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Biomedical subjects

T Nakatani

Publications and source records attributed to T Nakatani.

At least 55 records · Page 3Linked to original sources
PubMed2001

CCR4 memory CD4+ T lymphocytes are increased in peripheral blood and lesional skin from patients with atopic dermatitis.

BACKGROUND: Recent studies have reported that TH1 and TH2 cells express CXCR3 and CCR4, respectively. OBJECTIVE: Our goal was to assess the association of CCR4 and CXCR3 expression with TH2 and TH1 cells and association of CCR4 and CXCR3 expression with inflammation in patients with atopic dermatitis (AD). METHODS: Intracellular cytokine production and chemokine receptor expression in blood T cells were examined by flow cytometry. Immunohistochemical expression of chemokine receptors was also investigated in chronically lesional skin. RESULTS: CCR4+ and CXCR3+ CD4+ T cells predominantly produced IL-4 and IFN-gamma, respectively. Although the frequency of CXCR3+ cells among CD4+ CD45RO+ T cells was similar for patients with AD (n = 29) and healthy control subjects (n = 19), patients with severe AD (n = 14) had a reduced frequency of CXCR3+ cells. In contrast, the frequency of CCR4+ cells and the CCR4/CXCR3 ratio were higher in patients with AD (n = 22) than healthy control subjects (n = 16) and correlated with disease severity of AD. The frequency of CCR4+ cells correlated positively with eosinophil numbers and serum IgE levels, whereas the frequency of CXCR3+ cells correlated inversely with eosinophil numbers. The frequency of CCR4+ or CXCR3+ cells was similar in patients with psoriasis (n = 6) and healthy control subjects. Immunohistochemical analysis showed that the frequency of CCR4+ cells among CD4+ T cells in chronically lesional skin of patients with AD (n = 9) was higher than that of patients with psoriasis (n = 4). CONCLUSION: Our data suggest the association of CCR4 expression with TH2 cells, the predominance of CCR4+ cells in blood from patients with AD, and an important role of CCR4 in the migration of TH2 cells from blood into AD lesional skin.

CD4-Positive T-Lymphocytes↗
PubMed2001

A potential approach for electrochemotherapy against colorectal carcinoma using a clinically available alternating current system with bipolar snare in a mouse model.

BACKGROUND: Although electrochemotherapy appears promising for the treatment of superficial tumors, its usefulness against internal tumors, such as colorectal carcinoma (CRC), has not been well examined. Furthermore, since direct current electric pulses have been used for electropermeabilization of tumors in all in vivo electrochemotherapy studies, including clinical trials, the usefulness of alternating current systems has not been examined at all. In a mouse model it was examined whether the alternating current system with a bipolar snare, which has been employed already as a clinical endoscopic treatment modality, was useful for electrochemotherapy against CRC. METHODS: Murine CRC colon 26 cells were implanted subcutaneously into syngeneic BALB/c mice and electrochemotherapy with bleomycin (BLM) using the alternating current system was performed against established CRC tumors. RESULTS: Electrochemotherapy significantly suppressed the growth of established CRC tumors, resulting in significantly prolonged survival of animals with CRC. Histological examination revealed that electrochemotherapy caused massive necrosis of CRC tumors. Subsequent analysis revealed that the delivery of alternating current electric pulses to CRC tumors profoundly increased intratumoral amounts of BLM. CONCLUSIONS: Because the alternating current system using a bipolar snare has been used widely as an endoscopic treatment modality in clinical settings, these results indicate that electrochemotherapy using the alternating current system may be a promising approach for the treatment of CRC.

Adenocarcinoma↗
PubMed2001

Balloon catheter-assisted endoscopic sclerotherapy for gastric fundal varices using alpha-cyanoacrylate monomer.

We present two patients with bleeding episodes from gastric fundal varices. The gastric fundal varices were treated by balloon catheter-assisted endoscopic sclerotherapy using alpha-cyanoacrylate monomer. The varices were successfully obliterated with no complications or hemodynamic changes to the gastrorenal shunts. This procedure may be considered a novel, feasible approach to the treatment of gastric fundal varices in the future.

