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T Nakao

Publications and source records attributed to T Nakao.

At least 37 records · Page 2Linked to original sources
PubMed2001

sFlt-1 gene-transfected fibroblasts: a wound-specific gene therapy inhibits local cancer recurrence.

Local recurrence occurs frequently at the site of injury after surgical resection. On the other hand, fibroblasts have been shown to accumulate in the injured area to heal and remodel the damaged tissues. Therefore, fibroblasts are likely to be useful as wound-specific vectors for delivery of genes to sites of surgically injury. The present study was performed to investigate wound-specific migration of exogenously administered fibroblasts and efficacy of gene therapy using genetically engineered fibroblasts in an i.p. wound recurrence model in rats. We demonstrated that fibroblasts transfected with the GFP gene accumulated specifically around the site of injury immediately after i.p. injection. Then, fibroblasts transfected with an adenovirus designated as AdFex that encoded the soluble form of Flt-1 (sFlt-1), a vascular endothelial growth factor receptor, were administered i.p. to the rats to examine inhibition of tumor growth. At day 16 after implantation, a significantly smaller tumor volume and less microvessel density in wound sites were observed in the AdFex/fibroblast-treated rats than in controls. Furthermore, this treatment also resulted in an improved survival rate. In conclusion, autologous fibroblasts show promise as a wound-specific vector for gene therapy, and administration of sFlt-1 gene-engineered fibroblasts contributed to local control of the tumor around the injured tissue.

Animals↗
PubMed2001

Selective down-regulation of high-affinity IgE receptor (FcepsilonRI) alpha-chain messenger RNA among transcriptome in cord blood-derived versus adult peripheral blood-derived cultured human mast cells.

Substantial numbers of human mast cells (MCs) were generated from umbilical cord blood (CB) and from adult peripheral blood (PB). A single CB progenitor produced 15 436 MCs, whereas a single PB progenitor produced 807 MCs on average. However, PB-derived MCs were far more active than CB-derived MCs in terms of high-affinity IgE receptor (FcepsilonRI)-mediated reactions. One million sensitized PB-derived MCs released 3.6 microg histamine, 215 pg IL-5, and 14 ng granulocyte macrophage-colony-stimulating factor (GM-CSF), whereas 10(6) sensitized CB-derived MCs released only 0.8 microg histamine, 31 pg IL-5, and 0.58 ng GM-CSF on anti-IgE challenge. However, ionophore A23 187 released similar levels of histamine from the 2 MC types. PB-derived MCs highly expressed surface FcepsilonRI alpha chain, and CB-derived MCs almost lacked it in the absence of IgE. PB-derived MCs expressed approximately 5 times higher levels of messenger RNA (mRNA) for FcepsilonRI alpha chain than CB-derived MCs, but mRNAs for beta and gamma chains of the receptors were equally expressed. Among the approximately 5600 kinds of full-length human genes examined by using the high-density oligonucleotide probe-array system, FcepsilonRIalpha was ranked the fifth most increased transcript in PB-derived MCs. The 4 other increased transcripts were unrelated to MC function. These results suggest that IgE-mediated reactions may be restricted during early infancy through the selective inhibition of FcepsilonRIalpha transcription, which is probably committed at progenitor stages and is, at least in part, cytokine-insensitive.

Adult↗
PubMed2001

Enhancement in fecal excretion of dioxin isomer in mice by several dietary fibers.

The effect of increased nutrients (protein, lipid, vitamins and minerals) on dioxin-induced toxic manifestations such as immune suppression, hepatic hypertrophy, splenic atrophy and enzyme induction was investigated in mice after oral administration of 1,2,3,4,7,8-HxCDD (HxCDD) as one of a representative compound of dioxin isomers. Consequently, it appeared that increased minerals and vitamins in the diet prevented immune suppression by HxCDD. In addition, to clarify the additive effect of nutrients and the ability to hasten the excretion of dioxins by dietary fiber, the adsorbing of dioxins by 16 dietary fibers was investigated by in vitro experiment. Among 16 dietary fibers, locust bean gum, pectin, alginic acid, guar gum, chitin and cellulose were effective in binding dioxin isomers. These dietary fibers also enhanced the fecal excretion of HxCDD in mice.

Absorption↗
PubMed2001

A suspected case of proximal diabetic neuropathy predominantly presenting with scapulohumeral muscle weakness and deep aching pain.

