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Biomedical subjects

M Maruyama

Publications and source records attributed to M Maruyama.

At least 109 records · Page 6Linked to original sources

[Long-term prognosis of asthmatic patients treated with low-dose beclomethasone dipropionate].

To clarify the prognosis of asthmatics treated with low-dose of inhaled beclomethasone dipropionate (BDP), we retrospectively assessed 43 patients treated with initial dose of 200 or 400 micrograms/day for 5 years, and obtained the following results. 1) 15 patients achieved step-down therapy (group A), 17 patients maintained initial dose of BDP (group B), and 11 patients required step-up therapy of BDP or daily use of oral prednisolone (group C). 2) There was no significant difference in age, sex, duration of disease, severity of disease, peripheral eosinophil counts, %FEV1 and histamine PC20 before BDP treatment among three groups. The percentage of atopic asthmatics was significantly higher in group C than in group A. 3) There was no significant difference in symptom and histamine PC20 between after 1 year state and after 5 years state in three groups. 4) After 1 year from the start of BDP treatment, only 18% patients got symptom free and neither patients exceeded 20,000 micrograms/ml of histamine PC20 in group C. Long-term treatment of low-dose BDP inhalation was effective on mild/moderate asthmatics. Patients requiring step-up therapy had not got sufficient improvement in bronchial hyperresponsiveness after one-year treatment.

Adult↗

Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism.

Autosomal recessive juvenile parkinsonism is a hereditary neurodegenerative disorder, usually beginning before the age of 40. We found three exonic deletions and two novel point mutations (Arg33Stop and Cys431Phe) in six families with autosomal recessive juvenile parkinsonism. In 1 family, in which an autosomal dominant mode of inheritance was suspected, multiple mutant alleles were identified. Although a wide range of ages at onset was observed, there was no correlation between age at onset and genotype.

Adolescent↗

[Experimental study on intraperitoneal versus intravenous CPT-11 for peritoneal seeding and liver metastasis].

CPT-11 is an effective antitumor agent for gastrointestinal malignancy, but the optimum route of administration is unclear. Intraperitoneal administration of this agent was compared with intravenous administration in mouse models of peritoneal seeding and liver metastasis. The peritoneal seeding model and liver metastasis model were established by inoculation of colon 26 tumor cells into the peritoneal cavity and spleen of female BALB/c mice, respectively. CPT-11 (40 mg/kg) was injected intraperitoneally or intravenously on days 2 and 5 after inoculation of tumor cells. Intraperitoneal administration of CPT-11 was significantly more effective than intravenous administration for control of both peritoneal seeding and liver metastasis. Intraperitoneal administration of CPT-11 may be a more efficient form of adjuvant chemotherapy for prevention of both peritoneal seeding and liver metastasis in patients with gastrointestinal cancer.

Animals↗

[Experimental study on CPT-11 intraperitoneal chemotherapy--metabolism of CPT-11 in malignant ascites].

The metabolism of CPT-11 in malignant ascites of gastric cancer patients with peritoneal seedings was studied in advance of the intraperitoneal chemotherapy of CPT-11 in humans. Malignant ascites and blood were drawn from gastric cancer patients. CPT-11 solution (20 mg/ml; 0.2 ml) was added into 3.8 ml ascites or plasma under 37 degrees C and CPT-11, SN-38 and SN-38GLU concentrations were measured with HPLC at times of 5, 30 and 60 minutes after addition of CPT-11. The change from CPT-11 to SN-38 was minimal not only in plasma, but also in malignant ascites. SN-38 GLU concentration was below the limit of measurement. This study showed that in malignant ascites, the enzymes such as carboxyesterase that convert CPT-11 to SN-38 were not present or minimal.

Antineoplastic Agents, Phytogenic↗

[Intraperitoneal administration of CPT-11 in rats--experimental study for pharmacokinetics].

The pharmacokinetics of CPT-11 administered into rats to evaluate the future possibility of i.p. administration was investigated. Serum, bile juice, and intraperitoneal fluid was collected to measure the concentration of CPT-11, its metabolite SN-38, and SN-38 glucuronized (SN-38 glu). The concentration of CPT-11 was elevated after CPT-11 administration into the peritoneal cavity. The serum and biliary concentrations of SN-38 and SN-38 glu were increased and prolonged shortly after i.p. administration of CPT-11. These results suggest the possibility of i.p. administration of CPT-11 in the future.

Animals↗

[Hepatic arterial infusion chemotherapy for liver metastasis from esophageal squamous cell carcinoma].

Since 1993, we have treated 9 patients with liver metastases from esophageal squamous cell carcinoma using hepatic arterial infusion chemotherapy (HAI). These patients underwent esophagectomy and reconstruction with a stomach roll, and without preoperative chemotherapy and/or radiotherapy, HAI was effective in 5 patients (56%) with a CR in 2 patients. Preceding systemic chemotherapy was done with 7 patients, and was effective in 3 of them. HAI was also effective in all of them. In 3 patients with hepatic arterial anomalies, the right gastroepiploic artery and right gastric artery feeding the stomach roll could be preserved after changing the hepatic arterial flow. Two stomach roll ulcers and one hepatic arterial stenosis were experienced due to the toxicity of HAI. However, the nausea, vomiting, diarrhea, and/or myelosuppression seen with the preceding systemic chemotherapy were not experienced. In spite of the technical difficulties in catheterization and toxicities to stomach roll, HAI is considered to be more effective and feasible than systemic chemotherapy.

Aged↗

[Hepatic arterial injection therapy (HAI) for metastatic liver tumor from gastric cancer].