Aged↗
PubMed2001

Sex hormone dependency of diethylnitrosamine-induced liver tumors in mice and chemoprevention by leuprorelin.

The prevalence of liver tumors throughout the world makes it imperative to seek chemopreventive agents. This tumor appears to be hormone-responsive and hormonal manipulations may therefore be beneficial. On this basis, both sexes of 12-day-old B6C3F(1) mice were injected i.p. with diethylnitrosamine (DEN) at the dose of 2.5 mg / g body weight and observed for 32 weeks (males) or 36 weeks (females). In 100% of male mice, liver tumors were observed with an average diameter of 2.72 mm and multiplicity of 60.8. Orchidectomy at 6 weeks of age in these mice inhibited the incidence, multiplicity and size to 63%, 5.6 and 1.54 mm, respectively. By further implantation with an E(2) pellet at monthly intervals, these parameters were reduced to 26%, 0.6 and 0.61 mm, respectively. Administration of a gonadotropin-blocking chemical, leuprorelin, to DEN-treated male mice significantly reduced the multiplicity and size of tumors to 18.3 and 2.54 mm (P < 0.01 compared to those of DEN only). In female mice, the incidence of liver tumor was significantly smaller than that of males. However, ovariectomy and / or testosterone supplement significantly increased the occurrence of liver tumor. An anti-estrogen, toremifene, caused a marked further decrease of liver tumors. Mitotic indices with bromodeoxyuridine in tumor tissues paralleled the occurrence of liver tumors. Serum testosterone levels were significantly reduced by orchidectomy or by leuprorelin administration. These results further confirm that liver tumor is testosterone-responsive and hormonal manipulation by surgical orchidectomy or by chemical orchidectomy i.e. by leuprorelin, could substantially prevent the appearance of liver tumors.

Animals↗
PubMed2001

A novel quinoline alkaloid possessing a 7-benzyl group from the centipede, Scolopendra subspinipes.

The novel quinoline alkaloid scolopendrine was isolated from the centipede, Scolopendra subspinipes mutilans L. Koch. The structure was determined to be 2-hydroxy-7-[(4-hydroxy-3-methoxyphenyl)methyl]-3-methoxy-8-quinolyl sulfate on the basis of high-resolution electron-spray ionization mass spectroscopy and two-dimensional NMR spectral data. Unlike quinoline alkaloids so far reported, scolopendrine is unique in having a 7-benzyl moiety in the quinoline ring.

Alkaloids↗
PubMed2001

Appropriate indications for the use of a percutaneous cardiopulmonary support system in cases with cardiogenic shock complicating acute myocardial infarction.

Percutaneous cardiopulmonary support (PCPS) is now available for hemodynamic support in patients with cardiogenic shock, but there are no guidelines for its use. The present study determined the appropriate indications for the use of the PCPS in patients with cardiogenic shock complicating acute myocardial infarction (AMI). Sixty-four consecutive patients with cardiogenic shock complicating AMI had hemodynamic support with an intraaortic balloon pump (IABP; n=38) and/or PCPS (n=26). The shock score (0-15) was calculated immediately before starting these support systems to quantify the severity of shock. Multivariate logistic regression analysis determined the clinical factors affecting in-hospital mortality. The relationship between in-hospital prognosis and the shock score was also examined in the 2 groups. The most significant factor related to the in-hospital prognosis was the shock score (p=0.0007; OR 2.16, 95% CI: 1.37-3.39). Another related factor was revascularization; however, this relationship did not reach statistical significance (p=0.069; OR 0.06). Among the 13 cases whose shock score was 4-8 (moderate shock), 5 survived in the PCPS group, but only 1 of 19 patients survived in the IABP group (p<0.05). None of the patients in either group whose shock score was more than 9 survived. The severity of shock is the most reliable independent predictor of in-hospital mortality in patients with cardiogenic shock complicating AMI. Using PCPS in patients with moderate cardiogenic shock may improve their in-hospital survival, but it must be used before the shock becomes severe.

Aged↗
PubMed2001

Overview of the effects of Ringer's acetate solution and a new concept: renal ketogenesis during hepatic inflow occlusion.

