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Biomedical subjects

S Ikeda

Publications and source records attributed to S Ikeda.

At least 541 records · Page 30Linked to original sources

An epimer of 5'-noraristeromycin and its antiviral properties.

A derivative of 5'-noraristeromycin epimeric at the 5'-nor center ((-)-3) has been prepared enantiospecifically in three steps from (+)-((1R,4S)-4-hydroxy-2-cyclopenten- 1-yl acetate. Compound (-)-3 was evaluated for antiviral activity against a large number of viruses and found to display marked activity against varicella-zoster virus, vaccinia virus, vesicular stomatitis virus, parainfluenza virus, reovirus, and cytomegalovirus. A similar antiviral activity spectrum was shown by the S-adenosylhomocysteine hydrolase inhibitors neplanocin A and carbocyclic 3-deazaadenosine. While equally potent as neplanocin A against most of the viruses tested, compound (-)-3 was significantly less cytotoxic. The results of this study suggest that (-)-3 should be pursued for the treatment of those virus infections [that is, pox (VV), rhabdo (VSV), paramyxo (parainfluenza), and reo] that appear to be exquisitively sensitive to the compound.

Adenosine↗

6H-pyrazolo[4,5,1-de]acridin-6-ones as a novel class of antitumor agents. Synthesis and biological activity.

The 7-substituted 6H-pyrazolo[4,5,1-de]acridin-6-ones with (aminoalkyl)amino and/or (hydroxyalkyl)amino groups in the side chains were synthesized by bromination using N-bromosuccinimide and the subsequent reaction with amines from the 7-substituted 5-bromo-2-methyl-6H-pyrazolo-[4,5,1-de]acridin-6-one. The substitution reaction of the amines with alkyl bromide (the C2 position) and aryl bromide (the C5 position) was accomplished by choosing the proper reaction conditions. These compounds show DNA intercalating ability in ethidium fluorescence assay and antiproliferative activity against Hela S3 cells. Impressive antitumor activity in vivo against murine P388 leukemia and murine sarcoma 180 solid tumor in mice was demonstrated for the 7-hydroxy analogs. In addition, some of these showed excellent antitumor activity against adriamycin-resistant murine P388 leukemia (P388/ADM) in mice.

Aminoacridines↗

Antiviral enantiomeric preference for 5'-noraristeromycin.

In order to determine if the potent antiviral properties of (+/-)-5'-noraristeromycin reside in one of its enantiomers, an analysis of each enantiomer has been carried out. A five-step route to the (+)-stereoisomer is described from (+)-(1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate, whereas the synthesis of the (-)-enantiomer had been reported previously from the same starting material. The (-)-2 and (+)-2 enantiomers were evaluated for antiviral activity against a large number of viruses and found to display an antiviral activity spectrum characteristic of (S)-adenosyl-L-homocysteine hydrolase inhibitors. The (-)-enantiomer retained the significant anticytomegalovirus properties previously reported for the racemic 2 and was, on the average, 10-fold more potent than (+)-2 in inhibiting virus replication, tumor cell growth, and (S)-adenosyl-L-homocysteine hydrolase activity.

Adenosine↗

Demonstration of amyloid beta-protein secretion in a mouse neuronal cell line.

We investigated the secretion of amyloid beta-protein (beta AP) in a mouse neuronal cell line SN49. SN49 cells stably transfected with mouse beta-amyloid precursor protein (APP) 695 cDNA released approximately three times greater amounts of a 4 kDa protein immunoreactive with anti-beta AP antibodies than untransfected and mock-transfected cells. This 4 kDa protein was further identified as mouse beta AP by direct amino acid sequence analysis. These results strongly suggest that the beta AP secretion occurs in mouse neuronal cells as in human cells.

Amino Acid Sequence↗

Familial amyloid polyneuropathy in Taiwan: identification of transthyretin variant (Leu55-->Pro).

We report a family with familial amyloid polyneuropathy (FAP), showing an early-onset and a fatal outcome before age 30. Transthyretin (TTR) gene analysis showed one point mutation (T-->C change) in the second base of codon 55, and the corresponding amino acid substitution of proline (Pro) for leucine (Leu) was confirmed at the protein level. This is the first FAP family of Taiwanese origin demonstrating a causative gene abnormality, and FAP with TTR-Pro55 was considered to be more serious compared with other forms of FAP.

Adolescent↗

Alpha-fetoprotein-producing early gastric cancer accompanying liver cirrhosis: a case report.

