Search PubMed⌕ Search

Biomedical subjects

T Akiba

Publications and source records attributed to T Akiba.

At least 19 recordsLinked to original sources
PubMed2002

Clinical effect of intravenous calcitriol administration on secondary hyperparathyroidism. A double-blind study among 4 doses.

BACKGROUND/AIMS: Although the PTH-suppressive effect of intravenous calcitriol has already been demonstrated by various studies, the precise dose-response to calcitriol has not been fully determined for uremic secondary hyperparathyroidism (2HPT). In order to investigate in detail the dose-response of intravenous calcitriol and the adequate initial dose against 2HPT, a randomized prospective double-blind study was conducted. METHOD: One-hundred and sixty-two patients with 2HPT undergoing hemodialysis three times per week were randomly assigned to four calcitriol (Ro21-5535) treatment groups, 0 (placebo), 1, 1.5 or 2 microg. Calcitriol or placebo was given intravenously after each dialysis for 12 weeks under double-blind conditions. RESULTS: Calcitriol dose-dependently reduced both intact-PTH and high-sensitivity assay mid-terminal (HS)-PTH levels. The rate of per-week change in intact-PTH was 0.0% in the placebo group, -7.8% in the 1-microg group, -18.9% in the 1.5-microg group and -24.1% in the 2-microg group. Calcitriol dose-dependently increased the rate of increase in serum Ca adjusted by albumin level. The per-week increases in adjusted serum Ca were -0.01, 0.08, 0.23 and 0.35 mg/dl in the placebo, 1-, 1.5- and 2-microg groups, respectively. Although the degree of PTH suppression was correlated with the adjusted serum Ca increase, by-patients investigation revealed that the number of patients with suppression of PTH despite of no or slight elevation of adjusted serum Ca level was largest in the 1-microg group among the three calcitriol groups. CONCLUSION: Intravenous calcitriol was found to have a clear dose-dependent effect on PTH reduction in patients with 2HPT, and the appropriate initial dose of this agent was determined to be 1 microg per dialysis session.

Adult↗
PubMed2001

Mice lacking CCAAt/enhancer-binding protein-alpha show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs.

The lung-specific surfactant proteins (SP) are essential for normal respiratory function. Transcription factors may play an important role in the regulation of surfactant proteins. The CCAAT/enhancer-binding protein (C/EBP) family consists of transcription factors that can stimulate expression of genes in lipid-metabolizing epithelial cells. C/EBPalpha-deficient mice have been shown to exhibit abnormal pulmonary histopathology. Recently, we demonstrated that C/EBP family members are differentially expressed in alveolar type II cell proliferation and in pulmonary fibrosis. In the present study, to investigate whether the C/EBP family would be involved in the regulation of surfactant proteins, we examined the protein expression of SP-A, and SP-C, and mRNA expression of SP-A, SP-B, and SP-C in the lungs from newborn C/EBPalpha-deficient mice. Using immunohistochemistry, we demonstrated that positive cells for SP-C, specific to alveolar type II cells, in the lungs were more abundant in the newborn C/EBPalpha-deficient mice than in control mice, which suggests the hyperproliferation of alveolar type II cells in the lungs of the C/EBPalpha-deficient mice. In situ hybridization analysis revealed that expression of SP-A, SP-B, and SP-C mRNAs were increased in the lungs of newborn C/EBPalpha-deficient mice. Northern blot analysis revealed that surfactant protein mRNAs were also increased. Thus, these results suggest that C/EBPalpha may play a key role in the proliferation of alveolar type II cells and the regulation of genes of surfactant protein.

Animals↗
PubMed2001

The wound-healing effect of fibrin glue for tracheal anastomosis in experimental pulmonary surgery.

The leakage of tracheal anastomoses is one of the major complications that occurs after tracheal reconstruction. Improved reinforcing methods for anastomoses would thus be clinically useful. To find a better technique, we examined the postoperative would-healing effect of fibrin glue on tracheal anastomosis in the rat. Experimental rats were divided into two groups. In the control group (n = 21), the trachea was anastomosed by interrupted absorbable sutures. In the fibrin glue group (n = 21), the trachea was anastomosed in the same manner as the control group, with the addition of fibrin glue around the area of anastomosis. In the two groups, we studied the amount of hydroxyproline and histological findings on the seventh, 14th, and 21st postoperative day. The amount of hydroxyproline and collagen fibers in the fibrin glue group was more than in the control group on the seventh postoperative day. These results suggest that fibrin glue has a promotive effect in the healing of tracheal anastomosis.

