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Biomedical subjects

T Nakazawa

Publications and source records attributed to T Nakazawa.

At least 127 records · Page 7Linked to original sources
PubMed1999

Lymphotoxin inhibits Chlamydia pneumoniae growth in HEp-2 cells.

Cytokines such as gamma interferon and tumor necrosis factor alpha (TNF-alpha) inhibit the intracellular replication of Chlamydia pneumoniae or Chlamydia trachomatis. In this study, we found that another cytokine, lymphotoxin (TNF-beta), restricts the growth of C. pneumoniae in HEp-2 cells. When lymphotoxin (10 U/ml) was added during incubation from 8 to 16 h postinoculation, inclusion body formation was severely reduced. In addition, we observed activation of nitric oxide production and the nuclear transition of NF-kappaB in HEp-2 cells in response to lymphotoxin. These results suggest that inhibition of chlamydial growth by lymphotoxin is mediated, at least in part, by nuclear transition of NF-kappaB, resulting in induction of nitric oxide synthase to produce nitric oxide, a potent bacteristatic agent. This is the first report on antichlamydial activity of lymphotoxin through induction of nitric oxide.

Animals↗
PubMed1999

Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca2+ sensitization.

The mechanism of Ca2+ sensitization of contraction has not been elucidated in airway smooth muscle (SM). To determine the role of a small G protein, rhoA p21, and its target protein, rho-associated coiled coil-forming protein kinase (ROCK), in receptor-coupled Ca2+ sensitization of airway SM, we studied the effect of (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexane carboxamide dihydrochloride, monohydrate (Y-27632), a ROCK inhibitor, on isometric contractions in rabbit tracheal and human bronchial SM. Y-27632 completely reversed 1 microM carbachol (CCh)-induced contraction of intact trachea with a concentration producing half-maximum inhibition of effect (IC50) of 1.29 +/- 0.2 microM (n = 5). Although 4beta-phorbol 12,13-dibutyrate (1 microM)-induced Ca2+ sensitization was relatively resistant to Y-27632 in alpha-toxin-permeabilized trachea, CCh (100 microM) plus guanosine triphosphate (GTP) (3 microM)- and guanosine 5'-O-(3'-thiotriphosphate) (10 microM)-induced contractions were relaxed completely by Y-27632 with IC50 of 1.44 +/- 0.3 (n = 6) and 1.15 +/- 0.3 microM (n = 6). Endothelin-1 (1 microM) plus GTP (3 microM)- developed force was also reversed by Y-27632 with IC50 of 4. 10 +/- 1.1 microM (n = 6) in the alpha-toxin-permeabilized bronchus. Both the rabbit and human SM expressed rhoA p21, ROCK I, and its isoform ROCK II. Collectively, rho/ROCK-mediated Ca2+ sensitization plays a central role in the sustained phase of airway SM contraction, and selective inhibition of this pathway may become a new strategy to resolve airflow limitation in asthma.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Effect of beta-agonists on production of cytokines by activated T cells obtained from asthmatic patients and normal subjects.

Intracellular levels of cAMP were found to regulate T cell activity. We examined whether beta2-agonists altered cytokine production and cyclic adenosine monophosphate (cAMP) accumulation in concanavalin A (ConA)-activated peripheral T cells from asthmatic patients. Procaterol and isoproterenol weakly decreased the ConA-elicited interleukin (IL)-4 and IL-5 secretion; however, the inhibitory effect of procaterol on the ConA-induced IL-2 secretion was inferior to that of isoproterenol in normal controls and was little in asthmatics. The intracellular accumulation of cAMP by procaterol was not altered compared with that by isoproterenol. Results suggest that there is a qualitative difference between procaterol- and isoproterenol-induced cAMP accumulation in T cells.

Adrenergic beta-Agonists↗
PubMed1999

[Efficacy and safety of endoscopic papillary balloon dilation for removal of common bile duct stones in the elderly].

From May 1996 through August 1998, endoscopic papillary balloon dilation (EPBD) was performed to remove common bile duct stones in 17 elderly patients, aged 75 to 87 (average 81.9), including 7 with juxtapapillary diverticulum. The balloon-tipped biliary catheter for EPBD was inflated at a pressure of 10 atm, for 2 minutes, and the maximum diameter of the inflated balloon reached 8 or 10 mm. After one or two ERCP sessions using EPBD alone, the bile duct stones were removed in 16 (94.1%) of 17 patients, and endoscopic mechanical lithotripsy was required in 6 (35.3%) patients. Another patient required additional sphincterotomy for removal of the stone. Massive bleeding or intestinal perforation, which can be major complications of EPBD, did not occur, and while the minor complication of transient abdominal pain was observed in 3 patients but there was no case of pancreatitis. The clearance rates of stones and complication rates in our EPBD procedure were similar to other reports and to those of our data in younger patients, aged under 75. EPBD was a safe and effective technique for the extraction of the common bile duct stones in elderly patients.

