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Biomedical subjects

K Shimoda

Publications and source records attributed to K Shimoda.

At least 109 records · Page 6Linked to original sources

[A study of audiologic findings in the elderly].

We divided people more than 65 years of age into groups, by 5- year age intervals, and performed hearing tests based on pure tone, speech sound, and inner ear and retrocochlear hearing functions. Thus, we studied the mechanism of hearing disorder progression with aging in an attempt to identify factors involved in decreased speech sound recognition. The following results were obtained. 1. The regression coefficient of speech discrimination ability and the mean hearing threshold level were greater in the elderly patients than in the younger patients with cochlear hearing loss. 2. Abnormal decreases in speech discrimination ability evaluated on the basis of the mean hearing threshold level occur more frequently with advancing age. 3. The SISI score increased rapidly in patients 80 years of age or older. 4. Directional hearing function (interaural time difference threshold) varied more markedly with age. 5. Little difference in SSB clipping speech articulation was seen among elderly subjects less than 80 years old, though scores were lower than those of the control group. However, it was decreased in patients 80 or more years old. These results show that the effect of a raised pure-tone hearing threshold due to decreased inner ear function and the effect of recruitment phenomenon on speech hearing were the same in patients from 65 to the late 70s; however, the effect of retrocochlear hearing loss clearly increased with age. Therefore, we consider patients 80 or more years old, to have an impaired inner ear function which is aggravated and that this, in association with advanced retrocochlear disturbance, leads to greatly decreased speech discrimination ability.

Aged↗

In vitro study of deoxymethylspergualin on functions of lymphocytes and bone marrow cells from healthy volunteers.

15-Deoxy-11-O-methylspergualin (MeDSG) is an analogue of 15-deoxyspergualin, which has potent immunosuppressive activity. The present study was designed to evaluate the in vitro effects of MeDSG on the functions of peripheral blood mononuclear cells (PBMC) and bone marrow cells derived from healthy volunteers. MeDSG failed to suppress the proliferation of PBMC stimulated with mitogens. In the allogeneic mixed lymphocyte reaction, MeDSG strongly suppressed both the proliferation of lymphocytes and the generation of alloreactive cytotoxic T lymphocytes, but did not affect the cytolytic activity of the established cytotoxic T lymphocytes. MeDSG had no effect on the cytolytic activity of natural killer cells. Concerning positive hematopoietic regulators, MeDSG had a slight enhancing effect on the release of granulocyte-macrophage colony-stimulating factor and a slight inhibitory effect on the release of interleukin-6 and granulocyte-colony-stimulating factor from PBMC stimulated with mitogens. Significantly, MeDSG completely suppressed the colony formation of bone marrow cells in the presence of granulocyte colony-stimulating factor.

Bone Marrow↗

High-frequency granuloid colony-forming ability of G-CSF receptor possessing CD34 antigen positive human umbilical cord blood hematopoietic progenitors.

The presence of granulocyte colony-stimulating factor receptor (G-CSFR) in CD34+ hematopoietic progenitors is demonstrated by flow cytometry. Cord blood mononuclear cells (MNCs) contain about 1.09 +/- 0.2% CD34+ cells, 0.32 +/- 0.1% CD34+/G-CSFR+ (G-CSFR+) cells, and 0.77 +/- 0.1% CD34+/G-CSFR- (G-CSFR-) cells. The colony-forming ability of G-CSFR+ cells in the presence of G-CSF, granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3), and erythropoietin (Epo) was higher than that of G-CSFR- cells (29.5 vs. 9.8%; p < 0.01). In the fraction of G-CSFR+ cells, the most frequently formed colony type was CFU-G/GM, while burst-forming unit-erythroid (BFU-E) or colony-forming unit-macrophage (CFU-M) were rare. On the other hand, the incidence of BFU-E and CFU-G/GM was similar in the fraction of G-CSFR- cells. This indicates that most granuloid colonies of CD34+ cells were derived from G-CSFR+ cells. These results suggest a lineage commitment for the vast majority of G-CSFR+ hematopoietic progenitors.

Antigens, CD↗

Laparoscopic approaches in the management of patients with early gastric carcinomas.

In eight Japanese patients, three different laparoscopic procedures were used to excise an early gastric carcinoma; partial resection in four, intragastric resection of the gastric mucosa in two, and laparoscopic-assisted distal partial gastrectomy with the abdominal wall-elevating method in two patients. Histological examinations revealed that the lesions were completely resected, and there was no evidence of lymphatic metastasis. The operation time ranged from 2 to 4 h. These forms of laparoscopic gastric surgery for patients with early gastric carcinomas may be useful from the standpoint of minimal access, rapid recovery, less pain, and good cosmesis.

