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Biomedical subjects

S Minami

Publications and source records attributed to S Minami.

At least 91 records · Page 5Linked to original sources

Relationship between brain atrophy estimated by a longitudinal computed tomography study and blood pressure control in patients with essential hypertension.

To evaluate the relationship between blood pressure control and the progression of brain atrophy in the elderly, patients with essential hypertension and brain atrophy were longitudinally evaluated using computerized tomography (CT). The study evaluated 48 patients with essential hypertension aged 46-78 years, and 30 sex- and age-matched normotensive control subjects. The extent of brain atrophy as determined by caudate head index (CHI), the inverse cella media index (iCMI), and Evans' ratio (ER) was estimated twice at an interval of 5-9 years (mean, 6.9 years). The mean annual increases in CHI (deltaCHI), iCMI (delta iCMI), and ER (deltaER) were evaluated. Mean blood volume in the common carotid artery (BF) and the decrease in BF per year (deltaBF) were also determined. The deltaCHI, delta iCMI, and deltaER increased with age in the hypertensive subjects as well as the control group across all age groups evaluated. The deltaCHI, delta iCMI, and deltaER were significantly greater in the patients with essential hypertension in their 50 s as compared with the controls. In patients with essential hypertension aged 65 years or older, the deltaCHI, delta iCMI, and deltaER were significantly lower in the group in whom the blood pressure was controlled within the range of borderline hypertension than the groups in which it was controlled in the range of normal or mild hypertension. In the younger patients under the age of 65 with essential hypertension, blood pressure control did not affect the deltaCHI, delta iCMI, and deltaER. The deltaCHI, delta iCMI, and deltaER were significantly correlated with deltaBF in both groups. These findings indicate that control of systolic blood pressure within the range of borderline hypertension may delay the progression of brain atrophy in elderly patients with essential hypertension.

Aged↗

Computerized digital image processing on radiographs of canine filariosis.

For objective evaluation in the lung arterial lesions, density histogram revealed by survey thoracic radiographies of fifteen canine filariosis and five normal canine were digitally analyzed, and preparation of pulmonary artery angiogram with inflated-fixed lung, the changes in the histogram and the pulmonary arterial lesion by a soft x-ray examination were compared. In the lung areas affected by filariosis, the density histogram increased the white level and decreased the black level in each part compared to a normal lung. In comparison with the normal parameters, those of the filariosis it were significantly increased in minimum grey level values (Min), maximum grey level values (Max), and the maximum frequency grey level values (Mode) and, it was significantly decreased in maximum frequency values (MaF). The pulmonary arterial lesion of the filariosis showed obvious morphological changes such as in distinction, pruning, angiectasis, and meandering. In the grade of pulmonary arterial lesion, the parameter Min, Max, Mode and MaF were changed significantly. From these results, it was clear that the methods for the lung arterial lesions analysis of x-ray images were confirmed to be highly beneficial in the lung arterial lesions for objective diagnosis.

Animals↗

Asymptomatic cerebrovascular lesions detected by magnetic resonance imaging in patients with systemic lupus erythematosus lacking a history of neuropsychiatric events.

OBJECTIVE: To clarify the extent of asymptomatic cerebrovascular involvement in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Cerebral magnetic resonance imaging (MRI) findings and ultrasonography findings of 100 patients with SLE lacking present or past clinical neurologic deficits were compared with 66 age-matched volunteers to determine the combined intima-media thickness (IMT) of the common carotid artery, and tests for anti-cardiolipin antibodies (aCL). RESULTS: Thirty-eight patients, but only 2 controls, showed imaging abnormalities. Among 23 SLE patients with cerebrovascular lesions by MRI who underwent single-photon emission computed tomography (SPECT), 14 showed hypoperfusion of the lesion. The IMT value and prevalence of aCL did not differ between the 55 SLE patients tested and controls. SLE disease activity index (SLEDAI) as assessed by a quantitative clinical index was significantly greater in patients with brain lesions than in those without. CONCLUSION: The prevalence of asymptomatic brain lesions in SLE patients is highs and shows a relationship to disease activity.

Adolescent↗

[Analysis of elderly patients, aged 60 years old or over, with acute lymphoblastic leukemia].

