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Biomedical subjects

S Sawada

Publications and source records attributed to S Sawada.

At least 127 records · Page 7Linked to original sources

Distribution and properties of kainate receptors distinct in the CA3 region of the hippocampus of the guinea pig.

To characterize the nature of kainate (KA) receptors distinct in the CA3 region of the hippocampus, properties of depolarizations induced by pulses of KA or AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) applied to dendrites of CA3 neurons with micropipettes were studied in thin transverse slices of the guinea pig hippocampus. KA induced depolarizations at negligible latencies only when administered to the most proximal dendritic areas. The depolarization was unaffected by tetrodotoxin or by a decrease in Ca2+ and an increase in Mg2+ concentrations. The declining slope of the KA-induced depolarization was significantly slower than that of the AMPA-induced depolarization. In comparison with the AMPA-induced depolarization, the KA-induced depolarization was much less susceptible to antagonists such as 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) and 1-(4-aminophenyl)-4-methyl-7, 8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI52466). 6, 7,8,9-Tetrahydro-5-nitro-1H-benz[g]indole-2,3-dione-3-oxime (NS-102) and (2S,4R)-4-methylglutamate (SYM 2081) were without effects. The threshold concentration of pressure-ejected KA to induce depolarizations was about 200 nM. Excitatory postsynaptic potentials elicited by mossy fiber stimulation were more potently suppressed by CNQX than by GYKI52466. These results indicate that receptors responsible for the slow KA depolarization in the CA3 region of the hippocampus are not AMPA receptors but KA receptors. They are localized in the most proximal part of the apical dendrite and distinct from those observed in primary cultures of hippocampal neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Significance of stem cell factor and soluble KIT in patients with systemic lupus erythematosus.

To determine the significance of stem cell factor (SCF) and soluble KIT (sKIT) in the serum of patients with systemic lupus erythematosus (SLE), levels of SCF and sKIT in patients with SLE were estimated, and their correlations with clinical parameters were examined. The sKIT levels in SLE patients (n = 106) were significantly lower than those in healthy controls (n = 40). A significant negative correlation was found between the SCF and sKIT levels of SLE patients. Although the SCF levels correlated with the titre of anti-RNP antibody, no significant relationship was found between SCF levels and blood cell counts, such as white blood cell, red blood cell and platelet counts. sKIT levels were significantly correlated with the platelet count, and were negatively correlated with the white blood cell count, titre of anti-DNA antibody, and SLE activity index (SLEDAI). sKIT levels were also negatively affected by high doses of corticosteroid. These results indicate that serum sKIT levels may be more closely related than SCF to the haematological abnormalities in SLE patients, and may reflect the clinical status of SLE patients and the effectiveness of high-dose corticosteroid treatment.

Adult↗

Properties of depolarization-induced suppression of inhibitory transmission in cultured rat hippocampal neurons.

Properties of depolarization-induced suppression of inhibitory transmission ("DSI") in cultured rat hippocampal neurons were examined, by recording inhibitory postsynaptic currents (IPSCs) evoked by single presynaptic neurons. In about 40% of the inhibitory synapses, transient suppression of IPSCs was induced by applying a depolarizing pulse (to 0 mV, > 2 s) to the postsynaptic neuron, which was identified to be gamma-aminobutyric acid dependent (GABAergic) in some pairs, and to be glutamatergic in some other pairs. This depolarization-induced suppression of IPSCs, "DSI", was Ca2+ dependent, and was associated with an increase in the paired-pulse ratio. Phorbol esters had an occluding effect on DSI when applied to the bath solution, but not to the pipette solution used for the postsynaptic neuron. Application of the opioid receptor antagonist naloxone had no effect on DSI. The present study demonstrates that a pair of cultured hippocampal neurons can exhibit DSI similar to that previously reported to occur in hippocampal slices; this suggests that a dissociated cell culture system can provide a useful model system for the study of DSI. Furthermore, it was found that inhibitory neurons, in addition to excitatory ones, can induce DSI, and that a process sensitive to phorbol esters, but not activation of opioid receptors, is involved in DSI.

Animals↗

Severely reduced left atrial appendage function: a cause of embolic stroke in patients in sinus rhythm?