Aged↗

G-CSF induces tyrosine phosphorylation of the JAK2 protein in the human myeloid G-CSF responsive and proliferative cells, but not in mature neutrophils.

Granulocyte colony-stimulating factor (G-CSF) stimulates a rapid phosphorylation on tyrosines of several proteins of Mr. 130, 100, 90, 70, 44 kd in human myeloid leukemia cell line cells, Kasumi-1, which respond to G-CSF to proliferate in vitro. In HL60 cells, only a 100 kd protein was phosphorylated, and no detectable phosphorylated proteins were observed in neutrophils by the stimulation of G-CSF. Among these proteins, the 130 kd protein was immunoprecipitated by anti- JAK2 serum. While JAK2 is a non receptor tyrosine kinase and is reported to be involved in the signal transduction by various cytokines including growth hormone, erythropoietin, and granulocyte-macrophage colony-stimulating factor/interleukin-3, it is strongly suggested that a signaling pathway that relates to the cell proliferation triggered by G-CSF in immature hematopoietic cells also involves JAK2.

Cell Division↗

Genotypes and titers of hepatitis C virus for predicting response to interferon in patients with chronic hepatitis C.

Interferon induces remission in about 50% of patients with chronic hepatitis C, but it is difficult to predict which patients will respond. Host and viral factors were evaluated for correlation with response to interferon in patients with chronic hepatitis C. Recombinant interferon alpha-2b with a total dose of 480-560 million units was given to 136 patients, of whom 74 (54%) responded. Genotypes of hepatitis C virus (HCV) in sera, I, II, III, IV, and V, were determined by polymerase chain reaction (PCR) with type-specific primers. In 72 patients, pretreatment levels of HCV RNA were titrated by PCR in serial tenfold dilutions of RNA extracted from serum. Response to interferon occurred in 34 (40%) of 85 patients infected with HCV of genotype II, less frequently than in 22 (85%) of 26 with genotype III (P < 0.001) or in 7 (70%) of 10 with genotype IV. Of 51 patients with genotype II HCV, 6 of 8 (75%) with HCV RNA titers < 10(6) responded, more frequently than 4 of 43 (9%) with titers > or = 10(6) (P < 0.001). Responders were younger than non-responders (45.7 +/- 11.7 vs. 50.3 +/- 9.6 yr) and had received transfusions less frequently (26/74 or 35% vs. 37/62 or 60%, P < 0.01). Response to interferon correlated inversely with the severity of liver histopathology. These results indicate that response to interferon is influenced by HCV genotypes and pretreatment levels of HCV RNA in serum.

Adult↗

Analysis of acute myeloid leukemia cells by flow cytometry, introducing a new light-scattering classification.

A combined flow-cytometric evaluation of light scattering and the immunophenotype of acute myeloid leukemia (AML) cells from 71 newly diagnosed consecutive patients was conducted. Light-scattering characteristic of AML cells examined by flow cytometry and multiple surface markers were also analyzed using the same samples, to enable a comparison with the French-American-British (FAB) classification. Our AML cases could be classified into three light-scattering classification (LSC) types according to their physical properties on flow cytometry. These were type A, where forward light scattering (FSC) of the leukemic cell population was larger than that of lymphocytes, while side light scattering (SSC) was the same or larger than that of lymphocytes but smaller than that of monocytes; type B, where FSC of the leukemic cell population was larger than that of lymphocytes and SSC spread toward that of monocytes; and type C, where both FSC and SSC of the leukemic cell population spread beyond those of monocytes. Although a clear relationship between the FAB classification and LSC classification by the light-scattering profile of AML was not established, we observed the following findings. The majority of cases were classified as type A (58%), while type B comprised 25% and type C comprised 17%. While CD7 expression on AML cells is considered to be an immature characteristic, CD7 was expressed more frequently among LSC type A cases. Furthermore, all but one of the FAB M1 cases were classified as type A. On the other hand, CD7 was not expressed on type C leukemic cells. The percentage of cases in which more than 60% of leukemic cells possessed another immature surface antigen, CD 34ö, was 13/18 (72%) among FAB M1 cases, much higher than among FAB M2 (35%) or FAB M4 (27%) cases. A negative correlation was observed between mature antigen CD33 and CD34 among the FAB M2 cases. The frequency of CD7 expression was 25% among the total cases, and CD7-positive cases were frequent among FAB M1 and M2, but not among FAB M3 cases. These findings concerning LSC and immunophenotyping indicate that the scattergram pattern analysis may contribute towards more precise immunophenotyping, in that it reflects the maturation stage of each AML case.

Acute Disease↗

Intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma: preliminary results.