In order to obtain the realistic background information on clinical features, and the present status of treatment and outcome in elderly patients with acute lymphoblastic leukemia (ALL), we carried out random survey of patients with ALL aged 60 or over who had been admitted to 13 general hospitals in the Nagoya region from January 1990 through December 1995. Among the 20 cases collected, ages ranged from 60 to 88 (median age 68), and the male to female ratio was 11:9. Nineteen cases were L2 subtype in FAB classification. Among 17 patients, 13 had B cell series surface phenotypes (76%), 2 had T cell series (12%), one had stem cell type (6%) and one had an undetermined phenotype (6%). Ph chromosomes were detected in 4 cases among 15 analyzed (27%), whereas 5 were found to have no chromosomal abnormality. Half of the patients had some concurrent disease at diagnosis, including two with treatment-limiting complications. Common induction regimens were the combination of adriamycin (ADM) + vincristine (VCR) + cyclophosphamide (CPM) + mitoxdn trone + L-asparaginase [4 patients]. ADM + VCR + PSL [4 patients]. VCR + PSL [4 patients] and others [8 patients]. The overall remission rate was 55.0% (11/20) without any significant difference according to age. The median survival time (MST) for all cases was 205 days. (1-year survival rate:17.9%, 2-year survival rate:10.8%). There was no significant difference in survival times among patients with the Ph chromosome, those with other chromosomal abnormalities and those without them. All the patients aged 75 or over were treated with attenuated induction therapy, and they had a shorter survival than those aged less than 75, but with no statistical significance [MST:121 days versus 276 days, p = 0.307 (generalized Wilcoxon test)].

Aged↗

No beneficial effect from addition of etoposide to daunorubicin, cytarabine, and 6-mercaptopurine in individualized induction therapy of adult acute myeloid leukemia: the JALSG-AML92 study. Japan Adult Leukemia Study Group.

To assess the efficacy of etoposide added to the standard remission induction therapy for acute myeloid leukemia (AML), newly diagnosed adult AML patients were randomized to receive either daunorubicin (40 mg/m2/day x 4 or more), behenoyl cytarabine (200 mg/m2/day x 10 or more), and 6-mercaptopurine (70 mg/m2/day x 10 or more) (BHAC-DM), or the same three drugs plus etoposide (100 mg/m2/day x 5) (BHAC-EDM) for response-oriented individualized induction therapy. The patients achieving complete remission (CR) received the same 3 courses of consolidation therapy followed by 6 courses of maintenance/intensification therapy. M3 patients were excluded because all-trans retinoic acid was used. Of 667 patients registered, 655 were evaluable. The median age was 49 (range 15 to 85). CR rates were 77% in the BHAC-DM group and 75% in the BHAC-EDM group. In 173 M4 patients, CR rates were 86% and 69% (P = 0.009), and in 32 M5 patients, 80% and 77% (P = 0.810) in the BHAC-DM and the BHAC-EDM groups, respectively. The predicted 6-year overall survival rates were 30% and 38% (P = 0.925) for the BHAC-DM and BHAC-EDM groups, and the disease-free survival rates of CR patients were 25% and 35% (P = 0.352), respectively. Nonhematological toxicities after the first course of induction therapy were almost equal among the two groups, with the exception of a greater loss of hair (P = 0.024) and more frequent diarrhea (P = 0.013) in the BHAC-EDM group. We concluded that in the present study, the addition of etoposide to the standard individualized induction therapy showed no advantage in adult AML, even among M4 and M5 patients.

Acute Disease↗

Infectious complications during remission induction therapy in 577 patients with acute myeloid leukemia in the Japan Adult Leukemia Study Group studies between 1987 and 1991.

The Japan Adult Leukemia Study Group analyzed infectious episodes in 577 patients with acute myeloid leukemia during remission induction therapy between 1987 and 1991. 542 patients (93.9%) experienced at least one infectious episode, 121 (21.0%) had microbiologically documented infection; there was clinically documented infection in 184 (31.9%) and unexplained fever in 237 (41.1%). Among 121 microbiologically documented infections, bacteremia/fungemia was observed in 68, pneumonia in 33, and other types of infections in 20. Among the bacteremia/fungemia, gram-negative bacteria accounted for 41.2% (Pseudomonas aeruginosa was the most common), gram-positive bacteria for 39.7%, fungi for 16.2% (Candida spp. being most frequent), and polymicrobial for 2.9%. The most frequent isolates among pneumonia were Pseudomonas aeruginosa and Aspergillus. A total of 70 patients (12.1%) died during remission induction. Mortality of 68 patients with bacteremia/fungemia was 26.5%; in these patients, mortality with concomitant pneumonia increased to 41.4%; without pneumonia, mortality was 15.4% (P < 0.05). Mortality according to the isolated microbes was 17.2% for gram-negative bacteria, 25% for gram-positive bacteria, and 54.5% for fungi. Mortality of 113 patients with pneumonia (33 microbiologically documented and 80 clinically documented), 20 with other microbiologically documented infections, 104 with other clinically documented infections, and 237 with unexplained fever was 25.7%, 5.0%, 5.8%, and 5.1%, respectively.

