Biomedical subjects

Takeshi Kawamura

Publications and source records attributed to Takeshi Kawamura.

At least 19 recordsLinked to original sources

PubMed2007

Alteration of cystatin C in the cerebrospinal fluid of multiple sclerosis.

The protein profiles in the cerebrospinal fluid of 10 patients with multiple sclerosis (MS), 10 patients with neuromyelitis optica (NMO), 8 inflammatory disease control patients, and 4 noninflammatory disease control patients were screened by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Peaks of 12.5 kDa were significantly lower in multiple sclerosis, NMO, and inflammatory disease control patients than in noninflammatory disease control patients, and 13.4 kDa peaks were higher in NMO than in inflammatory disease control patients. Further analyses demonstrated that both peaks were cystatin C. Enzyme-linked immunosorbent assay showed that the cystatin C levels tended to be lower in multiple sclerosis and NMO. Alterations of cystatin C may relate to the pathogeneses of demyelinating diseases.

Cystatin C↗

PubMed2006

Rituximab therapy for Epstein-Barr virus-related chronic hepatitis following living donor kidney transplantation.

A patient who underwent living donor kidney transplantation was infected with Epstein-Barr virus (EBV) that resulted in persistent EBV infection and EBV-associated chronic hepatitis, determined by abnormally elevated anti-EBV antibody titers and high frequency of EBV-infected B lymphocytes. Despite decreases in immunosuppressant doses, persistent EBV infection and chronic hepatitis persisted for several years. Therapy using anti-CD20 monoclonal antibody (rituximab) virtually eliminated peripheral B lymphocytes and EBV-encoded small RNA 1 (EBER-1)-positive cells. Moreover, hepatic enzyme levels normalized and histological findings indicated marked improvement in hepatic inflammation. Although peripheral CD20(+) B lymphocyte and EBER-1-positive cell levels began to increase 4 months after the end of therapy, the number of EBER-1-positive cells remained very low, and liver function test results remained within normal ranges. The present case illustrates the significance of early diagnosis, monitoring of viral load, and vigorous management of EBV-related disorders associated with organ transplantation.

Adolescent↗

PubMed2006

Clinical efficacy of an alpha1A/D-adrenoceptor blocker (naftopidil) on overactive bladder symptoms in patients with benign prostatic hyperplasia.

AIM: We evaluated the efficacy of an alpha1a/d blocker, naftopidil, on storage symptoms in patients with benign prostatic hyperplasia (BPH), using frequency/volume charts (FVC). METHODS: A total of 81 patients with BPH (52-91 years, mean age 69.0 years) were studied. The inclusion criteria were: (i) one or more episode(s) of urinary urgency/day; (ii) a score of eight or more points on the International Prostate Symptom Score (I-PSS); and (iii) three or more points in any of the scores for three items (frequency, nocturia, and urgency) of the I-PSS. The patients received 50-75 mg/day of naftopidil for 6 weeks. All the patients were examined for 2-day FVC before and after the administration of naftopidil. I-PSS, quality of life index, and uroflowmetry were also evaluated. RESULTS: Total I-PSS decreased from 19.1 to 10.5 points (P < 0.0001), with significant improvement of both storage and voiding symptom scores (P < 0.0001, both). The score for urgency decreased from 3.1 to 1.4 (P < 0.0001). Daytime and night-time frequency decreased from 9.3 to 8.0 (P < 0.0001) and from 2.7 to 2.0 (P = 0.0009), respectively. Mean volume/void increased from 174.0 to 188.6 mL (P = 0.0453). Nocturia decreased from 3.2 to 2.3 (P < 0.0001) in 40 patients who suffered from nocturia two times or more. Notably, significant improvement of nocturia was observed in the patients both with and without nocturnal polyuria (P = 0.0006 and 0.0135, respectively). CONCLUSION: The alpha1a/d blocker naftopidil improves not only voiding symptoms but also storage symptoms, and is effective for nocturia in patients with BPH regardless of the existence of nocturnal polyuria.

Adrenergic alpha-Antagonists↗

PubMed2005

Disease proteomics toward bedside reality.