Recently, attention has been focused on transesophageal echocardiographic detection of left atrial appendage function to assess of risk of thrombus formation because of potential benefit of anticoagulation therapy. However, most of these studies have been conducted in patients with atrial fibrillation or mitral valve disease. In this article we review cases of 2 patients without valvular disease who had embolic stroke in sinus rhythm. Transesophageal echocardiography revealed thrombi in the left atrial appendage in both patients. The left atrial appendage function in these patients was compared with that in patients with chronic atrial fibrillation and a control group in sinus rhythm. Left atrial appendage function in the patients with stroke and sinus rhythm was significantly lower than that of patients in the control group in sinus rhythm (P < .001) and was similar to the appendage function in patients with chronic atrial fibrillation. These observations provide further evidence that the finding of reduced left atrial appendage function can be a cause of stroke in patients with sinus rhythm even in the absence of mitral valve disease. Reduced left atrial appendage function may identify patients with unexplained stroke who should receive anticoagulation therapy even in the absence of detectable appendage thrombi.

Adult↗

A close correlation between electron spin resonance (ESR) dosimetry from tooth enamel and cytogenetic dosimetry from lymphocytes of Hiroshima atomic-bomb survivors.

PURPOSE: To estimate gamma-ray doses received by Hiroshima atomic bomb survivors using electron spin resonance (ESR) of tooth enamel and to compare the results with cytogenetic data. MATERIALS AND METHODS: Tooth enamel ESR was performed for 100 teeth donated from 69 Hiroshima survivors, and conventional cytogenetic examinations were conducted for 61 of the tooth donors. To evaluate possible contamination from dental X-ray exposure, which primarily affects the tooth's buccal surface, each tooth was divided into buccal and lingual parts for subsequent independent enamel isolation and ESR measurement. RESULTS: Almost 20 teeth showed considerably larger buccal doses than lingual doses, but most of these discrepant teeth were incisors and canines. The results are probably attributable to solar light exposure. In contrast, the buccal and lingual doses found in molars were similar. Conventional translocation data of lymphocytes and ESR-estimated doses of 40 donors of molars showed the dose-response for translocations to be almost the same as that expected from in vitro gamma-ray irradiation experiments. CONCLUSIONS: Both tooth enamel ESR and lymphocyte cytogenetics are useful measures for individual biodosimetry of acute radiation exposure, even half a century after the exposure occurred.

Aged↗

In vivo genotoxicity and DNA adduct levels in the liver of rats treated with safrole.

The induction of chromosome aberrations, sister chromatid exchanges (SCEs), and the formation of DNA adducts was studied in hepatocytes of F344 rats exposed in vivo to safrole. Hepatocytes were isolated 24 h after a single dose of safrole or five repeated doses (once a day) by gastric intubation and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor. Cells were fixed after 48 h in culture. Safrole-DNA adducts were detected by a nuclease P1-enhanced 32P-post-labeling assay in isolated hepatocytes from the rats. While a single dose was not sufficient to induce detectable levels of chromosome aberrations at the time of assay, five repeated doses induced these changes with a maximum frequency of 13.4%, compared with the control value of 1.8%. Both a single dose and five repeated doses induced significant SCEs, to a maximum frequency of 0.81 SCEs per chromosome, while the control value was 0.59 SCEs per chromosome. Two major and two minor DNA adducts were detected after treatment with either a single dose or five repeated doses. The maximum amount of total DNA adducts was 89.8 DNA adducts/10(7) nucleotides. These results show that safrole is a genotoxic carcinogen in the rat liver in vivo and suggest that the cytogenetic effects of this compound may result from covalent DNA modification in the rat liver. This in vivo cytogenetic assay should provide a useful means of evaluation of the genotoxicity of hepatocarcinogens.

Animals↗

Interleukin-1 alpha producing synovial sarcoma with prolonged fever: a case report.

The patient had a synovial sarcoma of the monophasic fibrous type accompanied by prolonged spike fever. Wide excision of the tumor resulted in the disappearance of her fever. The tumor cells showed interleukin-1 alpha (IL-1 alpha) expression immunohistochemically. IL-1 alpha cDNA was detected in the tumor by RT-PCR, the sequences of which were identical with those of normal human IL-1 alpha molecules. These results indicated that IL-1 alpha, one of the fever-inducing cytokines, was expressed by sarcoma cells in the present case, which were thought to be a causative factor of the fever.

Aged↗

Intravenous injection with antisense oligodeoxynucleotides against angiotensinogen decreases blood pressure in spontaneously hypertensive rats.