Anastomosis, Surgical↗
PubMed2001

Effects of operating conditions on selectivity of a plasma fractionator in double filtration plasmapheresis.

In a typical double filtration plasmapheresis treatment, plasma fractionation between albumin and some immunoglobulins associated with toxins is limited because none of the currently available plasma fractionators has a strict cutoff property for these proteins. Selectivity of immunoglobulins over albumin depends not only on the cutoff properties of the membrane but on the operating conditions such as the flow rate of the supplied plasma (Q(P)) and retained plasma to be discarded (Q(D)) in the plasma fractionator. We carried out an in vitro study using human plasma harvested by single plasma exchange treatments to assess the selectivity of a plasma fractionator, Evaflux 2A-F (Kawasumi Laboratories, Inc., Tokyo, Japan), under various operating conditions. The results of rate-constant filtration experiments showed that the concentrations in the feed tank and the sieving coefficient (SC) values of every protein were decreased slightly within 2 h after the start of the experiment because of membrane trapping, adsorption, and/or plugging. The time-averaged SC value of albumin increased with flow rate ratio (Q(P)/Q(D)) due to increasing filtration fraction (FF), but relative removal efficiency (mD/mP*) for albumin decreased with Q(P)/ Q(D) due to decreasing Q(D). For immunoglobulins, on the other hand, the SC values were almost unchanged, and the mD/mP* values increased with Q(P)/Q(D) due to an increase in FF. Both increasing Q(P) and decreasing Q(D) are effective means of improving selectivity between these proteins in the plasma fractionator. Membrane fouling is, however, obvious beyond a Q(P)/Q(D) value that is thought to be a critical point. Operation should be conducted below the critical Q(P)/Q(D) value, which depends on the patient's plasma components and the cutoff property of the membrane.

Humans↗
PubMed2001

Efficient and ligand-dependent regulated erythropoietin production by naked dna injection and in vivo electroporation.

The development of an in vivo gene transfer approach to deliver physiologic levels of recombinant proteins to the systemic circulation would represent a significant advance in the treatment of protein deficiencies-disorders. However, the ability to regulate transgene expression will become paramount for safety and efficacy in gene transfer therapy. We have described the construction of an efficient and ligand-dependently regulated erythropoietin (EPO) production system using naked plasmid and in vivo electroporation. Two plasmids, one encoding the chimeric GeneSwitch protein and the other encoding an inducible transgene for human EPO, were developed. Modulation of the level of secretion of EPO into the serum was achieved by intraperitoneal administration of mifepristone (MFP). Rats were divided into 4 groups: one group received EPO plasmid with MFP for 30 days, a second group received with EPO plasmid MFP for 9 days, a third group received EPO plasmid without MFP, and a fourth group received control plasmid. A pair of electrodes was inserted into the muscle of the right thigh and 100 micrograms of each plasmid was injected. In vivo electrporation (8 times at 100 V for 50 milliseconds) was performed. The presence of vector-derived EPO mRNA was detected by reverse transcriptase-polymerase chain reaction only in the EPO and MFP(+) group. The hematocrit levels increased continuously from the preinjection level of 42.7% to 53.8% on day 28 in the EPO and MFP(+) group. The serum EPO levels increased only in the EPO and MFP(+) group. There was no significant change in hematocrit levels and EPO levels in the EPO and MFP(-) group. These results demonstrate that EPO gene transfer with the GeneSwitch system by in vivo electroporation is a useful procedure for efficient and drug-dependent regulated delivery of EPO.

Animals↗
PubMed2001

Clinical effects of maxacalcitol on secondary hyperparathyroidism of uremic patients.

Maxacalcitol (22-oxacalcitriol [OCT]) is a newly developed vitamin D analogue in Japan. OCT has shown less calcemic action and a strong suppressive effect on parathyroid hormone (PTH) in uremic rats and dogs. In uremic patients with secondary hyperparathyroidism, OCT dose-dependently suppressed PTH secretion and increased serum calcium levels. However, more than 60% of patients achieved a greater than 30% decrease in intact PTH level from baseline with long-term OCT treatment up to 1 year without an unphysiological increase in mean serum calcium levels. Long-term treatment also brought about a reduction in bone metabolic markers, including bone alkaline phosphatase, tartrate-resistant acid phosphatase, and bone gra-protein. These results suggest that although careful attention should be paid to the onset of hypercalcemia and oversuppression of PTH, OCT is one of the effective tools for the treatment of secondary hyperparathyroidism.