A 48-year-old man with a 14-year history of type 2 diabetes with proliferative diabetic retinopathy and distal symmetrical diabetic polyneuropathy visited our hospital. Eight months later, he subacutely developed difficulty in both shoulder movement and trouble standing up from a squatting position. This was accompanied by severe bilateral shoulder and thigh pain. Magnetic resonance imaging of the brain, cervical and lumbar spine, computed tomography of the shoulder and X-ray films of the cervical spine and shoulder revealed no abnormality. Cerebrospinal fluid showed a mild elevation of protein (0.93 g/l) without cell infiltration. Antiganglioside antibodies and point mutation of mitochondrial DNA at position 3243 were not found. Neuropathology of the sural nerve showed a moderate myelinated fiber loss, active axonal degeneration, but onion-bulb formation, endoneurial or epineurial vasculitis were not observed. Electromyography revealed neurogenic changes in the proximal upper limb muscles. Nerve conduction studies revealed mild bilateral slowing in nerve conduction velocity in both of the upper and lower limbs. The diagnosis of this patients was suspected to be a proximal diabetic neuropathy (diabetic amyotrophy). The pain and muscle weakness had persisted more severely in the shoulder than in the thigh throughout the clinical course. His unbearable symptoms could be partially alleviated by an administration of a selective serotonin reuptake inhibitor, fluvoxamine maleate. Proximal diabetic neuropathy is a rare disabling type of neuropathy, which is characterized with subacute bilateral muscle weakness and wasting in the proximal part of the lower limbs. The involvement of the scapulohumeral region observed in this case is very unusual in proximal diabetic neuropathy.

Anorexia↗
PubMed2001

Inhibitory effect of Y-27632, a ROCK inhibitor, on progression of rat liver fibrosis in association with inactivation of hepatic stellate cells.

BACKGROUND/AIMS: Activation of hepatic stellate cells (HSCs) is a final common pathway of liver fibrosis. Recently, it has been demonstrated that the small GTPase Rho is involved in HSCs activation, and that Y-27632, an inhibitor of Rho-kinase which is an effector that acts downstream of Rho, inhibits Rho-associated effects. The objective of the current study was to investigate the inhibitory effects of Y-27632 on the activation of HSCs and the progression of liver fibrosis. METHODS: Y-27632 (1, 10, 100 microM) was added to HSCs isolated from normal rat liver. RESULTS: HSCs maintained the 'star-like' configuration of the quiescent stage in the presence of Y-27632, as well as inhibition of the expression of Na+/Ca2+ exchanger mRNA which was reported to be an indicator of HSCs activation. In addition, when Y-27632 (30 mg/kg body weight) was administered to rats with carbon tetrachloride-induced liver fibrosis, collagen deposition was inhibited, the hepatic hydroxyproline content was decreased, and the serum hyaluronic acid level was reduced. Moreover, Y-27632 reduced the number of smooth muscle alpha-actin-positive cells and transforming growth factor-beta1-positive cells, and inhibited the expression of Na/Ca2+ exchanger mRNA. CONCLUSIONS: These findings indicate that Y-27632 may be useful for the clinical management of liver fibrosis.

Amides↗
PubMed2001

Increased antibody levels to desmogleins 1 and 3 after administration of carbamazepine.

Desmoglein (Dsg) 1 and Dsg3 are recognized as the autoantigens in pemphigus foliaceus and pemphigus vulgaris. Pemphigus-like syndromes have been reported to occur in individuals after exposure to a variety of drugs, but pemphigus caused by carbamazepine is not common. We found that anti-Dsg1 and anti-Dsg3 antibody titres were increased in three individuals administered carbamazepine. Antibody titres against Dsgs 1 and 3 were measured by enzyme-linked immunosorbent assay (ELISA). Of 42 serum samples (25 patients administered carbamazepine, eight patients administered valproic acid and nine healthy volunteers) tested by ELISA, three patients administered carbamazepine showed positive reactivity against both Dsg1 and Dsg3. The patient with the highest titre against Dsg1 and Dsg3 (the index values of anti-Dsg1 and anti-Dsg3 were 79.3 and 86.4, respectively) was a 23-year-old woman (Case 1). The other two patients with positive reactivity were a 5-year-old boy (Case 2) and a 65-year-old man (Case 3). In addition, indirect immunofluorescence study showed intercellular antibodies to the cell surface of the whole epidermis with a titre of 1 : 64 in Case 1 and 1 : 2 in Cases 2 and 3. However, no skin or mucosal involvement was found in any of these cases. There was no difference in the serum concentrations of carbamazepine between the three positive cases and the 22 negative cases of carbamazepine administration. From these facts, the lack of skin diseases may be explained by relatively low values of anti-Dsg 1 and 3 antibodies in Cases 2 and 3. However, it cannot be excluded that undefined exogenous and/or endogenous factors are involved in an outbreak of pemphigus. Furthermore, these findings might be helpful for preventing susceptible individuals from exposure to the suspect drugs.

