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Biomedical subjects

S Miyake

Publications and source records attributed to S Miyake.

At least 109 records · Page 6Linked to original sources

Effects of voglibose on glycemic excursions, insulin secretion, and insulin sensitivity in non-insulin-treated NIDDM patients.

OBJECTIVE: To investigate the effects of voglibose, an alpha-glucosidase inhibitor, on daily glycemic excursions, insulin secretion, and insulin sensitivity in non-insulin-treated NIDDM patients. RESEARCH DESIGN AND METHODS: An open prospective study was conducted in 27 NIDDM patients receiving diet therapy alone or treatment with a sulfonylurea drug. Of the study subjects, 14 patients were treated with voglibose; the remaining 13 patients served as the control group. The metabolic parameters were evaluated before treatment and at week 4 of treatment as follows: glycemic excursions by M-value and 1,5-anhydro-D-glucitol (1,5-AG), insulin secretion by area under the curve of daily serum insulin (AUCinsulin), and insulin sensitivity by the K index of the insulin tolerance test (KITT). RESULTS: After the study treatment, HbA1c and plasma glucose in the patients who had received voglibose were comparable to those of patients in the control group. M-value was lower in the patients treated with voglibose than in the control subjects (5.7 +/- 0.9 vs. 9.8 +/- 1.2, P < 0.05). 1,5-AG was higher in the patients treated with voglibose than in the control subjects (12.2 +/- 1.0 vs. 8.2 +/- 0.7 micrograms/ml, P < 0.01). A statistically significant increase in AUCinsulin occurred after treatment with voglibose (2,223.5 +/- 390.6 to 1,546.7 +/- 303.4 pmol.l-1.h, P < 0.05), but no change occurred in the control group (2,364.5 +/- 315.4 to 2,464.2 +/- 269.3 pmol.l-1.h, P = 0.60). Insulin sensitivity (KITT) was improved to a statistically significant level in both the patients treated with voglibose and the patients in the control group. KITT in the patients after voglibose treatment was comparable to that of the control group (3.18 +/- 0.30 vs. 3.21 +/- 0.23%/min, P = 0.94). CONCLUSIONS: The results suggest that voglibose lowers the daily glycemic excursions and inhibits overwork of the pancreatic beta-cells but has little effect on insulin sensitivity in NIDDM patients.

Blood Glucose↗

High incidence of chemotherapy-induced acral erythema in female patients with non-Hodgkin's lymphoma treated with the VACOP-B regimen.

Seven patients, all females out of 29 with non-Hodgkin's lymphoma (NHL) (16 males and 13 females) treated with the VACOP-B regimen utilizing granulocyte-colony-stimulating factor (G-CSF) support developed chemotherapy-induced acral erythema (CAE). In contrast, none of 32 patients with NHL who were treated with CHOP, MACOP-B, or biweekly CHOP regimens without G-CSF developed CAE. Total dose intensities of VACOP-B regimen were higher than those of the three other regimens. However, no significant difference in dose intensities of each drug in the patients treated with the VACOP-B regimen was found between male and female patients and between female patients with or without CAE. The cause of the high incidence of CAE (7/13) in the female patients treated with VACOP-B regimen remains unknown. However, female sex hormones may increase susceptibility to CAE. Since the occurrence of CAE interrupts intensive chemotherapy and reduces the cure rate, high risk patients for CAE should be carefully monitored for early symptoms and signs of CAE and should be treated early and appropriately.

Antineoplastic Combined Chemotherapy Protocols↗

Idiopathic spinal cord herniation. Report of two cases and review of the literature.

The authors describe two occurrences of idiopathic spinal cord herniation, an entity that has been reported previously in only 11 cases. The patients described in this report presented in midlife with Brown-Séquard syndrome. Computerized tomography myelography and magnetic resonance (MR) imaging showed ventral displacement of the spinal cord with no apparent dorsal mass. Intraspinal cerebrospinal fluid (CSF) flow studies in which phase-contrast pulse sequence cine MR imaging was used displayed a normal pattern dorsal to the spinal cord. Percutaneous intrathecal endoscopic observation did not disclose dorsal intradural cysts, but ventral adhesions were seen between the spinal cord and the dura. Microsurgical intradural exploration revealed ventrolateral herniation of the cord and a ventral root through a dural defect into an epidural arachnoid cyst. The adhesions were released, the cord was repositioned intradurally, and the dural defect was patched. The patients showed gradual improvement postsurgery, as did most of the patients in the previously reported cases. The CSF flow and endoscopic studies were found to be particularly informative, and dural patching with surgical membrane is recommended.

