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Biomedical subjects

T Goto

Publications and source records attributed to T Goto.

At least 577 records · Page 32Linked to original sources

A mutation of mitochondrial DNA in Japanese families with Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease characterized by optic nerve degeneration associated with severe bilateral visual loss in young men and occasionally in women. A mitochondrial DNA (mtDNA) replacement mutation in LHON patient, G to A transition at nucleotide position (nt) 11778 converting the 340th arginine to histidine in the NADH dehydrogenase subunit 4, was detected as SfaNI site polymorphism (Wallace et al., Science, 242: 1427-1430, 1988). To evaluate if the SfaNI site loss can be used to diagnose LHON patients, mtDNAs from peripheral blood of six affected males including five probands from five unrelated Japanese families with LHON, a pair of parents and a normal sister of one of the probands and 4 control persons were analyzed using PCR amplification method. The mutation of leukocyte mtDNA at nt 11778 was identified in all of the affected patients, the normal mother and the sister examined, while the father who is normal and 4 control persons did not show the change. These findings support that the mutation at nt 11778 is also associated with LHON in the Japanese and the test of the SfaNI site loss described here is useful for confirming the clinical diagnosis of LHON patients with the mutation at nt 11778.

Asian People↗

Effect of platelet-activating factor on lipoprotein lipase and blood lipids.

We investigated the effect of platelet-activating factor (PAF) and of the PAF specific antagonist CV-6209 on plasma lipid metabolism, and particularly on post-heparin plasma lipolytic activity in male Wistar rats. Lipoprotein lipase (LPL) activity was enhanced by intravenous injection of PAF before intravenous injection of heparin when the PAF dose was low (0.2 micrograms/kg). PAF activated hepatic triacylglycerol lipase (HTGL) activity dose-dependently. Plasma triacylglycerols (TG) significantly decreased with the activation of LPL and/or HTGL. Plasma total cholesterol (TC) and phospholipid (PL) levels decreased at a low dose of PAF (0.2 micrograms/kg), but increased when higher doses were used. The PAF antagonist CV-6209 partially reversed the PAF induced effects on HTGL, TC and PL.

Animals↗

Thermal decomposition of Lingula shell apatite.

Lingula shell is composed of apatite with a preferred orientation. The shell apatites of Lingula unguis(Lu) and Lingula shantoungensis(Ls) were characterized and compared with apatite of human tooth enamel. Insight into the Lingula apatite was studied by following the change of lattice parameter, transformation to beta-tricalcium phosphate (beta-TCP), and the loss and change of CO3, OH, and H2O after heating up to 1,000 degrees C in air and N2 for 24 hours. The OH stretching band was not observed in unheated apatites and in apatites heated in dried N2. Lu and Ls apatite produced 26 and 17 wt% of beta-TCP at 700 degrees C, respectively. Fifty to 60% of H2O was lost at 200 degrees C, being accompanied by a drastic contraction of the a- and c-axis and a drastic decrease in the crystallinity. These results indicate that (1) Lu and Ls shell apatite is CO3 containing F + Cl-apatite, and (2) the structural H2O of the Lingula apatite is loosely bounded such that they are lost at lower temperature than tooth enamel.

Animals↗

Morphological characterization of a newly established human osteosarcoma cell line, HS-Os-1, revealing its distinct osteoblastic nature.

A newly established human osteosarcoma cell line, HS-Os-1, from an osteoblastic tumor arising in the left humerus of an 11-year-old girl was morphologically characterized in vitro and in vivo. HS-Os-1 cells in a monolayer have been maintained for more than 2 years since the initial cultivation, and were round or polygonal in shape with marked pleomorphism. Their cytoplasm was strongly positive for specific markers of osteoblasts, such as alkaline phosphatase and osteocalcin. Tumors induced in nude mice by HS-Os-1 cell inoculation at passage 12 or 23 revealed typical histological features of osteoblastic osteosarcoma, similar to those observed in the original tumor, producing prominent osteoid matrix with calcification. Ultrastructurally, HS-Os-1 cells in vitro and tumor cells in vivo showed similar well-developed, markedly dilated rough endoplasmic reticulum, polysomes and microfilaments in their cytoplasm. Additionally, many collagen fibers associated with deposition of electron-dense material were detected in the stroma featuring osteoid matrix. Thus, the HS-Os-1 cell line was shown to exhibit its osteoblastic nature in vitro and in vivo, and therefore might become an extremely useful tool for various pathomorphological investigations on human osteosarcomas.

