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Biomedical subjects

I Yamada

Publications and source records attributed to I Yamada.

At least 145 records · Page 8Linked to original sources
PubMed1989

Differences between ocular and generalized myasthenia gravis: binding characteristics of anti-acetylcholine receptor antibody against bovine muscles.

We studied the binding characteristics of anti-acetylcholine receptor antibody (AChR Ab) in sera of nine patients with myasthenia gravis (MG) using affinity-purified extraocular muscles (EOM) and foot muscles (FM) of bovine species. The titer of AChR Ab measured with EOM was the same as that measured with FM for both ocular and generalized MG. In patients with ocular MG, the affinity of AChR Ab, determined by Scatchard analysis, was higher for FM than for EOM (P less than 0.05), whereas it was the same for EOM and FM in those with generalized MG. On the other hand, the affinity of AChR Ab for FM was lower in generalized MG than in ocular MG (P less than 0.05), but that for EOM did not differ between the two types of MG. The affinity of AChR Ab did not change after passing the patients' sera through an EOM-affinity column. The EOM-affinity column treatment of the sera decreased the AChR Ab titer measured with EOM in all patients, but the AChR Ab titer measured with FM was decreased in only some of the patients. These data indicate that there are polyclonal or heterogeneous AChR Abs in the sera of MG patients, which does not help to explain the clinical difference between ocular and generalized MG.

Animals↗
PubMed1989

Gastric pH profile and its control in fasting beagle dogs.

The gastric pH of fasting beagle dogs was measured by using an ion-selective field effect transistor pH sensor. In addition, a novel procedure to control the gastric pH in fasting beagle dogs was investigated. Inter- and intra-day variations in the gastric pH of the dogs were observed. The gastric pH of the dogs could be controlled by a single intravenous administration of omeprazole, an H+, K+-adenosine triphosphatase (ATPase) inhibitor (1 mg/0.25 ml/kg). The pH in the stomach was 6.6 +/- 0.2 (mean +/- S.D., n = 6) at 1 h after the omeprazole treatment, and this level of pH was maintained for a period of at least 3 h. Beagle dogs in which the gastric pH has been controlled by omeprazole are considered to be useful as an animal model to be used for the pharmaceutical evaluation of drugs in subjects with a low acidity level.

Animals↗
PubMed1989

Effect of gastric acidity on bioavailability of N,N-dimethylcarbamoylmethylalpha, 2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate, a new prodrug-type anti-inflammatory agent.

The effect of gastric acidity on the bioavailability of N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b] pyridine-7-acetate (1), a new anti-inflammatory agent, was investigated in gastric acidity-controlled beagle dogs. The dissolution rates of this compound in media of pH 1.2 and 3.0 were greater than those in media of pH 5.0 and 6.8. Reflecting these dissolution characteristics, the peak plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC0-12h) were reduced by shifting the gastric acidity to low levels (more than pH 6) with omeprazole treatment. In designing dosage forms of 1, it is necessary to develop pharmaceutical preparations whose bioavailability is not affected by the gastric acidity.

Animals↗
PubMed1989

[Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates].

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.

Animals↗
PubMed1989

[Dissolution properties and bioavailability of ground mixture of N,N-dimethylcarbamoylmethyl alpha, 2-dimethyl-5H-[1]benzopyrano[2,3-b]-pyridine-7-acetate with various pharmaceutical ingredients].

Ground mixture of N,N-dimethylcarbamoylmethyl alpha, 2-dimethyl-5H-[1]benzopyrano-[2,3-b]pyridine-7-acetate (1) with various pharmaceutical ingredients were prepared in order to investigate their dissolution behaviors and bioavailability. Taking into account the weakly basic property of 1, the dissolution rate was determined in the 2nd fluid (pH 6.8) of disintegration test, JP XI. Dissolution rates of the ground mixtures (1 : 1, w/w) of 1 with hydroxypropylcellulose-L (HPC-L), low substituted hydroxypropylcellulose (L-HPC) or lactose respectively, showed a significant increase compared with compound 1 alone. Three kinds of experimental fine granules were prepared; type A: produced from ground mixture of 1, HPC-L, L-HPC and lactose; type B: produced from physical mixture having the same composition as type A; type C: produced 1, L-HPC and lactose. In these fine granules, only type A exhibited pH-independent dissolution profiles. Bioavailability study was carried out in beagle dogs whose gastric acidity was controlled in advance to low levels by administration of omeprazole. The test was conducted in a cross over design. Reflecting their dissolution characteristics, type A granules showed better bioavailability than the others. These results suggest that grinding is useful for the improvement of the dissolution property and bioavailability of 1, a weakly basic compound.

Adjuvants, Pharmaceutic↗
PubMed1988

Involvement of HLA in clinical courses of myasthenia gravis.

