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Biomedical subjects

K Yoshitake

Publications and source records attributed to K Yoshitake.

At least 37 records · Page 2Linked to original sources

Involvement of protein kinase C in mucus secretion by hamster tracheal epithelial cells in culture.

Abnormal regulation of airway mucus secretion may underlie many pulmonary diseases. The exact evidence for the involvement of intracellular signaling mechanisms in mucus secretion has not been fully elucidated to date. The purpose of this study is to clarify the involvement of protein kinase C in the secretion of high-molecular-weight glycoconjugates (HMWG) by hamster tracheal epithelial cells in culture, which elute in the void volume on Sepharose CL-4B column chromatography. HMWG were secreted by the cells cultured on the thick collagen gel, but not on the plastic plate. Two known activators of protein kinase C, 4 beta-phorbol 12 alpha-myristate 13-acetate (PMA) and 1-oleoyl-2-acetyl-sn-glycerol (OAG), stimulated HMWG secretion. In contrast, 4 alpha-phorbol 12,13-didecanoate, a biologically inactive phorbol, did not influence HMWG secretion. D-Sphingosine, an inhibitor of protein kinase C, suppressed the maximal PMA- (10(-8) M) and OAG- (200 microM) stimulated HMWG secretion. PMA induced protein kinase C translocation from cytosol to membrane. These data indicate that protein kinase C is involved in HMWG secretion in hamster tracheal epithelial cells in culture.

Animals↗

[Intra-arterial combination chemotherapy using both regimen selected by chemosensitivity test and caffeine to increase effect for osteosarcoma in extremity].

We treated three patients with osteosarcoma in extremity with intra-arterial combination chemotherapy using a regimen selected by succinate dehydrogenase inhibition chemosensitivity test, and used caffeine to enhance its effect. In two patients with osteosarcoma in distal diametaphysis of the radius and extraskeletal osteosarcoma in sole of the foot, the effect of intra-arterial combination chemotherapy was increased and followed by the functional limb salvage procedure. But in one patient with osteosarcoma in the proximal tibia, the effect of pre-operative intra-arterial combination chemotherapy could not be increased, so amputation was required. He was changed to a post-operative intra-venous combination chemotherapy regimen selected by chemosensitivity test of the surgical material. All patients have been continuously disease-free at five to twelve months after surgery.

Adolescent↗

[A case of left ventricular hemangioma].

Left ventricle hemangioma in a 54-year-old man is reported. He was admitted to our hospital for chest discomfort. Coronary angiograms showed normal coronary arteries and a contrast blush in the left interventricle septum. Transesophageal echocardiogram also demonstrated the small floating tumor in the ventricular septum below the right coronary cusp. With the aid of cardiopulmonary bypass, the tumor was resected completely through transaortic approach. Histological examination revealed capillary hemangioma. The patient had uneventful recovery. To our knowledge, this is the seventh case of a left ventricular hemangioma treated surgically reported in the world literature.

Heart Neoplasms↗

The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on the antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs.

The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs was studied. Ketotifen was used as a reference drug. S-1452 at doses of 1 and 3 mg/kg (per oral administration, 1 h before the injection of U-46619) clearly inhibited U-46619-induced pulmonary pressure increase. Ketotifen at a dose of 10 mg/kg did not affect U-46619-induced bronchoconstriction. S-1452 at doses of 3 and 10 mg/kg and ketotifen at a dose of 10 mg/kg inhibited the antigen-induced bronchoconstriction in guinea pigs which had been passively sensitized with guinea pig IgE antibody. S-1452 at a dose of 10 mg/kg inhibited repeated antigen provocation-induced airway hyperresponsiveness in guinea pigs. The accumulation of inflammatory cells by antigen provocation in bronchial alveolar lavage fluid (BALF) was inhibited by ketotifen but not by S-1452. These results indicate the efficacy of S-1452 on antigen-induced bronchoconstriction and antigen-induced airway hyperresponsiveness in guinea pigs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Ionic and nonionic fluoride levels in blood of dialyzed and undialyzed patients with renal failure and kidney transplanted patients.

The present study revealed that the total fluoride level in human whole blood is closely related to the renal function. For the undialyzed patients who had not undergone hemodialysis, the total fluoride level in whole blood linearly increased with the increase of creatinine (Cr) value. The increased fluoride was found to be nonionic in the other blood part than serum, while the nonionic fluoride level in serum was almost constant. That is, the hemodialysis treatment finally reduced the nonionic fluoride level in the other blood part than serum. On the other hand, one hemodialysis treatment could excrete ionic fluoride, but not nonionic fluoride. These results suggest that the ionic fluoride is transformed to nonionic fluoride to be accumulated in other blood part than serum and the nonionic fluoride is transformed to the ionic fluoride to be excreted. Thus the accumulation of nonionic fluoride in other blood part than serum plays a role of the buffer in preventing a too high serum fluoride level.

