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Biomedical subjects

I Sano

Publications and source records attributed to I Sano.

At least 19 recordsLinked to original sources

[Castleman disease of the inter-lobar lymph node origin].

We report a case of Castleman disease which originated from the inter-lobar lymph node, with a review of literatures. A 19-year-old woman complaining of cough was pointed out to have an abnormal shadow in the left lung field on chest X-ray. Chest computed tomography (CT) and magnetic resonance imaging (MRI) with enhancement revealed a homogeneous mass lesion at the left inter-lobar portion of the lung. Bronchoscopic findings demonstrated mucosal telangiectasis of the left lower bronchus. We performed the usual axillary thoracotomy and succeeded in extirpation of the tumor without large amount of bleeding. The tumor was elastic and hard, and 70 x 55 x 45 mm in size. Her postoperative course was uneventful and she was discharged on the 12th postoperative day.

Adult↗

Prolonged survival of rat cardiac allograft with proinflammatory cytokine inhibitor.

BACKGROUND: Proinflammatory cytokines, such as tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1), play important roles in acute allograft rejection. FR167653 is an inhibitor of these cytokines that acts through inhibition of the mitogen-activated protein kinase p38 pathway. We examined the effect of FR167653 on allograft rejection. METHODS: We used Brown-Norway and Lewis rats as donors and recipients, respectively. We performed heterotopic cardiac transplantation. The control group consisted of untreated rats. In the experimental groups, recipients were intraperitoneally injected with FR167653 just after operation, followed by daily injection of the drug from Day 1 to 10. We divided 20 rats into 5 groups, which received varying doses of FR167653, ranging from 75 to 300 mg/kg/day. RESULTS: In the control group, the mean graft survival was 6.8 +/- 0.3 days. FR167653 at 150 mg/kg/day significantly prolonged the survival period (up to 12.1 +/- 1.5 days, p = 0.002). Histologically, FR167653 markedly suppressed cellular infiltration on Day 5 post-transplantation. The serum level of TNF-alpha in the control group was persistently elevated from 9.3 +/- 3.9 pg/ml to 11.3 +/- 3.8 pg/ml, whereas FR167653 significantly suppressed the level to <1.4 +/- 1.4 pg/ml. CONCLUSIONS: FR167653 prolonged rat cardiac allograft survival by suppressing the action of proinflammatory cytokines.

Animals↗

OPC-8212, a quinoline derivative, counteracts the reduction in type III collagen mRNA due to lipopolysaccharides in cultured rat cardiac fibroblasts.

Fibrillar collagen plays an essential role in ventricular remodeling, which is a major prognostic factor in various heart diseases. Inflammatory cytokines, including tumor necrosis factor alpha (TNFalpha), have been reported to play a role in various heart diseases and OPC-8212, a quinolinone derivative, has been demonstrated to reduce TNFalpha production. No studies have examined the effects of OPC-8212 on collagen metabolism in connection with inflammatory cytokine and growth factors. Using lipopolysaccharides as a tool to enhance TNFalpha, we examined the effects of OPC-8212 on the expression of type III collagen mRNA [alpha1(III)] in cultured neonatal rat cardiac fibroblasts. We also measured the concentration of TNFalpha and transforming growth factor beta (TGFbeta) in the cultured medium. Northern blot analysis revealed that LPS reduced the expression of alpha1(III) mRNA, and OPC-8212 counteracted this reduction (on average 25% above the reduced level by LPS stimulation). LPS enhanced the TNFalpha concentration in the medium, and OPC-8212 inhibited this enhancement. LPS increased the TGF-beta1 concentration in the cultured medium, while OPC-8212 did not affect this increase. In summary, OPC-8212 counteracted the reduction in type III collagen mRNA expression by LPS accompanied by suppression of the increase in TNFalpha.

Animals↗

Localization of type IV collagen alpha chain in the myocardium of dilated and hypertrophic cardiomyopathy.