Animals↗

Suppressive effect of SUN1165 on supraventricular tachycardia.

The electrophysiologic properties of SUN1165 and its suppressive effect on supraventricular tachycardia were assessed in 14 patients, nine with atrioventricular reentrant tachycardia (AVRT) and five with atrioventricular nodal reentrant tachycardia (AVNRT). This new agent prolonged the PR interval and QRS duration but did not alter the QT interval or the corrected QT interval. It did not alter the sinus cycle length or sinus node recovery time. The drug prolonged the AH interval, HV interval, and intraatrial conduction time but did not change the effective refractory periods of the right atrium or right ventricle. SUN1165 prevented the induction of tachycardia in six of nine patients with AVRT by a complete retrograde block of the accessory pathway and prevented AVNRT in four of five patients by a complete retrograde block of the fast atrioventricular nodal pathway as well. We conclude that SUN1165 is very effective in preventing AVRT or AVNRT. Larger studies with more patients are warranted.

Administration, Oral↗

Commissural neurons in the cat upper cervical spinal cord.

We have begun a study of the intrinsic circuitry of the cat's upper cervical cord, in part to elucidate the role of spinal interneurons in vestibulocollic reflexes. Using retrograde labelling with Fluoro-Gold and intraspinal microstimulation, we have identified commissural neurons projecting to the contralateral ventral horn. Neurons tended to be in the medial half of lamina VIII. Approximately half of the neurons were propriospinal neurons that could be activated antidromically from the rostral border of the cervical enlargement. Most of the tested, spontaneously active neurons were driven by stimulation of the ipsi- and/or contralateral vestibular nerve, in some cases disynaptically.

Animals↗

A scanning electron microscopic study of the contraction of vascular wall cells in dog dental pulp.

Ultrastructural changes in vascular wall cells in dog dental pulp after removal of connective tissue components were studied by scanning electron microscopy following administration of norepinephrine (0.2 mg/kg). Contracted smooth-muscle cells were frequently seen in arterioles of all sizes. The surfaces of these cells were highly irregular with numerous evaginations and invaginations, varying considerably in configuration and size. Many evaginations ran longitudinally or obliquely to the long axis of the vessel. Some meandering evaginations were also observed as, rarely, were small spherical or bulbous projections. Spidery smooth-muscle cells frequently seen in the tunica media of terminal arterioles and thought to be primitive smooth-muscle cells exhibited fewer irregularities than the typical spindle-shaped smooth-muscle cells beneath them. Pericytes in the larger post-capillary venules (20 microns or larger in diameter) often showed evaginations and invaginations, mainly running parallel to the vessel axis. On the other hand, no surface irregularities could be seen in pericytes of either the smaller post-capillary venules (less than 20 microns in diameter) or the capillaries, although occasional evaginations running parallel to the vessel axis were noted on the outer surface of the endothelium.

Animals↗

Preparation and biological activity of 2-[4-(thiazol-2-yl)phenyl]propionic acid derivatives inhibiting cyclooxygenase.

A series of 2-[4-(thiazol-2-yl)phenyl]propionic acids substituted at various positions were prepared by the reaction of diethyl 2-methyl-2-(4-thiocarbamoylphenyl)malonates with alpha-bromoaldehyde diethyl acetals or alpha-haloketones followed by hydrolysis of esters. The inhibition of prostaglandin H synthetase (cyclooxygenase) was assayed by use of an enzyme preparation from guinea pig polymorphonuclear leukocytes. Examination of the structure-activity relationship of these compounds indicated that the substitution pattern with halogens at position 3 (R1) of the benzene ring and a methyl group in position 4 (R2) and/or 5 (R3) of the thiazole ring were favorable for inhibitory activity. The compounds bearing bulky alkyl or polar functional groups at the R2 position were weak inhibitors. The potent inhibitors of cyclooxygenase were tested for their ability to reduce carrageenin-induced inflammation of rat paws. These derivatives had strong anti-inflammatory activity based on their strong inhibition of cyclooxygenase, with some exceptions, including those with a thiomethyl group at R1.