The human genome has been sequenced, and investigation of its products has become possible in a sequence-based framework. More than 200,000 protein species are expressed in the body from approximately 30000 human genes. The term proteome, coined as a linguistic equivalent to the concept of genome, is used to describe the complete set of proteins that is expressed, and modified following expression, by the entire genome in a cell at any one time. Protein types and amounts expressed in a body vary greatly depending upon whether it is healthy or ill. Therefore, proteomics is attracting an increasing interest in its application to better understanding of disease processes, to development of new biomarkers for diagnosis and early detection of disease, and to accelerate drug development. There are numerous opportunities for medicine, although it is quite challenging to meet the needs for high sensitivity and high throughput required for disease-related investigations.

Algorithms↗

PubMed2005

Hepatitis induced by an IgM monoclonal antibody against procarboxypeptidase R.

Procarboxypeptidase R (proCPR), also known as thrombin-activatable fibrinolysis inhibitor (TAFI), is present in plasma and can be activated to carboxypeptidase R (CPR) by trypsin-like enzymes such as thrombin and plasmin. CPR has the carboxypeptidase B-like activity that can inactivate the inflammatory peptides such as C5a by removing the C-terminal arginine and can interfere with fibrinolysis by removing C-terminal lysine residue of fibrin. In the present study, we conducted to produce monoclonal antibodies (mAbs) by using spleen cells from proCPR-deficient mice immunized by partially purified mouse proCPR. The mAbs obtained were IgM isotype and reacted with proCPR and interfered with activation of proCPR to CPR by thrombin-thrombomodulin complex. Some BALB/c mice implanted with the hybridoma died in 7 days, and intravenous injection of the mAb to BALB/c mice induced transient elevation of GOT and GPT in plasma although injection to the deficient mice did not. Furthermore, the histological features showed the focally lesions in liver tissue of BALB/c mice injected with the mAb. Since liver is the major site of proCPR synthesis, IgM mAb to proCPR should have induced local inflammation at the side resulting in induction of hepatitis.

Alanine Transaminase↗

PubMed2005

Physiologically based pharmacokinetic modelling of the three-step metabolism of pyrimidine using C-uracil as an in vivo probe.

AIMS: Approximately 80% of uracil is excreted as beta-alanine, ammonia and CO2 via three sequential reactions. The activity of the first enzyme in this scheme, dihydropyrimidine dehydrogenase (DPD), is reported to be the key determinant of the cytotoxicity and side-effects of 5-fluorouracil. The aim of the present study was to re-evaluate the pharmacokinetics of uracil and its metabolites using a sensitive assay and based on a newly developed, physiologically based pharmacokinetic (PBPK) model. METHODS: [2-(13)C]Uracil was orally administrated to 12 healthy males at escalating doses of 50, 100 and 200 mg, and the concentrations of [2-(13)C]uracil, [2-(13)C]5,6-dihydrouracil and beta-ureidopropionic acid (ureido-(13)C) in plasma and urine and (13)CO2 in breath were measured by liquid chromatography-tandem mass spectrometry and gas chromatograph-isotope ratio mass spectrometry, respectively. RESULTS: The pharmacokinetics of [2-(13)C]uracil were nonlinear. The elimination half-life of [2-(13)C]5,6-dihydrouracil was 0.9-1.4 h, whereas that of [2-(13)C]uracil was 0.2-0.3 h. The AUC of [2-(13)C]5,6-dihydrouracil was 1.9-3.1 times greater than that of [2-(13)C]uracil, whereas that of ureido-(13)C was 0.13-0.23 times smaller. The pharmacokinetics of (13)CO2 in expired air were linear and the recovery of (13)CO2 was approximately 80% of the dose. The renal clearance of [2-(13)C]uracil was negligible. CONCLUSION: A PBPK model to describe (13)CO2 exhalation after orally administered [2-(13)C]uracil was successfully developed. Using [2-(13)C]uracil as a probe, this model could be useful in identifying DPD-deficient patients at risk of 5-fluorouracil toxicity.

Adult↗

PubMed2005

Post-transplant early recurrent proteinuria in patients with focal glomerulosclerosis--angiotensin II immunostaining and treatment outcome.