A total of 6 alpha chains [alpha 1 (IV) to alpha 6 (IV)] have been identified in type IV collagen. We examined the localization of these chains in the myocardium of patients with dilated (DCM) and hypertrophic (HCM) cardiomyopathy. The localization of alpha 1 (IV)-alpha 6 (IV) in biopsy specimens of 5 patients with DCM and 4 with HCM was examined using immunohistochemistry with monoclonal antibodies. Both alpha 1 (IV) and alpha 2 (IV) immunostaining formed thin homogeneous outlines around myocytes in control hearts. In the DCM specimens, alpha 1 (IV) and alpha 2 (IV) immunostaining formed thick and irregular patterns around myocytes. Staining for alpha 1(IV) and alpha 2 (IV) was also observed in some enlarged intercellular spaces. In 3 DCM hearts, moderate staining for alpha 1 (IV) and alpha 2 (IV) was observed in small replacement fibrotic lesions. In large replacement fibrotic lesions, no alpha 1 (IV) or alpha 2 (IV) staining was observed. In the HCM specimens, alpha 1 (IV) and alpha 2 (IV) staining formed thick homogeneous patterns around myocytes. In the enlarged intercellular spaces, no alpha 1 (IV) or alpha 2 (IV) staining was observed. No labeling for alpha 3 (IV)-alpha 6 (IV) was observed in any heart examined. In conclusion, the present results demonstrate that type IV collagen consisting of alpha 1 and alpha 2 chains appears in the fibrotic lesions of DCM, indicating its contribution to the development of fibrotic changes in the myocardium of DCM patients. In contrast, type IV collagen was restricted to the myocyte membrane in the HCM hearts. Fibrotic processes in the intercellular spaces may differ between DCM and HCM hearts.

Adult↗

[A case of advanced gastric cancer with virchow's metastasis responding remarkably to combination chemotherapy of low-dose CDDP and 5-FU].

The patient was a 72-year-old female who had Stage IVb advanced gastric cancer with Virchow's and paraaortic lymph node metastases. She was considered nonresectable and placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 1 course of administration, Virchow's metastasis disappeared, and the tumor was remarkably reduced in size. However, this chemotherapy was interrupted by toxicity of grade 3 appetite loss, nausea and vomiting, so that total gastrectomy and splenectomy were performed, which were non-curative operation because of paraaortic lymph node metastases. Histopathological examination of the section of the primary tumor revealed that cancer cells had almost disappeared, and only a few atypical cells remained in the granulation tissue. Eleven months after the surgery, there has been no progression of Virchow's and paraaortic lymph node metastases. Combination chemotherapy of low-dose CDDP and 5-FU appears useful as an inductive approach to advanced gastric cancer.

Adenocarcinoma↗

Time-dependent changes of serum carboxy-terminal peptide of type I procollagen and carboxy-terminal telopeptide of type I collagen concentrations in patients with acute myocardial infarction after successful reperfusion: correlation with left ventricular volume indices.

To test the hypothesis that in patients with acute myocardial infarction (AMI), changes in the concentrations of the serum carboxy-terminal peptide of type I procollagen (PICP) and the carboxy-terminal telopeptide of type I collagen (ICTP) reflect extracellular matrix reformation and degradation, respectively, in the infarct healing processes, we measured these serum concentrations by RIA and compared their values with left ventricular (LV) indices obtained by left ventriculography. We studied 13 consecutive patients with their first AMI who underwent successful reperfusion. Blood samples were taken the day of admission and on days 2, 3, 4, 5, 7, and 14. LV volume indices were determined at 1 month after AMI, when LV remodeling was almost completed. The serum concentrations of both PICP and ICTP changed in a time-dependent manner. The average serum PICP concentration was lower than 1 SD below the mean control values on days 2 and 3 and increased thereafter, returning to the lower end of the control range at day 14. The area under the curve (AUC) for PICP was significantly correlated with the LV end systolic (ES) and end diastolic (ED) volume indices and LV ejection fraction for the first 14 days after AMI. The serum PICP on days 5-14 was inversely correlated or tended to be correlated with the LVES and LVED volume indices. The average serum ICTP concentrations on admission were within the control range, began to increase on day 2, and reached maximal concentrations on day 5, remaining at a plateau concentration until day 14. Although the AUC of ICTP for 14 days, the ICTP concentrations on days 1 and 14, and the minimal and maximal concentrations were significantly correlated with creatine kinase (CK) release and the period from AMI onset to the peak CK time, the concentrations were not significantly correlated with any LV indices except for the concentration on day 4, which was weakly correlated with the LVES volume index. The serum concentrations of PICP showed a significant time-dependent change that correlated with LV indices, indicating that PICP may provide additional information for evaluating the healing process because it affects LV remodeling after AMI. Although the serum concentration of ICTP changed in association with CK release, the ICTP concentration was found to be a poor indicator for LV indices.