Developments in infusion therapy with sodium lactate administered with its isomer, and developments in acetate utilization, both as an infusate or a dialysate, have been previously described, as have the various effects of sodium acetate on cardiovascular function, metabolism and fluid replacement. Unfavorable effects of acetate infusate or dialysate, such as cardiovascular depression, have also been reported, and although the number of studies reporting favorable effects on cardiovascular metabolism is increasing, it is still a matter of controversy. It is clear, however, that acetate can be metabolized in the liver as well as in extrahepatic organs yielding bicarbonate, which can be utilized as an alkalizing agent. Recently, the authors reported new experimental findings that sodium acetate was metabolized to ketone bodies by the kidney during hepatic inflow occlusion. Ketone bodies attract considerable attention as energy substrates in the stress phase and in the reduced redox state. Administration of sodium acetate under such conditions may therefore contribute as substrate supply.

Adenosine Triphosphate↗
PubMed2001

Intravenous readministration of an adenoviral vector performed long after the initial administration failed to induce re-expression of the original transgene in rats.

Although most humans have been exposed to wild-type adenoviruses in their childhood, titers of neutralizing antibodies against viruses decrease with the passage of time. In the present study, we infused adenoviruses carrying the lacZ gene into the tail vein of rats, and re-infused the same adenoviruses long after the initial administration. However, development of neutralizing antibodies against adenovirus and proliferation of adenovirus-specific T cells were elicited profoundly by adenoviral readministration, and transgene expression was not induced in rats. Our results may have important implications for efficacy considerations when adenoviral vectors are employed in clinical settings for the treatment of cancer.

Adenoviridae↗
PubMed2001

Adenovirus-mediated gene transfer into tumors: evaluation of direct readministration of an adenoviral vector into subcutaneous tumors of immunocompetent mice.

Because systemic administration of adenoviruses appears to be limited by their immunogenicity, we examined the feasibility of intratumoral administration of adenoviruses. Direct intratumoral administration of adenoviruses resulted in efficient but transient transgene expression. When adenoviruses were readministered directly into tumors, re-expression of the transgene was achieved. Transgene expression induced by the adenoviral readministration was, however, markedly weaker than that induced by the initial administration. Furthermore, intratumoral readministration of adenoviruses elicited profound humoral and cellular immune responses to adenoviruses. These results may have important implications for efficacy considerations when adenoviral vectors are used for clinical cancer gene therapy.

Adenoviridae↗
PubMed2001

Amelioration of retrovirus-mediated gene transfer into hepatocellular carcinoma cells.

Recombinant retroviruses are by far the most frequently used vehicle in clinical gene therapy. No serious side-effects have been reported so far in clinical gene therapy trials using recombinant retroviral systems. Low titers of recombinant retroviruses, however, have limited the usefulness of recombinant retroviruses. To improve the efficiency of retrovirus-mediated gene transfer, we previously introduced the polyomavirus early region into amphotropic PA317 cells and established a modified retroviral packaging cell line, PAMP51. We demonstrate here that recombinant retroviruses produced by PAMP51-derived retroviral producing cells have approximately 10-fold higher titers compared with those produced by conventional PA317-derived retroviral producing cells. Importantly, recombinant retroviruses produced by PAMP-derived retroviral producing cells could infect hepatocellular carcinoma cells much more efficiently and could induce much stronger expression of a lacZ reporter gene in HCC cells compared with those produced by PA317-derived ones. These results indicate that recombinant retroviruses prepared from PAMP51-derived retroviral producing cells are much more useful than those prepared from PA317-derived ones and that the use of PAMP51 retroviral packaging cells may open up new avenues for the treatment of various types of cancer including hepatocellular carcinoma.

Animals↗
PubMed2001

The angiotensin-I-converting enzyme inhibitor perindopril suppresses tumor growth and angiogenesis: possible role of the vascular endothelial growth factor.