Adolescent↗
PubMed2001

Endocrine profiles and embryo quality in Japanese black cattle superovulated with human menopausal gonadotrophin and porcine follicle stimulating hormone.

Induction of superovulation using human menopausal gonadotriphin (hMG) in Japanese Black cattle can result in the recovery of a higher percentage of high quality embryos compared with that using porcine follicle stimulating hormone (FSH). In order to clarify the endocrinological mechanism involved in this discrepancy, 30 superovulation sessions of 17 Japanese Black cattle were studied. Fifteen cattle were super-stimulated with hMG (total 600 IU), and the remaining 15 cattle were given FSH (total 20 mg). The plasma profiles of LH, estradiol-17beta (E2) and progesterone (P4) were correlated, and the embryo quality was investigated. The total number of ova recovered and the number of transferable embryos tended to be larger in the hMG-treated group than in the FSH-treated group. The percentage of excellent embryos tended to be higher in the hMG-treated group than in the FSH-treated group (54.3 and 28.7%, respectively, p < 0.10). The E2 level increased during the first 3 days after the initial administration of either hMG or FSH and was higher in the hMG-treated group than in the FSH-treated group (p < 0.05). During this period, the E2 level could be categorized into one of the following three types according to whether it increased or decreased and according to the degree of increase or decrease: (1) increase by a factor of 1.2 or more (quick increase type) (2) slight increase by a factor less than 1.2 (slow increase type), and (3) no increase (unstable increase type). In the group treated with hMG, 66.7% of the animals (10 of 15 cattle) showed a quick increase in the E2 level. However, in the FSH-treated group, 40% (six of 15) of the animals showed a slow increase in the E2 level. The plasma LH level increased dramatically 8 h prior to the peak level in both the hMG- and FSH-treated groups, and then it returned to the basal level 12 h later. After the administration of prostaglandin (PG)F2alpha, the LH peak level was attained within 44 h in 80% of the animals in the hMG-treated group, whereas in the FSH-treated group, the LH peak level tended to be reached later. The P4 level did not increase during the period of hMG or FSH treatment and decreased drastically following administration of PGF2alpha. After the onset of oestrus, the P4 level was higher in the hMG group than in the FSH group, and 5 to 7 days after oestrus, the level remained higher in the hMG group than in the FSH group (p < 0.05). After the first 3 days of hMG administration, the E2/P4 ratio was higher than that after FSH administration. Furthermore, on the day following PGF2alpha administration, the ratio was significantly higher in the hMG group than in the FSH group (p < 0.05). These results indicate that superovulation in cattle given hMG results in a significant increase in plasma E2 during the first 3 days and that the increase in the plasma P4 level is larger a few days after oestrus and thereafter compared with FSH-induced superovulation. Therefore, such plasma level profiles may be related to the increased recovery rate of high quality embryos.

Animals↗
PubMed2001

RECK gene expression in hepatocellular carcinoma: correlation with invasion-related clinicopathological factors and its clinical significance. Reverse-inducing--cysteine-rich protein with Kazal motifs.

The RECK (reversion-inducing-cysteine-rich protein with Kazal motifs) gene was initially isolated as a transformation suppressor gene. It encodes a membrane-anchored glycoprotein with multiple serine protease inhibitor-like domains. The RECK gene is expressed widely in normal organs but is undetectable in many tumor-derived cell lines. When artificially expressed in such cell lines, RECK suppresses their invasive and metastatic activities. Clinical implications of these findings, however, remained undefined because of the lack of studies using fresh human tumor samples. In the present study, we have addressed this issue by analyzing the levels of RECK gene expression in hepatocellular carcinoma (HCC). RECK mRNA was detectable by RNA blot hybridization in all the tumorous and contiguous nontumorous tissues obtained from 64 patients with HCC. In 26 cases, the RECK expression in tumorous tissues was higher than that in nontumorous tissues. The expression of RECK protein in these tissues could also be demonstrated by immunohistochemistry. Patients with high RECK mRNA expression in tumorous tissues tended to show better survival (P =.02), and such tumors had a tendency to be less invasive. Univariate and multivariate analysis revealed that the RECK mRNA expression is a novel and independent variable affecting overall survival (P =.01). These findings support the hypothesis that RECK has negative effects on the invasiveness of HCC cells and suggest the feasibility of RECK mRNA as a promising prognostic molecular marker for HCC.