We reviewed the transplantation data and results of histopathological studies with additional angiotensin II (AII) immunostaining of renal graft biopsies of nine cases (10 grafts) with recurrent proteinuria and three controls without recurrent proteinuria that received renal transplantation for primary focal segmental glomerulosclerosis (FSGS) between 1986 and 2002. Recurrent FSGS was confirmed in six grafts from nine cases by light microscopy. In cases with recurrent proteinuria, loss of graft function was noted in all six renal grafts received between 1986 and early 1992 but in none of four grafts received between late 1992 and 2002. Two of four patients of the late group but none of those of the early group received angiotensin converting enzyme (ACEI) or angiotensin II receptor blocker (ARB) with plasma exchange (PE). In control cases without proteinuria, AII immunostaining was detected in tubules but not in glomeruli in 1-hour biopsies as well as later on. In cases with recurrent proteinuria, AII immunostaining was detected in both tubules and glomeruli, although glomerular AII staining was not observed in 1-hour biopsies. Our results suggest that effective treatment of post-transplantation recurrent FSGS requires ACEI or ARB with PE in the absence of another etiology.

Adolescent↗

PubMed2005

Clinical course of congenital nephrotic syndrome and Denys-Drash syndrome in Japan.

BACKGROUND: The prognosis of Japanese patients with congenital nephrotic syndrome (CNS) and Denys-Drash syndrome (DDS) is not clear. METHODS: Five patients with CNS and four patients with DDS, which causes secondary CNS, were studied retrospectively. RESULTS: Seven patients were sporadic and two DDS patients were identical twins. Five CNS patients presented with edema within 3 months of birth. In four DDS patients, edema was not noted and end-stage renal disease developed between 7 months and 6 years of age. Of these five CNS patients, one patient had cerebral thrombosis and cytomegalovirus pneumonia at the onset and another patient died during dialysis. Frequent intravenous albumin administration required, growth and development during infancy were varied. Of the nine patients with CNS and DDS, seven received renal transplantation and were alive with functioning grafts at the last follow up. Catch-up growth was observed in five patients after transplantation. Five school-aged patients attended school and received adequate grades and two adults worked full-time. Of the DDS patients, dysuria due to hypospadias persisted in one patient and treatment for hypogonadism was needed in one patient. CONCLUSIONS: CNS and DDS were diagnosed early after onset and adequate treatment was started. Growth and development after renal transplantation were relatively good. Thrombotic episodes or severe infection in CNS patients was difficult to manage and complications resulting from DDS affected the quality of life.

Denys-Drash Syndrome↗

PubMed2005

[A case of prostatic cystadenoma].

We report a case of prostatic cystadenoma. A 81-year-old man visited our hospital with the chief complaint of urinary difficulty. RUG and DIP showed bladder and prostatic urethra deviated to the left side. TRUS, CT and MRI revealed multilocular cyst in the pelvic cavity. Resection of the cystic wall was performed under the diagnosis of pelvic cyst. The cysts were originated from the right side of the prostate and adhered with the bladder severely. The histopathological diagnosis was prostatic cystadenoma. Fortyfive cases of prostatic cyst in the Japanese literature are reviewed.

Aged↗

PubMed2004

Identification of 36 kDa phosphoprotein in fibrous sheath of hamster spermatozoa.

In our previous studies (Fujinoki et al., 2001, 2003), we reported that two types of 36 kDa proteins, designated 36K-A protein and 36K-B protein, obtained from hamster sperm flagella, are associated with motility activation and phosphorylated in a cAMP-dependent manner at serine residues. In the present experiments, we focused on the hamster (Mesocricetus auratus) 36K-A protein, which was analyzed by peptide mass finger printing and amino acid sequencing. The results suggest that 36K-A protein is a pyruvate dehydrogenase E1 component beta subunit lacking the N-terminal 30 amino acids. Moreover, our results suggest that 36 K-A protein is localized in the fibrous sheath of the principal piece of hamster spermatazoa.

Amino Acid Sequence↗

PubMed2004

Activation of nuclear factor-kappa B and macrophage invasion in cyclosporin A-and tacrolimus-treated renal transplants.

This retrospective study was designed to compare the efficacy of cyclosporin A (CyA) and tacrolimus (FK506) on chronic rejection (CR) associated with nuclear factor-kappa B (NF-kappaB) activation and macrophage invasion. Non-episodic day 50 protocol renal biopsy was performed in 63 consecutive patients with renal transplants from living donors, treated with either CyA or FK506. Southwestern histochemistry for NF-kappaB, immunostaining for CD68, and Banff classification were performed, and these findings were compared with outcome over 34 +/- 13 months. Compared with specimens from FK506-treated patients (n = 20), specimens from CyA-treated patients (n = 43) showed a significant increase in tubulointerstitial CD68-positive cells (1.5 +/- 0.9 vs. 0.9 +/- 0.8, p < 0.01), although no significant differences were observed in NF-kappaB activation. Specimens with Banff acute rejection (AR) grade > or = 1A (n = 20) showed increased macrophages (p < 0.01) compared with specimens with AR < 1A (n = 43). Specimens from patients with clinical AR prior to day 50 biopsy (n = 23) also showed increased macrophage invasion (p < 0.01) compared with specimens from patients without prior clinical AR (n = 40). The cumulative well-functioning (serum creatinine < 1.5 mg/dL) graft survival rate was significantly lower in patients with increased tubulointerstitial CD68-positive cells (n = 63, p < 0.05). Our findings suggest that tacrolimus is more effective than CyA against CR with respect to macrophage invasion and AR.

