.

Acetaminophen↗

PubMed1997

Identification of rat and human cytochrome P450 forms involved in the metabolism of the thromboxane A2 receptor antagonist (+)-S-145.

(+)-S-145 [5-(+)-(Z)-7-[(1R, 2S, 3S, 4S)-3-phenylsulfonylaminobicyclo[2.2.1]hept-2-yl]-heptenoic acid] and its beta-oxidized metabolites [two [bisnor or dihydro (DH)-bisnor] or four (tetranor) carbon-shortened products at the carboxyl side chain] are hydroxylated at the C-5 or C-6 position of the bicyclo ring by microsomal monooxygenases. We investigated the oxidative metabolism of (+)-S-145 and its beta-oxidized metabolites with liver microsomes from rats and humans to identify which cytochrome P450 (P450) forms are involved in these reactions. In rats, phenobarbital or dexamethasone treatment significantly increased 5- and 6-hydroxylation activities toward (+)-S-145 and its beta-oxidized metabolites, suggesting the involvement of P4503A forms. Immunoinhibition studies suggested that P4503A2 was mainly responsible for the 5-hydroxylation of (+)-S-145, bisnor, and DH-bisnor and the 6-hydroxylation of bisnor and tetranor. Furthermore, P4502C6, a phenobarbital-inducible 2C form in the rat, was involved in the 6-hydroxylation of (+)-S-145, bisnor, and DH-bisnor. P4502C11, the major constitutive form (male rats), was partly involved in the 5-hydroxylation of DH-bisnor and the 6-hydroxylation of bisnor and DH-bisnor. Reconstitution studies with purified human enzymes and immunoinhibition studies suggest that P4503A4 is primarily involved in the 5-hydroxylation of (+)-S-145 and bisnor and the 6-hydroxylation of tetranor; P4502C9/10 mainly catalyzed the 5-hydroxylation of tetranor and the 6-hydroxylation of (+)-S-145. Results of the present study indicated that the same subfamily P450 forms are responsible for the oxidative metabolism of (+)-S-145 in rats and humans. P4503A enzymes were shown to be involved in the formation of 6-hydroxy tetranor, the main metabolite of S-1452 in vivo.

Animals↗

PubMed1997

[Interferon treatment for hepatitis G virus infection in patients with chronic hepatitis C].

Clinical features of HGV infection as a novel virus infection have not yet been clarified enough. We studied the implication of HGV in the activity of hepatitis and the sensitivity of HGV to IFN. We treated 10 HGV RNA positive patients with chronic hepatitis C with IFN. HGV RNA was identified in serum by RT-PCR method using the primer derived from the base sequences of the NS5 region of HGV genome. HGV RNA became negative in the all of 10 patients during IFN treatment, but returned to be positive again in the all patients after the completion of IFN treatment. In 5 of 10 patients, HCV RNA became persistently negative. In 3 of these 5 patients, ALT was continuously normal and hepatitis subsided biochemically and clinically after IFN treatment. We assume that HGV is sensitive to IFN, but could not be implicated in hepatitis or liver damage.

Adult↗

PubMed1997

CT and MR findings of denervated tongue after radical neck dissection.

PURPOSE: To describe the CT and MR findings in the denervated tongue after a radical neck dissection. METHODS: We retrospectively evaluated the radiologic findings in seven patients who had hypoglossal paralysis following radical neck dissection. None of the patients had clinical or radiologic evidence of tumor recurrence. RESULTS: The side of the tongue operated on showed low density on CT scans. At MR imaging, denervated tongues were clearly seen as hyperintense relative to muscle on T2-weighted images; on T1-weighted images, the signal was hypointense to hyperintense, representing increased extracellular water or fatty degeneration. CONCLUSION: In patients who have undergone a neck dissection for a malignant process, abnormal imaging findings in the tongue not only might indicate a recurrence of tumor involving the hypoglossal nerve but also suggest the possibility of postoperative change. Our findings emphasize the importance of the denervated tongue in differentiating inflammatory from neoplastic diseases of the the tongue.

Adult↗

PubMed1997

Immunocytochemical study of dystrophin localization in cone cells of mouse retinas.

PURPOSE: Previously, the authors reported that dystrophin was observed under the rod cell membranes in rat retinas. However, it was not determined whether dystrophin is located in cone cells. In the current study, the authors clarify dystrophin localization in cone cells of mouse retinas. METHODS: Immunoblotting, confocal laser scanning microscopy, and immunoelectron microscopy were used to investigate retinal dystrophin with a monoclonal antibody raised against the human dystrophin C-terminus. RESULTS: Immunoblotting analysis showed some immunoreactive bands from retinal extracts. Confocal images indicated two different immunostaining patterns: One was a tiny dot, and the other was a larger, aggregated dot. Immunoelectron microscopy revealed that retinal dystrophin was localized in cone cells as well as in rod cells. CONCLUSIONS: Retinal dystrophin is a common component of cone and rod cells and probably is related to the physiological function of photoreceptor cells.

Animals↗