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Biomedical subjects

K Miyoshi

Publications and source records attributed to K Miyoshi.

At least 19 recordsLinked to original sources

Synthesis and inotropic activity of pyrazolo[4,3-c]pyridine-4-ones and related compounds.

Two series of 3,6-dimethyl-1-phenyl-1H-pyrazolo[4,3-c] pyridine-4-ones (5-9) and 3,6-dimethyl-1-phenyl-1H-pyrazolo[4,3-c] pyridine-4-thiones (11-13) were prepared from dehydroacetic acid as starting material and evaluated for positive inotropic activity in vitro. Moreover, the activity of the synthesized compounds was compared with that of mirlinone as a reference. Among these compounds, the positive inotropic activity of 8a, 11a, and 12 were approximately 1.24, 1.77, and 1.11 times more potent, respectively, than that of mirlinone.

Animals

A case of ileus caused by a spiruroid nematode.

A 34-year-old male living in Aichi Prefecture, Japan, complained of lower abdominal pain. Ileus was suspected based on his clinical history and symptoms, and a laparotomy was performed. Four sections of a nematode were found in a large eosinophilic granuloma in the intestinal wall, and were identified as the larva of a spiruroid nematode. This is the third reported case of a spiruroid nematode infection found in the ileum.

Adult

Detection of herpes simplex and varicella-zoster virus DNA by field-inversion gel electrophoresis from clinical materials.

A simple method using field-inversion gel electrophoresis (FIGE) was applied to detect herpes simplex virus (HSV) and varicella-zoster virus (VZV) genomes in clinical specimens. The whole genomes of these viruses could be detected in small vesicle tissues by the FIGE method regardless of their clinical stages of skin lesions. And the sensitivity of the FIGE method was equivalent to that of an immunofluorescent (IF) method. These data indicated usefulness of the FIGE method to detect the whole genomes of HSV and VZV in clinical specimens.

DNA, Viral

Anticellular and antitumor activity of duocarmycins, novel antitumor antibiotics.

The anticellular and antitumor activities of novel antitumor antibiotics, duocarmycins (DUMs), were examined against human and murine tumor cells. DUMs consist of five compounds, A, B1, B2, C1 and C2, which possess a pharmacophore similar to that of CC-1065, a previously isolated antibiotic. Among them, DUMA exhibited ultrapotent growth-inhibitory activity with an IC50 value of 6 pM against human uterine cervix carcinoma HeLa S3 cells. DUMA and DUMB1 also inhibited the growth of adriamycin (ADM)-resistant lines of human nasopharynx carcinoma KB cells and breast carcinoma MCF-7 cells as well as their sensitive lines. DUMs inhibited the growth of s.c.-inoculated murine tumors such as B16 melanoma, sarcoma 180, M5076 sarcoma and colon 26. DUMs were also significantly effective in increasing the lifespan of i.p.-inoculated B16 melanoma-bearing mice, although their effect was marginal against other i.p.-inoculated tumors. As a whole, DUMB1 exhibited superior activity to the other four compounds. DUMB1 rapidly inhibited the incorporation of [3H]-TdR into macromolecules of HeLa S3 cells as compared with that of [3H]UR or [3H]leucine. DNA strand breaks were detected in DUMB1-treated HeLa S3 cells by agarose gel electrophoresis with a contour-clamped homogeneous electric field apparatus. These results indicate that DUMs possess interesting biological activities as DNA-targeting antitumor antibiotics.

Animals

[Laboratory tests in primary care medicine: "essential laboratory tests" (2). Usefulness of hematological, biochemical and serological tests in diagnosis of new outpatients].

We evaluated diagnostic utility of the hematological, biochemical and serological tests comprised in the "essential laboratory tests" advocated by the Japan Society of Clinical Pathology in 1,026 new patients visiting the outpatient unit of Comprehensive Medicine, National Defense Medical College. Of 750 evaluable patients, 52 showed anemia associated with such conditions as ulcer or cancer of digestive tract, inflammatory disease, or renal failure. Leukocytosis (greater than 9,000/microliters) was found only in 25 of 112 CRP-positive (greater than 0.3 mg/dl) patients, suggesting bacterial infection. Forty-four patients showed hypoproteinemia and/or hypoalbuminemia indicating chronic conditions including liver and inflammatory disease. Elevation of serum creatinine level was found in 4 patients subsequently diagnosed with renal failure, whereas 32 patients demonstrated elevated BUN. After application of the "essential laboratory tests", 97 patients were diagnosed with hyperlipidemia (total cholesterol greater than 230 mg/dl and/or triglyceride greater than 250 mg/dl). Determination of serum enzyme activity was useful not only for the diagnosis of liver dysfunction or biliary tract disease but also for those of hematological malignancies or myogenic disorders; however, in patients with abnormal values of LDH, gamma-GT and ALP, clinical significance was not clarified in 53%, 38% and 59%, respectively. These results indicate that the "essential laboratory tests" are useful in the following aspects of primary care medicine: for (1) estimation of the degree or nature of infection or inflammatory status; (2) classification of anemia and its relation to underlying diseases; (3) evaluation of patient general condition and protein-producible function of liver; (4) evaluation of renal function; (5) ambulatory screening for metabolic diseases such as hyperlipidemia; and (6) diagnosis of liver and biliary tract diseases.

Ambulatory Care

Reversal of learning impairment in ventral globus pallidus-lesioned rats by combination of continuous intracerebroventricular choline infusion and oral cholinergic drug administration.

