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Biomedical subjects

M Miyauchi

Publications and source records attributed to M Miyauchi.

At least 145 records · Page 8Linked to original sources

Cephalosporin antibiotics. II. Synthesis and biological properties of CS-461 and related compounds.

The synthesis, structure-activity relationships, and biological properties of 3-thiazoliomethyl cephalosporins are described. 7-[2-(2-Aminothiazol-4-yl)-(Z)-2- methoxyiminoacetamido]-3-[5-(2-hydroxyethyl)-4-methylthiazoliomethyl+ ++]-3- cephem-4-carboxylate sulfate (CS-461) showed potent antibacterial activity against a wide variety of bacteria both in vitro and in vivo. Furthermore, CS-461 exhibited significantly low acute toxicity in mice.

Animals↗

[Objective evaluation of nuclear grade in preoperative aspiration materials from breast cancers--special reference to the relationship of coefficiency variant of nuclear area with pathological prognostic features].

The prognostic significance of cytomorphometry was investigated in 84 invasive ductal breast cancer patients. All patients were clinically followed for at least 5 years after radical mastectomy. The value of coefficiency variant of nuclear area (NA.CV) calculated from morphometor had good correlation with nuclear grade determined subjectively by cytologist on optical microscope. NA.CV in patients who had metachronous metastases (39.0 +/- 7.5%) was significantly higher than that in recurrence free cases (26.8 +/- 4.9%). The recurrence free period was also related to the value of NA.CV. In 39 cases (90.7%) out of 43 recurrence free survivors, the value of NA.CV was less than 30%, whereas it was over 40% in 11 (45.8%) out of 24 cases with short time (less than two years post operatively) metastases. NA.CV was the most variable, independent prognostic factor among several pathological prognostic features. The data assessed in this study showed that the value of NA.CV on cytological materials as the objective evaluation of nuclear grade may provide clinically relevant information with respect to the degree of malignancy and prognosis of patients with breast cancer at preoperative period.

Biopsy, Needle↗

[Electrophysiological comparison between patients with Binswanger's encephalopathy and Alzheimer's disease].

Short-latency somatosensory (SSEPs), brainstem auditory evoked potentials (BAEPs) and event-related potentials (ERPs) were studied in 7 patients with Binswanger's encephalopathy, 12 patients with Alzheimer's disease and 17 normal subjects. Patients with Binswanger's encephalopathy showed significantly prolonged central conduction time (CCT) and P300 latency, and prolonged tendency of I-V IPL compared to those of normal subjects. In particular, CCT showed significant prolongation compared to that of patients with Alzheimer's disease. In patients with Alzheimer's disease, I-V IPL and P300 latency were significantly prolonged compared to those of normals although there was no significant difference in CCT between Alzheimer's disease and normal subjects. These results indicate some difference between Binswanger's encephalopathy and Alzheimer's disease from the electrophysiological aspects although both of these entities are characterized by progressive mental deterioration.

Aged↗

Characterization and anticancer activity of the micelle-forming polymeric anticancer drug adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer.

Adriamycin (ADR), an anthracycline anticancer drug, was bound to the poly(aspartic acid) chain of poly(ethylene glycol)-poly(aspartic acid) block copolymer by amide bond formation between an amino group of Adriamycin and the carboxyl groups of the poly(aspartic acid) chain. The polymeric drug thus obtained was observed to form a micelle structure possessing diameter of approximately 50 nm, with a narrow distribution, in phosphate-buffered saline and to show excellent water solubility despite a large amount of ADR introduction. Further, it was able to be stored in lyophilized form without losing its water solubility in the redissolving procedure. Increased stability of the bound Adriamycin molecules in phosphate-buffered saline and elimination of binding affinity for bovine serum albumin due to the micelle formation were further advantages of this polymeric drug. In vivo high anticancer activity of this micelle-forming polymeric drug against P 388 mouse leukemia was obtained with less body weight loss than that seen with free ADR, due to low toxicity as compared with free ADR.

Animals↗

Changes of lymphocyte subsets in peripheral blood before and after operation of patients with advanced ovarian carcinoma.

