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Biomedical subjects

K Takei

Publications and source records attributed to K Takei.

At least 73 records · Page 4Linked to original sources

Diurnal variation of peak expiratory flow in children with cough variant asthma.

Cough variant asthma (CVA) is thought to be a variant form of asthma in which cough is the sole clinical manifestation of airways hyperresponsiveness, a characteristic feature of asthma. Another characteristic feature of asthma includes an increased diurnal variation of peak expiratory flow (PEF) compared to normal subjects. To examine whether diurnal variation of PEF might also increase in children with CVA, we have examined the degree of diurnal variation of PEF in these children (n = 7) by measuring peak flow serially for a week, and compared it with those in mild to moderate asthma (n = 17) and in control children without cough (n = 8). In control children without cough, the average value of the mean diurnal variation of PEF was 10.4 +/- 0.8%. In both groups of children with asthma and with CVA, there was a significant increase in the value (20.5 +/- 1.3% and 23.6 +/- 3.6%, respectively) compared to that in control children (p < 0.01 in both groups), although there was no significant difference between these 2 groups. These results show that mild, but significant airway obstruction is occurring in children with CVA, although clinical wheezing is not recognized. Serial measurements of diurnal variation of PEF may be helpful for the diagnosis of CVA in children.

Asthma↗

Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15.

Synaptojanin 1 is an inositol 5-phosphatase with a putative role in clathrin-mediated endocytosis. Goal of this study was to provide new evidence for this hypothesis. We show that synaptojanin 1 is concentrated at clathrin-coated endocytic intermediates in nerve terminals. Furthermore, we report that synaptojanin-170, an alternatively spliced isoform of synaptojanin 1, binds Eps15, a clathrin coat-associated protein. Binding is mediated by the COOH-terminal region of synaptojanin-170 which we show here to be poorly conserved from rat to humans, but to contain in both species three asparagine-proline-phenylalanine (NPF) repeats. This motif has been found to be the core of the binding site for the EH domains of Eps15. Together with previous data, our results suggest that synaptojanin 1 can be recruited to clathrin-coated pits via a multiplicity of interactions.

Adaptor Proteins, Signal Transducing↗

Amphiphysin I is associated with coated endocytic intermediates and undergoes stimulation-dependent dephosphorylation in nerve terminals.

Amphiphysin I is an abundant presynaptic protein that interacts via its COOH-terminal src homology 3 (SH3) domain with the GTPase dynamin I and the inositol-5-phosphatase synaptojanin. Both dynamin I and synaptojanin I have a putative role in synaptic vesicle recycling and undergo rapid dephosphorylation in rat brain synaptosomes stimulated to secrete by a depolarizing stimulus. We show here that amphiphysin I also undergoes constitutive phosphorylation and stimulationdependent dephosphorylation. Dephosphorylation of amphiphysin I requires extracellular Ca2+ and is unaffected by pretreatment of synaptosomes with tetanus toxin. Thus, Ca2+ influx, but not synaptic vesicle exocytosis, is required for dephosphorylation. Dephosphorylation of amphiphysin I, like dephosphorylation of dynamin I and synaptojanin I, is inhibited by cyclosporin A and FK-506 (0.5 microM), two drugs that specifically block the Ca2+/calmodulin-dependent phosphatase 2B calcineurin, but not by okadaic acid (1 microM), which blocks protein phosphatases 1 and 2B. We also show by immunogold electron microscopy immunocytochemistry that amphiphysin I is localized in the nerve terminal cytomatrix and is partially associated with endocytic intermediates. These include the clathrin-coated buds and dynamin-coated tubules, which accumulate in nerve terminal membranes incubated in the presence of guanosine 5'-3-O-(thio)triphosphate. These data support the hypothesis that amphiphysin I, dynamin I, and synaptojanin I are physiological partners in some step(s) of synaptic vesicle endocytosis. We hypothesize that the parallel Ca2+-dependent calcineurin-dependent dephosphorylation of amphiphysin I and of its two major binding proteins is part of a process that primes the nerve terminal for endocytosis in response to a burst of exocytosis.

Animals↗

Synaptic vesicle endocytosis impaired by disruption of dynamin-SH3 domain interactions.

