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Biomedical subjects

K Kakimoto

Publications and source records attributed to K Kakimoto.

At least 19 recordsLinked to original sources
PubMed2003

Increased hepatocyte growth factor level in cerebrospinal fluid in Alzheimer's disease.

BACKGROUND & OBJECTIVE: Hepatocyte growth factor (HGF), also known as the scatter factor, is a potent mitogen for mature hepatocytes, and also has multifunctional effects on some cells in various organs. Recently, we have found expression and localization of HGF in white matter astrocytes in human brain tissues. Furthermore, immunohistochemistry using anti-HGF antibody revealed more intense immunolabeling in Alzheimer's disease (AD) than control brains. The aim of the study is to investigate the level of HGF in cerebrospinal fluid (CSF) from patients with AD. MATERIAL AND METHODS: We examined the level of HGF in CSF from 34 AD and 15 age-matched disease control patients by highly sensitive enzyme-linked immunoabsorbent assay (ELISA) system. RESULTS: Consistent with the immunohistochemical data, a significantly higher concentration of HGF in AD CSF was found as compared with controls. A significant correlation was also seen between CSF HGF levels and white matter high-signal foci determined on brain magnetic resonance imaging (MRI) in AD patients. CONCLUSION: These results indicate that CSF HGF levels correspond with the white matter damage in AD brain.

Aged↗
PubMed2003

Long-term follow-up study of HTLV-I infection in bottle-fed children born to seropositive mothers.

Human T-lymphotropic virus Type-I (HTLV-I) infects children via mother's milk. Infection of Human T-lymphotropic virus Type-I (HTLV-I) was investigated by long-term follow-up surveys of modified milk-fed children. Our observations of modified milk-fed infants revealed that: 1 of 154 (0.6%) at year 1, 5 of 129 (3.9%) at 1.5 years, and 5 of 108 (4.6%) at year 2 were anti-HTLV-I antibody-positive. No infants or children became newly antibody-positive thereafter. Modified milk feeding could prevent the HTLV-I infection of infants from mothers in many cases, however the infants who had became anti-HTLV-I antibody-positive due to established infection by the age 2 remained positive at age 11-12 with persistent infections. Modified milk-fed infants who had been born from HTLV-I seropositive mothers did not show that they had complete protection from HTLV-I infection, but a low infection rate was seen, showing that modified milk feeding is useful to protect from HTLV-I infection.

Animals↗
PubMed2003

Long-term follow up study of vertical HTLV-I infection in children breast-fed by seropositive mothers.

Infection of Human T-lymphotropic virus type-I (HTLV-I) was investigated by long-term follow up surveys of mother's milk-fed infants. HTLV-I infections of infants via seropositive mother's milk, that is, anti-HTLV-I antibody-positive infants, increased in number up to the age 2, but no infants became antibody-positive thereafter. Infants who had became antibody positive by age 2 remained so at age 11-12. HTLV-I infection via feeding with mother's milk was established by the age 2. While in epidemiologic surveys an increase of the anti-HTLV-I antibody-positive rate has been reported, this survey revealed that after acquisition of HTLV-I from breast feeding, there was no further horizontal transmission prior to puberty.

Breast Feeding↗
PubMed2002

Hepatocyte growth factor in gingival crevicular fluid and the distribution of hepatocyte growth factor-activator in gingival tissue from adult periodontitis.

Hepatocyte growth factor (HGF), also known as scatter factor, is a broad-spectrum and multifunctional cytokine required for the development, growth and regeneration of various organs and tissues. The expression of HGF in human gingival fibroblasts is induced by inflammatory cytokines such as interleukin 1. Thus, although it is possible that content of HGF in gingival crevicular fluid (GCF) in periodontitis is increased, this has not so far been reported because the volume of GCF is too small to determine HGF by the available enzyme-linked immunosorbent assay (ELISA). A recently developed, highly sensitive ELISA for HGF, with a detection limit of 1 pg/ml sample, has now enabled HGF to be measured in GCF.The mean HGF content in GCF from sites with clinically healthy gingiva, defined by the absence of overt signs of gingival inflammation and a probing depth (PD) <3 mm, was 1.7 ng/ml, and that of periodontitis, defined by obvious alveolar bone loss detected by radiographic examination and a PD> or =3 mm, was 3.23 ng/ml. Although treating the periodontitis did not significantly decrease the HGF concentration despite significantly improved clinical scores such as PD and Gingival Index, the total amount of HGF in GCF did decrease significantly after treatment. HGF was expressed by gingival fibroblasts and inflammatory cells as determined by in situ hybridization. HGF-activator (HGFA), which converts inactive pro-HGF to active mature HGF, was detected in gingival epithelial cells by immunostaining. The expression of HGFA was also confirmed in gingival tissue by reverse transcription-polymerase chain reaction (RT-PCR). These findings indicate that HGF is synthesized and activated in gingiva that is clinically healthy or associated with periodontitis.