Acute Disease↗

Acute myeloid leukemia in the elderly:--159 Nagoya case studies--Nagoya Cooperative Study Group for Elderly Leukemia.

To obtain background information on elderly acute myeloid leukemia (AML), unselected data covering 159 patients aged 60 years or over with AML from 14 hospitals in Nagoya, Japan was analyzed retrospectively. Among these patients, 119 had de novo acute AML, 32 had AML which evolved from myelodysplastic syndrome (MDS-AML), and 8 had other types of leukemia. The survey showed that MDS-AML tended to be more prevalent in patients aged 70 years and older and that MDS-AML showed a significantly more severe degree of leukopenia and anemia than de novo AML. MDS-AML also showed a significantly lower complete remission (CR) rate than that of de novo AML [6.9% (2/29) vs 58.3% (67/11), P < 0.01] and significantly shorter survival times than those of de novo AML [median: 3.6 months vs 9.6 months, P < 0.01 (generalized Wilcoxon test; GW]. In de novo AML, the proportion of patients treated with conventional therapy (CT group) decreased significantly, and that of those with attenuated therapy (AT group) increased significantly as age elevated (P < 0.01). The CT group showed a significantly higher CR rate (65.4% vs 41.2%, P < 0.05) and a significantly longer survival period than those of the AT group [median: 11.6 months vs 4.8 months, P < 0.05 (GW)]. Overall survival rates of the older age groups became significantly shorter with aging [P < 0.01 (GW)].

Acute Disease↗

Chitin and chitosan stimulate canine polymorphonuclear cells to release leukotriene B4 and prostaglandin E2.

The effects of chitin and chitosan on the release of arachidonic acid products were investigated in this study. Supernatants of canine polymorphonuclear cell (PMN) suspensions incubated with chitin and chitosan contained a leukotriene B4 (LTB4) concentration high enough to induce canine PMN migration in vitro. The supernatants also contained the same concentration of prostaglandin E2 (PGE2) as that normally found in the peripheral blood of dogs. Intraperitoneal administration of chitosan to dogs induced peritoneal exudative fluid (PEF), but chitin did not. The PEF contained numerous PMNs and macrophages. The supernatant of PEF contained both heat-stable and heat-labile chemotactic factors for canine PMNs. It also contained enough LTB4 to attract the canine PMNs in vitro.

Animals↗

p53-Independent activation of the gadd45 promoter by Delta12-prostaglandin J2.

A p53-inducible gene, the growth arrest and DNA damage-inducible gene 45 (gadd45), is associated with cell growth inhibition, DNA damage response and DNA repair. Here we report that Delta12-prostaglandin J2 (Delta12-PGJ2), an in vivo metabolite of arachidonic acid, which inhibits cell proliferation, induces gadd45 mRNA in HeLa cells. Because the p53 protein in HeLa cells is inactivated by papilloma virus E6, this type of gadd45 induction appears to be p53-independent. The induction was dose-dependent, and the maximum induction was observed at a concentration of 7.5 microgram/ml. In a time course study, gadd45 mRNA was induced 3 h after the addition of 7.5 microgram/ml Delta12-PGJ2. To investigate the transcriptional mechanism of gadd45 mRNA induction, we cloned a human genomic DNA fragment containing the gadd45 promoter region, and investigated the effect of Delta12-PGJ2 on the gadd45 promoter activity. In HeLa cells, 7.5 microgram/ml Delta12-PGJ2 markedly stimulated the gadd45 gene promoter about 20-fold or more. On the other hand, Delta12-PGJ2 did not stimulate the promoter activity of a reporter plasmid containing only p53 binding sites in HeLa cells, indicating that the gadd45 promoter activation by Delta12-PGJ2 was not mediated by p53. These results suggest that one of the mechanisms of cell growth arrest by Delta12-PGJ2 is mediated through a p53-independent induction of gadd45.

Cell Division↗

Complex formation of SMAP/KAP3, a KIF3A/B ATPase motor-associated protein, with a human chromosome-associated polypeptide.