The proline-rich COOH-terminal region of dynamin binds various Src homology 3 (SH3) domain-containing proteins, but the physiological role of these interactions is unknown. In living nerve terminals, the function of the interaction with SH3 domains was examined. Amphiphysin contains an SH3 domain and is a major dynamin binding partner at the synapse. Microinjection of amphiphysin's SH3 domain or of a dynamin peptide containing the SH3 binding site inhibited synaptic vesicle endocytosis at the stage of invaginated clathrin-coated pits, which resulted in an activity-dependent distortion of the synaptic architecture and a depression of transmitter release. These findings demonstrate that SH3-mediated interactions are required for dynamin function and support an essential role of clathrin-mediated endocytosis in synaptic vesicle recycling.

Amino Acid Sequence↗

Treatment for non-Hodgkin's lymphoma (stage I, II) of the elderly: usefulness of local and regional irradiation and reduced dose chemotherapy.

PURPOSE: To examine the usefulness and safety of a new treatment regimen consisting of irradiation to the involved area and adjacent lymph node area, and reduced dose chemotherapy for elderly patients with non-Hodgkin's lymphoma. METHODS AND MATERIALS: The core of this study was 38 elderly patients older than 65 years old with intermediate or high grade non-Hodgkin's lymphoma, and concomitantly suffering from some other geriatric disease. They received involved area irradiation (40 Gy), adjacent lymph node irradiation (30 Gy), and reduced dose chemotherapy (two cycles of 50-70% ACOP: Doxorubicin, Cyclosphosphamide, Vincristine, Prednisone or 70% MACOP-B: Doxorubicin, Cyclophosphamide, Vincristine, Methotrexate, Bleomycin, Prednisone for 4 weeks). RESULTS: The completion rate of the treatment regimen was 100%. The 5-year local control rate was 98%. The 5-year disease-free survival rate and the 5-year cause-specific survival rate for all patients were 70 and 82%, respectively. No treatment deaths were observed, and the rate of serious complications arising from the treatment was 3%. CONCLUSIONS: The newly conducted treatment regimen proved to be safe and useful for elderly patients with non-Hodgkin's lymphoma concomitantly suffering from some other geriatric disease.

Aged↗

Cholesterol-lowering effects of soybean, potato and rice proteins depend on their low methionine contents in rats fed a cholesterol-free purified diet.

Rats were fed cholesterol-free purified diets containing casein, rice (RP), potato (PP) or soybean (SP) proteins having different amounts of methionine (25.9, 21.3, 16.2 and 10.9 g methionine/kg, respectively). Each protein was fed at 250 g/kg diet for 14 d. Growth rates of rats were the same in all groups. Serum total cholesterol concentrations were lower in rats fed SP, PP and RP than in those fed casein. Fecal bile acid plus neutral steroid excretion was significantly higher in rats fed the RP, PP and SP diets compared with those fed casein. There was a significant negative correlation between serum cholesterol concentration and fecal total steroid excretion (r = -0.490, P = 0.01). However, a stronger positive correlation was observed between serum cholesterol concentration and dietary methionine concentration (r = 0.674, P = 0.0003) or methionine:glycine ratios (r = 0.656, P = 0.0005). In a separate experiment in rats fed diets containing amino acid mixtures simulating the RP, PP and SP diets, serum total cholesterol concentrations were lower than in rats fed simulated casein. Fecal total steroid excretion was the same in all groups. A strong correlation was found between serum cholesterol concentration and dietary methionine concentration (r = 0.743, P = 0.0002) or the methionine:glycine ratio (r = 0.685, P = 0.0009) in rats fed the amino acid mixtures. Finally, we examined the hypocholesterolemic effects of 250 g SP or casein/kg diet with or without supplementation with 0.3 g/100 g sodium taurocholate (TC). Supplementation with TC did not alter the hypocholesterolemic effect of SP. These results support the view that RP, PP and SP lower serum cholesterol concentration in a similar manner.

Amino Acids↗

Histopathologic study of islets of Langerhans in patients after gastrectomy.

In autopsy specimens removed after gastrectomy from patients who had survived for 2.5 to 40 years after surgery, we found hyalinization of the islets of Langerhans in 9 of 15 cases (60%) with Billroth's I anastomosis (B-I) and in 8 of 16 cases (50%) with Billroth's II anastomosis (B-II). The hyalinization in the postgastrectomy patients was significantly increased compared with that in controls (p < 0.01). The percentage of hyalinized islets of Langerhans in the 17 cases showing hyalinization ranged from 0.2% to 14.3%. The percentage increased relative to the period after gastrectomy in the B-I patients but not in those with B-II. The blood glucose level was mildly elevated in three B-I patients, whereas it was increased in only one patient with B-II. Hyalinization of the islets of Langerhans may be due to vagotomy or to excessive stimulus and hyperactivation of the islets. In any event, the islets of Langerhans in patients after gastrectomy were frequently replaced by hyalinization, which might cause impaired glucose tolerance.