A rare case of alpha-fetoprotein (AFP)-producing early gastric cancer with liver cirrhosis is presented. A 61-year-old man was admitted to Shimane Medical University Hospital in 1988 because of abnormal liver function test results suggestive of liver cirrhosis with mild elevation of AFP. Liver cirrhosis was confirmed laparoscopically and histologically. Gastric cancer was found in fluoroscopic and endoscopic studies. After partial gastrectomy, the serum AFP level fluctuated transiently within normal limits, and then gradually increased soon after the operation. Therefore, complication of hepatocellular carcinoma was suspected, but no tumor in the liver was detected by any imaging examination, including angiography. Two years after the operation, swelling of abdominal periaortic lymph nodes was noted at a periodic checkup, but still no hepatic tumor was found. At this point, AFP-producing gastric cancer was suspected, and an AFP staining test was carried out on the tissue of the resected specimen. AFP-positive cells were recognized immunohistochemically. Thus, we diagnosed the condition as post-operative recurrence of an AFP-producing gastric cancer accompanying liver cirrhosis.

Adenocarcinoma↗

Gallbladder expansion induced by feeding.

By using ultrasound we were able to observe any increase in the size of human gallbladders during feeding. In 91 of 123 cases (74%), the gallbladder expanded for a short time prior to contraction during feeding. The examination on eight patients after gastrectomy and seven patients after a medically induced vagotomy revealed contraction only in response to feeding. In seven normal adults, 200 ml of air injected rapidly into stomach through a gastric tube was seen to induce gallbladder expansion. These results suggest that the gallbladder expands in response to feeding via a cholinergic vago-vagal reflex.

Adult↗

Acetylcholine regulates glucagon secretion from human glucagonoma cells.

Human glucagonoma cells were isolated and maintained in vitro. Incubation experiments showed that carbachol (Cch) induced the simultaneous release of glucagon, VIP (vasoactive intestinal polypeptide), and pancreatic polypeptide (PP) at levels significantly higher than basal levels. Atropine abolished the stimulatory effect of Cch on glucagon, VIP, and PP release. An immunohistological study of the tumor tissues revealed that the cells contained glucagon, VIP, and PP. These findings demonstrate, for the first time, the in vitro release of glucagon from glucagonoma cells by Cch stimulation.

Carbachol↗

DNA aneuploidy of adult T-cell leukemia cells.

To clarify the biological characteristics of adult T-cell leukemia (ATL), immunophenotyping and DNA aneuploid analysis were performed in 72 ATL cases, using flow cytometric techniques. DNA aneuploidy was found in 45 cases (62.5%); the DNA index ranged from 1.03 to 2.16 (mean: 1.24). The incidence of aneuploidy in smoldering, chronic, acute, and lymphoma ATL subtypes was 20.0%, 46.6%, 76.3%, and 77.8%, respectively. The aneuploid patients had a greater tumor burden (adenopathy, hepatosplenomegaly, and leukocytosis with ATL cells), a higher level of serum LDH, and a higher incidence of hypercalcemia, compared with the diploid group. Further, unusual aberrant immunophenotypes were identified predominantly in the aneuploid group. Patients with aneuploidy had a 7.6 month median survival time (MST) with a 2 year survival rate of 24.6%, significantly worse than in the patients with diploidy, whose MST was 25.4 months with a 2 year survival of 60.1%. In some aneuploid patients, the disease often progresses from a static to an aggressive form. Thus, the determination of aneuploidy and unusual immunophenotype should be useful for detecting clinical behavior and for monitoring ATL patients, particularly in regard to such progression.

Adult↗

Aneurysm of bilateral persistent sciatic arteries with ischemic complications: case report and review of the world literature.

A case of bilateral persistent sciatic artery (PSA) aneurysms with thromboembolic complications is presented along with a review of the 167 cases of PSA reported in the world literature. Its embryology, anatomy, clinical features, diagnosis, and treatment are reviewed and provide the following findings: The incidence of PSA is estimated to be from 0.025% to 0.04%, based on angiographic studies. Ages range from 6 months to 89 years, with a mean of 54 years. There is no gender predilection. A PSA was present on the right side in 32%, on the left side in 29%, bilaterally in 22%, and on either side in 18%. The "complete" type of PSA was 69%. Aneurysmal change was present in 46% of all PSAs. Overall, 59% had symptoms, including ischemia in 31% (acute in 14% and chronic in 17%), a gluteal mass in 26% (painful in 10%, painless in 6%, and pulsatile in 13%), gluteal pain in 2%, and ischialgia in 5%. Exclusion of the aneurysm or PSA by surgical or interventional techniques, with a femorodistal bypass as required for the resultant ischemia is currently the treatment of choice.