Adult↗

Sodium azide induces relaxation of the canine gastric body by activating a guanylate cyclase-dependent pathway.

In order to study the inhibitory mechanism by which sodium azide eliminates smooth muscle contraction in vivo and in vitro, gastrointestinal motility was monitored via chronically implanted force transducers in the stomach and duodenum of conscious dogs. Circular smooth muscle strips with myenteric plexus from the canine gastric body were used for in vitro measurement of isometric tension. In conscious dogs, sodium azide (50 micrograms kg-1, i.v.) abolished both the spontaneously occurring phase III contractions and postprandial motility. Exogenous motilin (100 ng kg-1)- and bethanechol (50 micrograms kg-1)-induced contractions were also abolished by sodium azide. In vitro, sodium azide and electrical field stimulation (EFS) caused a concentration- or frequency-dependent nonadrenergic noncholinergic relaxation in the gastric body strips. The relaxation induced by EFS, but not sodium azide, was abolished by tetrodotoxin. NG-nitro-L-arginine and oxyhaemoglobin failed to attenuate the relaxant effect of sodium azide, but strongly inhibited EFS-induced relaxation. Methylene blue inhibited both sodium azide- and EFS-induced relaxation. cGMP concentrations in muscle strips were markedly increased by sodium azide. These findings indicate that sodium azide induces relaxation in the canine gastric body through a direct action on smooth muscle, by activating a guanylate cyclase-dependent pathway; endogenous NO synthesis does not participate in this inhibitory mechanism.

Adrenergic alpha-Antagonists↗

Effect of 5-hydroxytryptamine on gastrointestinal motility in conscious guinea-pigs.

Many studies have suggested that 5-hydroxytryptamine (5HT, serotonin) plays an important role in the control of gastrointestinal motility. However, most of these studies have been carried out on guinea-pig ileum in vitro. Therefore, we investigated the mechanisms of action of 5HT on gastrointestinal motility in conscious guinea-pigs. In order to investigate the effects of 5HT on gastrointestinal motility, extraluminal force transducers were sutured onto the serosal surfaces of the gastric antrum, duodenum and ileum and 5HT was infused intravenously. One of three types of 5HT antagonist or atropine was given before a 5HT infusion of 3.0 micrograms kg-1 min-1 was started. Regular cyclic patterns were observed from the gastric antrum to the ileum in both the fasted and fed states. 5HT increased the contraction amplitudes at all sites. 5HT-induced contractions in the gastric antrum and duodenum were significantly inhibited by methysergide, ondansetron and atropine, but not by ketanserin. In the ileum, only atropine inhibited 5HT-induced contractions. These results suggest that 5HT increases the gastrointestinal contraction amplitude mainly via a cholinergic pathway. 5HT3 receptors and 5HT1-like and/or 5HT2C receptors appear to be responsible for 5HT-induced gastric antral and duodenal contractions, but 5HT receptors other than 5HT1-like, 5HT2A, 5HT2C and 5HT3 receptors induce ileal contractions.

Animals↗

Time dependent alterations of serum matrix metalloproteinase-1 and metalloproteinase-1 tissue inhibitor after successful reperfusion of acute myocardial infarction.