The relationship between the histocompatibility leukocyte antigen (HLA) phenotypes and the clinical course of myasthenia gravis (MG) was studied in 53 Japanese patients with MG. The frequency of HLA-DRw9 antigen was high in the MG patients who did not need immunosuppressive therapy but only anticholinesterase agents (RR = 4.52; CP less than 0.02), who achieved remission of the disease (RR = 2.98; CP less than 0.05) or who showed a decrease in AChR antibody (Ab) titer (RR = 6.32; CP less than 0.0002), whereas the frequency of HLA-DRw8 antigen was increased in MG patients who underwent immunosuppressive therapy (RR = 4.03; CP less than 0.01), who did not have remission (RR = 4.75; CP less than 0.1) or who showed an increase in AChR Ab titer (RR = 6.48; CP less than 0.01). These data suggest that immunogenetic heterogeneity in MG might be reflected in its clinical course.

Adolescent↗
PubMed1988

[Carotid endarterectomies for cerebral ischemia: a follow up study of surgical results and late neurologic complications].

Twenty five carotid endarterectomies were performed in 24 patients with cerebral ischemia due to atherosclerosis. Four of these patients were asymptomatic, 7 suffered from hemispheric TIA (hemispheric attack group), 7 suffered from nonhemispheric TIA (nonhemispheric attack group) and other 6 had previous completed stroke (completed stroke group). The average length of follow-up study was two and half years with a range of 2 months to 6 years. Completed strokes occurred in 1 patient following the operation and in 3 patients during the follow-up period (16.7%). Two patients were reoperated upon because of recurrent carotid stenosis (8.3%). Four patients continued to have neurologic symptoms postoperatively. Ultimately 10 of 24 patients had some neurologic complications even following carotid endarterectomies (41.7%). The first postoperative year was the worst period because almost all late neurologic complications occurred in that time. Kaplan-Meier's analysis demonstrated a relatively favorable result in the hemispheric attack group among these 3 groups. The completed stroke group was followed by that and the nonhemispheric attack group was proved to be the worst, although there was no statistical significance.

Aged↗
PubMed1987

Heterogeneity in myasthenia gravis: HLA phenotypes and autoantibody responses in ocular and generalized types.

HLA phenotypes and autoantibody responses were studied in 71 Japanese patients with myasthenia gravis. HLA-A2, Bw61, and DRw9 were associated with ocular myasthenia gravis (corrected p [CP] less than 0.05 relative risk [RR] = 2.88; CP less than 0.02, RR = 3.60; and CP less than 0.001, RR = 4.63, respectively) and HLA-DRw8 was associated with generalized myasthenia gravis (CP less than 0.001, RR = 5.40). Neither HLA-B8 nor DR3 was found in Japanese patients. The titer of antiacetylcholine receptor antibody (AChR Ab) and the incidence of autoantibodies other than AChR Ab were higher in patients with generalized myasthenia gravis than in those with the ocular type (2.77 +/- 0.62 versus 0.17 +/- 0.03 pmol/ml, p less than 0.001; and 60.6 versus 29.0%, p less than 0.02, respectively). Patients with a high titer of AChR Ab or with autoantibodies had an increased frequency of HLA-DRw8 (CP less than 0.02, RR = 4.61, and CP less than 0.005, RR = 4.53, respectively); whereas patients with a low titer of AChR Ab or without autoantibodies had an increased frequency of HLA-DRw9 (CP less than 0.001, RR = 8.26, and CP less than 0.005, RR = 4.08, respectively). These findings suggest that ocular and generalized myasthenia gravis might have different immunogenetic backgrounds.

Adolescent↗
PubMed1987

The cytotoxicity of cysteinylcatechols and related compounds to human melanoma cells in vitro.

L-3,4-Dihydroxyphenylalanine (L-dopa) and its structural analogs are known to be potently cytotoxic to melanoma cells. We examined the effects of cysteinylcatechols and related compounds, which were newly synthesized as cysteinyl derivatives of L-dopa, on the growth of human melanoma cells in vitro, and their actions were compared with those of L-dopa. 4-S- and 3-S-Cysteinylcatechols showed significantly more potent cytotoxicity to melanoma cells than did L-dopa, and 2-S-cysteinylhydroquinone was next to the catechols in potency. The mechanism of action may involve interaction with the melanocyte-specific enzyme, tyrosinase, for which the cysteinylcatechols could become a better substrate than L-dopa itself. 4-S-Cysteaminylphenol was almost comparable to L-dopa in cytotoxicity, suggesting that this phenol might be oxidized to the corresponding catechol by tyrosinase within the melanoma cells.

Antineoplastic Agents↗
PubMed1987

[Three cases of thoracic or thoracoabdominal aortic aneurysm successfully treated with cell saver].