Comparison was made between lymphocyte subsets in peripheral blood from patients with benign ovarian tumor and those with advanced ovarian carcinoma. In addition, changes of lymphocyte subsets of patients with ovarian carcinoma before and after operation were also examined. The percentage and absolute number of CD3-/HLA-DR+ (B cells) in peripheral blood from patients with advanced ovarian carcinoma were significantly lower than values from patients with benign ovarian tumor, whereas both percentage and absolute number of CD3-/HLA-DR- (null cells) cells in patients with advanced ovarian carcinoma were significantly higher. Although there was no significant difference in natural killer (NK) cell subsets (CD57+ CD16- and CD57+ CD16+ cells) between patients with benign ovarian tumor and ovarian carcinoma, the percentage and absolute number of CD57-/CD16+ (highly differentiated NK cells) cells in patients with ovarian carcinoma were significantly higher than those in patients with benign ovarian tumor. Both the absolute number and percentage of CD3+/HLA-DR+ (activated T cells) cells in ovarian cancer patients with minimal residual tumors after operation were significantly increased, compared to the levels before operation, while the values in the patients with large residual tumors were significantly decreased. In addition, the percentage and absolute number of CD3-/HLA-DR- (null cells) cells in the patients with minimal residual tumors were significantly decreased after operation, while values in the patients with large residual tumors remained unchanged before and after operation. The patients with minimal residual tumors after operation were characterized by a significant increase in the percentage of CD57- CD16+ (highly differentiated NK cells) cells. On the other hand, in the patients with large residual tumors no change of the NK cell subsets was observed before and after operation.

Adult↗

Spitz nevus of the palate. Report of a case.

A 4-year-old Japanese girl with a nonpigmented nodule on the anterior portion of the palate since birth is described. The overall microscopic appearance of the lesion was very similar to that of Spitz nevus of the skin. Diagnosis of Spitz nevus (mixed epithelioid cell and spindle cell nevus) was made on the basis of the clinical and histologic criteria for differentiating this lesion from malignant melanomas and common compound nevi. Positive immunostaining of epithelioid and spindle cells for S-100 protein and neuron-specific enolase was also indicative of their nevocellular nature. Review of the cases of Spitz nevus from the literature revealed that the present case most probably represents the first reported instance of this type of nevus in the oral cavity.

Biomarkers, Tumor↗

The cellular composition of basal cell adenoma of the parotid gland: an immunohistochemical analysis.

Four cases of basal cell adenoma of the parotid gland were examined immunohistochemically to characterize their cellular composition. In all cases epithelial membrane antigen and keratin were detected in the inner luminal cells; some cells also showed positive staining for secretory functional markers, indicating their differentiation toward secretory epithelium. In tubular and trabecular types the outer cells consistently displayed an intense staining for vimentin and some were also positive for actin, indicating their myoepithelial nature. In the solid type, most tumor cells resembled the ductal cells or basal cells of larger ducts in normal gland with regard to their immunoreactivity. Our results may suggest that the proportion and arrangement of heterogeneous tumor cells are responsible for different histologic patterns of the salivary basal cell adenoma.

Adenoma↗

Restorative effects of calmodulin antagonists on reduced cisplatin uptake by cisplatin-resistant human ovarian cancer cells.

In the present study, we attempted to determine effects of calmodulin antagonists (W-7 and W-5) on cisplatin uptake by human ovarian cancer cells, using KF cells derived from serous cystadenocarcinoma of the ovary and cisplatin-resistant cells (KFr). The degree of cisplatin resistance of the KFr cells was about 3.7-fold higher than that of the parent KF cells, with regard to the concentration of cisplatin required for 50% inhibition of cell proliferation (IC50). When KF and KFr cells were incubated with 10 micrograms/ml cisplatin for 4 hr, cisplatin-content in the KF cells was significantly higher than that in the KFr cells. When KF cells were incubated in the presence of W-7 (but not W-5), cisplatin uptake significantly increased, compared to cells treated with cisplatin alone. On the other hand, when KFr cells were incubated in the presence of 5 micrograms/ml W-7 or W-5, cisplatin uptake was significantly higher than uptake by KFr cells treated with cisplatin alone, being comparable to that by KF cells treated with cisplatin alone. Such an increase in cisplatin uptake seemed to bring about adjuvant effects to cisplatin of KFr cell proliferation in vitro. The KF tumor grown in nude mice took up 24.8 ng/g dry wt of cisplatin 4 hr after intraperitoneal administration. When cisplatin was administered with calmodulin antagonists, cisplatin uptake by the KF and KFr tumors was significantly increased, compared to that after treatment with cisplatin alone. In particular, the cisplatin uptake by the KFr tumor was about 2.5-fold higher than that by the KFr tumor treated with cisplatin alone. These results suggest that coadministration of calmodulin antagonists and cisplatin may be of use in patients with refractory ovarian cancer.