Aged↗
PubMed1999

[Current concept of the pathogenesis of autoimmune type 1 diabetes mellitus].

In type 1 diabetes, the beta cell is selectively destroyed by T lymphocytes in a genetically susceptible individual. Susceptible HLA-class II molecules which have low binding affinity with putative beta cell antigens may fail in induction of self-tolerance. beta cell-reactive T cells may expand and infiltrate around the islet (benign insulitis) by stimulation with environmental factors through molecular mimicry and/or beta cell antigens per se. Benign insulitis may develop to destructive insulitis under overexpression of Th1 cytokines, which may be affected by non-MHC genes. Immune interventions to shift a cytokine balance to Th2 dominance in the insulitis lesion may be most realistic approach to suppress development of type 1 diabetes after the induction of autoimmunity.

Animals↗
PubMed1999

[Dependence and obsession].

Alcoholism, especially the urge to drink and relapse from abstinence, is deeply associated with obsession. And also alcoholics on abstinent 10 years or more are still higher on the obsessive-compulsive symptom dimension more than the depression and interpersonal sensitivity. Obsession was introduced by Kraepelin in 1915 and has been studied extensively since. When a person with obsession becomes exhausted with chronic rumination accompanied suspicion, he or she is driven to impulsive acts like alcoholics, and develops a personality disorder that displays persistent abnormal activities. Impulsive-compulsive spectrum characterizes by dimensions of risk-aversive/risk-seeking and harm-avoidant/harm- minimizing behaviors. Disorders on the compulsive end of the spectrum include obsessive-compulsive disorder, hypochondriasis, body dysmorphic disorder, anorexia nervosa an depersonalization. Mixed compulsive and impulsive disorders include Tourette's disorder, trichotillomania, pathologic gambling, sexual compulsions and alcoholism. Disorders on the impulsive end of the spectrum include borderline personality disorder and antisocial personality disorder. Using 123I-IMP SPECT, regional cerebral blood flow significantly decreased in alcoholics without Korsakoff sign (WAIS FIQ 90 or over) than alcoholics with Korsakoff signs (WAIS FIQ 89 or under) and control on the frontal lobe and thalamus. Recent model of obsessive-compulsive pathophysiology demonstrating that cortical regions have different effects on the direct and indirect pathways, indicates that the the different effects of serotonergic agents in the cortex alone could result in a change in balance between the direct versus indirect basal ganglia pathway. This article reviews alcoholism and obsession, ego dystonic and ego syntonic, approach-avoidance conflict, a recent biological approach to alcoholics and a spectrum for obsession.

Alcoholism↗
PubMed1999

[Intracerebral hemorrhage associated with long-lasting deficiency of factor XIII].

A 5-year-old boy had an intracerebral hematoma evacuated from the left parieto-occipital region at a local hospital. There was a difficulty in hemostasis during the operation. Postoperatively his neurological state gradually deteriorated. CT scans showed a gradual increase in intracerebral hemorrhage at the operated site. He was transferred to our clinic for further treatment. The preoperative blood coagulation profile showed that the activity of factor XIII was only 4%. The hematoma was removed without any trouble under administration of factor XIII. Postoperative course was also uneventful although the plasma level of factor XIII did not go up higher than 26% in spite of its daily administration. Although factor XIII administration was terminated one month after cranioplasty, the patient showed good recovery and the level of factor XIII spontaneously normalized in 6 months. The cause of the extremely low level of factor XIII in this case is not known, but it could be ascribed to massive hemorrhage.

Cerebral Hemorrhage↗
PubMed1999

[The value of intracellular CD41 antigen detection to the diagnosis of acute megakaryoblastic leukemia].