Adult↗

PubMed2004

Detection of Helicobacter pylori in the stools of newborn infants.

To investigate the transmission route of Helicobacter pylori, stool specimens of 50 infants 3 days old were studied by a stool antigen immunoassay and polymerase chain reaction (PCR). By PCR, H. pylori DNA was detected in 15 neonates (30%). The stool antigen test was positive in only 1 neonate with a positive PCR. The detection rate of H. pylori DNA in neonates was significantly higher for those with mothers having urines positive for anti-H. pylori IgG antibody (60%) than for those mothers with negative urines (17%) (P < 0.01). A follow-up study was done 24 months later on 8 of the 15 infants with positive PCR results, including the infant with a positive stool antigen test. All infants were negative by both PCR and stool antigen test.

Base Sequence↗

PubMed2004

Clinical outcome and accommodation in ABO incompatible kidney transplantation.

We performed 84 ABO-incompatible kidney transplants at Toho University since 1989, with plasmapheresis and exchange replacing AB blood group plasma as pre-conditioning to reduce anti-donor blood group antibodies. Our current immunosuppression protocol consists of basiliximab, MMF, steroid, and cyclosporine or tacrolimus, including splenectomy. Overall patient/ graft survival rates (n=84) were 95/93 at one year, 94/92 at 3 years, 87/80 at 5 years, 87/75 at 7 years, and 83/67 at 10 years. The outcomes are similar to those of ABO-compatible living donor transplants. We have achieved 100% graft and patient survival rates (n=48) for the 7 years since January 1997. Our findings suggest that post-conditioning is not necessary to control titers of anti-donor blood group antibodies or to overcome acute humoral rejection. Infection control is critical in achieving good outcomes in ABO-incompatible transplants. We found that only anti-donor blood group antibodies in blood group O recipients of ABO-incompatible kidneys were specifically suppressed one year after transplantation. This appeared to be a type of accommodation in which there was no immunological response despite the co-existence of donor antigen and antibody, and might have been caused by down-regulation of B cells to produce anti-donor antibody.

ABO Blood-Group System↗

PubMed2003

Clinical characteristics of primary vesicoureteral reflux in infants: multicenter retrospective study in Japan.

PURPOSE: We evaluate clinical characteristics of primary vesicoureteral reflux in infants in a multicenter study in Japan with special reference to the relation of renal parenchymal damage to urinary tract infection and gender. MATERIALS AND METHODS: Infants younger than 1 year old with primary vesicoureteral reflux were recruited from 14 hospitals during the 3-year registration period beginning in January 1996 and ending in December 1998. Various clinical parameters as well as renal parenchymal lesion on dimercaptosuccinic acid scintigraphy were evaluated. RESULTS: Of 356 infants enrolled 296 (83%) were male and 60 (17%) were female. In 85% of infants presenting symptom was febrile urinary tract infection. There were 204 bilateral (57%) and 152 unilateral (43%) cases. Reflux was bilateral in 56% of males versus 65% of females, and high grade (grades IV and V) in 58% of males versus 55% of females. Diffuse parenchymal lesion was similarly noted in infants with or without prior urinary tract infection (38% and 46%, respectively) and was more often noted in male than in female infants (42% versus 25%). CONCLUSIONS: Despite the current use of screening prenatal ultrasound, many infants are still diagnosed as having vesicoureteral reflux only after the occurrence of urinary tract infection. The greater severity of renal parenchymal lesion in male infants combined with similar incidence of diffuse parenchymal lesion in those with or without prior infection suggests preexisting congenital abnormalities in the male refluxing kidney.

Female↗

PubMed2003

Living related kidney transplantation in a patient with autosomal-recessive Alport syndrome.