Biological Transport↗

Lectin binding of rat gingival epithelia.

Oral gingival epithelium (OGE), oral sulcular epithelium (OSE) and junctional epithelium (JE) were examined histochemically by using different lectins as markers for epithelial differentiation. The staining pattern of gingival epithelia was compared with that of the buccal and palatal epithelia. Binding of WGA had a uniform distribution in all the epithelia examined. A positive reaction was found in all the basal and spinous layers, but not in the cornified layer of the epithelia. BPA binding was seen in the lower spinous layer of OGE, OSE, buccal and palatal epithelia, and in most of the JE. The basal layer and the cells directly attached to the tooth surface at the apical part of JE were nonreactive with BPA. GS-I reacted with the basal and suprabasal layers of each epithelium and with the cells attached to the tooth at the apical part of JE. UEA-I reacted with the upper spinous layer of OGE, OSE and epithelia of hard palate, but not with any of the cells of the JE. Our results agree with previous data suggesting that OGE and OSE exhibit squamous differentiation similar to that of the masticatory epithelium of hard palate. Furthermore, our results suggested that the JE cells undergo differentiation equivalent to that of the suprabasal and lower spinous cells of OGE. The cells along the tooth surface at the apical part of JE, however, form a distinct population of cells with basal nature.

Animals↗

Studies on penem and carbapenem. I. Syntheses and oral absorption of ester-type prodrugs of sodium (5R,6S)-2-(2-fluoroethylthio)-6-[(1R)-1-hydroxyethyl]penem-3-c arboxylat e.

Acyloxyalkyl esters (2a-d), alkyloxycarbonyloxyalkyl esters (2e-g) and (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester (2h) of (5R,6S)-2-(2-fluoroethylthio)-6-[(1R)-1-hydroxyethyl]penem-3- carboxylic acid (1) were synthesized. Enhanced oral absorption was observed in mice reflecting increased lipophilicity, compared with the parent 1 itself. Among them, the ester 2h showed a prolonged plasma level and a large area under the blood concentration-time curve (AUC) in rats. These ester-type prodrugs of penem 1 in phosphate buffer (pH 6.86) were much more stable than those of cephalosporins which easily degraded via isomerization to delta 2 cephalosporins.

Animals↗

Studies on orally active cephalosporin esters. V. A prodrug approach for oral delivery of 3-thiazoliomethyl cephalosporin.

Oral delivery of 3-thiazoliomethyl cephalosporin 1 was attempted through a prodrug approach by applying thiamine chemistry. The 3-thiazoliomethyl group was modified to a ring-opened structure with no ionic charge, and the 4-carboxyl group was converted to pivaloyloxymethyl ester. Lipophilicity of the resulting derivatives (8-10) was suitable for passive absorption from the intestinal tract, and chemical stability in phosphate buffer solution (pH 6.86) was moderate. When administered orally to mice, these derivatives were mainly transformed to a novel 3-spiro cephalosporin 11, and desired reconversion to the 3-thiazoliomethyl cephalosporin was minor. Isomerization to delta 2-cephalosporin 14 was also observed. These results showed that the derivatives (8-10) tested in this study did not serve as orally active prodrugs of 3-thiazoliomethyl cephalosporin 1.

Administration, Oral↗

Studies on orally active cephalosporin esters. VI. Synthesis and antimicrobial activity of 3-(3-isoxazolyl)oxymethylcephalosporin derivatives.

