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Biomedical subjects

K Hamaguchi

Publications and source records attributed to K Hamaguchi.

At least 109 records · Page 6Linked to original sources
PubMed1993

Suppression of inflammatory responses to 12-O-tetradecanoyl-phorbol-13-acetate and carrageenin by YM-26734, a selective inhibitor of extracellular group II phospholipase A2.

1. YM-26734 [4-(3,5-didodecanoyl-2,4,6-trihydroxyphenyl)-7-hydroxy-2-(4-hydroxyph eny l) chroman] dose-dependently inhibited the activities of extracellular phospholipase A2 (PLA2): rabbit platelet-derived group II and porcine pancreas-derived group I PLA2, with IC50 values of 0.085 (0.056-0.129, n = 5) and 6.8 (5.0-9.6, n = 5) microM, respectively. 2. In contrast, YM-26734 did not reduce the activity of intracellular PLA2 prepared from mouse macrophages, which preferentially hydrolyzed arachidonoyl phospholipids at concentrations up to 50 microM. YM-26734 also showed no effect against either sheep seminal vesicle cyclo-oxygenase or rat leukocyte 5-lipoxygenase. 3. Linewater-Burk analysis showed that YM-26567-1 behaved as a competitive inhibitor of group II PLA2 derived from rabbit platelets, with a Ki value of 48 nM. 4. In mice, YM-26734 inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microgram/ear)-induced ear oedema in a dose-dependent manner, with ED50 values of 45 (30-67) micrograms/ear (n = 5) and 11 (4-32) mg kg-1, i.v. (n = 5), but did not decrease arachidonic acid (4 mg/ear)-induced ear oedema at 1 mg/ear and 30 mg kg-1, i.v. 5. In rats, the accumulation of exudate fluids and leukocytes in the pleural cavity in response to carrageenin injection (2 mg) was significantly less in a group treated with YM-26734 (20 mg kg-1, i.v.) than in the control group (0.43 +/- 0.02 vs 0.59 +/- 0.03 g per cavity and 3.8 +/- 0.2 vs 4.9 +/- 0.3 x 10(7) cells per cavity, respectively; n = 5). 6. These results suggest that YM-26734 is a potent and competitive inhibitor of extracellular PLA2 with selectivity for group II PLA2, and that the inhibition of group II enzymes activity may cause the suppression of inflammatory responses to TPA and carrageenin.

Animals↗
PubMed1993

[Pseudohyperkalemia in myotonic dystrophy].

Serum electrolytes were measured in 14 patients with myotonic dystrophy and 25 healthy controls. The serum level of sodium was 144.8 +/- 3.2 (mean +/- SD) mEq/l in myotonic dystrophy and 142.0 +/- 1.9 mEq/l in the controls, and the level of potassium was 4.6 +/- 0.4 mEq/l and 4.0 +/- 0.3 mEq/l, respectively. Both electrolyte levels were significantly higher in the disease (p < 0.01, p < 0.001). Blood samples obtained from 5 patients and 5 controls were allowed to stand at room temperature, and serum electrolyte levels were repeatedly measured at 5, 30, 60, 120 minutes after blood collection. The measurement of serum potassium in myotonic dystrophy was elevated in the parallel with standing-time. The serum potassium was significantly higher in the patients than in the controls at 60 and 120 minutes standing. These results suggest that myotonic dystrophy has red blood cell membrane abnormality which allows potassium to leak.

Adult↗
PubMed1993

[A case of paraneoplastic autonomic and sensorimotor neuropathy with dysfunction in the afferent limb of baroreflex arc].