Adult↗
PubMed2002

Hepatocyte growth factor in cerebrospinal fluid in neurologic disease.

OBJECTIVE: To investigate hepatocyte growth factor (HGF) concentration in cerebrospinal fluid (CSF) in neurologic disease. MATERIALS AND METHODS: We determined CSF concentration of HGF with human-HGF-specific enzyme-linked immunosorbent assays (ELISA) in 121 patients: Alzheimer's disease (AD) (33), amyotrophic lateral sclerosis (ALS) (10), Parkinson's disease (PD) (5), progressive supranuclear palsy (PSP) (3), spinocerebellar degeneration (7), acute disseminating encephalomyelitis (ADEM) (6), human T-lymphotropic virus-1 (HTLV-1)-associated myelopathy (HAM) (6), multiple sclerosis (MS) (7), aseptic meningitis (AM) (12), and peripheral neuropathy and myopathy as control diseases (32). RESULTS: HGF concentrations in CSF were significantly higher with diseases of the central nervous system (CNS) than control diseases and were slightly higher with AD than other neurodegenerative diseases. Values were highest with ADEM but decreased during corticosteroid treatment. We found no relationship between HGF in CSF and CSF cells or protein, immunoglobulin index, or Q albumin. CONCLUSION: It is suggested that high concentrations of HGF in CSF may be partially related to CNS pathology, especially to demyelinating disease.

Adult↗
PubMed2001

Strong inhibition of crystal-cell attachment by pediatric urinary macromolecules: a close relationship with high urinary citrate secretion.

OBJECTIVES: To investigate other reasons for the low incidence of pediatric urolithiasis, we evaluated the difference in the crystal-cell adhesion inhibitory activity of urinary macromolecules (UMMs) between children and adults. We also evaluated whether citrates influence the above inhibitory activity, because citrates are important in pediatric urine. METHODS: Urine samples were collected from children and healthy male adults during a 24-hour period, and urinary components with a molecular weight of 3 kDa or greater were extracted as UMMs to compare their inhibitory activity during the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells between children and adults. Subsequently, various concentrations of citrates were added to adult UMMs to evaluate the changes in the crystal-cell adhesion inhibitory activity of UMMs. RESULTS: Pediatric UMMs more strongly inhibited the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells at a concentration of 0.1 mg/mL compared with adult UMMs. In addition, pediatric UMMs contained higher proportions of fibronectin and glycosaminoglycans, both of which exhibit crystal-cell adhesion inhibitory activity. When citrates were added to adult UMMs, the crystal-cell adhesion inhibitory activity of UMMs was increased in a dose-dependent manner. However, citrates alone did not result in any differences in the inhibitory activity at any of the three different concentrations. CONCLUSIONS: We speculate that the incidence of pediatric urolithiasis is low because pediatric UMMs more potently inhibit the adhesion of calcium oxalate crystals to renal tubular cells or because the higher proportion of citrates in pediatric urine enhances the crystal-cell adhesion inhibitory activity of UMMs in a dose-dependent manner.

Adult↗
PubMed2001

Laparoscopic diagnosis and treatment of nonpalpable testis.

OBJECTIVE: Laparoscopy has become one of the important diagnostic modalities of nonpalpable testis and has been developed and applied in the treatment of this disease. In the present study, we investigated the usefulness of laparoscopy in the diagnosis and treatment of nonpalpable testis. METHODS: Laparoscopy was carried out under general anesthesia on 21 patients (23 testes) from October 1991 to October 1999. If the internal spermatic vessels and vas deferens made their way into the internal inguinal ring, the inguinal canal was dissected with an incision in the inguinal region to look for the testis. Patients with intra-abdominal testis underwent laparoscopic orchiopexy or orchiectomy. If the internal spermatic vessels terminated with a blind end intraperitoneally, making it impossible to identify the testis, the case was judged to be vanishing testis and the operation was finalized without any further examination. RESULTS: In eight of 23 testes (35%), the internal spermatic vessels and vas deferens made their way into the internal inguinal ring. The inguinal region was examined in all the eight testes. Orchiopexy was carried out on two testes and orchiectomy was carried out on six testes. An intra-abdominal testis was detected in eight of 23 testes (35%). Laparoscopic orchiopexy was carried out on seven testes. One-stage orchiopexy was carried out on two of the seven testes and two-stage Fowler-Stephens orchiopexy was carried out on five of the seven testes. Orchiectomy was carried out on the remaining testis. Blocking or lack of the internal spermatic vessels and vas deferens was seen in seven of the 23 testes (30%) and this condition was diagnosed as vanishing testis. CONCLUSION: Laparoscopy for nonpalpable testis is considered to be the most effective technique for diagnosing the presence or absence of the testis and the location of the testis.