Adolescent↗

[Simultaneous operation of gastrectomy, cholecystectomy and coronary artery bypass grafting using right gastroepiploic artery].

We present a case who received the simultaneous surgical corrections of unstable angina, acute gastric ulcer, and cholelithiasis. A 72-year-old man was admitted to our hospital due to unstable angina. An emergency coronary angiography was performed and we found severe 2 vessels disease (RCA ostium and proximal LAD lesions). After the admission, the angina was poorly controlled and the surgical treatment had been considered. The patient developed sudden hematemesis due to the uncontrolled bleeding from gastric ulcer. Then the emergency operation was performed. Partial gastrectomy with preservation of RGEA and cholecystectomy were done followed by CABG to RCA with RGEA and to LAD with autologous saphenous vein. The postoperative course was uneventful and the patient is in good condition to date.

Acute Disease↗

[Post-operative intra-arterial chemotherapy for high grade malignant musculoskeletal sarcoma].

Twenty-nine patients with high grade malignant musculoskeletal sarcoma were treated with chemotherapy. Intra-arterial chemotherapy was performed post-operatively for patients with local recurrence, patients with poor response to pre-operative chemotherapy or patients with intra-lesional or marginal surgical margin. The local recurrence rate in patients with intra-arterial chemotherapy (8.8%) was lower than in those with intravenous chemotherapy (37.5%). Patients with post-operative intra-arterial chemotherapy showed no local recurrence. Of the 29 patients except stage 3 with intra-arterial chemotherapy, the metastatic rate in patients with intra-arterial chemotherapy (41.4%) was lower than in chemotherapy patients with intravenous chemotherapy (83.3%). The rate in the post-operative group (28.6%) was lower than in the pre-operative group (42.9%) or pre- and post-operative group (50.0%). The ten-year survival curve of patients given intra-arterial chemotherapy (51.0%) was higher than in patients on intravenous chemotherapy (17.9%). Among the 34 patients who underwent intra-arterial chemotherapy, the survival rate in the other pre- and post-operative groups and the post-operative group (55.6%) was higher than in the pre-operative group and pre- and post-operative group (49.8%).

Antineoplastic Combined Chemotherapy Protocols↗

Malignant fibrous histiocytoma. A tumor of facultative histiocytes showing mesenchymal differentiation in cultured cell lines.

The histogenesis of malignant fibrous histiocytoma (MFH) is controversial. To elucidate the cellular origin and characteristics of this neoplasm, the authors analyzed cell lines grown from 17 patients (15 soft tissue MFH and 2 bone MFH) by using light and electron microscopy, immunocytochemistry, enzyme cytochemistry, and functional tests for receptors for the Fc portion of immunoglobulin (Fc receptors) and immunophagocytosis. Each culture exhibited a storiform/pleomorphic pattern with mixed cellular populations consisting of spindle cells, polygonal cells, and bizarre giant cells; these morphologic features corresponded to the histologic characteristics of the primary tumors. The cells in each MFH line displayed histiocytic functional markers such as lysosomal enzymes, Fc receptors and immunophagocytosis. However, these cells differed from monocyte-derived macrophages (histiocytes) in immunoreactivity; the MFH cells expressed a mesenchymal antigen (FU3) distributed among perivascular cells and fibroblasts but demonstrated no positive reactions with Leu-M1 (CD15) and Leu-M3 (CD14), which recognize the cells of the monocyte-macrophage lineage. In conclusion, these findings suggest that MFH is not a tumor of true histiocytes but of facultative histiocytes showing mesenchymal differentiation in vitro. Chromosomal analysis performed in one MFH line demonstrated abnormal karyotypes; the modal chromosome number was 58, with 5 marker chromosomes.

Adult↗

Immunohistochemical localization of proliferating cell nuclear antigen/cyclin in human skin.

Expression of proliferating cell nuclear antigen/cyclin (PCNA/cyclin) in skin tissue specimens and cultured keratinocytes was studied using a monospecific antibody, obtained from a patient with systemic lupus erythematosus, and a monoclonal antibody. Indirect immunofluorescent staining revealed that cultured keratinocytes obtained from human foreskins expressed PCNA/cyclin as variable nuclear patterns in 15-30% of the cells. In normal human skin tissue specimens, PCNA/cyclin was demonstrated in only a few basal cells. Interestingly, PCNA/cyclin was expressed strongly in almost all the cells of the lowest layer of the epidermis adjacent to squamous cell carcinomas, whereas the tumor aggregates themselves had no positive staining. In contrast, no such characteristic staining was demonstrated in specimens of basal cell carcinoma. The staining pattern of PCNA/cyclin was different from that of Ki-67 in the skin tissue specimens. Our results suggest that PCNA/cyclin could be a useful marker of cell proliferation.