Brown-Sequard Syndrome↗

[Introduction of new GCP (good clinical practice)].

In 1997, a new GCP has taken effect by the Ministry of Health and Welfare, Japan, and will be enforced as of April, 1998. The GCP regulates the method of clinical trials in the light of ethics and science. The New GCP requires written informed consent, enforcement of the responsibility of the client and so on.

Antineoplastic Agents↗

[Procainamide-induced lupus in a patient with bilateral pleural effusion].

A 70-year-old physician was admitted to our hospital because of bilateral pleural effusion and left-sided chest pain on deep inspiration. On admission, the APTT was prolonged and was not corrected with a 1:1 mixture of normal plasma. Results of serological examinations included a positive lupus-anticoagulant test and a positive ANA test at a titer of 1:1,280 in a homogeneous pattern. The patient's age, sex, symptoms, signs, and laboratory results all argued against the diagnosis of SLE except for ANA and lupus anticoagulant test. Because procainamide had been prescribed (250 mg every 6 h) for premature ventricular contractions for eight years before admission, procainamide-induced lupus was suspected. Procainamide was discontinued. Chest pain persisted and tests for c-reactive protein were positive. Prednisolone was administered. Procainamide induced lupus was diagnosed, because anti-histone H 2 A-H 2 B complex antibodies were high by enzyme-linked immunosorbent assay, and IgM-class anti-histone antibodies were found in response to H1, H 2 B and H 2 A-H 2 B complex (immunoblotting), which suggested the drug induced lupus. There are only a few reports of drug induced lupus in which the lupus-anticoagulant test was positive and prednisolone was indicated. The measurements of anti-histone antibodies and of expression of anti-histone antibodies were useful in distinguishing drug-induced lupus from SLE.

Aged↗

Factors influencing mental workload indexes.

Several findings of the author's own mental workload research are reviewed. Especially, factors, except task demand, influencing mental workload indexes are discussed. First, an experiment using the National Aeronautics and Space Administration Task Load Index (NASA TLX) is reviewed and the effects of a prior task load on a subsequent subjective workload are described. In a physiological measures section, the low reliability of the heart rate variability (HRV) parameters when the subjects' respiration pattern are highly irregular, and the existence of low sweat respondent, although perspiration seems to be sensitive to the workload, are indicated. Furthermore, results of the task specific physiological responses and of a HRV parameter affected by the individual characteristics, like type A behavior pattern, are shown. Discrepancy between autonomic nervous system activity measures may be solvable by introducing a new concept of autonomic space (synergism of sympathetic and parasympathetic nervous system). Finally, the need for strategies of data management concerning the individual differences is emphasized.

Autonomic Nervous System↗

Development of flexible ventriculoscope (Yamadori-type VII) and its application to experimental animals.

We developed a new ventriculoscope (Yamadori-type VII), a 2.1 mm calibrated fiberscope with a monopolar coagulator, that can be inserted from the cisterna cerebellomedullaris into the third cerebral ventricle of experimental animals, like dogs. With the improved performance of the neuroendoscope compared to its prototype, Yamadori III, it was possible to inspect clearly and to produce electrocoagulative lesions accurately on any part of the intraventricular structures with minimal injury to nearby vital brain areas.

Animals↗

Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia.

To clarify whether the expression of the WT1 gene in leukemic cells is aberrant or merely reflects that in normal counterparts, the expression levels of the WT1 gene were quantitated for normal hematopoietic progenitor cells. Bone marrow (BM) and umbilical cord blood (CB) cells were fluorescence-activated cell sorting (FACS)-sorted into CD34+ and CD34- cell populations, and the CD34+ cells into nine subsets (CD34+ CD33-, CD34+ CD33+, CD34+ CD38-, CD34+ CD38+, CD34+ HLA-DR-, CD34+ HLA-DR+, CD34+ c-kit(high), CD34+ c-kit(low), and CD34+ c-kit-) according to the expression levels of CD34, CD33, CD38, HLA-DR, and c-kit. Moreover, acute myeloid leukemic cells were also FACS-sorted into four populations (CD34+ CD33-, CD34+ CD33+, CD34- CD33+, and CD34- CD33-). FACS-sorted normal hematopoietic progenitor and leukemic cells and FACS-unsorted leukemic cells were examined for the WT1 expression by quantitative reverse transcriptase-polymerase chain reaction. The WT1 expression in the CD34+ and CD34- cell populations and in the nine CD34+ subsets of BM and CB was at either very low (1.0 to 2.4 x 10(-2)) or undetectable (< 10(-2)) levels (the WT1 expression level of K562 cells was defined as 1.0), whereas the average levels of WT1 expression in FACS-sorted and -unsorted leukemic cells were 2.4 to 9.3 x 10(-1). Thus, the WT1 expression levels in normal hematopoietic progenitor cells were at least 10 times less than those in leukemic cells. Therefore, we could not find any normal counterparts of BM or CB that expressed the WT1 at levels comparable with those in leukemic cells. These results indicate an aberrant overexpression of the WT1 gene in leukemic cells and imply the involvement of this gene in human leukemogenesis.