Adolescent↗
PubMed2001

Comparison of fibronectin content in urinary macromolecules between normal subjects and recurrent stone formers.

OBJECTIVES: Fibronectin (FN: 230 kD) is a multifunctional alpha(2)-glycoprotein distributed throughout the extracellular matrix and body fluids. Recent studies have shown that a variety of molecules, including FN, inhibit the endocytosis of calcium oxalate (CaOx) crystals in vitro. We recently reported that FN was oversecreted from the renal tubular cells as a result of the stimulation of CaOx crystals, and inhibited the aggregation of CaOx crystals and the adhesion of CaOx crystals to the renal tubular cells. In the present study, we investigated the difference of FN content in urinary macromolecules (UMMs) between normal subjects and recurrent stone formers. MATERIALS AND METHODS: Urinary parameters in relation to urolithiasis of normal subjects and recurrent stone formers were measured. Proteins in extracted UMMs from urine of normal subjects and recurrent stone formers were measured with a BioRad protein assay, GAGs in each UMMs with a modified DMB assay and the FN content with the ELISA method. RESULTS: In urinary parameters, citrate was significantly higher in urine from normal subjects (female) than normal subjects (male) or recurrent stone formers, and the other parameters showed no differences between each group. The protein concentrations in UMMs showed no differences between each group. Normal subjects (male and female) showed a significantly higher concentration of GAGs than recurrent stone formers (with and without silent stone). Compared with normal subjects and recurrent stone formers without silent stones, higher FN levels were found in recurrent stone formers with silent stones. Normal subjects showed a significantly higher concentration of FN than recurrent stone formers without silent stones. No difference in FN level was shown between normal subjects (male) and normal subjects (female). CONCLUSION: Recurrent stone formers with silent stones showed a significantly higher concentration of FN in UMMs than normal subjects. This finding suggests that FN might be oversecreted from the renal tubular cells as a result of the stimulation of CaOx stones in vivo. Recurrent stone formers without silent stones showed a significantly lower concentration of FN in UMMs than normal subjects. From this finding it is suggested that FN might play a role as a potent inhibitor of CaOx urolithiasis in a clinical setting.

Adult↗
PubMed2001

Expression of prolactin gene in spontaneous mammary tumors in aging Fischer 344 rats.

Expression of extra pituitary prolactin (PRL) has been recently reported in the mammary gland. However, spontaneous mammary tumors occurring in aging rats have not been investigated for PRL production. The present study was undertaken to examine the expression of PRL gene in rat mammary tumors spontaneously arisen in rats with pituitary prolactinomas among 130 female Fischer-344 (F-344) rats. The tumors examined were fibroadenoma (adenomatous type) in the 18-month old rat and adenocarcinoma (alveolar/tubular type) in the 21-month old rat. PRL mRNA was examined by solution and in situ reverse transcription-polymerase chain reaction (RT-PCR) method. The predicted amplified products for PRL mRNA were identified in both tumors, and its expression was confirmed to be in the cytoplasm of epithelial cells. The results of the present study showed that PRL gene is expressed in spontaneously arising mammary tumors.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2000

Development of highly sensitive enzyme-linked immunosorbent assays for hepatocyte growth factor/scatter factor (HGF/SF): determination of HGF/SF in serum and urine from normal human subjects.

A sandwich enzyme-linked immunosorbent assay (ELISA) using rabbit anti-hepatocyte growth factor (HGF) IgG for human HGF, also known as the scatter factor, has previously been developed for determining increases in serum HGF levels in various liver diseases. The sensitivity limit of the ELISA is, however, approximately 0.2 ng/ml sample, and HGF concentrations in about 50% of normal subjects are not accurately measurable by this method, because the mean level of HGF in normal serum is close to the sensitivity limit. In the present study, chicken Fab' from egg yolk anti-HGF immunoglobulin Y and rabbit Fab' from rabbit anti-HGF IgG were conjugated with beta-D-galactosidase. With these conjugates as the second antibodies, we developed two sandwich ELISAs for human HGF and found that the sensitivities were about 20 pg/ml with the former conjugate and 2 pg/ml with the latter. The HGF concentration in sera from 138 normal subjects determined by the ELISA with the rabbit conjugate was 244+/-65 (SD) pg/ml serum, and it correlated very well with the number of leukocytes. Moreover, the ELISA with the rabbit conjugate permitted the determination of HGF levels in urine from normal subjects without first concentrating the sample. The determination of HGF in various biological fluids other than blood and urine by these ELISAs may aid the diagnosis and prognosis of various diseases.

Adult↗
PubMed2000

Effects of peroxisome proliferator-activated receptor-alpha and -gamma agonist, JTT-501, on diabetic complications in Zucker diabetic fatty rats.