Antigens, Neoplasm↗

Proliferating cell nuclear antigen expression in normal, preneoplastic, and neoplastic colonic epithelium of the rat.

Expression of the proliferating cell nuclear antigen (PCNA) was examined in normal rat intestinal tissues and in carcinogen-treated nonneoplastic and neoplastic colonic mucosa. In the normal intestine, PCNA expression was confined to the expected region of the proliferative compartment. A strong correlation was observed between PCNA labeling index and both [3H]thymidine labeling index (R = 0.993, P = 0.007) and percent of cells in S phase as determined by flow cytometry (R = 0.982, P = 0.018) and between the location of the maximal staining for PCNA and [3H]thymidine (R = 0.997, P less than 0.05). In animals treated with dimethylhydrazine (DMH), crypt hyperplasia, an increased PCNA labeling index, and shifts in both the region of maximal and the upper extent of PCNA expression were observed during DMH exposure; significant crypt hyperplasia and expansion of the PCNA-positive compartment persisted after completion of DMH injections. The patterns of PCNA expression and bromodeoxyuridine incorporation were similar in DMH-induced tumors. It is concluded that PCNA immunohistochemistry can be used as a reliable marker of the proliferative compartment in both normal and neoplastic colonic mucosa.

1,2-Dimethylhydrazine↗

Chromosome abnormalities in liposarcomas.

We performed a cytogenetic study of short-term cultures from fresh surgical specimens obtained from four patients with liposarcoma. Myxoid liposarcomas (cases 1-3) were associated with a specific translocation between chromosomes 12 and 16. Trisomy 8, a nonrandom secondary aberration in myxoid liposarcoma, was observed in the third case as the only additional change. Round cell liposarcoma (case 4) showed complex chromosomal aberrations affecting chromosomes 1, 2, 5, 6, 7, 13, 14, 17, 19, and 22. Neither band 12q13 nor 16p11 was visibly rearranged. Three subgroups of liposarcomas are proposed. The first group is characterized by t(12;16)(q13;p11), the second group by ring chromosomes, telomeric associations, and giant markers, and the last by complex numerical and structural aberrations.

Adult↗

The effect of three novel thromboxane A2 receptor antagonists (S-1452, AA-2414 and ONO-3708) on the increase in pulmonary pressure caused by Forssman anaphylaxis in guinea-pigs.

The effects were studied of three novel thromboxane A2 (TXA2) receptor antagonists (S-1452, AA-2414 and ONO-3708) on the increase in pulmonary pressure caused by Forssman anaphylaxis in guinea-pigs. Three TXA2 antagonists at doses of between 1 and 10 mg/kg administered orally 1 h before the challenge clearly inhibited the pulmonary pressure increase. At a dose of 10 mg/kg, all three antagonists inhibited the pulmonary pressure increase caused by leukotriene D4 (LTD4) and U-46619, but not that caused by histamine. The decrease in peripheral platelet counts caused by Forssman anaphylaxis was also clearly inhibited by the three TXA2 antagonists. However, the decreased peripheral leukocyte counts were unaffected by the three agents. The decrease in serum complement activity (CH50) was inhibited by S-1452 and AA-2414 at a dose of 10 mg/kg. In bronchoalveolar lavage fluid (BALF), significant increases in eosinophils and neutrophils were observed after Forssman anaphylaxis. Three TXA2 antagonists at a dose of 10 mg/kg (except for AA-2414 on eosinophils) did not affect the changes of leukocyte counts in BALF. Moreover, increases in the TXB2 and 6-keto-PGF1 alpha levels of the BALF brought about by Forssman anaphylaxis were unaffected by the three TXA2 receptor antagonists. Histamine and LTD4 were not changed in the BALF after Forssman anaphylaxis. These results indicate the efficacy of TXA2 receptor antagonists on the increase in pulmonary pressure caused by Forssman anaphylaxis in guinea-pigs by direct antagonism to released TXA2.

6-Ketoprostaglandin F1 alpha↗

Myxoid liposarcoma with t (12; 16)(q 13; p 11). Possible usefulness of chromosome analysis in a poorly differentiated sarcoma.

A chromosomal study was used to establish diagnosis of a poorly differentiated soft-tissue sarcoma occurring in the right thigh of a 57-year-old Japanese female. Histopathologically the excised tumor consisted of a poorly differentiated myxoid neoplasm, without specific features to enable the identification of neoplastic cells. Although a tentative diagnosis of poorly differentiated myxoid liposarcoma was made, ultrastructural examination and Oil Red O fat stain failed to demonstrate the evidence of lipoblastic differentiation, except that occasional cells possessed a small number of fine fat droplets. The diagnosis of liposarcoma was suggested by chromosome analysis of the fresh tumor tissue after short time culture and trypsin-Giemsa banding technique. The tumor cells demonstrated a clonal abnormality characterized by a reciprocal translocation, t(12; 16)(q 13; p 11), which is known as a specific aberration in myxoid liposarcoma. Thus, chromosome study seems to be useful for identifying undifferentiated mesenchymal tumors, which lack morphologic evidence of any specific differentiation, as in the present case.