Animals↗

[Early experience with an ileocolic bladder substitution (Mainz pouch) in 11 cases].

In the last decade, many continent urinary diversions have been developed for the cystectomy patients. Mainz pouch, which seems to be a sophisticated one without using an alloplastic prosthesis, was adopted in our clinic. We preliminarily report our result in 11 patients who underwent a Mainz pouch procedure in the last 2 years: 1 for bladder augmentation, 5 for total bladder substitution after cystoprostatectomy and 5 (including 2 females) for continent urinary diversion. The mean age of them was 54 years old and the follow up periods ranged from 6 to 24 months. The antimesenteric longitudinal incision of the ileum and cecum and their sutures were performed similarly to the usual detubularized intestinal pouch. The ureteral reimplantation to the colonic segment was accomplished by the submucosal tunnel method. Although the ureteral hiatus was initially positioned at the anal edge of the colon, a new hiatal creation by stabbing the more oral portion of the colon according to the Goodwin's ureterocolic anastomosis was subsequently employed to avoid the trouble of closure of this portion. When the urethral anastomosis was achieved by 4-5 interrupted sutures between the most dependent portion of the cecum and the urethral stump after cystoprostatectomy, the mucosa was everted to the colonic serosa to prevent the stricture. The continent stoma was created by an intussusception of the proximal ileum, which was stabilized by the seromuscular stripping and 2-3 rows of external metal staples. Complication of the alimentary system occurred in 6 of 11 cases (55%), though they were successfully treated by an appropriate conservative management except one who suffered an ileostomy and nephrostomy because of severe panperitonitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Noninfectious doughnut-shaped human immunodeficiency virus type 1 can induce syncytia mediated by fusion of the particles with CD4-positive cells.

A defective doughnut-shaped human immunodeficiency virus type 1 (HIV-1)-producing cell clone (designated as L-2) was isolated from persistently HIV-1-infected MT-4 cells. The syncytium-forming capacity of the cell and virus particle fractions was examined in human CD4-positive T cells. Several cell lines producing infectious HIV-1 particles, such as persistently HIV-1-infected MOLT-4 (MOLT-4/HIV-1) cells, were used as controls. Syncytia were formed within 20 h by the cell fraction of both L-2 and MOLT-4/HIV-1 and the virus particle fraction of L-2, but not MOLT-4/HIV-1. These formations were not affected by 3'-azido-3'-deoxythymidine (ZDV). In contrast, similar syncytium formation was first observed 2 days after the incubation of the virus particle fraction of MOLT-4/LAV-1 and this syncytium formation mediated by the cell fractions of MOLT-4/HIV-1 and L-2 or the virus particle fraction of L-2 differently.

Antibodies, Monoclonal↗

Geographic clustering of myeloma in Tokushima.

Between 1978-1988, seven cases of multiple myeloma were found in T Town (population 9,000), which is located at the mouth of a large river within the boundaries of Tokushima City, Japan. This is a significantly high incidence, 7.06 per 100,000 as compared with an incidence of 1.20 in Tokushima City itself and 1.53 in Japan as a whole. The clinical and laboratory features of these patients were typical of myeloma. Although the causes of this small but apparent cluster of multiple myeloma remain obscure, the fact that five of the seven patients had been working for long periods as fishermen was notable.

Adult↗

Alpha-interferon broadens the difference between surviving fractions of normal and leukemic progenitor cells in vitro by heat: its application to marrow purging.