Aged↗

Clinical stage IE primary lymphoma of the nasal cavity: radiation therapy and chemotherapy.

PURPOSE: To determine the appropriate radiation therapy and chemotherapy for primary lymphoma of the nasal cavity to improve the local control and survival rates. MATERIALS AND METHODS: Of the 25 adult patients with stage IE nasal lymphoma, nine underwent local radiation therapy alone and 16 underwent radiation therapy and chemotherapy (intravenous infusion). Radiation doses to the involved area were 22-54 Gy (median dose, 49 Gy). RESULTS: The 5- and 10-year cause-specific survival rates were 91% and 73%, respectively. The 5- and 10-year disease-free survival rates were 83% and 59%, respectively. Eight patients developed recurrent disease: six at the local site, one in the cervical nodes, and one in the small intestine. Five of the six patients with local recurrence received less than 50 Gy. Four of the six patients developed recurrent disease in the treated area; the other two patients developed marginal recurrences. Prognostic factors such as age, sex, maximum tumor size, and lactate dehydrogenase level were of limited value. CONCLUSION: The most common recurrence site was the local site. To improve the local control rate, the involved area should be treated with high-dose radiation therapy. The clinical results did not demonstrate the usefulness of combination chemotherapy for stage IE nasal lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

Clastogenic effects of different Ureaplasma urealyticum serovars on human chromosomes.

The possibility that Ureaplasma urealyticum might play an important role in human infertility was first raised more than 20 years ago, but this association remains speculative. Considering the hypothesis that the pathogenicity of Ureaplasma urealyticum may depend on its serotypes, the clastogenic effects of different strains of Ureaplasma urealyticum, at concentrations of 10(3) CCU (color changing units)/ml, 10(4) CCU/ml and 10(5) CCU/ml, were evaluated in vitro in short-term cultures of human lymphocytes. Total or partial mitotic inhibition was produced by Ureaplasma urealyticum serotypes 2, 3 and 10 independent of the concentration (10(3) CCU/ml, 10(4) CCU/ml or 10(5) CCU/ml) of the microorganisms employed. In contrast, the clastogenic effects observed with serotypes 1, 7 and 12 varied according to the concentration employed in the test. Mitotic alterations were observed in Ureaplasma urealyticum serotypes 5, 6, 7, 8, 9, 11 and 12. Chromatid gaps (53.0%) and chromatid breaks (13.9%) were the most frequent types of alterations observed. The results of this in vitro assay demonstrated that the clastogenic effects varied with the Ureaplasma urealyticum serotypes evaluated.

Chromatids↗

Roxithromycin attenuates acid-induced cough and water-induced bronchoconstriction in children with asthma.

In the present study, we evaluated the effect of roxithromycin, a semisynthetic macrolide antibiotic, on the cough response to inhaled acetic acid (AA) and on the bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with asthma. Ten hospitalized asthmatic children (8 boys and 2 girls, mean +/- SEM age 12.6 +/- 0.4 years) were enrolled in this study. They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects. All the patients underwent AA inhalation challenge before and 2, 4, and 8 weeks after the administration of roxithromycin. Seven of the 10 patients, who had a fall in FEV1 of at least 20% after UNDW inhalation, underwent UNDW inhalation challege at the same time. The cough threshold values, the lowest concentrations of AA eliciting coughs, and UNDW provocative dose producing a 20% fall in FEV1 (UNDW PD20) values 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p < 0.05). No significant change was observed in baseline FEV1 or serum theophylline concentrations throughout the study. These results support the notion that administration of roxithromycin may have favorable results in the treatment of childhood asthma.

Acetic Acid↗

[Study of mechanisms of pancreatic fibrosis and structural changes in liver cirrhotic patients].

Pancreatic intralobular fibrosis in liver cirrhotic patients was studied immunohistochemically using alpha-smooth muscle actin (alpha SMA). Similarly micronodular arrangements of acinar cells and hypertrophy of Langerhans' islands in liver cirrhotic patients were studied using proliferating cell nuclear antigen (PCNA). In addition, pancreata in liver cirrhotic patients were studied from apoptotic side. We investigated the histopathologic autopsy findings of 103 patients: 15 patients with alcoholic liver cirrhosis, 49 patients with non-alcoholic liver cirrhosis and, as controls, 39 patients without a history of alcohol abuse or liver dysfunction. alpha SMA positive area ratio and PCNA positive cell ratio in liver cirrhotic patients were higher than in the controls. In contrast, apoptotic cell ratio in liver cirrhotic patients was lower than in the controls. alpha SMA positive area ratio in patients with pancreatic intralobular fibrosis was higher than in patients without pancreatic intralobular fibrosis. PCNA positive cell ratio in patients with micronodular arrangements of the acinar cells was higher than in patients without micronodular arrangements of the acinar cells. We conclude that pancreata in liver cirrhotic patients are predominant of proliferating changes.