Calcitriol↗
PubMed2001

Outcomes of hemodiafiltration based on Japanese dialysis patient registry.

Effectiveness of various therapeutic modalities was analyzed among 1,196 patients entered in the registry of the Japanese Society for Dialysis Therapy who were on hemopurification therapy as of the end of 1998 and developed dialysis-related amyloidosis during 1999. In the investigation, the effectiveness of various hemopurification modalities on the dialysis-related amyloidosis was ranked as exacerbation, unchanged, or alleviation, so as to analyze the possible relationship between the hemopurification modality and its effectiveness. The analysis was performed using a logistic regression approach, and the results were shown as "the risk of a worse therapeutic ranking" among the hemopurification modalities. The smaller "the risk of a worse therapeutic effect" was, the more effective the treatment modality. When the risk of a worse therapeutic effect for the hemodialysis patients treated by a regular membrane was put at 1.0, the risk for hemodialysis patients using high-flux membrane was 0.489, the off-line hemodiafiltration risk was 0.117, the on-line hemodiafiltration risk was 0.013, and the risk of push/pull hemodiafiltration was 0.017. For hemodialysis with a beta(2)-microglobulin adsorption column, a low risk of 0.054 was found. The results indicated that hemodiafiltration therapy and simultaneous hemodialysis with beta(2)-microglobulin adsorption therapy were more effective treatment for dialysis-related amyloidosis.

Amyloidosis↗
PubMed2001

[Serovar-distribution, drug-resistance, and DNA analysis of Salmonella strains isolated from sporadic diarrhea cases or healthy cases in Tama, Tokyo (1991-2000)].

Serovar-distribution and drug-resistance of a total of 421 Salmonella strains, which were 98 stains from sporadic diarrhea cases and 323 strains from healthy cases between 1991 and 2000 in Tama, Tokyo were investigated. In serological typing tests, the strains tested were classified into 26 different kinds of serovar in diarrhea cases, 58 in food handlers, and 25 in individuals for health care. Salmonella serovar Enteritidis (S. Enteritidis) was the most predominant serovar in three cases. Following, S. Typhimurium and S. Infantis in diarrhea cases, S. Hadar, S. Montevideo and S. Thompson in food handlers, or S. Typhimurium, S. Lichfield and S. Oranienburg in healthy individuals were frequent. The drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, SXT, NA, FOM, and NFLX) showed that 57.1% of the strains from diarrhea cases and 36.8% from the healthy cases were resistant to one or the other of the drugs examined. Drug-resistance patterns of those showed 13 types in diarrhea cases and 25 types in healthy cases. Out of them, strains which showed a predominant and common pattern in both cases were SM resistant-S. Enteritidis and CP.TC.SM.ABPC resistant-S. Typhimurium. In addition, the latter strains were also resistant to sulfiso-xzole (SU). In DNA analysis by RAPD method of their strains, common DNA finger-prints were observed in both cases through out the investigation period.

DNA, Bacterial↗
PubMed2001

Soluble osteopontin and vascular calcification in hemodialysis patients.

BACKGROUND: Vascular calcification often occurs in patients with uremia. As osteopontin (OPN) is not only involved in the physiological but also the pathological calcification of tissues, OPN may be associated with the pathogenesis of aortic calcification in hemodialysis (HD) patients. METHODS: We examined the expression of OPN in atherosclerotic aortas of HD patients. In addition, we performed a prospective longitudinal study by using CT scans to detect aortic calcifications and by measuring the plasma OPN concentration by ELISA in HD patients (20 men, 16 women; mean age 55.2 +/- 21.3 years) and in healthy volunteers (18 men, 17 women; mean age 54.0 +/- 13.2 years). RESULTS: By immunohistochemical staining, OPN was abundantly localized in atherosclerotic plaques of HD patients. The macrophages surrounding the atheromatous plaques were identified as the OPN-expressing cells. We furthermore found that the concentration of soluble plasma OPN was significantly higher in HD patients as compared with the concentrations in age-matched healthy volunteers (837.3 +/- 443.2 vs. 315.1 +/- 117.4 ng/ml, p < 0.01). The OPN concentration was positively correlated with the aortic calcification index in HD patients (r = 0.749, p < 0.01). CONCLUSION: These data suggest that OPN, secreted by macrophages, plays a role in the calcification of atheromatous plaques in HD patients.