Angiotensin-I converting enzyme (ACE) inhibitor is used widely as an antihypertensive agent, and it has been suggested recently that it decreases the risk of cancer (A. F. Lever et al., Lancet, 352: 179-184, 1998). In this study, we examined the effect of several ACE inhibitors and angiotensin-II type 1 receptor (AT(1)-R) antagonists on tumor development and angiogenesis in a murine hepatocellular carcinoma model. Among ACE inhibitors, perindopril appeared to be a potent inhibitor of tumor development and angiogenesis, whereas AT(1)-R antagonists did not exert such an inhibitory effect. The inhibitory effect of perindopril was achieved even on established tumors. The level of the potent angiogenic factor, vascular endothelial growth factor (VEGF), in the tumor was significantly suppressed by perindopril. In vitro studies showed that perindopril-derived active form, perindoprilat, suppressed the endothelial cell tubule formation. Perindoprilat treatment also significantly inhibited VEGF mRNA expression in BNL-HCC cells in vitro. These results showed that the ACE inhibitor perindopril inhibited tumor development and angiogenesis independent from AT(1)-R blockage, and that VEGF alternation may be involved in the mechanism of this inhibitory effect. Because perindopril is widely used in clinical practice, it may represent an effective new strategy for anticancer therapy.

Angiotensin Receptor Antagonists↗
PubMed2001

[Complete remission of brain metastases from prostate cancer by gamma knife radiosurgery: a case report].

A 59-year-old male visited us with a chief complaint of dysuria. The serum prostate specific antigen (PSA) level was within normal limits, and intravenous pyelography and urethrocystography showed no abnormal findings. Because of his urinary retention, transurethral resection of prostate was performed under a clinical diagnosis of benign prostatic hyperplasia. The pathological diagnosis was poorly differentiated adenocarcinoma of the prostate. Not only combination hormone therapy with goserelin acetate and flutamide, but also intermittent arterial infusion chemotherapy with cisplatin (CDDP) and pirarubicin (THP) using a reservoir system was administered. Additionally total pelvic irradiation was delivered. Magnetic resonance imaging (MRI) demonstrated that his prostate was reduced to less than 50% in size and he had no difficulty in voiding. He suddenly developed dysarthria and hemiplegia 3 months later. MRI and computed tomography (CT) revealed multiple brain metastases. After the gamma knife radiosurgery, neurological findings disappeared and MRI showed dramatic shrinkage of metastatic brain tumors. Metastasis to the pancreas was recognized on CT and he died of multiple organ failure 30 months after his first visit.

Adenocarcinoma↗
PubMed2001

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1999)].

From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64 micrograms/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063 microgram/ml. Generally, all drugs showed strong activities against H. influenzae with MIC80s of 4 micrograms/ml or below. MICs of ofloxacin ranged between 0.063 microgram/ml and 4 micrograms/ml in 1998, however, those were 0.125 microgram/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC80s of 1 microgram/ml. Number of isolated P. aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063 microgram/ml. On the patients' characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M. (B.) catarrhalis in 12.0% and S. aureus in 10.6%. The frequency of S. aureus after administration over 15 days was almost the same as that before administration, but the frequency of P. aeruginosa (both mucoid and non-mucoid) was 36.8% which was higher than that before administration. The frequency of isolated S. pneumoniae was decreased after administration and none of them was isolated after completion of administration. However, that of H. influenzae was decreased to 7.1% after administration within 3 days, and many H. influenzae were isolated after completion of administration as 21.4%.

Adolescent↗
PubMed2001

Clinical study on 53 cases of cadaveric kidney transplantation at Osaka City University Hospital.

BACKGROUND: In this study, we examined the effects of nonimmunological factors on cadaver kidney transplant. METHODS: Fifty-three cadaver kidney transplant recipients were studied. They were divided into two groups, Group I ( donor age<60, n=38 ) and Group II ( donor age > or = 60, n=15). These patients were studied to determine whether donor age and recipient Body Mass Index (BMI) affected transplant outcome. RESULTS: The 3 and 5-year overall graft / patient survival was 80.6 / 100% and 72.7 97.3%, respectively. The best S-Cr after transplantation was significantly (p<0.05) lower in Group I compared to Group II. The 1, 5 and 8-year graft survival was significantly (p<0.05) better in Group I. In the low BMI patients of Group II, 5-year graft survival was significantly (p<0.01) better than high BMI patients. DISCUSSION: An aged cadaver donor was a risk factor for decreased posttransplant renal functions and lower graft survival. However, if a recipient with a low BMI can be selected, the outcome of cadaver kidney transplants from aged donors may be improved.