Adult↗

[Clinical investigation for recurrence and progression in Ta grades 1 and 2 bladder cancer].

We treated 107 new patients with stage Ta, grades 1 and 2 transitional cell bladder carcinoma by transurethral resection during the past 23 years. The clinicopathological factors evaluated were grade, size, number and form of tumor. Fifty-five patients (51%) had recurrent tumors after initial resection and progression (muscle invasion or metastasis) occurred in four patients (3.7%). The 5-year and 10-year recurrence free rates were 47.3 and 29.8%, respectively. Seven patients (6.5%) had grade 3 tumor (grade-up) at recurrence. An increase in T category to T1 (stage-up) occurred in 13 patients (12%), only one of whom later developed an invasive tumor (pT4). The size of tumor significantly affected the rate of recurrence (p < 0.01). Sessile tumor were at a significantly greater risk for progression (p < 0.05). Stage-up did not have a significant effect on progression, but grade-up was significantly risky for progression (p < 0.01). Initial grade 2 tumors were highly related to grade-up (p < 0.05).

Adult↗

[A case of retroperitoneal fibrosarcoma in the perirenal space].

A case of retroperitoneal fibrosarcoma is reported. A 52-year-old man with the complaint of left abdominal mass was referred to our hospital. Computed tomography showed a left retroperitoneal tumor surrounding the left kidney in the perirenal space. Angiography showed some feeding vessels from the branch of the posterior segmental artery of the left kidney. The tumor was completely resected with the left kidney, but para-aortic lymph node metestases were found. Histopathological diagnosis was a retroperitoneal fibrosarcoma with lymph node metastases. The patient died of the disease 3 months after the operation.

Fibrosarcoma↗

[Renal cell carcinoma diagnosed by ring-like growth of preexistent calcification: a case report].

A 53-year-old woman was referred for further examination of a left renal cyst detected ultrasonographically during a health checkup. Computerized tomography (CT) scan and magnetic resonance imaging revealed an irregular cystic mass at the center of the left kidney as well as a calcified lesion at the left upper pole. Angiography and cyst puncture confirmed the cystic mass to be unilocular and benign. However, followup CT scan after 22 months demonstrated enlargement of the calcification into a ring-like configuration 3 cm in diameter. Since the lesion showed neovascularity on angiography, radical nephrectomy was performed. Histopathological diagnosis was renal cell carcinoma, alveolar type, common type at the center, but solid type, spindle cell type at the periphery.

Calcinosis↗

[A case of spontaneous rupture of renal cell carcinoma].

Spontaneous rupture of the kidney is uncommon. We report a case of spontaneous rupture of the kidney due to a renal cell carcinoma. A 53-year-old man presented with right renal tumor. Computed tomography demonstrated a 70 mm right renal tumor which involved the entire upper pole of the kidney and extended into the renal vein. A few days later, the patient had sudden severe right flank pain. Computed tomography of the abdomen revealed a large perirenal hematoma of the right kidney. Angiography demonstrated no vascular abnormality. Nephrectomy was performed. The histological examination showed rupture of a renal cell carcinoma in the right kidney.

Carcinoma, Renal Cell↗

Alzheimer amyloid protein precursor is localized in nerve terminal preparations to Rab5-containing vesicular organelles distinct from those implicated in the synaptic vesicle pathway.

In order to localize amyloid protein precursor (APP) in nerve terminals, we have immunoisolated vesicular organelles from nerve terminal preparations using antibodies to Rab5 and synaptophysin. These immunoisolates were then analyzed by electron microscopy and by immunoblotting. The synaptophysin immunoisolates represented a nearly homogeneous population of small synaptic vesicles, with less than 10% contamination by other organelles, and very little APP. In contrast, Rab5 immunoisolates contained, in addition to small synaptic vesicles, substantial numbers of large uni- and bilamellar vesicles and high levels of APP. Thus, it appears that nerve terminal APP is contained predominantly in large vesicular organelles, distinct from synaptic vesicles and from the synaptic vesicle recycling pathway.

Alzheimer Disease↗