In the renin-angiotensin system, renin is known to cleave angiotensinogen to generate angiotensin I, which is the precursor of angiotensin II. Angiotensin II is a vasoactive peptide that plays an important role in blood pressure. On the other hand, the liver is the major organ responsible for the production of angiotensinogen in spontaneously hypertensive rats (SHR). To test the hypothesis that a reduction of angiotensinogen mRNA in the liver by antisense oligodeoxynucleotides (ODNs) may affect both plasma angiotensinogen and angiotensin II levels, as well as blood pressure, we intravenously injected antisense ODNs against rat angiotensinogen coupled to asialoglycoprotein carrier molecules, which serve as an important regulator of liver gene expression, into SHR via the tail vein. The SHR used in the present study were studied at 20 weeks of age and were fed a standard diet throughout the experiment. Plasma angiotensinogen, angiotensin II concentrations, and blood pressure all decreased from the next day until up to 5 days after the injection of antisense ODNs. These concentrations thereafter returned to baseline by 7 days after injection. A reduction in the level of hepatic angiotensinogen mRNA was also observed from the day after injection until 5 days after injection with antisense ODNs. However, in the SHR injected with sense ODNs, plasma angiotensinogen, angiotensin II concentrations, and blood pressure, as well as hepatic angiotensinogen mRNA, did not significantly change throughout the experimental period. Although the exact role of angiotensinogen in hypertension still remains to be clarified, these findings showed that intravenous injection with antisense ODNs against angiotensinogen coupled to asialoglycoprotein carrier molecules targeted to the liver could thus inhibit plasma angiotensinogen levels and, as a result, induce a decrease in blood pressure in SHR.

Angiotensinogen↗

Interaction of mRNAs for angiotensin II type 1 and type 2 receptors to vascular remodeling in spontaneously hypertensive rats.

We administered angiotensin II (Ang II) receptor type 1 (AT1) blockade (losartan, 40 mg x kg-1 x d-1), type II receptor (AT2) blockade (PD123319, 100 mg x kg-1 x d-1), or angiotensin-converting enzyme (ACE) inhibitor (enalapril, 30 mg x kg-1 x d-1) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age. Control SHR and Wister-Kyoto rats (WKY) received a placebo for the same period. At the end of treatment, losartan and enalapril were both found to have significantly reduced the arterial systolic blood pressure and the collagen concentration to the level of WKY, whereas PD123319 had no effect. Enalapril and PD123319 significantly reduced the media cross-sectional area of the aorta in comparison to that of untreated SHR, which was still larger than that of the WKY; however, losartan did not change it. Using reverse transcription-polymerase chain reaction, we next examined the mRNA expressions for ACE, AT1 receptor, and AT2 receptor in experimental animals. We observed significantly enhanced mRNA expression for AT1 and AT2 receptors and ACE in untreated SHR compared with WKY. The AT1 mRNA level was also significantly decreased in the SHR treated with either losartan or enalapril, whereas the AT2 mRNA level was significantly decreased in the SHR treated with either PD123319 or enalapril in comparison to untreated SHR. The level of ACE mRNA was significantly decreased only in the SHR treated with enalapril. These results indicate that AT1 receptor, but not AT2 receptor, plays a crucial role in the remodeling of matrix tissue, while AT2 receptor may play a role in the development of hypertrophy of smooth muscle in aorta in SHR, and that the reduction of hypertrophy of smooth muscle does not fully account for the suppression of hypertension.

Angiotensin Receptor Antagonists↗

Experimental study of partial liquid ventilation in the setting of acute respiratory failure induced by sea water lung lavage in rabbits.

To study the effect of partial liquid ventilation (PLV) with perfluorocarbon on acute respiratory failure, 3 groups of 17 rabbits were examined to compare. After acute respiratory failure was induced by lung lavage with sea water in 12 of the 17 rabbits, 7 of the 12 rabbits were treated with conventional mechanical ventilation (AC group) and 5 of the 12 rabbits were treated with PLV using perfluorocarbon (AP group). The remaining 5 normal rabbits without acute respiratory failure were treated with PLV with perfluorocarbon as a control group (PL group). In the PL group, PaO2, PaCO2, blood pH, pulmonary compliance or pathological findings were not so changed after PLV. In the AC and AP groups, PaCO2 significantly increased, and in contrast, PaO2 and pulmonary compliance significantly decreased after lung lavage. However, these findings improved to almost the same levels as those of a control group within 2 h after the PLV treatment in the AP group, but in the AC group, these gradually deteriorated over time. As for the pathological findings, pulmonary vascular congestion, alveolar hemorrhage and inflammatory infiltration were observed in the AC group. However, these findings were not observed in the specimens of the AP group. From these results, PLV with perfluorocarbon was shown to be useful to improve gas exchange and pulmonary functions without major side effects.

Acute Disease↗

[Interferon-alpha treatment for chemotherapy-resistant primary macroglobulinemia with stomach and lung invasion].