We have recently isolated SMAP (Smg GDS-associated protein; Smg GDS: small G protein GDP dissociation stimulator) as a novel Smg GDS-associated protein, which has Armadillo repeats and is phosphorylated by Src tyrosine kinase. SMAP is a human counterpart of mouse KAP3 (kinesin superfamily-associated protein) that is associated with mouse KIF3A/B (a kinesin superfamily protein), which functions as a microtubule-based ATPase motor for organelle transport. We isolated here a SMAP-interacting protein from a human brain cDNA library, identified it to be a human homolog of Xenopus XCAP-E (Xenopus chromosome-associated polypeptide), a subunit of condensins that regulate the assembly and structural maintenance of mitotic chromosomes, and named it HCAP (Human chromosome-associated polypeptide). Tissue and subcellular distribution analyses indicated that HCAP was ubiquitously expressed and highly concentrated in the nuclear fraction, where SMAP and KIF3B were also present. SMAP was extracted as a ternary complex with HCAP and KIF3B from the nuclear fraction in the presence of Mg-ATP. The results suggest that SMAP/KAP3 serves as a linker between HCAP and KIF3A/B in the nucleus, and that SMAP/KAP3 plays a role in the interaction of chromosomes with an ATPase motor protein.

Adaptor Proteins, Signal Transducing↗

Effect of HMG-CoA reductase inhibitors on plasma polyunsaturated fatty acid concentrations in patients with hyperlipidemia.

We investigated the effect of 12 months' HMG-CoA reductase inhibitor treatment on plasma polyunsaturated fatty acid concentrations in 19 patients with hyperlipidemia. Arachidonic acid concentrations were significantly increased following treatment (from 110.1 +/- 20.4 mg/l to 129.2 +/- 31.6 mg/l, P < 0.05). The ratio of eicosapentaenoic acid to arachidonic acid was significantly decreased at the end of 12 months' treatment (from 0.702 +/- 0.370 to 0.541 +/- 0.204, P < 0.05). These results suggest that HMG-CoA reductase inhibitors may increase the synthesis of metabolites from arachidonic acid in patients with hyperlipidemia, and that the addition of fish oil is more effective for the prevention of coronary heart disease than HMG-CoA reductase inhibitors alone.

Aged↗

New remote-controlled growing-rod spinal instrumentation possibly applicable for scoliosis in young children.

Progressive scoliosis in young children has been treated with "spinal instrumentation without fusion" to avoid interference with spinal growth. Patients have to undergo a series of operations to have instruments exchanged for maintaining the correction. We have developed a newly designed remote-controlled growing-rod spinal instrumentation system proposed for the treatment of progressive scoliosis in young children. It can be used to stretch and correct the spinal deformities repeatedly and non-surgically, by means of a remote controller, after the first instrumentation operation. The purpose of this study is to describe the possible clinical application of this system for the treatment of progressive scoliosis in young children. To this end, we used the system in five beagle dogs with induced scoliotic deformities. The maximum distraction force of the instrument was 194 N. Correction of 1 cm was performed non-surgically in awake animals 3 weeks after the instrumentation operation, and then correction of 1 cm was carried out again 6, 9, and 12 weeks after the operation. The average initial Cobb's angle of the induced scoliotic deformities was 25 degrees; this was corrected to 20 degrees, 15 degrees, 8 degrees, and 3 degrees, after the distractions at 3, 6, 9, and 12 weeks, respectively, postoperatively. All corrections were performed non-surgically without apparent complications. By repetitive distractions with the use of our new system, we may be able to reduce the number of operations required in young scoliotic children.

Animals↗

Immunohistochemical localization of activin A in human endometrial tissues during the menstrual cycle and in early pregnancy.

OBJECTIVE: To investigate the possible localization of activin A in human endometrial tissue. METHODS: Human endometrial tissue was collected from 33 patients who were undergoing abdominal hysterectomy. Human decidual tissue was collected from 11 patients, who were having a therapeutic abortion. Tissue was fixed in Bouin's solution and made into paraffin sections. Tissue sections were stained with monoclonal antibodies against the inhibin/activin alpha- and betaA-subunits and activin A using an avidin-biotin-peroxidase complex technique. RESULTS: No immunostaining with antibody against the alpha-subunit was observed in the human endometrium during the menstrual cycle or in the decidua during early pregnancy. By contrast, immunostaining for the betaA-subunit and activin A was observed in the cytoplasm of endometrial glands at all phases of the menstrual cycle and in the decidua during early pregnancy. The intensity of immunostaining for the betaA-subunit was strong during the menstrual phase, became weaker during the early proliferative phase, and was intense again at the late proliferative phase. The immunostaining for the betaA-subunit was weak during the early secretory phase and became very intense toward the midsecretory and late secretory phases. The intensity of immunostaining for activin A changed during the menstrual cycle and showed a tendency similar to that for betaA-subunit. The stromal cells were weakly immunoreactive with antibodies against the betaA-subunit and activin A from the menstrual to the midsecretory phase and became strong in the late secretory phase. Intense staining for the betaA-subunit and activin A was observed in the cytoplasm of decidual cells during early pregnancy. CONCLUSION: Activin A, but not inhibins, is localized in the endometrial tissue. The endometrium may be a major source of activin A during the normal menstrual cycle, and the decidua may be one of the sources of activin A during early pregnancy.