Adult↗
PubMed2000

CYP4B1 is a possible risk factor for bladder cancer in humans.

In experimental animals such as rats and rabbits, CYP4B1 has an important role in mutagenic activation of procarcinogens in bladders. In human bladders, it is not clear whether CYP4B1 has such role or not. In the present study, human bladder microsomes activated 2-aminofluorene which is a typical substrate for CYP4B1 and is a bladder carcinogen. CYP4B1 was detected in the human bladder microsomes by immunoblotting. Furthermore, we developed a microassay for CYP4B1 mRNA by performing real-time RT-PCR. Using this method, CYP4B1 mRNA levels were assayed in transurethal resection samples from the bladders of patients with bladder tumors. The bladder-tumor patients had a significantly higher expression of CYP4B1 than the nonbladder tumor patients. These findings suggest that a high expression of CYP4B1 increases the risk of bladder tumor by activation of carcinogenic aromatic amines. This approach could be an important tool in the assessment of human bladder cancer risk.

Adult↗
PubMed2000

Immunomodulation with FK506 around the time of intravenous re-administration of an adenoviral vector facilitates gene transfer into primed rat liver.

Although adenoviruses are an attractive vehicle for gene transfer into tissues including various tumors, in vivo adenoviral administration elicits a neutralizing antibody response which eliminates or substantially reduces the efficacy of subsequent treatments. Transiently immunosuppressive strategies at the time of initial adenoviral exposure have shown to prevent the formation of neutralizing antibodies and permit the successful adenoviral readministration in animals. Initial treatment in humans may, however, correspond to adenoviral readministration into animals, because the exposure to wild-type adenoviruses is common in humans. In the present study, we infused Adex1CAlacZ adenoviruses carrying the lacZ gene into the tail vein of rats, and examined whether a transient treatment with the immunosuppressant FK506 around the time of i.v. readministration of adenoviruses could induce the re-expression of the lacZ gene in animals primed with adenoviruses. Although i.v. infusion of adenoviruses carrying the lacZ gene resulted in transiently high levels of transgene expression in rat liver, i.v. reinfusion of adenoviruses failed to induce detectable levels of transgene expression. Conversely, when animals were treated transiently with FK506 around the time of adenoviral reinfusion, development of neutralizing antibodies and antigen-specific T cell proliferation in response to adenoviral reinfusion were significantly suppressed, and re-expression of the transgene was achievable.

Adenoviridae↗
PubMed2000

Apoptosis induced by chelation of intracellular zinc is associated with depletion of cellular reduced glutathione level in rat hepatocytes.

Zn(2+) has multiple implications in cellular metabolism, including free radicals metabolism and cell death by apoptosis. In the present study, we examined the role of Zn(2+) in the regulation of apoptosis in cultured rat hepatocytes. The chelation of Zn(2+) by a membrane permeable metal ion chelator, N, N, N', N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), induced apoptosis. Addition of ZnSO(4) prevented TPEN-induced apoptosis. Unlike the effect of TPEN, a membrane impermeable metal ion chelator, diethylenetriamine pentaacetic acid (DTPA), did not induce apoptosis, indicating that chelation of intracellular Zn(2+) was required to trigger apoptosis. Caspase-3-like proteolytic activity, a general biochemical mediator of apoptosis in a variety of cells and tissues, was also activated with the treatment of TPEN but not DTPA. TPEN treatment, but not DTPA, also resulted in the depletion of intracellular reduced glutathione (GSH) but addition of Zn(2+) recovered the GSH level. N-acetyl-L-cysteine (NAC), a thiol antioxidant, prevented TPEN-induced apoptosis. These results taken together suggest that intracellular Zn(2+) interfere with the apoptosis process, possibly through the regulation of cellular redox potential involving GSH.

Acetylcysteine↗