OBJECTIVE: To test the hypothesis that changes in serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase-1 (TIMP-1) after acute myocardial infarction reflect extracellular matrix remodelling and the infarct healing process. PATIENTS: 13 consecutive patients with their first acute myocardial infarction who underwent successful reperfusion. METHODS: Blood was sampled on the day of admission, and on days 2, 3, 4, 5, 7, 14, and 28. Serum MMP-1 and TIMP-1 were measured by one step sandwich enzyme immunoassay. Left ventricular volume indices were determined by left ventriculography performed four weeks after the infarct. RESULTS: Serum concentrations of both MMP-1 and TIMP-1 changed over time. The average serum MMP-1 was more than 1 SD below the mean control values during the initial four days, increased thereafter, reaching a peak concentration around day 14, and then returned to the middle control range. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum MMP-1 on day 5, when it began to rise, and for the magnitude of rise in MMP-1 on day 5 compared to admission. Serum TIMP-1 at admission was more than 1 SD below the mean control value, and increased gradually thereafter, reaching a peak on around day 14. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum TIMP-1 on days 5 and 7, and for the magnitude of rise in TIMP-1 on days 5 and 7 compared to admission. CONCLUSIONS: Both MMP-1 and TIMP-1 showed significant time dependent alteration after acute myocardial infarction. Thus MMP-1 and TIMP-1 may provide useful information in evaluating the healing process as it affects left ventricular remodelling after acute myocardial infarction.

Adult↗

Laminin alpha 1, alpha 2, alpha 4 and beta 1 chain mRNA expression in mouse embryonic, neonatal, and adult hearts.

We examined the relative expression of laminin alpha 1, alpha 2, alpha 4 and beta 1 chain genes in the heart of embryonic, neonatal and adult BALb/c mice. The reverse transcriptase-polymerase chain reaction was employed to determine the mRNA expression of these chains because of the relatively small amount of RNA extracted from rat embryonic hearts. Glyceraldehyde 3-phosphate dehydrogenase and beta-actin were used as internal controls. Among the hearts examined, a relatively high expression of laminin alpha 1 chain was observed in the embryonic hearts, while its expression was very weak in the neonatal and negligible in the adult hearts. Conversely, expression of laminin alpha 2 chain was virtually not observed in the embryonic hearts, but this chain was expressed weakly in the neonatal and substantially in the adult hearts. Similar to laminin alpha 1, laminin alpha 4 was expressed in the embryonic hearts, while its expression was relatively weak in the neonatal and adult hearts. Laminin beta 1 was expressed in the hearts of mice at all stages examined. These results demonstrate that the laminin chain gene expression changes in the different developmental stages of the hearts of BALb/c mice.

Animals↗

Decremental oscillation curve fitting of heart rate response following face immersion into cold water.

Using 18 healthy volunteers, we attempted to fit the heart rate response to a decremental oscillation curve by the least-squares method following facial immersion into cold water. The decremental oscillation equation was as follows: HR = alpha.e(-betat) sin omegat + gamma, where HR is the instantaneous heart rate at t s, alpha the maximum amplitude of the decremental oscillation, beta the decremental rate, omega the angular velocity and gamma the basal heart rate. Each subject immersed his/her face fully in a basin filled with ice-cold water (4 degrees C) for 30 s. The heart rate response to facial immersion was significantly fitted to the decremental oscillation curve with a correlation coefficient > 0.75 in all the trials. Double trials with a 15-min intertrial interval did not show any significant change in the coefficients. Atropine sulfate decreased the value of coefficient omega and increased that of gamma but did not change alpha or beta, indicating that omega is determined mainly by parasympathetic tone. There were no differences for any coefficient between men and women. The coefficients beta and gamma increased in association with age. Given the significant fitting to the decremental oscillation curve of the heart rate response, we propose that the corresponding electrical circuit consists of a resistance and an inductor connected in series, with a condenser in a parallel circuit with a direct current impulse. This method of fitting with the corresponding electric circuit may be useful for analysis of the heart rate response to physiological stimulus.

Age Factors↗

Pharmacological characterization of 5-hydroxytryptamine-induced motor activity (in vitro) in the guinea pig gastric antrum and corpus.