We reported a case of primary macroglobulinemia with stomach and pulmonary invasion. The patient was 71 years-old who had cervical lymphadenopathy and abdominal pain. Biopsy material of cervical lymph node showed non-Hodgkin's lymphoma, and he was diagnosed primary macroglobulinemia by IgM immunological histo-chemical staining of materials of stomach biopsies. Combination chemotherapies were not effective for the reduction of IgM-lambda protein, and organ invasion seemed to be progressive, so we tried interferon-alpha (IFN-alpha) to control M component. Daily injection of 6 megaunits of IFN-alpha induced significant reduction of M component and pulmonary invasion. This favorable changes were observed for 1 year. However, his pulmonary invasion on X-ray films relapsed and he died of respiratory failure by reason of severe pneumonia. IFN-alpha is currently available for myeloproliferative disease, especially chronic myelogenous leukemia and multiple myeloma. This case report showed that IFN-alpha was also available for primary macroglobulinemia.

Aged↗

Clinical outcome of stenting in superior vena cava syndrome associated with malignant tumors. Comparison with conventional treatment.

PURPOSE: We analyzed the clinical outcome of treatment with the expandable metallic stent (EMS) for the superior vena cava (SVC) syndrome associated with malignant tumors, and the results were compared with those of radiotherapy. MATERIAL AND METHODS: Of 33 patients with the SVC syndrome, 23 were treated by Gianturco EMS placement and 10 were treated by radiotherapy and/or chemotherapy alone. Of the 23 EMS patients, 11 had treatment before EMS placement and 12 had no treatment before EMS placement. RESULTS: After stenting, the clinical symptoms disappeared in 78% (18/23) of the patients, i.e. in 50% of the patients with intraluminal tumors, and in 93% of those with extrinsic compression. The clinical symptoms improved in 80% of patients who received radiotherapy. The mean duration of survival was 145 days in patients who underwent stenting, and 146 days in those receiving radiotherapy. However, the survival period differed significantly between patients with intraluminal tumors (44.9 days) and those with extrinsic compression (198.6 days). Between patients with previous treatment and those with no previous treatment, there was no significant difference in response rate or in survival period which were 82% versus 75%, and 127 days versus 162 days, respectively. CONCLUSION: The clinical symptoms showed similar improvement in patients receiving EMS placement or radiotherapy. EMS placement was effective in relieving clinical symptoms in patients who had failed to respond to radiotherapy.

Adult↗

Chordoid meningioma in a child. Case report.

A case of chordoid meningioma occurring in a 15-year-old girl is presented. The patient manifested seizures as the initial symptom and subsequently exhibited subclinical microcytic hypochromic anemia. The tumor, located in the falcotentorial region and associated with diffuse edema, was totally resected. On histological examination of the surgical specimen, the clustering pattern of partly vacuolated cells in the mucoid stroma mimicked chordoma; however, positive staining of individual cells for vimentin and epithelial membrane antigen led to a diagnosis of meningioma. Interestingly, the tumor cells were surrounded by a periodic acid-Schiff- and type IV collagen-positive substance. Electron microscopy demonstrated a strikingly dense and thick basal lamina. The patient's microcytic hypochromic anemia disappeared after the tumor was removed. Both the clinical and pathological features of this case resemble those of chordoid meningioma, a rare meningioma variant.

Adolescent↗

Atrial natriuretic peptide inhibits the expression of tissue factor and plasminogen activator inhibitor 1 induced by angiotensin II in cultured rat aortic endothelial cells.

The pharmacological characteristics of atrial natriuretic peptide (ANP), such as natriuresis, vasodilation, or suppression of smooth muscle cell proliferation, are well investigated. However, this is the first study to report its role on blood coagulation and fibrinolysis mediated by vascular endothelial cells. In this study, the effects of ANP on the enhanced expression of tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) by angiotensin II (Ang II) in cultured rat aortic endothelial cells (RAECs) were examined. The expressions of TF and PAI-1 mRNA were detected by northern blotting methods. The activities of TF on the surface of RAECs and PAI-1 in the culture media were measured by chromogenic assay. ANP suppressed mRNA expressions of TF and PAI-1 induced by Ang II in a concentration-dependent manner. This suppression was accompanied by the decreased activities of TF and PAI-1.

Angiotensin II↗

Elevation of soluble CD23 in sera from patients with infectious mononucleosis.

CD23 is induced in B cells upon infection by Epstein-Barr virus (EBV) and a soluble form (soluble CD23: sCD23) is found in culture supernatants from EBV-transformed B cell lines. Based on these observations, we measured serum sCD23 levels in patients with infectious mononucleosis (IM) caused by EBV infection. Sera from patients with IM at the time of diagnosis contained more sCD23 than sera from normal control subjects. Changes in serum sCD23 levels during the course of disease showed that serum sCD23 levels were elevated at the time of diagnosis and they decreased to the normal levels during the convalescent phase defined by the improvement of symptoms of IM. These results indicate that the elevated levels of sCD23 were observed at the acute phase of IM and may be useful in diagnosing IM.

Adolescent↗