During a three-month period from January to March 1986, reconstructive surgery was performed on three patients with thoracic or thoracoabdominal aortic aneurysm using a temporary bypass procedure. To reduce the amount of blood transfusion required during operation, an autologous blood recovery system, Cell Saver, was used in these three cases. The amount of blood loss, including the blood passing through the Cell Saver, was 7,020g in Case 1, 6,600g in Case 2 and 16,700g in Case 3. The amount of blood transfusion given to these three cases was 1,400g, 4,400g and 6,800g, respectively. The results indicated that the ratio of transfused blood amount to blood loss during operation was successfully reduced to a level of 20-67% of two other cases with thoracoabdominal aortic aneurysm, operated upon without using Cell Saver. Cell Saver was especially effective in Case 3 in which the blood for transfusion was restricted, for it was difficult to collect enough donors to complete operation because of rare blood type of Rh(-) in this case. That is, Cell Saver withdrew 15,000ml of blood through the sucker from the patient and returned it as concentrated and washed RBC during operation.

Aorta, Abdominal↗
PubMed1986

Distribution of demyelinating lesions in pontine and extrapontine myelinolysis--three autopsy cases including one case devoid of central pontine myelinolysis.

Three autopsy cases of pontine and extrapontine myelinolysis are reported; one, a malignant lymphoma in a man of 66 years, the other an alcoholic liver cirrhosis in a man of 54 years, and an esophageal cancer in a woman of 68 years who presented only with extrapontine myelinolysis, but lacked central pontine myelinolysis (CPM). The extrapontine lesions in these three cases revealed a characteristic and common localization; they occurred mostly in the bundles of myelinated fibers in the gray matter, such as in the pons, basal ganglia, and thalamus; and in the white matter surrounded by massive gray matter, such as the deeper layers of the cortex and subjacent white matter of the crowns and sides of the cerebral gyri, the white matter of the cerebellar folia and internal, external, and extreme capsules. Therefore, the third patient was classified as a subtype of pontine and extrapontine myelinolysis, which may be called the "extrapontine form" because of absence of CPM. Moreover, bilateral demyelination of the mamillary body was found in all cases, and laminar cortical astrocytosis and necrosis similar to Morel's cortical laminar sclerosis in two of them. From the clinical and pathologic findings, the significance of the changed osmolarity of the blood as a cause and the importance of some specificity of the tissue architecture in the pathogenesis are discussed.

Aged↗
PubMed1986

Natural history of intermittent claudication in the Japanese.

The natural history of intermittent claudication (IC) was surveyed in 59 limbs of 44 patients. The mean follow-up period was 3 years (1 to 8.3 years). During the follow-up period, 72.0 per cent of the limbs with a solitary arterial lesion improved or remained unchanged. However, detailed analysis showed that 53.3 per cent of limbs with iliac artery stenosis and 50.0 per cent of those with femoropopliteal artery stenosis worsened, whereas only 18.7 per cent of limbs with iliac artery occlusion and no limbs with femoropopliteal artery occlusion had worsening of symptoms. Of limbs with multiple arterial lesions, 62.5 per cent worsened. Although the natural history of IC is relatively favorable, IC due to a solitary arterial stenosis tends to worsen, whereas IC due to a solitary arterial occlusion will, in more than 80 per cent of cases, improve or remain unchanged. In cases of arterial stenosis, therefore, more careful follow-up, including control of risk factors, is mandatory.

Aged↗
PubMed1986

Flow velocity measurement using digital subtraction angiography for hemodynamic evaluation in arterial occlusive disease.

A method for mean flow velocity measurement using digital subtraction angiography (DSA) was evaluated, along with the results of phantom and animal experiments. The validity of its clinical use was studied by applying this technique in the arteries and bypass grafts in patients with arterial occlusive disease. Mean flow velocity was reliably determined by this method, but it could not be used as a determinant of arterial occlusive disease, because of a considerable overlapping between limbs with and without significant arterial lesions. A low value of mean flow velocity was not itself a reliable prognostic indicator of bypass failure. However, measurement of mean flow velocity was valuable in detecting functional abnormalities of the graft.

Animals↗
PubMed1985

Antagonistic effect of delta-aminovaleric acid on bicuculline-insensitive gamma-aminobutyric acid B (GABA B) sites in the rat's brain.

The effect of delta-aminovaleric acid (delta-AV) on bicuculline-insensitive gamma-aminobutyric acid B (GABA B) sites in the central nervous system (CNS) was investigated by binding studies and experiments on slices in vitro. delta-AV inhibited [3H]GABA (10 nM) binding to GABA B sites in a rat brain membrane preparation with an IC50 value of 10(-4) M. It also inhibited [3H]baclofen (20 nM) binding with an IC50 value of 10(-4) M. In preparations of hippocampal slices, (-)-baclofen (5 microM) reduced the population spikes evoked by stimulating the Schaffer collaterals in CA1 pyramidal cells in the presence of 100 microM bicuculline. delta-AV (1 mM) antagonized this inhibitory action of baclofen. Since baclofen is an agonist of GABAB sites, our results indicate that delta-AV has an antagonistic effect on GABAB sites in the CNS.

Amino Acids↗