Adult↗
PubMed2001

Analysis of beta(2)-microglobulin kinetics in hemodialysis by a modified variable-volume one-compartment model.

It has been reported that deposition of beta(2)-microglobulin (BMG) is associated with the occurrence of dialysis-related amyloidosis (DRA) in long-term hemodialysis (HD) patients. Though reduction of the BMG burden is essential in preventing DRA, simple BMG kinetic models applicable to clinical practice have not been established. We have reported a modified variable-volume one-compartment model (1CM) for analyzing urea nitrogen (UN) kinetics, in which no specific parameters other than a modification factor are necessary. If there is a constant relation between the BMG concentration of the dialyzer arterial line and the mean BMG concentration in the body during HD, the modified 1CM may also be applied to BMG. As such, in order to verify its validity, we analyzed UN and BMG kinetics by the modified 1CM in 28 HD patients in whom polysulfone dialyzers were used, and compared the calculated and measured solute rebound. In 3 of the patients, the spent dialysate was collected in a tank, and the BMG removal mass, calculated by the modified 1CM, was compared with that recovered in the tank. The BMG rebound ratio (%), calculated by the modified 1CM, was not different from the measured one (36.3 +/- 9.9 vs. 36.5 +/- 11.5, p = 0.954), as in the case of UN (15.8 +/- 4.5 vs. 16.3 +/- 4.6, p = 0.541). The solute dilution in the blood circuit by solute disequilibrium and blood recirculations for BMG was estimated to be 74% stronger than that for UN. The normalized solute generation rate (mg/min/l) and the time-averaged solute concentration over a 1-week period (mg/l) were 0.142 +/- 0.023 and 448 +/- 68 for UN and 0.00578 +/- 0.00125 and 22.4 +/- 4.6 for BMG, respectively. The differences between these two solutes resulted in a Dilution index for BMG that was 23% lower than that for UN (2.62 +/- 0.44 vs. 3.21 +/- 0.39, p < 0.0001). The modified 1CM overestimated the BMG removal mass (mg) by about 20% compared with that recovered in the tank (195 +/- 22 vs. 162 +/- 17, p < 0.0001). One of the causes of this discrepancy was speculated to be adsorption of BMG by polysulfone dialyzers. It was concluded that, despite several problems in quantitative analysis, the modified 1CM would be a useful model for estimating the dialysis efficiency for BMG removal in clinical practice.

Adsorption↗
PubMed2001

Glomerulonephritis after methicillin-resistant Staphylococcus aureus infection resulting in end-stage renal failure.

A 58-year-old man developed proteinuria and renal dysfunction following pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin was administered, and prednisolone pulse therapy and plasmapheresis were performed. Subsequently, serum creatinine was decreased. Eight months later, creatinine and CRP were again elevated, and MRSA was detected. Vancomycin was again administered and plasmapheresis was performed. However, renal function was not improved and continuous hemodialysis was initiated. This case indicates that complete eradication of MRSA is necessary to treat MRSA-associated glomerulonephritis, and if this is not attained, a permanent loss of renal function occurs.

Anti-Bacterial Agents↗
PubMed2001

IgA nephropathy with complement deficiency.

We treated a female patient suffering from immunoglobulin A (IgA) nephropathy and congenital deficiency of the ninth component of the complement system (C9). She was admitted with hematuria and proteinuria, and the C9 deficiency was diagnosed based on the low hemolytic activity of 50 % of the hemolytic unit of the complements (CH50) and the normal C3 level in the plasma. Renal biopsy revealed mild mesangial proliferation, and immunofluorescence examination revealed mild mesangial deposits of IgA and C3 with the same distribution. We discuss the pathogenesis of IgA nephropathy and the role of the complements in its progression.

Adult↗
PubMed2001

Analysis of Japanese encephalitis epidemic in Western Nepal in 1997.