Acute Disease↗

Lineage- and differentiation stage-specific expression of LSM-1 (LPAP), a possible substrate for CD45, in human hematopoietic cells.

CD45, a transmembrane tyrosine phosphatase, is found on almost all nucleated hematopoietic cells and plays a crucial role in lymphocyte activation and differentiation. We recently achieved isolation of the human LSM-1 (hLSM-1) gene, whose product is a possible substrate for CD45, and we raised antibodies against the hLSM-1 protein. hLSM-1 expression in hematopoietic cells was examined with Northern and Western blot, fluorescence-activated cell sorter, and immunocytochemical analyses. It was found that in the lymphoid lineage, T and B lymphocytes as well as NK cells expressed LSM-1, whereas terminally differentiated plasma cells did not. As for the myeloid lineage, immature myeloid cells expressed LSM-1, whereas terminally differentiated granulocytes and monocytes did not. In the erythroid lineage, normal erythroblasts expressed very low levels of LSM-1, while erythroid cell lines (K562 and HEL) did not. Megakaryocytes did not express LSM-1. Both CD34+/CD33- and CD34+/CD33+ hematopoietic progenitor cells weakly expressed LSM-1. These results showed that LSM-1 is expressed in a lineage- and differentiation stage-specific fashion.

Blotting, Western↗

Phosphotyrosine binding domain-dependent upregulation of the platelet-derived growth factor receptor alpha signaling cascade by transforming mutants of Cbl: implications for Cbl's function and oncogenicity.

Recent studies have demonstrated that Cbl, the 120-kDa protein product of the c-cbl proto-oncogene, serves as a substrate of a number of receptor-coupled tyrosine kinases and forms complexes with SH3 and SH2 domain-containing proteins, pointing to its role in signal transduction. Based on genetic evidence that the Caenorhabditis elegans Cbl homolog, SLI-1, functions as a negative regulator of the LET-23 receptor tyrosine kinase and our demonstration that Cbl's evolutionarily conserved N-terminal transforming region (Cbl-N; residues 1 to 357) harbors a phosphotyrosine binding (PTB) domain that binds to activated ZAP-70 tyrosine kinase, we examined the possibility that oncogenic Cbl mutants may activate mitogenic signaling by deregulating cellular tyrosine kinase machinery. Here, we show that expression of Cbl-N and two other transforming Cbl mutants (CblY368 delta and Cbl366-382 delta or Cb170Z), but not wild-type Cbl, in NIH 3T3 fibroblasts leads to enhancement of endogenous tyrosine kinase signaling. We identified platelet-derived growth factor receptor alpha (PDGFR alpha) as one target of mutant Cbl-induced deregulation. In mutant Cbl transfectants, PDGFR alpha was hyperphosphorylated and constitutively complexed with a number of SH2 domain-containing proteins. PDGFR alpha hyperphosphorylation and enhanced proliferation of mutant Cbl-transfected NIH 3T3 cells were drastically reduced upon serum starvation, and PDGF-AA substituted for the maintenance of these traits. PDGF-AA stimulation of serum-starved Cbl transfectants induced the in vivo association of transfected Cbl proteins with PDGFR alpha. In vitro, Cbl-N directly bound to PDGFR alpha derived from PDGF-AA-stimulated cells but not to that from unstimulated cells, and this binding was abrogated by a point mutation (G306E) corresponding to a loss-of-function mutation in SLI-1. The Cbl-N/G306E mutant protein, which failed to induce enhanced growth and transformation of NIH 3T3 cells, also failed to induce hyperphosphorylation of PDGFR alpha. Altogether, these findings identify a novel mechanism of Cbl's physiological function and oncogenesis, involving its PTB domain-dependent direct interaction with cellular tyrosine kinases.

3T3 Cells↗

The Cbl protooncogene product: from an enigmatic oncogene to center stage of signal transduction.