Activins↗

Response-oriented individualized induction therapy with six drugs followed by four courses of intensive consolidation, 1 year maintenance and intensification therapy: the ALL90 study of the Japan Adult Leukemia Study Group.

Adult patients with acute lymphoblastic leukemia (ALL) were treated according to the ALL90 study, the second prospective study for ALL of the Japan Adult Leukemia Study Group (JALSG). Its characteristics included response-oriented individualized induction therapy with six drugs (doxorubicin, mitoxantrone, vincristine, prednisolone, [corrected] cyclophosphamide and L-asparaginase), and a prospective comparison between allogeneic bone marrow transplantation (allo-BMT) and chemotherapy alone in patients below 45 years of age. The protocol consisted of one or two courses of induction, four courses of consolidation, and three courses of intensification including 12 month maintenance and six times of central nervous system (CNS) prophylaxis. Of 180 evaluable patients (median age, 43), 125 (69%) achieved complete remission (CR). Predicted overall survival (OAS), event-free survival and disease-free survival (DFS) were 15, 10 and 14%, respectively at the median follow-up period of 62 months. No specific toxicities were observed. Leukocytes < 30,000/microliter, normal karyotype, and blasts < 10% in bone marrow at day 15 of induction therapy were significantly favorable prognostic factors for the achievement of CR, DFS and OAS by univariate analysis. Multivariate analysis showed leukocytes < 30,000/microliter and blasts < 10% on day 15 was a significant factor for the achievement of CR, DFS and OAS. Ph-chromosome was found in 28% (36/130) of patients examined and was one of the worst prognostic factors. All Ph positive patients were predicted to die within 600 days. Allo-BMT was not significantly superior to chemotherapy with respect to DFS (P = 0.226). The overall results were inferior to those of the former ALL87 protocol. As reasons, the older median age of 43 years old (vs. 38 years old) and lower dose intensity, especially of l-asparaginase, etc. were suggested. However, patients with good prognostic factors (leukocyte < 30,000/microliter and age < 30 years old) showed better survival than others (P < 0.0001), and the result was similar to that of older children, the high risk group of childhood ALL, suggesting that ALL could be a disease of single entity, showing higher resistance to chemotherapy as patients become older.

Adult↗

Growth factors increase pericellular proteoglycans independently of their mitogenic effects on A10 rat vascular smooth muscle cells.

Proliferation of vascular smooth muscle cells with the accumulation of proteoglycans in the extracellular matrix is one of the significant changes found in atherosclerotic lesions. In order to clarify the relationship between pericellular proteoglycan and cell growth, we established a simple method for quantitatively estimating the amount of pericellular proteoglycans and investigated the effects of various growth factors on the synthesis of pericellular proteoglycans by cultured A10 rat smooth muscle cells. Analysis of trypsin accessible [35SO4]-labeled material in the pericellular area of the A10 cell culture by Q-sepharose anion-exchange chromatography showed two peaks. One peak, eluted at 0.55 M NaCl, disappeared after treatment with 2 mU/ml of heparitinase, indicating that heparan sulfates (HS) were present. The other peak, which eluted at 0.65 M NaCl, disappeared with 20 mU/ml of chondroitinase ABC, indicating the presence of chondroitin sulfates and dermatan sulfates (CS/DS). We estimated the effects of several growth factors on the synthesis of the pericellular proteoglycans by measuring heparitinase- and chondroitinase-ABC-sensitive radioactivities. Although PDGF-AB significantly stimulated cell proliferation and the synthesis of pericellular CS/DS, its dose-dependent effect on the cell growth did not coincide with that on the proteoglycan synthesis. IGF-I (1 nM) increased pericellular CS/DS but not the cell number, while basic FGF (1 nM) and EGF (1 nM) increased the cell number but not pericellular CS/DS. All the growth factors we examined had no effect on the synthesis of pericellular HS. These results indicate that growth factors increase pericellular proteoglycans independently of their mitogenic effects.

Animals↗