A 65-year-old man visited our hospital with complaints of tingling sensation in the distal parts of his extremities and dysuria, which first appeared 2 months before admission. He had no abnormal findings on physical examination. Neurological examination revealed sensory impairment of glove and stocking type, mild motor weakness and muscular atrophy in the proximal parts of arms and legs, and absent tendon reflexes in knees and ankles. Fasciculation was observed on his shoulders and upper extremities, and myokymia on the abdominal wall and bilateral calves. He had hyponatremia, which was proved to be caused by SIADH. Anti-acetylcholine receptor antibody, anti-GM1 ganglioside antibody and anti-galactocerebroside antibody were detected in the serum. Chest X-ray showed mass shadows in the mediastinum, which were confirmed as malignant thymoma by needle biopsy. Orthostatic hypotension, neurogenic bladder and anhidrosis were observed by the autonomic function tests. Lesions responsible for orthostatic hypotension and SIADH were suspected in the afferent fibers from baroreceptors, since an reactive increase of plasma arginine vasopressin to orthostatic hypotension was blunted and reflex hypertension in the cold pressor test was well-preserved, while overshoot in Valsalva's maneuver was absent. It is important that afferent baroreceptor dysfunction may be associated with paraneoplastic neurological syndrome, since lesions in acute autonomic neuropathy are usually in the efferent fibers.

Afferent Pathways↗
PubMed1992

Stabilization of a protein by removal of unfavorable abnormal pKa: substitution of undissociable residue for glutamic acid-35 in chicken lysozyme.

Glu35 in chicken lysozyme has an abnormally high pKa (6.1) partly due to the hydrophobic environment provided by Trp108. The relationship between protein stability and abnormal pKa was investigated in detail by using mutant lysozymes in which Glu35 was replaced by undissociable residues and an oppositely ionizable residue. It was found that lysozyme was stabilized at alkaline pH range by the replacement of Glu35 with an undissociable residue, Gln (E35Q lysozyme) or Al (E35A lysozyme). On the other hand, when Glu35 was replaced by His (E35H lysozyme), which could have an opposite charge to Glu by ionization, the introduced His35 was found to have an abnormally low pKa (3.6), leading to the destabilization of lysozyme at acidic pH. These observations are completely consistent with the situation that the environment around Glu35 is highly hydrophobic and therefore the placement of either a positive or negative charge in such an environment leads to destabilization of lysozyme. These observations also indicate that the replacement of an acidic residue having abnormally high pKa or a basic residue having abnormally low pKa by an undissociable residue is a very efficient and general method for stabilization of a protein.

Animals↗
PubMed1992

Purification of serine hydroxymethyltransferase from Bacillus stearothermophilus with ion-exchange high-performance liquid chromatography.

The gene of serine hydroxymethyltransferase (SHMT) of a thermophilic bacterium Bacillus stearothermophilus was expressed in Escherichia coli, and SHMT was successfully purified from the crude extract of E. coli in two steps while maintaining the enzymatic activity. The purification steps involved ammonium sulphate precipitation followed by high-performance liquid chromatographic separation using the anion-exchange column Fractogel EMD DEAE-650(S). In addition to the DEAE column, three other types of anion- and cation-exchange columns were also studied for their ability to separate SHMT, and the performance of the four columns were compared.

Ammonium Sulfate↗
PubMed1992

Significance of the serum CA125 level in recurrent ovarian cancer.

Thirty-four recurrent cases of 89 patients with ovarian cancer treated in our department between 1985 and 1989 were examined for changes in serum CA125 level. 1) Upon confirmation of recurrence, 17 patients were positive for CA125 and 15 were negative. 2) According to the histopathological type, the rate of CA125 positivity in patients with recurrence was high for serous adenocarcinoma, suggesting that determination of CA125 is useful for detection of recurrence. In contrast, all patients with mucinous adenocarcinoma or endometrioid adenocarcinoma were negative for CA125. 3) The CA125 positivity rate upon confirmation of recurrence was 9% in patients whose CA125 was less than 1,000 U/ml on initial examination, suggesting that close management of such patients is necessary. 4) Elevation of CA125 by 3 steps or more within the normal range (less than 35 U/ml) was useful for predicting recurrence. 5) The cut-off level of CA125 during follow-up should be set at 16 U/ml. 6) It was difficult to evaluate remission with only the serum CA125 level. It is impossible to avoid second look operation at present. These results indicate that pretreatment values and changes of the parameter within the normal range (less than 35 U/ml) have to be considered when using CA125 as a marker of tumor recurrence.