The c-cbl protooncogene was first identified as the cellular homologue of a viral oncogene v-cbl that induces pre-B lymphomas and myeloid leukemias in mice. Until recently, the biochemical basis for Cbl's transforming potential and its physiological role remained unclear. However, a convergence of biochemical studies in mammalian cells and genetic studies in C. elegans and Drosophila has now identified Cbl as a negative regulator of tyrosine kinase signaling. The N-terminal transforming region of Cbl (Cbl-N) and an adjacent RING finger domain are the elements most conserved during evolution. The Cbl-N region has now been shown to contain a novel phosphotyrosine-binding (PTB) domain that directly interacts with autophosphorylated tyrosine kinases via a D(N/D)XpY motif. A critical role of the PTB domain in Cbl function is demonstrated by the localization of a loss-of-function mutation in C. elegans Cbl homologue SLI-1 within this region. The corresponding mutation in human Cbl inactivates the PTB domain function and abrogates Cbl-mediated regulation of tyrosine kinase function. Recent studies have also identified a novel signaling pathway initiated by the interaction of mammalian Cbl proteins with the SH2 domains of Crk adaptor molecules, which results in Cbl's linkage with C3G, a guanine nucleotide exchange protein for Rap1 family of small G-proteins. Presently, Rap1 is thought to antagonize Ras function, although Rap1-specific targets have emerged recently. Thus, recent advances have firmly placed the little known protooncoprotein Cbl on the center stage of tyrosine kinase-mediated signal transduction.

Amino Acid Sequence↗

Non-Hodgkin's lymphoma with pulmonary infiltrates mimicking miliary tuberculosis.

Miliary infiltrates observed on chest films in non-Hodgkin's lymphoma are extremely rare. We report a case with pulmonary infiltrates mimicking miliary tuberculosis associated with prominent eosinophilia and elevated IgE levels. The levels of circulating eosinophils correlated with disease activity as they transiently returned to normal after effective chemotherapy in a short period. However, the patient developed acute respiratory failure due to the rapid progression of the disease even with intensive chemotherapy. We emphasize that small nodular shadows appear to be a sign of the rapid progression of the disease and a poor prognosis.

Diagnosis, Differential↗

Hemolysis, elevated liver enzymes, and low platelets syndrome associated with primary anti-phospholipid antibody syndrome.

A 28-year-old woman with a history of a spontaneous abortion developed thrombocytopenia, Coombs-negative hemolytic anemia, and liver dysfunction at the sixteenth week of pregnancy. These findings were compatible with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome (hemolysis, elevated liver enzymes, and low platelet counts). Moreover, serum anti-phospholipid antibodies were positive, suggesting the association of anti-phospholipid antibody syndrome. An artificial abortion, anti-coagulation therapy, and plasma exchange were performed concomitantly with corticosteroid therapy. She responded to the therapy, a remission was obtained. Anti-phospholipid antibodies may play a role in the pathogenesis of HELLP syndrome.

Abortion, Induced↗

Glucose tolerance, insulin secretion, and insulin sensitivity in nonobese and obese Japanese subjects.

OBJECTIVE: To investigate the relative contributions of insulin secretion and insulin resistance to the development of glucose intolerance in Japanese subjects. RESEARCH DESIGN AND METHODS: A cross-sectional study of 756 Japanese subjects (530 nonobese, 226 obese) was performed. A 75-g oral glucose tolerance test (OGTT) was given, and subjects were classified according to the World Health Organization (WHO) criteria (normal glucose tolerance [NGT], impaired glucose tolerance [IGT], and diabetes). Early-phase insulin secretion was assessed by the insulinogenic index (the ratio of the increment of insulin to that of plasma glucose [PG] 30 min after a glucose load [delta IRI0-30 min/delta PG0-30 min]). Total insulin secretion was assessed by mean immunoreactive insulin (IRI) during the OGTT, and insulin resistance was assessed by use of the homeostasis model [HOMA(R)]. RESULTS: Early-phase insulin secretion was significantly decreased in IGT, compared with patients with NGT, in both the nonobese and obese subjects (0.70 +/- 0.05 vs. 0.37 +/- 0.03, P < 0.01 and 1.36 +/- 0.19 vs. 0.73 +/- 0.08, P < 0.01, respectively). However, mean IRI and HOMA(R) in both nonobese and obese subjects with IGT and NGT were not statistically different. Subjects with diabetes showed a significant decline in early-phase and total insulin secretion and a significantly higher level of insulin resistance than did subjects with IGT. When the fasting glucose (FPG) exceeded 100 mg/dl, early-phase insulin decreased progressively. The graphed relationship between FPG and mean IRI did not show an inverted U-shape, and mean IRI decreased progressively when FPG exceeded 100-130 mg/dl. The pattern of changes in insulin secretion and insulin resistance associated with the progression of glucose intolerance was similar in both the nonobese and obese subjects. CONCLUSIONS: The worsening from NGT to IGT in Japanese subjects may be associated with a decrease in early-phase insulin secretion in nonobese as well as in obese subjects. Hyperinsulinemia in IGT is not common. We suggest that impaired early-phase insulin secretion may be the initial abnormality in the development of glucose intolerance in Japanese people. Insulin resistance may be a consequence of hyperglycemia and/or obesity.