An 11-month-old boy was transferred to our hospital because of fever and bleeding tendency on March 13, 1998. Laboratory studies showed a white blood cell count of 43,360/microliter with 75% blasts, a hemoglobin concentration of 8.4 g/dl, and a platelet count of 23 x 10(3)/microliter. Surface marker analysis with a flow cytometer revealed that only 21% and 11% of the blasts, respectively, were positive for CD41 and CD42b. Treatment with a permeabilizing agent apparently increased the reactivity of the blasts with anti-CD41 monoclonal antibody (MoAb), which can recognize IIb independently of IIIa. However no significant differences were observed in reactivity with anti-CD41 MoAb (which recognizes the IIb/IIIa complex) anti-CD61 MoAb and anti-CD42b MoAb before or after fixation. Blasts positive for platelet peroxidase were observed by electron microscopy, thus confirming the diagnosis of acute megakaryoblastic leukemia. We concluded that the detection of intracellular antigens is useful for the quick diagnosis of acute megakaryoblastic leukemia characterized by low surface expression of megakaryocytic lineage antigens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Sensitivity of sputum eosinophil cationic protein level for monitoring asthmatic patients with normal peak expiratory flow].

Previous studies have shown that eosinophils and eosinophil cationic protein (ECP) levels in the sputum of patients with asthma closely reflect inflammatory activity of the bronchial mucosa. We examined whether the ECP level or eosinophil count in induced sputum provides information useful in determining whether to taper the dose of medications or to terminate treatment especially with inhaled corticosteroids in patients with well controlled asthma. We studied 15 adults with asthma who consistently maintained a peak expiratory flow (PEF) value within 80% or more of their predicted value (green zone) for at least 4 weeks with no asthmatic symptoms. All patients underwent at least two hypretonic saline inhalation tests. Forty sputum samples were obtained for evaluation of cell count and ECP level. Before the tests, patients were requested to record asthmatic symptoms, medications received, and morning and evening PEF values in a diary for more than 3 months. The relations among clinical and laboratory variables, including symptoms scores, medication scores, asthma scores (= symptom scores + medication scores). PEF values, forced expiratory volume (FEV1.0) during the test, and sputum eosinophil count or sputum ECP, were analyzed. The sputum ECP level correlated significantly with the percentage of eosinophils in the sputum (rs = 0.783). There were also significant correlations between the sputum ECP level and the mean weekly symptom scores (rs = 0.500-0.510), medication scores (rs = 0.510-0.540), and asthma scores (rs = 0.509-0.548). However, there were no significant correlations among sputum ECP level, mean morning PEF or evening PEF, daily variation in PEF, and FEV1.0. We conclude that the sputum ECP level is a sensitive laboratory variable useful in monitoring the presence of eosinophilic inflammation in the bronchial mucosa of patients with bronchial asthma, especially those who have mild or no symptoms with normal PEF.

Adult↗
PubMed1999

Chemotaxis and motility of Helicobacter pylori in a viscous environment.

The chemotactic activity of Helicobacter pylori is important for its colonization. H. pylori exhibited chemotactic responses to urea and potassium bicarbonate, which can be supplied from human gastric epithelium. The chemotactic activities of H. pylori in a fluid environment were higher on the urease-positive strain than on the isogenic urease-negative strain. In a viscous solution containing 3% polyvinylpyrrolidone, the urease-positive strain showed stimulated chemotactic activity, whereas the urease-negative mutant did not show such stimulation. These results were in accordance with the fact that the mutant strain did not show swarming, which is a form of bacterial active motility in the viscous environment in soft agar regardless of having flagella. Incubation of the wild-type strain with urease inhibitors partially inhibited the chemotactic activities in the viscous solution. Inhibition of the chemotactic activity by urease inhibitors paralleled the inhibition of urease activity. The chemotactic activity of H. pylori has been shown to utilize proton motive force for motility. These results highlighted the importance of cytoplasmic urease for chemotactic motility of H. pylori possibly by an increase in the proton motive force under a condition that mimics the gastric mucus layer, in which the bacteria reside. These results indicated a possible application of drugs having urease-inhibiting potential for eradicating H. pylori. The significance of swarming in the expression of bacterial virulence was also discussed.

Chemotaxis↗
PubMed1999

Relapse of duodenal ulcers after successful eradication of Helicobacter pylori in gastric ulcer patients.