The effects of separate or combined oral administration of THA (9-amino-1,2,3,4-tetrahydroacridine hydrochloride) and NIK-247 (9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b] quinoline monohydrate hydrochloride) and intracerebroventricular choline infusion using an osmotic minipump were investigated by observing locomotor activity, shock sensitivity, passive avoidance response and cerebral choline and acetylcholine contents in the bilateral ventral globus pallidus-lesioned rat. Evaluation of locomotor activity and shock sensitivity revealed no sensorimotor disturbances caused by combined administration. Intracerebroventricular choline infusion (100 mumol/day) and oral THA or NIK-247 administration (0.5 mg/kg) had no effect on the acquisition of the passive avoidance response, while the combination of oral THA or NIK-247 administration (0.5 mg/kg) and intracerebroventricular choline infusion (100 mumol/day) elicited good acquisition of passive avoidance learning and produced a significant increase of choline and acetylcholine in the cerebral cortex of the bilateral ventral globus pallidus-lesioned rat. These findings suggest that continuous intracerebroventricular choline infusion may intensify the ameliorating effect of THA or NIK-247 on learning disturbance.

Acetylcholine

Combined photic and nonphotic electro-oculographic responses in the clinical evaluation of the retinal pigment epithelium.

In an attempt to simplify the recording technique in electrophysiologic evaluation of the retinal pigment epithelium, we combined the electro-oculographic light rise, hyperosmolarity and acetazolamide responses in a single recording session. Recordings were performed in six normal subjects and in seven patients with diabetic retinopathy or retinitis pigmentosa. In the patients with background diabetic retinopathy, the hyperosmolarity responses were slightly reduced, while the acetazolamide response and the light rise was normal. In the patients with proliferative diabetic retinopathy, the hyperosmolarity response and light rise were remarkably reduced, while the acetazolamide response was normal. In the patients with retinitis pigmentosa, the hyperosmolarity response and light rise were decreased, while the acetazolamide response was normal. Despite a small study population, we concluded that the clinical results from our combined recording protocol were essentially the same as those reported for each response separately. Because this recording technique simplifies electrophysiologic evaluation of the retinal pigment epithelium, it may help clarify the mechanisms or localization of retinochoroidal and pigment epithelial diseases.

Adolescent

An autopsy case of mitochondrial encephalomyopathy with prominent degeneration in olivo-ponto-cerebellar system.

We describe a sporadic case of adult-onset, complex I deficiency mitochondrial encephalomyopathy (MEM), the clinical and pathological features of which failed to fit any of the known subgroups of MEM, such as Kearns-Sayre syndrome, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes or myoclonus epilepsy with ragged-red fibers. Clinically, this patient had only progressive cerebellar ataxia, generalized muscle weakness and hearing loss. The principal finding at autopsy was degeneration of the olivo-ponto-cerebellar system. This case suggests that mitochondrial disease could underlie some cases of olivo-ponto-cerebellar atrophy.

Cerebellum

The existence of filaments connecting the granules and the cell membrane in rat peritoneal mast cells.

SEM images of rat peritoneal mast cells showed that microtubule-like filaments seemed to penetrate the granules and project several branches just beneath the granular surface. Each granule appeared to be a cluster of microgranules. TEM observations frequently revealed microtubules connecting the granule surface to the subplasmalemmal network or to the adjacent granule surface and on some occasions, microtubules also appeared to penetrate the granule membranes. Moreover, TEM revealed that individual granules seemed to consist of a mass of microgranules, each 10-15 nm in diameter; freeze-fracture images showed similar configurations. These findings suggest that the microtubule-like filamentous structures in mast cells play a role corresponding to that of the open canalicular system in platelets.

Animals

Echocardiographic evaluation of fibrous replacement in the myocardium of patients with Duchenne muscular dystrophy.

OBJECTIVES: To study myocardial echo amplitude in Duchenne muscular dystrophy and to examine the implications of increased echo amplitude. DESIGN: Regional echo amplitude, wall motion, and uptake of thallium-201 were examined in the left ventricular wall and the relation between these variables was investigated. SETTING: Hara National Sanatorium, Japan. PATIENTS: Seven healthy controls aged 10-28 years and 14 patients with Duchenne muscular dystrophy aged 12 to 30 years. INTERVENTIONS: Echocardiography with a sector scanner (Hitachi EUB-150, Japan) and a 3.5 MHz transducer (Hitachi EUP-S21, Japan); thallium-201 myocardial single photon emission computed tomography at rest with a rotating gamma camera system (Hitachi RC-135DT, Japan). MAIN OUTCOME MEASURES: Echo amplitude of the myocardium, thickness and wall motion of the posterior wall and ventricular septum, and myocardial uptake of thallium-201. RESULTS: Areas of increased echo amplitude were detected along the outer half of or throughout the posterior wall of left ventricle in nine of the 14 patients. Their posterior walls showed significantly decreased maximal systolic and diastolic endocardial velocities (mean (SE) 31.4 (16.0) and 55.6 (53.5) mm/s) compared with normal subjects (57.7(19.4) and 113.0 (27.5) mm/s), and decreased uptake of thallium-201. Their ventricular septa, however, showed normal echo amplitude and wall motion and normal uptake of thallium-201. CONCLUSION: Areas of increased echo amplitude were detected in the posterior walls of left ventricles of patients with Duchenne muscular dystrophy. These areas were suspected to be the sites of myocardial fibrosis.

Adolescent