Adenocarcinoma↗
PubMed1992

Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice.

Endogeneous retroviral expression in beta cells is a feature of prediabetes in nonobese diabetic (NOD) mice. The purpose of this study was to characterize the class-specific pattern of retroviral gene expression in NOD/Lt beta cells versus a related, but diabetes-resistant strain, NON/Lt. Electron microscopic comparison of beta cells from both strains indicated low constitutive expression of the intracisternal type A (IAP) retroviral class. However, NOD beta cells, in contrast to NON beta cells, expressed an additional intracisternal retroviral form resembling a type C particle. Antibodies against both IAP and type C were detected in NOD, with the humoral response to type C, but not IAP, preceding decline in beta cell function. RNA was extracted from freshly isolated islets from NOD and NON males. Comparative Northern blot analysis of total type C retroviral gene expression using a gag-pol DNA probe corroborated expression of endogenous type C proviruses in both NOD and NON islet cells and thymus. Use of class-specific retroviral probes identified the class of expressed endogenous retrovirus distinguishing the two inbred strains. The single ecotropic provirus present in both the NOD and NON genome (Emv-30) was not expressed in islets or thymus of either strain. Comparison of endogenous xenotropic provirus content by Southern blot analysis revealed two unique xenotropic loci (Xmv-65, -66) in NOD; 8.4 and 3.0 kb xenotropic envelope (env) RNA transcripts were detected in NOD, but not NON islets and thymus. NON contained three xenotropic loci common to other inbred strains (Xmv-21, -25, and -28). Both strains were partially characterized for content of recombinant (polytropic and modified polytropic) proviruses. IAP RNA expression was common to both NOD and NON islets and hence could not be specifically associated with the unique intracisternal type C particle found in NOD, but not NON beta cells. In conclusion, this study shows that expression of xenotropic type C but not IAP distinguishes retroviral activity in NOD/Lt versus NON/Lt beta cells. The potential pathogenic role of retroviral gene expression in NOD beta cells is discussed.

Animals↗
PubMed1992

[An examination of Metzger's theory on geometrical illusions by using the illusion of major and minor axes in ellipse].

An experiment with ellipses was conducted to evaluate the validity of Metzger's theory on geometrical illusions (the law of good Gestalt) by examining whether its major axis is underestimated and its minor axis overestimated. If the horizontal or vertical dimension of a circle with a fixed diameter is reduced, " smaller" ellipses with major axes equal to the circle's diameter will be constructed. On the other hand, if the dimension is enlarged, "larger" ellipses with minor axes equal to the circle's diameter will be produced. Ten university students estimated the apparent lengths of such axes. It was found that the major axes were underestimated, while the minor axes were overestimated, irrespective of the relative sizes of the ellipses. The same result was obtained when the orientation of the axis was rotated 90 degrees. These results may be interpreted in line with Metzger's theory to the illusion of major and minor axes in ellipse.

Adult↗
PubMed1992

[A case of giant pigmented nevus with multiple meningiomas].

A 36-year-old female had a giant congenital pigmented nevus on her anterior trunk. She complained of muscle weakness of the right arm and leg in August 1988, and she was admitted to our hospital to take medical examinations in September 1988. Neurological examination revealed right hemiparesis and exaggerated deep tendon reflexes. Three small falx meningiomas were shown on CT scans and MR images, but they did not appear to be causes of her symptoms. CT-myelography and MR images revealed an intradural extramedullary tumor spreading from the foramen magnum to C2. Oncotomy and C1 laminectomy were performed. Histological finding was compatible with transitional meningioma. Neurological symptoms markedly improved after operation. This patient is considered as a case of neurocutaneous syndrome with central nervous system tumors. Considering that both giant pigmented nevus and meningioma originate from neural crest, they appear to be closely related each other. Such a combination of giant pigmented nevus and meningioma has not yet been reported.