An important objective for patients with unresectable hepatocellular carcinoma (HCC) is the development of effective chemotherapy. We administered a combination of biological response modifiers and anticancer agents to 24 patients with unresectable HCC. Each case had an implanted infuser port which was connected to a catheter placed in the hepatic artery for the intraarterial (i.a.) administration of chemotherapy. The following agents were administered to each patient: recombinant interleukin-2 (800,000 JRU/day infused i.a. continuously for 6 days/week); OK-432 (5 KE injected i.a. twice in 4 weeks and i.m. three times per week); Adriamycin (10 mg injected i.a. twice in 4 weeks); cyclophosphamide (300 mg injected i.a. twice in 4 weeks), and famotidine (40 mg/day administered orally). Objective response was assessed according to tumor size measured by computed tomography and angiography before and after treatment. We observed a complete response (CR) in 4, partial response (PR) in 3, minor response (MR) in 7, no change (NC) in 7, and progressive disease (PD) in 3. The response rate (CR+PR+MR) was 58.3%. The overall 2-year survival rate was 52%. The 2-year survival rate of the responders (CR+PR+MR) was 80%, while that of the non-responders (NC+PD) was 0%. There was a significant difference between the responders and non-responders in respect to survival rate (P < 0.05). The percentages of CD25+ cells, CD56+ cells, and Leu7-CD16+ cells and NK activity in the peripheral blood showed a significant increase following the regimen. Serum levels of tumor necrosis factor alpha TNF alpha rose after the initiation of OK-432. TNF alpha levels were higher in the responders than in the non-responders. Adverse effects included high fever (all patients) and severe transient hypotension (15 patients) that was controlled by conservative therapy. Combined immunochemotherapy administered intraarterially may be a new strategy for treating unresectable HCC.

Aged↗

Extensive lymphadenectomy for thoracic esophageal carcinoma: a two-stage operation for high-risk patients.

Extensive lymphadenectomy (ELA) for esophageal carcinoma has always been limited to low-risk patients; however, we have developed a two-stage operation which extends the indications for ELA to include certain high-risk patients. Of 70 patients who underwent transthoracic subtotal esophagectomy for thoracic esophageal carcinoma between 1986 and 1991, 48 qualified for ELA which was performed on 45, including 27 low-risk patients (group A) whom underwent the traditional one-stage operation, while 18 high-risk patients underwent the two-stage operation (group B). The number of hospital deaths and postoperative complications was similar between the two groups. The median survival was 26 months in group B and 17 months in group A. The 40-day delay in resection of the neck and abdominal nodes in the two-stage operation did not significantly affect lymph node metastases, postoperative recurrence, or long-term survival. Thus, the two-stage operation is an oncologically meaningful approach to the treatment of high-risk patients who present with thoracic esophageal carcinoma.

Esophageal Neoplasms↗

Clinical course of acute hepatitis C and changes in HCV markers.

Chronological measurements of various HCV markers were conducted to clarify the course and prognosis of acute hepatitis C. Among 49 patients with acute non-A, non-B hepatitis, 32 (65.3%) were diagnosed as having acute hepatitis C by these markers. Twenty-four (82.8%) of 29 patients with posttransfusion hepatitis were type C, while only eight (40.0%) of 20 patients with sporadic hepatitis were type C. Patients were also divided into those who returned to normal within one year based on changes in s-ALT levels and unresolved cases. Anti-HCV was present in 11 (44.4%) of 25 resolved cases and in 21 (87.1%) of 24 unresolved cases. Only one case was continuously positive for HCV-RNA although s-ALT levels returned to normal. In addition, quantitative determinations were conducted on those positive for anti-HCVs. Anti-second generation tested positive in all HCV-RNA-positive cases and positive rates were highest from the onset of hepatitis. In unresolved patients with continuous HCV infection, anti-core increased and titers at 12 months were 10 units or more in all cases. On the other hand, in eight of 10 resolved cases, titers declined gradually after initial seroconversion and titers were 10 units or less at 12 months. From these results, second generation anti-HCV was considered most useful in early diagnosis of acute hepatitis C and anti-core titer was considered most useful in predicting prognosis of acute hepatitis C.

Acute Disease↗

IgG2 deficiency in methicillin-resistant Staphylococcus aureus infections after esophageal surgery.

We previously reported the selective development of methicillin-resistant Staphylococcus aureus (MRSA) infections following esophageal surgery in patients with a reduced ability to produce anti-pneumococcal polysaccharide (PPS) IgG. Since the response to the PPS vaccine is correlated to the serum IgG2 levels, we measured IgG2 in the same series of esophageal cancer patients. IgG subclasses were determined in 21 patients, 8 of whom developed MRSA infections. IgG2 was thus found to be significantly lower (P < 0.01) in patients with MRSA infections (453 mg/dl) than in those without such infections (666 mg/dl). There was also a significantly positive correlation (r = 0.61) between anti-PPS IgG and serum IgG2. Therefore, the preoperative measurement of serum IgG2 is considered to be useful in detecting patients who are at risk for developing an MRSA infection after esophageal surgery.