We discuss a patient with Alport syndrome who received a renal transplant from a donor with thin basement membrane disease. A 30-year-old woman, diagnosed with Alport syndrome on the basis of sensorineural hearing loss, characteristic renal biopsy findings and a family history of microhaematuria, entered chronic haemodialysis therapy. She then received a renal transplant donated from her father, who had sensorineural hearing loss and persistent microhaematuria. On the day of renal transplantation, a 1-h graft biopsy after reperfusion showed thin basement membrane disease. We re-tested the patient's native kidney biopsy specimen by immunohistochemical staining using alpha-chain-specific collagen type IV monoclonal antibodies. There was no expression of collagen type IV alpha3-, alpha4- and alpha5-chain on glomerular basement membrane, but positive staining of alpha5-chain on Bowman's capsular basement membrane was noted. A diagnosis of autosomal-recessive Alport syndrome was made. We concluded that this family might display different phenotypic expressions of the same genotype: one suffered end-stage renal disease and the other thin basement membrane disease.

Adult↗

PubMed2003

Identification of 36-kDa flagellar phosphoproteins associated with hamster sperm motility.

In our previous paper [M. Fujinoki et al. (2001) BIOMED: Res. 22, 45-58], we reported that two types of 36-kDa protein, which were designated as 36K-A protein and 36K-B protein, obtained from hamster sperm flagella were phosphorylated at serine residues associated with the regulation of motility activation. In the present experiments, it was suggested that these two types of 36-kDa protein were phosphorylated in a cAMP-dependent manner associated with motility activation of hamster spermatozoa. Because the 36K-B protein was the most intensely phosphorylated in a cAMP-dependent manner, attempts were made to further characterize it. The 36K-B protein was assumed to be localized in the middle piece. The localization of the 36K-B protein was the same as that of the 36-kDa protein reported in our previous paper [Y. Si et al. (1999) Mol. Reprod. Dev. 52, 328-334]. In order to identify the 36K-B protein, it was analyzed by peptide mass finger printing and amino acid sequencing. The results suggested that the 36K-B protein was a pyruvate dehydrogenase E1 component beta subunit and a component of the mitochondrial sheath of the middle piece.

Amino Acid Sequence↗

PubMed2003

Identification of the 58-kDa phosphoprotein associated with motility initiation of hamster spermatozoa.

In our previous paper [M. Fujinoki et al. (2001) BIOMED: Res. 22, 45-58], we reported that the 58-kDa protein obtained from hamster sperm flagella was phosphorylated at serine residues in association with the start of motility. In the present experiments, we identified and localized the 58-kDa protein. The 58-kDa protein was assumed to exist in the acrosomal region domain of the sperm head and the whole sperm flagellum. In particular, a large amount of 58-kDa protein was localized in the equatorial segment of the acrosomal region domain of the sperm head and the middle piece of the sperm flagellum. In the next step, the 58-kDa protein was identified by peptide mass finger printing and LC-MS/MS analysis. The results suggested that the 58-kDa protein was ATP synthase H(+) transporting F1 beta, which is one of the mitochondrial components. Therefore, it is likely that the 58-kDa protein is associated with ATP production in the mitochondrial sheath in the middle piece of the sperm flagellum, and H(+) transport in the sperm head and the sperm flagellum except for the middle piece, since ATP synthase also acts as an H(+) pump.

Amino Acid Sequence↗

PubMed2003

Modulation of procarboxypeptidase R (ProCPR) activation by complementary peptides to thrombomodulin.

We designed complementary peptides (C-peptides) using a novel computer program (MIMETIC), which generates a series of peptides designed to interact with a target peptide sequence. Carboxypeptidase R (CPR) is an unstable basic carboxypeptidase found in fresh serum in addition to carboxypeptidase N (CPN) which is stable. CPR is generated from its precursor form (proCPR) by trypsin-like enzymes, and its activation is mediated by thrombin generated in the coagulation cascade. The efficiency of activation is enhanced approximately 1,200-fold when thrombin (T) is bound to thrombomodulin (TM). We attempted to generate C-peptides which recognize the T-binding site within TM assuming that some of these might interfere with the generation of T and TM complexes (T-TM). Among three peptides designed, two inhibited the enhancement in activation of proCPR by T in the presence of TM. One of the peptides at 16 microM reduced the activation of proCPR to the level obtained by T alone.

Carboxypeptidase B2↗