The synthesis and biological activities of a series of 3-(isoxazol-3-yl)oxymethyl cephalosporins are described. 7-[2-(2-Aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3- [(isoxazol-3-yl)oxymethyl]-3-cephem-4-carboxylic acid (7a) showed potent activity against both Gram-positive and Gram-negative bacteria including some beta-lactamase producing species. Its pivaloyloxymethyl ester provided a good urinary recovery after oral administration to mice.

Bacteria↗

[Expression of embryonal and differentiational proteins in chordomas and in the notochord].

The expression of the embryonal and of the differentiational proteins in 12 cases of chordoma and in the notochord of a 4-month-old and a 5-month-old human embryo have been examined immunohistologically by the ABC method using polyclonal antibodies to CEA, AFP, or S-100, and the monoclonal antibody to cytokeratin. It was found that S-100 was expressed in all cases of chordoma and in the notochords examined. CEA and cytokeratin also were found expressed in some cases of chordoma but not in the notochords. These proteins were found expressed more strongly in chordomas without a metastasis than in those with a metastasis. In the metastatic lesions, these proteins were expressed more strongly than in the primary lesions. The antibody to AFP reacted with neither the chordomas nor the notochords tested. These results suggest a possible link between the gene-expression of the tumor cells and the microenvironment in which they are harbored.

Adult↗

[Effect of body temperature changes on evoked potentials].

Short-latency somatosensory (SSEPs) and brainstem auditory evoked potentials (BAEPs) were recorded in 12 patients with fever due to respiratory infection (age, 44.3 +/- 20.9 years, mean +/- SD) to clarify the effect of body temperature change on conduction in the central somatosensory and brainstem auditory pathways. Subjects were studied during episodes of fever (37.9 +/- 0.8 degrees C) and after their body temperature had decreased (36.6 +/- 0.3 degrees C). The central conduction time (CCT), which is the peak latency between N 13 and N 20, was significantly longer after body temperature had decreased than during fever. Likewise the interpeak latency between waves I and V (I-V IPL) was significantly prolonged following decrease in body temperature. These results suggest that increases in body temperature have an effect upon conduction in the central somatosensory and brainstem auditory pathways.

Body Temperature↗

[A statistical study on the orthodontic patients in Meikai University Hospital].

We analyzed statistically two thousand orthodontic patients in Meikai University Hospital (formerly Josai Dental University Hospital) who have undergone treatment since the establishment of the hospital (1970-1985). By classifying the data in various ways, we obtained the following statistics; 1) The number of new patients increased quickly after the first class graduated from our university; 2) The number of patients from six to fifteen years old was the largest, with the peak being nine years old; 3) For the time of the first visit, many new patients came during spring and summer vacations, and a few junior high school and high school students came just season before taking their entrance examination; 4) The female sex predominated in most age groups; however, among patients in their twenties, the male sex was predominant, and in recent years the male ratio tended to increase; 5) Most patients came from a radius of less than 20 km from the hospital (mostly from along Tohbu railway line), with few from beyond 30 km; 6) Anterior crossbite and anterior crowding cases were many, particularly, young patients comprised many of the anterior crossbite cases; and in adult patients large overjet cases increased with the advance of age.

Adolescent↗

Morphological and antigenic variations of human T cell leukemia virus type I particles in human lymphocytes.

HTLV-I particles grown in 4 human lymphocyte cultures were observed by electron microscopy. Particles in all cell lines showed marked size and structural variations that were characteristic of each cell line. Profiles of size-distributions were found to be similar among virus particles of the same origin in different cell lines. Immunogold electron microscopy using monoclonal antibody to HTLV-I-p15, -p19, or -p24 revealed varying reactivities of individual particles. By double-labeling technique using antibody to HTLV-I-p19 or -p24, particles were found to be classifiable into 4 groups: p19+p24+, p19+p24-, p19-p24%, and p19-p24-. Each cell line showed the characteristic profile of distributions of virus particles of each group as observed at different in vitro passage levels. These antibodies reacted with certain structures in the extracellular space and in the cytoplasm. Results of this study demonstrate variations in morphology and antigenicity, as well as the morphogenesis of HTLV-I particles in different host cells.

Cell Line↗