Adult↗
PubMed2001

Analysis of IL-18 bioactivity and IL-18 mRNA in three patients with adult T-cell leukaemia, acute mixed lineage leukaemia, and acute lymphocytic leukaemia accompanied with high serum IL-18 levels.

Interleukin-18 (IL-18) bioactivity in sera and IL-18 mRNA expression in leukaemia cells of three patients with adult T-cell leukaemia (ATL), acute mixed lineage leukaemia (AMLL) and acute lymphocytic leukaemia (ALL) accompanied with high serum IL-18 levels have been analysed. There was little serum IL-18 bioactivity in the three patients with ATL, AMLL and ALL, while IL-18 mRNA expression was detected in leukaemia cells of all three patients.

Acute Disease↗
PubMed2001

[Appetite and regulation of food intake in uremia].

Anorexia, nausea and vomiting are common symptoms in patients with severe renal failure. Abnormalities in body fluids volume, serum electrolytes concentrations and acid-base balance and accumulations of uremic toxic substances might be primarily contributing to the suppression of appetite. However, the detailed mechanisms that cause appetite suppression in uremia are poorly understood. Impaired gastric emptying, constituents of peritoneal dialysate, plasma high leptin, high cholecystokinin and low neuropeptide Y are also considered to be contributing to appetite suppression in uremia.

Animals↗
PubMed2001

Initial remission-inducing effect of very low-dose cyclosporin monotherapy for minimal-change nephrotic syndrome in Japanese adults.

AIM: Cyclosporin A (CsA) in combination with corticosteroids can be used effectively in steroid-sensitive nephrotic syndrome. However, reports documenting the effectiveness ofCsA monotherapy against such a condition have been scarce. In 11 adults with minimal-change nephrotic syndrome, we have tried very low-dose CsA in the hope of inducing remission without using either corticosteroid or any other immunosuppressive drugs. PATIENTS AND METHODS: Indications for treatment included steroid-sensitive relapsing nephrotic syndrome (7 patients) and first-episode nephrotic syndrome (4 patients). In all patients, corticosteroid and cytotoxic agents had not been given before entry. CsA was administered orally at an initial dose of 2.4 (range 1.5 - 3.1) mg/kg per day. RESULTS: Analysis of the clinical course revealed that 8 of 11 patients entered complete remission after a mean duration of 44 +/- 31 days, whereas 3 patients failed to enter remission to CsA alone, resulting in complete remission combined with methylprednisolone pulse therapy without conventional oral prednisolone. CsA dosages and trough levels between responders and non-responders were similar. Non-responders had much higher levels of serum total cholesterol and higher daily urinary excretion of protein than those of responders, respectively. No patients had significant decrease in creatinine clearance, development of hypertension or suffered from other CsA associated serious side-effects. CONCLUSION: The present data suggest that CsA monotherapy at a very low dose could induce complete remission in adult patients with minimal-change nephrotic syndrome. Conversely, severe hypercholesterolemia would be likely to inhibit the action of CsA against nephrotic conditions.

Adult↗
PubMed2001

[Evaluation of polymerase chain reaction method for monitoring of fungal infection in compromised hosts].

Diagnosis of fungal infections in compromised hosts has been difficult because of insufficient sensitivity and specificity of conventional methods such as culturing and serum testing. Therefore, antifungal agents are usually started in febrile patients who are resistant to antibiotics even if these monitoring tests were negative. In this study, therefore, in order to increase the reliability of these monitoring, polymerase chain reaction (PCR) methods for detection of blood fungus were also performed in compromised hosts including 14 patients with hematological malignancies and one with solid tumor who were undergoing chemotherapies. From these patients, total of 56 peripheral blood samples was collected periodically, irrespective of the presence of infectious signs. At each time point of venopuncture, status of the patient was allocated to one of the followings: A, receiving an intravenous antifungal therapy because of sustaining fever which had not responded to prior antibiotic therapies and also positive for culturing and/or serum beta-D-glucan tests; B, receiving an additional intravenous antifungal therapy but negative for culturing and serum-tests; C, febrile but not yet receiving any intravenous fungal therapy; D, afebrile status. During the study, 10 blood samples from 3 patients were allocated in group A, and one sample of them was positive while remaining 9 were all negative for PCR. Six samples from 4 patients were in group B, and one was PCR positive while remaining 5 were negative. Fifteen samples from 7 patients were in group C, and 3 were positive and 12 were negative for PCR. Twenty-five samples were in group D, and 5 were positive and 20 were negative for PCR. Thus, the results from fungal PCR in these patients were in some case showed discrepancies from those expected from the clinical course and/or conventional monitoring tests. Further evaluation of fungal PCR may gain insight into the more precise diagnosis of fungal infection in these patients.