Esophageal Neoplasms↗

Prostaglandin E2 levels and lymphocyte subsets in portal venous drainage of colorectal cancers.

Local immunosurveillance may play an important role in the growth and spread of tumors. To investigate the local immune response, we determined prostaglandin E2 (PGE2) levels (n = 23) and lymphocyte subsets (n = 10) in the portal vein draining the tumors of patients with colorectal cancer. PGE2 levels in the portal vein were significantly higher than those in the radial artery. Portal PGE2 levels in patients with advanced stage tumors (Duke's C and D) and lymph node metastases were significantly higher than those of patients with Duke's A and B tumors without lymph node metastases. Moreover, four of the nine patients with portal PGE2 levels greater than 100 pg/mL had liver metastases within 2 years of surgery. There were no differences in lymphocyte subsets between the portal vein and the radial artery. PGE2 levels in the portal vein draining colorectal tumor may thus be closely related to tumor progression and recurrence and may serve as a predictor of tumor recurrence in patients with colorectal cancer.

Adult↗

Introduction of oxygenated functional groups into 3-carene and 2-pinene by cultured cells.

The biotransformation of the monoterpene hydrocarbons 3-carene and 2-pinene by cell suspension cultures of Nicotiana tabacum and Catharanthus roseus was investigated. The cultures have the ability to regio- and enantioselectively introduce the oxygenated functional groups into the C = C double bond and the allylic positions of the substrates.

Bicyclic Monoterpenes↗

Spermatocyte-specific transcription by calmodulin gene II promoter in transgenic mice.

Transgenic mice carrying a fused gene of the 294-base upstream and 68-base leader sequences of a rat calmodulin gene, CaMII, and beta-galactosidase gene were made. Only spermatocytes expressed the transgene mRNA in the testes of four independent transgenic lines. The localization of transgene mRNA was consistent with that of the mouse endogenous CaMII analyzed by in situ hybridization with the probe of 3'-noncoding region of mouse CaMII. Thus, this short promoter of CaMII evidently conferred the expression of transgene only on spermatocytes but not on spermatogonia nor on spermatids of the testis. The rat CaMII promoter up to -294 contained no sequences that corresponded to any of the reported sequence features of genes expressed in the testis. Therefore, this short promoter region of CaMII seemed to carry a certain novel machinery for the spermatocyte-specific gene expression.

Animals↗

Astrocyte-dependent and -independent phases of the development and survival of rat embryonic day 14 mesencephalic, dopaminergic neurons in culture.

A primary neuronal culture was prepared from the ventral mesencephalon, centered on the A8, A9 and A10 dopaminergic nuclei of the embryonic day 14 rat, and studied from 12 h to 28 days. At 12 h after plating, and before cell death ensued, 95% of the cells stained positive for neuron specific enolase; 20% for tyrosine hydroxylase; 5% for vimentin and < 0.1% for glial fibrillary acidic protein. In the presence of the mitotic inhibitor cytosine arabinoside (2.0 microM), neuronal growth and survival were surprisingly normal up to the ninth day in culture, but deteriorated rapidly thereafter. In the absence of a mitotic inhibitor, and in the presence of proliferating but non-confluent glia, the tyrosine hydroxylase positive neurons that survived to the 10th day, had retracted neurites and a rounded soma, suggesting an inhibition of cell development. Those tyrosine hydroxylase positive neurons that survived this adverse phase of development tended to produce elaborate neuritic profiles after the 11th day, coincident with confluence of the astrocyte monolayer at the 12th day. By the 21st day in culture, and persisting up to the 28th day, 60% (61 +/- 10, n = 20) of the surviving neurons stained positive for tyrosine hydroxylase. When plated on an established, ventral mesencephalic monolayer of astrocytes, at the seventh day in culture, neuritic growth and branching of the tyrosine hydroxylase positive neurons were greater, compared with similar neurons grown on poly-D-lysine, and the signs of arrested development (retraction of neurites and rounded soma) seen at the 10th day after plating on poly-D-lysine, were not observed. We conclude that in the primary culture studied, and under the experimental conditions used, the survival of dopaminergic neurons was independent of glia during the first nine days, and critically dependent on glia thereafter. The resurgence of growth of dopaminergic neurons after 10 days in vitro, and their subsequent selective survival in culture, suggest that confluent type-1 astrocytes produce factors that act selectively on the dopaminergic neuronal phenotype. The successful identification of these dopaminergic-specific, neurotrophic factors could lead to an increased understanding of the etiology of Parkinson's disease, and suggest new directions for therapeutic intervention.

Animals↗