Alpha-interferon (IFN) may inhibit the proliferation of human leukemic progenitor cells (L-CFU) in vitro and enhance the anti-tumor effects by heat. In this study, the combined effects of IFN and hyperthermia on the growth of L-CFU and human granulocyte-macrophage progenitors (CFU-GM) were examined to determine if this combination resulted in a greater selective killing of L-CFU than that obtained by heat treatment alone. The survival of normal CFU-GM without IFN decreased at elevated temperatures (42-44 degrees C). However, IFN added during heating (42 and 43 degrees C) appeared significantly to protect against the hyperthermic killing of CFU-GM in vitro leaving over 50% of CFU-GM surviving. The optimal dose to protect CFU-GM in vitro dropped to a rather low dose (100 U/ml). On the other hand, the addition of IFN to leukemic cell suspensions enhanced the hyperthermic killing of myeloid leukemic cell lines (HEL and KG-1) as well as a T lymphoblastic cell line (CEM) in a dose-related manner. In addition, similar results were observed in the study of L-CFU from patients with acute myelogenous leukemia. These results suggest that IFN can be used to broaden the difference between surviving fractions of CFU-GM and L-CFU by heat. Thus, this combination could be applied effectively and safely for the elimination of residual clonogenic leukemic cells in autologous remission marrow graft before autologous bone marrow transplantation.

Bone Marrow Purging↗

Isolation and identification of bile salts conjugated with cysteinolic acid from bile of the red seabream, Pagrosomus major.

Bile salts present in gallbladder of wild and cultured red seabream, Pagrosomus major, a marine teleost were analyzed. The bile from wild red seabream was found to contain two previously unknown bile salts along with two known bile salts, taurocholate and taurochenodeoxycholate. Isolation of each bile salt was performed by column chromatography. Fast atom bombardment mass spectra of the unknown bile salts showed the molecular ions (M-H)- of m/z 544 and 528 which are shifted 30 mass units upfield compared to those (m/z 514 and 498) of taurocholate and taurochendeoxycholate, respectively; this is consistent with the presence of cysteinolic acid (mol wt 155) instead of taurine (mol wt 125). Enzymatic hydrolysis of the bile salts released cholic acid and chenodeoxycholic acid, respectively, and an amino acid that was identified as D-cysteinolic acid by direct comparison with an authentic sample. From these results, the bile salts in the bile of wild red seabream were identified as the conjugates of cholic acid and chenodeoxycholic acid with cysteinolic acid. 1H- and 13C-magnetic resonance spectra of the bile salts were also consistent with the proposed structure. The cysteinolic acid conjugates were found only in wild and not in cultured red seabream; this distinction seems to result from differences in dietary cysteinolic acid.

Animals↗

[Clinical effect of nitroglycerin (GTN) on prevention of cerebral vasospasm].

Nitroglycerin (GTN) is widely used as a safe and effective dilator in patients with ischemic heart disease, and it is said that it dilates the cerebral vessels. So the authors are now using GTN for the prevention of cerebral vasospasm. 125 patients classified as Fisher's Group 2, 3 or 4 were operated on within 72 hours after subarachnoid hemorrhage due to ruptured cerebral aneurysm. 58 patients (GTN group) were treated with continuous intravenous infusions of GTN (0.5-1.0 micrograms/kg/min) for about 2 weeks after their operation, and another 67 patients (control group) were not administered GTN. The frequency of occurrence of symptomatic vasospasm decreased in each GTN group of Fisher's classification, and the severity of angiographic vasospasm also tended to decrease. Especially in patients with severe subarachnoid hemorrhage classified as CT group 3 or 4, symptomatic vasospasm occurred in 11 patients (30.6%) in the GTN group, but in 26 patients (63.4%) in the control group. Regarding the outcome, 10 patients (17.2%) in the GTN group showed poor results or died, as opposed to 22 patients (32.9%) in the control group. This difference was significant. Moreover the GTN group had no cases of mortality due to cerebral vasospasm. These results indicate that GTN can be effective for prevention of cerebral vasospasm and improve the prognosis in patients with serious subarachnoid hemorrhage due to a ruptured aneurysm.

Adult↗