We conducted an epidemiological study of a Japanese encephalitis (JE) outbreak in the southwestern part of Nepal in 1997. A high density of JE infections was found and it was estimated that 27.9% the total population were infected with JE virus in the study area. The fatality rate was 13.2% and there was no difference in the fatality rate between males and females over 5 years old. However, the case fatality rate was 2.1 times higher in females than in males (14.6% vs. 6.9%) among children under 5 years of age. Fifty-three blood samples were collected from suspected JE cases during the epidemic period in 1998. Findings for JE specific IgM revealed that clinical diagnoses of JE were serologically confirmed in an average 78% (70-93%) of patients in three collaborating hospitals. These studies demonstrated that JE was highly prevalent in the area and clinical diagnoses were reliable. Effective preventive measures should be taken against this vaccine-preventable disease.

Adolescent↗
PubMed2000

Analysis of urea nitrogen and creatinine kinetics in hemodialysis: comparison of a variable-volume two-compartment model with a regional blood flow model and investigation of an appropriate solute kinetics model for clinical application.

To investigate an appropriate solute kinetics model for clinical application, we analyzed urea nitrogen (UN) and creatinine (Cr) kinetics by a variable-volume two-compartmental model (2CM) and a regional blood flow model (RBF) in 44 hemodialysis patients with varying proportions of first compartmental volume and regional volume (p(1)). Solute kinetics could not be solved in some of the patients with higher p(1) values, and there were more solution failures by the RBF than by the 2CM. The solute generation rate (g) and solute distribution volume in the dry state (V(D)) increased with increases in p(1) in both models, but there were some differences between the two models. When g was normalized by V(D), it became relatively constant, irrespective of the p(1) value or model used (0.133 +/- 0.029 mg/min/l by the 2CM and 0.132 +/- 0.029 mg/min/l by the RBF for UN; 0.0200 +/- 0.0049 mg/min/l by the 2CM and 0.0198 +/- 0.0048 mg/min/l by the RBF for Cr). The intercompartmental mass transfer coefficient (K(c); liters/min) calculated by the 2CM decreased as p(1) increased (K(c) = -1.77.p(1) + 1.16, p < 0.0001, R = 0.999 for UN; K(c) = -0.847.p(1) + 0.556, p < 0.0001, R = 1.000 for Cr). The systemic blood flow (Q(sys); liters/min) calculated by the RBF also decreased as p(1) increased (Q(sys) = -11.1.p(1) + 6.21, p < 0.0005, R = 1.000 for UN; Q(sys) = -5.22.p(1) + 2.90, p < 0.001, R = 0.999 for Cr). Since the RBF more frequently failed to solve the solute kinetics and since there was a difference in its Q(sys) values for UN and Cr, the 2CM was considered to be a superior model. When p(1) was extremely low, the 2CM could be transformed into a modified variable-volume one-compartment model (1CM) which presented a similar g/V(D) (0.133 +/- 0.029 for UN; 0.0200 +/- 0.0048 for Cr). This modified 1CM was considered to satisfy appropriate conditions for clinical application, since it is simpler than the 2CM and provides useful information on the dialysis dose.

Aged↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 12). Effects of cyclophosphamide on spermatogenesis.

To determine what is an appropriate administration period for evaluation of the testicular toxicity of cyclophosphamide, the compound was administered orally to male Crj:(CD)SD rats at doses of 5, 10, 20 and 40 mg/kg/day for 2 weeks and at doses of 2.5, 5 and 10 mg/kg/day for 4 weeks. All animals in the 2-week treatment group given 40 mg/kg/day died during the treatment period. After repeated dosing, weights of testes and epididymides did not change significantly in either 2-week or 4-week treatment groups. On conventional histopathological examination, changes in spermatogonia were too subtle to allow simple quantitative evaluation. Therefore the quantitative analysis described by Matsui et al. (1995) was employed. After 4-weeks treatment all types of germ cells decreased significantly in all stages of seminiferous tubules examined in the 10 mg/kg/day group. Spermatogonia type A in all stage seminiferous tubules examined and spermatogonia type B in stage V seminiferous tubules decreased significantly in the 5 mg/kg/day group. With 2-weeks treatment, spermatogonia type A in all stage seminiferous tubules examined were similarly decreased significantly in 10 mg/kg/day or more groups. Spermatogonia type B and pachytene spermatocytes in stage V, preleptotene spermatocytes in stage VII and zygotene spermatocytes in stage XII were decreased in 20 mg/kg/day group. Sertoli cells and the Leydig cells and epididymides were not affected in any treatment group. In conclusion, testicular toxicity induced by cyclophosphamide could be detectable after 2-weeks as well as after 4-weeks treatment if precise histopathological examination including quantitative analysis of spermatocytes are conducted.

Administration, Oral↗