Aneurysm↗

An attempt to treat intractable skin ulcers with autologous dermal graft.

Five patients with a total of seven chronic intractable skin ulcers and impaired peripheral blood circulation were treated with autologous dermal grafts which did not contain any epidermal component. These ulcers were refractory to conventional therapy. Results from the dermal grafting were variable, with four of the ulcers (in two patients) healing 1-8 months after 1-5 graftings. These findings suggest the possibility that dermal grafting may be a simple yet effective treatment for deep, super-infected skin ulcers in which tendons and bones have become exposed. Dermal grafting may also provide an additional method by which to treat chronic skin ulcers which do not respond to conventional surgical therapy and where amputation of affected extremities is being considered.

Adult↗

Management of acute otitis media. Assessment of therapeutic strategy in Japan today.

Currently, myringotomy is widely used in the routine initial treatment of acute otitis media in Japan. In an attempt to evaluate the validity of this strategy, a number of issues that demand reassessment or clarification have been identified. These issues and factors contributing to the persisting uncertainty about myringotomy are examined.

Acute Disease↗

Determination of 2,2,2-trichloroethanol in plasma and urine by ion-exclusion chromatography.

A simple and rapid chromatographic method has been developed for the determination of 2,2,2-trichloroethanol (TCEOH) and its glucuronide in plasma and urine. A glass column (150 x 6.6 mm i.d.) packed with Aminex A-5 cation-exchange resin (potassium form) following the slurry method was used as the analytical column, and an admixture of 10 mmol l-1 potassium sulfate and 10 mmol l-1 potassium hydroxide solution as the eluent (pH 12.2). Diluted plasma samples and urine samples were directly injected into the chromatograph through a 0.45 micron membrane filter without deproteinization. The amount of TCEOH conjugated to glucuronide was determined following treatment with beta-glucuronidase (200 U) for 30 min at 37 degrees C. This allowed the concentration of free, total, and conjugated TCEOH to be determined. The calibration graph was rectilinear from 5 to 500 mg l-1 of TCEOH, with a detection limit of 3 mg l-1, 2 sigma, being the signal-to-noise ratio. The analytical recovery of TCEOH, obtained by analysing spiked plasma and urine samples, was in the range 98.4-102% and the relative standard deviation was less than 3.5%.

Adult↗

Applying RUG-III in Japanese long-term care facilities.

A U.S. nursing home case-mix system, Resource Utilization Group, Version III (RUG-III), was tested in a variety of Japanese long-term care facilities. Staff time and resident characteristics were measured for a sample of 871 patients. Acceptable reliability was found for items defining RUG-III, and the system explained 44% of the variance in wage-weighted staff time (cost). Also, Japanese and U.S. costs had similar patterns across RUG-III categories. However, there was wide discrepancy between the stated purpose of Japanese facilities and their patient populations, and the current payment mechanism did not reflect actual use of resources.

Aged↗

Localization of the gene whose mutations underlie Hailey-Hailey disease to chromosome 3q.

Hailey-Hailey disease (familial benign chronic pemphigus) is an autosomal dominant skin disease characterized by impaired keratinocyte cohesion and consequent blister formation. In the present study we have used linkage analysis to map the gene for this disease to a region of chromosome 3q between D3S1589 and D3S1316. The maximum combined two point lod score in four families studied was 14.60 at theta = 0 at the D3S1290 microsatellite repeat. These findings suggest the presence of a gene not previously known to be involved in keratinocyte cohesion at this site.

Chromosome Mapping↗

Hailey-Hailey disease is not allelic to Darier's disease.

Hailey-Hailey (Familial Benign Chronic Pemphigus) Disease is a rare autosomal dominant disorder characterized by blisters caused by suprabasal epidermal acantholysis. Another autosomal dominant skin disease, Darier's disease, has clinical and histologic features which overlap those of Hailey-Hailey disease and recently has been mapped to chromosome 12q23-q24.1. We have used linkage analysis to test whether or not a mutation in this region might also underlie Hailey-Hailey disease. This analysis, using polymorphic loci tightly linked to Darier's disease, excluded this region as the site for the disease-causing mutation in two kindreds affected with Hailey-Hailey disease.

Adolescent↗