This study has investigated the effects of JTT-501, a peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma agonist, on the pathogenesis of diabetic complications in the Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes. Comparison is made with troglitazone, a PPAR-gamma agonist. The ZDF rats exhibited hyperglycaemia and hyperlipidaemia, and developed diabetic complications such as cataract, nephropathy, and neuropathy. Treatment with JTT-501 from the prediabetic stage controlled glycaemia and lipidaemia, and prevented the development of diabetic complications. Troglitazone was less effective in controlling serum cholesterol and neuropathy. ZDF rats developed diabetic osteopenia with reduced bone turnover, and this was prevented by JTT-501 and troglitazone, possibly mediated by increased bone turnover and bone formation. Since JTT-501 controlled glycaemia and lipidaemia in ZDF rats and prevented several diabetic complications, it is suggested that treatment with JTT-501, which activates both PPAR-alpha and PPAR-gamma, could provide a valuable therapeutic approach against diabetic complications in type 2 diabetes.

Absorptiometry, Photon↗
PubMed2000

Expression of prolactin mRNA in rat mammary gland during pregnancy and lactation.

We studied the expression of prolactin (PRL) mRNA in the mammary gland of resting, pregnant, lactating, and weanling rats using in situ and solution reverse transcriptase-polymerase chain reaction (RT-PCR). In mid- to late pregnancy and throughout lactation, PRL mRNA was detected in both in situ and solution RT-PCR. These PRL mRNA signals were clearly identified in the cytoplasm of alveolar and ductal mammary epithelial cells by the in situ RT-PCR method. In mid- to late pregnancy, such as at the initiating point of PRL mRNA expression, we confirmed in some cases a lack of PRL mRNA by solution RT-PCR. In addition, in the early weaning phase, no signals were detected by solution RT-PCR. However, slight focal signals were detected in some poorly vacuolated cytoplasm of regressing acinar cells by in situ RT-PCR. These findings suggest that PRL mRNA in rat mammary gland begins in mid- to late pregnancy in parallel with the development of the mammary gland, continues throughout lactation, and declines in the early phase of weaning, with regression of mammary epithelial cells.

Animals↗
PubMed1999

Cobaltous chloride-induced mutagenesis in the supF tRNA gene of Escherichia coli.

The spectrum of mutations induced by cobalt(II) chloride (CoCl2) was examined using plasmid pUB3 DNA, which was propagated after transfection into Escherichia coli SY1032/pKY241 host cells. The vector plasmid carried an E.coli supF suppressor tRNA gene as a target for mutations. After CoCl2 treatment, 64 independent nalidixic acid-resistant, ampicillin-resistant and Lac+ (SupF-) clones were obtained and the altered sequences of the mutated supF genes were determined. Deletions and frameshifts were the predominant mutational event (61%) induced by CoCl2 and base substitutions were induced to a lesser degree (29%). Analysis of sequence alterations at all the sites of mutation revealed that: (i) 18 of 19 base substitutions and eight of 10 frameshifts occurred at G:C sites, suggesting that the formation of N7G-Co(II) adducts may be responsible for premutagenic lesions of these mutations; (ii) short sequence repeats were mostly found at the sites of deletions and frameshifts. Slippage-misalignment is also suggested to be a mechanism for the induction of mutations at these sites.

Antimutagenic Agents↗
PubMed1999

[A case of renal cell carcinoma associated with tuberous sclerosis].

Tuberous sclerosis is associated commonly with renal angiomyolipoma. On the other hand, the relation between tuberous sclerosis and renal cell carcinoma is not widely recognized. We report a case of renal cell carcinoma of the right kidney associated with tuberous sclerosis.

Adult↗
PubMed1999

[Three cases of metastatic renal tumor].

Since solitary metastatic renal tumors are not commonly diagnosed before death, the conclusive treatment of the metastatic renal tumor has not been established. We report three cases of metastatic renal tumors and discuss the indication of surgical therapy for metastatic renal tumors. The first case was in a 64-year-old male who underwent esophagectomy for squamous cell carcinoma. Seven months after the operation, a right renal tumor was found. The second case was in a 63-year-old male who underwent right upper pneumonectomy for adenocarcinoma with a right renal tumor, which seemed to be a solitary metastasis. The third case was in a 69-year-old male who underwent right pneumonectomy for adenocarcinoma. One month after the initial operation, a left renal cystic tumor was found. Since, in all cases, the tumors seemed to be solitary metastatic renal tumors without any other metastatic lesions, nephrectomy was performed. Unfortunately, however, the nephrectomy did not improve prognosis and all three patients did within 10 months after the nephrectomy. Nephrectomy may not be recommended in cases of metastatic renal tumors even if no other metastatic lesions can be found by various image examinations.

Adenocarcinoma↗