Relapse of duodenal ulcers was observed endoscopically after Helicobacter pylori eradication therapy for gastric ulcer patients in 2 of 32 successful cases. One patient, a 40-year-old woman, received dual therapy with lansoprazole 60mg and amoxicillin 1000mg for 2 weeks because of an intractable, easily-relapsing gastric ulcer accompanied by duodenal ulcer scars that had not relapsed for 5 years. The H. pylori status was assessed by a rapid urease test, light microscopy, culture, and anti-H. pylori antibody. At 24 months after the cure of H. pylori she had upper abdominal pain and showed relapse not of the gastric ulcer but of the duodenal ulcer. The H. pylori status remained negative. The other patient, a 44-year-old man, showed an active gastric ulcer and duodenal ulcer scars at the first endoscopy. He received the same regimen as described above. Ten weeks after completion of the eradication therapy, endoscopy showed healing of the gastric ulcer and relapse of the duodenal ulcer despite successful eradication. These two cases suggest that H. pylori eradication modifies the pathophysiological condition of gastric acid secretion and facilitates relapse of duodenal ulcers.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

InsP3, but not novel Ca2+ releasers, contributes to agonist-initiated contraction in rabbit airway smooth muscle.

1. To examine the contributions of the putative Ca2+ releasers, inositol 1,4,5-trisphosphate (InsP3), cyclic ADP ribose (cADPR), and nicotinate adenine dinucleotide phosphate (NAADP), to carbachol (CCh)-induced contraction in airway smooth muscle, we measured force development of permeabilized rabbit tracheal smooth muscle, human bronchial smooth muscle and guinea-pig ileum longitudinal smooth muscle. 2. In the presence of 50 microM GTP, CCh and InsP3 contracted alpha-toxin-permeabilized tracheal smooth muscle dose dependently; the EC50 values for CCh and InsP3 were 1.84 microM and 363 microM, and the maximum responses (normalized to the 30 mM caffeine response) to 100 microM CCh and to 800 microM InsP3 were 206 +/- 13.4 % (mean +/- S.E.M.) and 84.4 +/- 5.3 %, respectively. 3. However, cADPR (10-300 microM), beta-NAD+ (2.5 mM), FK506 (30 microM) and NAADP (100 microM) neither contracted the strip by themselves nor affected the subsequent CCh (1 microM) response. alpha-Toxin-permeabilized bronchial smooth muscle and ileum smooth muscle also responded to caffeine, InsP3 and CCh but not to cADPR. 4. Both 100 microM 8-amino-cADPR, a selective cADPR antagonist, and 100 microM thionicotinamide-NADP, a selective NAADP antagonist, failed to inhibit the CCh response, although procaine abolished the caffeine, InsP3 and CCh responses in the permeabilized tracheal smooth muscle. 5. Although inhibition of the caffeine response by 30 microM ryanodine was nearly complete, approximately 30 % of the InsP3 (300 microM) plus GTP (50 microM) response was retained, and the resultant response disappeared after the caffeine response was evoked in the presence of ryanodine. 6. Heparin (300 microg ml-1) blocked InsP3 (300 microM) and CCh (3 microM) responses in beta-escin-permeabilized tracheal smooth muscle, while Ruthenium Red (100 microM) partially inhibited the CCh response. 7. Collectively, InsP3 but not cADPR or NAADP plays a key role in CCh-initiated contraction, and InsP3 utilizes a single compartment of the caffeine/ryanodine-sensitive stored Ca2+ in airway smooth muscle.

Adenosine Diphosphate Ribose↗
PubMed1998

Autoantibodies against CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) that impair glucose-induced insulin secretion in noninsulin- dependent diabetes patients.

Cyclic ADP-ribose (cADPR) has been shown to be a mediator for intracellular Ca2+ mobilization for insulin secretion by glucose in pancreatic beta cells, and CD38 shows both ADP-ribosyl cyclase to synthesize cADPR from NAD+ and cADPR hydrolase to hydrolyze cADPR to ADP-ribose. We show here that 13.8% of Japanese non-insulin-dependent diabetes (NIDDM) patients examined have autoantibodies against CD38 and that the sera containing anti-CD38 autoantibodies inhibit the ADP-ribosyl cyclase activity of CD38 (P </= 0.05). Insulin secretion from pancreatic islets by glucose is significantly inhibited by the addition of the NIDDM sera with anti-CD38 antibodies (P </= 0.04-0.0001), and the inhibition of insulin secretion is abolished by the addition of recombinant CD38 (P </= 0.02). The increase of cADPR levels in pancreatic islets by glucose was also inhibited by the addition of the sera (P </= 0.05). These results strongly suggest that the presence of anti-CD38 autoantibodies in NIDDM patients can be one of the major causes of impaired glucose-induced insulin secretion in NIDDM.

ADP-ribosyl Cyclase↗