Adult↗

Insulin resistance and arteriosclerosis obliterans in patients with NIDDM.

OBJECTIVE: To investigate the risk factors for arteriosclerosis obliterans (ASO) in NIDDM, we measured insulin sensitivity and other risk factors including lipoprotein(a) [Lp(a)] in NIDDM patients with and without ASO. RESEARCH DESIGN AND METHODS: A case-control study in 100 patients with NIDDM, 35 with and 65 without ASO, was performed. Insulin sensitivity was assessed by the short insulin tolerance test's K index (KITT). Duration of diabetes, a history of smoking, prevalence of hypertension, prevalence of coronary artery disease (CAD), serum C-peptide, 24-h urinary C-peptide, serum lipids, and Lp(a) were compared in the two groups. RESULTS: Age, BMI, HbA1c, and fasting plasma glucose were comparable in the two groups. Patients with ASO were significantly more insulin resistant than patients without ASO (KITT 2.16 +/- 0.16 vs. 3.00 +/- 0.13%/min, P < 0.0001, respectively), had a longer duration of diabetes (10.3 +/- 1.2 vs. 7.5 +/- 0.8 years, P < 0.05), included a greater number of smokers (68.6 vs. 40.0%, P < 0.01), had a higher prevalence of CAD (60.0 vs. 16.9%, P < 0.01), and had a greater percentage of insulin therapy (48.6 vs. 29.2%, P < 0.05). However, urinary and serum C-peptide levels, serum lipids, and Lp(a) levels were comparable in the two groups. Multiple logistic regression analysis indicated that a history of smoking (odds ratio 3.70, P = 0.011), insulin resistance (odds ratio 3.68, P < 0.001), and an elevated Lp(a) level (odds ratio 1.03, P = 0.020) were independently related to ASO. When patients with CAD were removed from the logistic regression analysis, insulin resistance was most strongly related to ASO (odds ratio 20.9, P < 0.001). CONCLUSIONS: Patients with ASO were characterized by a higher prevalence of CAD, a greater percentage of smokers, a greater percentage of insulin therapy, and a higher insulin resistance than were patients without ASO. Insulin resistance, especially, may be the most powerfully related to ASO. Lp(a) may play a minor role in the development of ASO.

Aged↗

[Treatment of hydrocephalus without shunt placement: third ventriculostomy].

Hydrocephalus is usually treated by placing an extracranial CSF shunt. Endoscopic third ventriculostomy, however, has been revived recently as a less invasive method for treatment. We intended to avoid shunting or to eliminate the previously placed shunt with this procedure. The authors review their experiences on third ventriculostomy employing a flexible neuroendoscope under video monitoring in 14 cases of pediatric hydrocephalus. The result was that we succeeded in 11 cases (79%) by third ventriculostomy alone; we avoided shunting in 8 cases and eliminated a previously placed shunt in 3 cases. Clinical summary is shown on Table 1, and illustrative cases are presented with the figures and legend. The patients' group consisted of 8 males and 6 females. Their age ranged from 1 month to 17 years (average age, 6 yr) old. Background diseases of hydrocephalus were brain tumor in 6 cases, Chiari type I malformation in 3, intraventricular hemorrhage in 3, neonatal meningitis in 1 and arachnoid cyst in 1 case. In the remaining 3 cases, however, we failed to avoid the necessity of placing shunt because of indirect reasons (recurrence of tumor, infection after another operation, subdural fluid collection). There was no major complication in relation to third ventriculostomy, except for a moderate elevation of temperature of several days' duration following the procedure. Indication and outcome of this operation is also discussed. Endoscopic third ventriculostomy is an efficacious procedure for the treatment of hydrocephalus in selected patients.

Adolescent↗