Adult↗
PubMed1992

[Studies on the erythrocyte membrane skeleton in a patient with chorea-acanthocytosis--theoretical speculation on the mechanism of neurological involvement].

Patients with chorea-acanthocytosis exhibit symptoms of self-biting, choreic movement, and acanthocytosis, but not dementia. The mechanism of choreic movements is still unknown. In order to clarify the etiologic mechanism underlying these movements, we evaluated the erythrocyte membrane in one patient with chorea-acanthocytosis. A 35-year-old female was admitted to Saitama Medical School Hospital because of involuntary movements. She was alert, well-oriented, and had no gross memory defects. She had slurred speech, choreic movements and lip biting. Laboratory examination showed acanthocytes in her peripheral red blood cells, normal serum lipid values, and caudate atrophy on her brain CT scan. In analyzing the acanthocytes, we initially evaluated the size of the acanthocyte population by incubating her red blood cells with plasma. The cell population approximately doubled after 2 hours incubation. Next we examined the protein composition of erythrocyte ghost by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). There was no significant difference between the patient's erythrocyte ghosts and those of a control. Then we investigated morphological changes in the patient's erythrocyte by scanning and transmission electron microscopy (SEM and TEM). SEM showed the typical acanthocyte shape. The quick-freeze, freeze-substitution method confirmed that the routine TEM section was not artifactual, and was in fact in accurate reflection of the actual features of acanthocytes. TEM of the sections prepared from erythrocyte ghosts demonstrated that spectrin tended to be accumulated in the thorn region. Furthermore, TEM of quick-freeze, deep-etched replica of the ghost revealed more clearly a spectrin network densely packed on the inner hydrophilic surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthocytes↗
PubMed1992

Growth regulation of ovarian cancer.

The disease referred to as ovarian cancer is composed of those tumors derived from the ovarian surface epithelium. Ovarian cancer incidence peaks in postmenopausal women, when the hormonal milieu is in a state of flux. The ovarian carcinomas have histologic characteristics of classical endocrine responsive tissues. For example, the serous tumors are similar in appearance to the epithelium of the fallopian tube, the mucinous tumors to that of the endocervix, and the endometrioid tumors to that of the endometrium. These observations alone suggest a role for hormones in disease etiology and progression. In addition, much experimental evidence has accumulated that shows direct hormonal and growth factor effects on the normal and neoplastic ovarian surface epithelium and the potential for responsiveness based on the presence of specific receptors. The concept that growth stimulatory substances, by their impact on mitosis and cell number, may influence the rate of mutations that could confer malignant transformation serves as an additional mechanism by which growth stimulatory substances can influence ovarian cancer initiation. With the emergence of new molecular biology techniques, future studies should unravel the mechanisms by which steroid hormones, peptide hormones, and peptide growth factors influence the development of ovarian cancer.

Female↗
PubMed1992

[A case of complete mediastinal thyroid cancer: aberrant goiter].

A 65-year-old man was admitted with the chief complaints of hoarseness and an abnormal mass shown by chest x-ray films. CT scan, MRI, thyroid scintigram, and angiogram showed a right upper mediastinal tumor. This was histologically diagnosed as malignant mediastinal goiter by percutaneous needle biopsy. Operation was performed using a collar incision and median sternotomy. The tumor was located in right upper mediastinum and had no relation to the cervical thyroid gland. It was 7 x 5 x 3.5 cm in size. Histological examination revealed papillary adenocarcinoma of the thyroid gland. To our knowledge, 17 cases of complete mediastinal malignant goiter have been reported in Japan, including our case. These 17 patients are reviewed with regard to their clinical features in this article.

Adenocarcinoma, Papillary↗