Adult↗
PubMed2001

[Serial changes in body composition in patients with chronic renal failure on peritoneal dialysis].

Nutritional status is one of the most important factors affecting mortality and morbidity in chronic dialysis patients. There are, however, few data on serial body composition changes in these patients. To investigate serial changes in body composition in patients on peritoneal dialysis, we measured intracellular fluid volume(ICF), extracellular fluid volume(ECF), body protein volume(BPV), body fat volume(BFV) and bone mineral content(BMC) using multifrequency bioelectrical impedance analysis (MF-BIA). MF-BIA was performed in 35 patients, consisting of 21 men and 14 women with a mean age of 51.3 +/- 10.9 years, before and after one year of observation. At the baseline in male patients, ICF was 37.0 +/- 3.4%, ECF 19.7 +/- 1.6%, BPV 20.7 +/- 1.7%, BFV 18.1 +/- 6.6% and BMC 4.5 +/- 0.4% of body weight, and in female patients ICF was 34.4 +/- 2.6%, ECF 17.8 +/- 1.9% BPV 19.0 +/- 1.6%, BFV 24.4 +/- 6.2% and BMC 4.5 +/- 0.4% of body weight. In the group of patients whose body weight increased more than 3 kilograms(n = 9), the increase rate of BFV was 32.3 +/- 20.2%, significantly higher than that of the other segments(p < 0.001). On the other hand, in the group of patients whose body weight decreased more than 3 kilograms(n = 5), each segment showed the same extent of decrease and there was no significant difference in the decrease rates among each segment. In the group of patients whose body weight was stable(n = 21), changes in each body composition segment were extremely small. It could be concluded that the body weight increase is due mainly to increase in BFV and body weight decrease results from a concurrent decrease in each body composition segment in peritoneal dialysis patients.

Adult↗
PubMed2000

The role of LH pulse frequency in ACTH-induced ovarian follicular cysts in heifers.

The aim of the present study was to induce ovarian cysts experimentally in cattle using ACTH and to closely examine the role of LH pulse frequency in ovarian cyst formation. Five regularly cycling Holstein-Friesian heifers (15-18-month-old) were used. Ovaries were scanned daily using an ultrasound scanner with a 7.5 MHz rectal transducer. Daily blood samples were obtained via tail venepuncture for hormone analyses. Additional blood samples (for FSH and LH pulses) were obtained through an indwelling jugular vein catheters every 15 min for 8 h on Days 2 (early luteal phase; ELP), 12 (mid-luteal phase; MLP) and 19 (follicular phase; FP) of control estrous cycle and on alternate days during follicular cyst (FC) formation and persistence. Cysts were induced using subcutaneous injections of ACTH (Cortrosyn) Z; 1 mg) every 12 h for 7 days beginning on Day 15 of the subsequent estrous cycle. Plasma concentrations of progesterone (P4), estradiol-17beta, FSH and LH were determined by double antibody radioimmunoassay while cortisol concentration was determined by enzyme immunoassay (EIA). Ovarian follicular and endocrine dynamics were normal during the control estrous cycles. Ovarian follicular cysts were induced in four of the five heifers. Mean maximum size of cysts was larger (P<0.05) than that of ovulatory follicles (26.78+/-3.65 versus 14.1+/-0.90 mm), respectively. Cortisol levels were increased during ACTH treatment. High concentrations of estradiol and low progesterone were observed after cyst formation. LH pulse frequency was significantly reduced (P<0.05) during cyst formation and persistence compared to ELP (7.5+/-0.75) and FP (6.5+/-0.58), but was not significantly (P=0.23) different from MLP (2.8+/-0.29) pulses. Mean LH pulse amplitude and concentrations were not different. Similarly, the mean pulse frequency, amplitude and concentration of FSH were not different between control study and cystic heifers. These results suggest that the LH pulse frequency observed following ACTH treatment may interact with high estradiol concentration to induce ovarian cyst formation in heifers.

Adrenocorticotropic Hormone↗