In order to characterize the receptor subtypes involved in 5-hydroxytryptamine (5-HT)-induced circular muscle motor responses of the guinea pig gastric antrum and corpus, we examined the effects of several antagonists in vitro. 5-HT evoked concentration-dependent contractions of the gastric antrum and relaxations of the corpus. 5-HT induced antral contractions were abolished by pretreatment with atropine and tetrodotoxin. Methysergide, ketanserin, granisetron and [1-[2-(methylsulphonylamino)ethyl]-4-piperidinyl]methyl 1-methyl-1 H-indole-3-carboxylate maleate salt (GRl13808A), but neither 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190) nor N2-[(4R)-4-hydroxy-1-(1-methyl-1 H-indol-3-yl)carbonyl-L-prolyl]-N- methyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide (FK888), inhibited 5-HT (3 x 10(-6) M: submaximal concentration)-induced antral contractions concentration dependently and shifted the 5-HT concentration-response curve to the right. 5-HT (3 x 10(-6) M)-induced corporal relaxation was not affected by tetrodotoxin, ketanserin, granisetron or GR113808A. At 10(-7) M, neither methysergide nor NAN-190 affected corporal relaxation, but at a high concentration (10(-6) M) they both inhibited it and shifted the 5-HT concentration-response curve to the right. We conclude that 5-HT-induced antral contraction is mediated by cholinergic neurons via 5-HT2A, 5-HT3 and 5-HT4 receptors, whereas corporal relaxation is mediated via 5-HT1-like receptors on smooth muscle that are sensitive to methysergide and NAN-190.

Animals↗

Bilateral atrial tumors--report of an elderly man with a heavily calcified left atrial tumor.

We report here an 88-year-old male who had been treated with antiarrhythmic drugs because of occasional premature ventricular contraction. The plain chest X-ray film showed a heavily calcified mass within the cardiac silhouette. Transthoracic echocardiography revealed a mobile tumor in the left atrium, which had not prolapsed through the mitral valve into the left ventricle. Transthoracic echocardiography also revealed a tumor in the right atrium. Magnetic resonance imaging of the heart showed that these tumors were attached to the atrial septum by a stalk. The patient had had no history of systemic embolization, syncopal attack or heart failure caused by these tumors. Considering his advanced age, a conservative treatment was agreed upon. At present, he is 93 year-old and in good health. Although the surgical treatment of cardiac tumors has progressed to the point where it represents low risk, even for elderly patients, our present case suggests that some cases of atrial tumors may have a good prognosis even with conservative treatment.

Aged↗

[The mechanism of controlling regional cerebral blood flow in patients with localization-related epilepsy].