Cell Differentiation↗

Malignant fibrous histiocytoma. Proliferative compartment and heterogeneity of "histiocytic" cells.

To elucidate the precise origin and characteristics of the proliferating cells in malignant fibrous histiocytoma (MFH), the authors analyzed 33 MFH tumors, using immunohistochemical techniques with a panel of 12 antibodies. All three types of MFH cells (spindle cells, polygonal cells, and bizarre giant cells) stained positively for mesenchymal antigens (FU3 and vimentin) but did not stain for macrophage/histiocyte markers (HAM 56 and CD68). Therefore, the MFH cells may not represent true histiocytes, although they may be mesenchymal-derived cells behaving as "facultative histiocytes" with superficial resemblance to actual histiocytes. Normal histiocytes in the stroma tested positive for macrophage/histiocyte antigens; the most common cells were HAM 56-positive cells constituting 30-80% of nonneoplastic stromal cells, followed by those positive for CD68 (10-50%), Mac 387 (less than 2%), and S-100 protein (less than 1%). Our results indicate the presence of heterogeneity of "histiocytic" cells in MFH. Proliferating-cell nuclear antigen (PCNA) was expressed not only in the spindle and polygonal MFH cells but also in the bizarre giant cells. These findings suggest that all three types of MFH cells participate in the proliferative compartment of MFH. Uneven PCNA staining of the irregular nuclear segments of the bizarre giant cells may result in abnormal DNA synthesis, possibly contributing to the marked diversity of nuclear morphology in MFH. Touton-type and osteoclast-like giant cells did not stain for PCNA but stained positively for histiocytic markers. Therefore, these giant cells may lack proliferative activity and probably result from normal histiocytes fusing together.

Adult↗

Removal of extracellular Mg2+ suppresses sulfation of glycoconjugates secreted from rabbit trachea in culture.

The influences of extracellular Ca2+ and Mg2+ concentrations on the basal secretion of glycoconjugates from rabbit trachea in organ culture were examined. Over 80% of the 35S-labeled and [3H]glucosamine-labeled glycoconjugates secreted by the trachea were digested upon incubation with chondroitinase ABC. The basal secretion did not occur in the medium at 4 degrees C, indicating an energy-dependent process. The basal secretion at 37 degrees C of 35S-labeled glycoconjugates was prominently suppressed in Mg(2+)-free Tyrode solution but not in Ca(2+)-free Tyrode solution containing ethyleneglycol bis(2-aminoethylether)tetraacetic acid (EGTA). In contrast, the basal secretion of [3H]glucosamine-labeled glycoconjugates was not affected by the Mg2+ concentration in the medium. The results suggest that extracellular Mg2+ largely contributes to sulfation of glycoconjugates basally secreted from rabbit trachea.

Animals↗

[Malignant fibrous histiocytoma of the heart].

A 59-year-old woman was referred to our hospital by a local cardiologist, with unknown cause of congestive heart failure and respiratory failure. No significant heart murmur was heard and a cardioechogram from the anterior chest was insufficient for diagnosis. On the night of admission, cardio-respiratory shock was found, and Swan-Gantz catheter data showed severe pulmonary hypertension. Transesophageal echo-cardiography (TEE) revealed a left atrial tumor, with wide neck anchored onto the posterior wall of the left atrium, and which was floating into the left ventricle during the diastolic phase. An emergency operation was performed and the tumor, (80 by 50 by 48 mm) was resected. The patient recovered well in the postoperation period. However the residual tumor continued to grow gradually in the pericardial cavity and the patient died 3 months after the operation. Primary MFH of the heart is rare and 29 cases have been reported. The prognosis of MFH is poor despite surgery. Whenever a left atrial tumor with a wide neck is attached to the posterior wall, it must be considered to be possibly malignant and surgical resection is recommended.

Emergencies↗

[A case of verrucous carcinoma showing a good partial response by C.P.E. (CDDP, PEP, etoposide) chemotherapy].

A 60-year-old woman was admitted to our hospital with a complaint of rough feeling on the oral mucosa and diagnosed as verrucous carcinoma with histopathological examination. She was treated with CPE chemotherapy, and showed a good response and improvement of clinical symptoms. Toxicities were leukopenia, alopecia and anorexia. However, these were slight side effects. The patient is currently healthy with no recurrence after two years and 3 months. CPE chemotherapy is considered to be effective for a patient with verrucous carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