INTRODUCTION: Hypoperfusion around the seizure foci has been reported in interictal CBF studies of partial epilepsy. Hypoperfusion may reflect some interictal pathophysiology characteristic of epilepsy, but the mechanism remains to be elucidated. In order to elucidate the controlling system of rCBF in patients with CPS (complex partial seizure), we measured by positron emission tomography rCBF and CO2 vasoreactivity performing a hyperventilatory task, and made comparisons between the affected and contralateral sides of the temporal lobes in CPS patients and the temporal lobe of normal volunteers. We also measured PaCO2, pH, PaO2 and respiratory rate at rest to elucidate the CBF maintaining system. SUBJECTS: 15 volunteers and 12 medically controlled patients with CPS were examined. The affected side of the brain of the patients was determined by dominance of EEG paroxysm. METHOD: For measuring rCBF, the Shimadzu HEADTOME-IV system (8mm FWHM) and H2(15)O (740-1480 [MBq]/scan) bolus injection method were employed. First a rest scan, then a hyperventilatory task scan was performed, at 20 min. intervals between each scan. During the rest scans, the subjects were required to close their eyes, which were covered through the transmission scan and all the other scans. They were monitered with EEG to insure that they were not asleep. Room lights were dimmed, room sounds were kept to a minimum and noises were damped with earplugs. During the hyperventilatory tasks, the subjects were asked to inspire deeply at a rate of 15/min. for 4.5 min. from 3 min. before the scan up to the end of the 1.5 min. scan, and monitored with a respiratory band around the abdomen. Arterial blood gas pressures (PaCO2, pH and PaO2) were also measured with a blood gas analyzer (Radio Meter ABL 330) at the beginning and at the end of the scans. [HCO3-] was calculated on the formula of Henderson-Hasselbalch. Vascular response to PaCO2 change: VrCO2 was defined as follows: VrCO2 = 100 x (CBFh-CBFr)/CBFr/(PaCO2h-PaCO2r) the subscripts h: hyperventilatory r: resting conditions. RESULTS: Blood gasses, rCBF and corrected-rCBF at rest: In the patients, PaCO2 (mmHg) = 46.11 +/- 2.32, pH = 7.374 +/- 0.020, [HCO3-] (mEq/ml) = 25.98 +/- 1.15, CBF (ml/100g/min) = 45.51 +/- 9.33, corrected-CBF (ml/100g/min) = 40.06 +/- 7.27. In the volunteers, PaCO2 = 40. 67 +/- 2.37, pH = 7.400 +/- 0.021, [HCO3-] = 24.36 +/- 1.66, CBF = 48.76 +/- 8.54, corrected-CBF = 48.02 +/- 9.04. PaCO2 and [HCO3-] in the patients were significantly higher than those in the volunteers. pH and corrected-CBF were significantly lower than those in the volunteers. CBF showed no difference. VrCO2 in the temporal lobe: In the affected side of the patients, VrCO2 = 1.976 +/- 0.54. In the contralateral side of the patients, VrCO2 = 2.145 +/- 0.667. In the temporal lobe of the volunteers, VrCO2 = 2.557 +/- 0.898. In both sides of the temporal lobe of the patients, VrCO2 was significantly lower than those in the volunteers. COMMENTS: The effect of anticonvulsant drugs and the suppressive mechanism around the foci are supposed to reduce CBF of CPS patients. We suppose another mechanism, which is vasoconstriction. A significant difference was noted in CO2-vasoreactivity in the temporal lobe between patients and volunteers. Also no difference was noted in rCBF in the temporal lobe between the volunteers and the patients, when the arteries were maximally constricted with the HIV-task. These two results suggest that vasoconstrictive mechanism may be among the factors for the hypoperfusion seen in the temporal lobe of the patients. In patients, PaCO2, [H+], [HCO3-] were significantly higher compared with the volunteers, which suggests the mechanism of respiratory acidosis. Owing to this hypercapnia, global CBF in the patients is maintained in compensation for the hyperfusion and vasoconstriction seen around the foci. CO2 acts as an anticonvulsant and also reduces glucose metabolites which accumulate around the foci.

Adult↗

[Preoperative plasmapheresis for lung cancer with multiple myeloma].

A 66-old-male admitted to our hospital was diagnosed multiple myeloma (IgA kappa type, Durie & Salmon stage IIIA) and squamous cell lung cancer (c-T2N0M0 stage I). The function of platelets was within a normal range (11.7 x 10(4)/mm3 and the bleeding time of two minutes), but the function of coagulation was reduced (prothrombin time, 13.1 seconds; activating prothrombin time, 45.1 seconds; and antithrombin III, 65%). The hyperviscosity syndrome was anticipated because of high IgA M protein (6,551 mg/dl). Plasmapheresis with 800 ml of fresh frozen plasma was performed before the left lower pulmonary lobectomy and R1 lymph node dissection. Then the function of coagulation was improved (prothrombin time, 12.6 seconds; activating prothrombin time, 31.3 seconds; and antithrombin III, 75%). IgA M protein was also decreased to 4,696 mg/dl. Postoperative bleeding necessitated a second thoracotomy. The cause of postoperative bleeding was the ablasion of the pleural adhesion due to tuberculous pleuritis as well as bleeding tendency of multiple myeloma. The plasmapheresis performed in this case did not fully improve the bleeding tendency. Cases of cancer complicated with multiple myeloma have been increasing and if an operation is needed, plasmapheresis should be considered. The indication and the extent of hematologic restoration to be achieved should be further investigated.

Aged↗