The results and problems of hepatic artery infusion therapy (HAI) for gastric carcinoma with synchronous liver metastasis were evaluated. The response rate of HAI with CDDP and 5-FU for metastatic liver tumor was 55% (1 CR + 5 PR/11). The median survival time for responders was 16.5 months, which was statistically longer than that of non-responders at only 5.5 months. Histologically, most responder cases were with AFP producing tumors and NSE positive tumors without distant lymph node involvement. Non-responder cases developed marked distant lymph node involvement besides the liver metastasis. Most of responder patients died of lymph node recurrence or distant metastasis other than liver tumor. It may be concluded that additional therapy to HAI is needed to improve the prognosis of gastric cancer patients with multiple liver metastases.

Aged↗

[Acute eosinophilic pneumonia induced by cigarette smoking: positive lymphocyte stimulation test of a cigarette extract].

A 21-year-old man was admitted to our hospital with high fever, general fatigue and dyspnea. Chest radiography on admission showed diffuse bilateral infiltrate shadows with Kerley's B lines, and a CT scan showed patches of infiltrates with thickened interlobular septa in both lungs. Examination of the bronchoalveolar lavage fluid and the clinical course led to a diagnosis of acute eosinophilic pneumonia. The patient improved without steroid therapy. We suspected that the disease was related to smoking because the patient had started smoking seven days before the onset of the symptoms. Because a lymphocyte stimulation test gave a positive reaction to a cigarette extract, a challenge test was done. After this, the patient had fever and hypoxemia. These findings suggest that cigarette smoking induces acute eosinophilic pneumonia.

Acute Disease↗

[A case of primary Sjögren's syndrome with interstitial pneumonia showing bronchiolitis obliterans organizing pneumonia pattern and lymphofollicular formation].

A 46-year-old woman with a 2-year history of xerostomia, who had had an episode of suspected Sjögren's syndrome in 1995, was admitted to our hospital because of a dry cough. Chest radiography on admission showed ground-glass infiltrates and reticular shadows in both lower lung fields. Primary Sjögren's syndrome was diagnosed by lip biopsy. Video-assisted thoracoscopic lung biopsies revealed the co-existence of interstitial pneumonia with the BOOP pattern and follicular bronchiolitis. Treatment with oral prednisolone improved the symptoms, and reduced the abnormal chest shadows. This was an interesting case of the BOOP pattern in a lung lesion associated with primary Sjögren's syndrome.

Administration, Oral↗

Central administration of prolactin-releasing peptide stimulates oxytocin release in rats.

The prolactin-releasing peptide (PrRP) is a novel hypothalamic peptide that has been purified as a ligand of an orphan receptor which is expressed in pituitary cells, and is known to stimulate prolactin release both in vitro and in vivo. We previously determined the immunocytochemical localization of PrRP neurons in the rat brain and our results suggest that PrRP takes part in a variety of brain functions. Additionally, in rats we have demonstrated the synaptic contact of PrRP neurons with oxytocin cell bodies in the paraventricular hypothalamic nucleus (PVH) and supraoptic nucleus (SON). This observation indicates that PrRP may regulate oxytocin secretion. In the present study, we performed intra-cerebroventricular administration of PrRP to conscious rats, and examined the effect of PrRP on the plasma levels of oxytocin and vasopressin. Our results show that central administration of PrRP increased the plasma oxytocin and vasopressin levels in female rats, but in male rats only oxytocin was increased. These results suggest that the PrRP acts as a neuro-modulator of the function of magnocellular neurons, especially oxytocin neurons, in the brain.

Animals↗

Improved human islet isolation by a tube method for collagenase infusion.

BACKGROUND: Collagenase infusion into the pancreatic duct is an essential step in human islet isolation. We developed a new method for ductal canulation and collagenese infusion. METHODS: A total of 53 pancreata were divided into two groups: group 1 (n=23), the new tube method, and group 2 (n=30), the standard angiocatheter method. In group 1, a polyethylene tube was inserted into the duct and pushed to the tail. The tail was first expanded, followed by expansion of the body and then the head, by pulling out the tube. RESULTS: Total islet number and number/g pancreas (mean+/-SE) were significantly higher in group 1 (481,123+/-43,218 and 8,010+/-722) (mean+/-SE) than in group 2 (300,974+/-35,122 and 5,090+/-515, P<0.01). Total islet equivalent number and islet equivalent number per gram pancreas were also significantly higher in group 1 (319,176+/-39,354 and 5,455+/-652) than in group 2 (202,022+/-23,331 and 3,722+/-468, P<0.04). Islet purity and fragmentation showed no differences between the groups. CONCLUSIONS: The tube method improved islet yields. We recommended this method for human islet isolation.

Catheterization↗

Reduction of post-ischemic lung reperfusion injury by fibrinolytic activity suppression.

BACKGROUND: Although extensive studies on the detailed mechanisms of ischemia-reperfusion injury have been conducted, the implication of the fibrinolytic system has not been known. To determine the role of the fibrinolytic system in ischemia-reperfusion injury, we used tranexamic acid, a synthetic specific plasmin and tissue-type plasminogen activator inhibitor, to suppress fibrinolytic activity in a rabbit lung ischemia-reperfusion model. METHODS: New Zealand White rabbits were randomly divided into two groups: a simple ischemia group and a group injected with tranexamic acid before left hilar occlusion. After 2 hours of warm ischemia, plasma was collected from pulmonary vessels. Fibrin zymography was used to ascertain fibrinolytic activity, and enzyme-linked immunosorbent assay was used to determine soluble thrombomodulin levels as a marker for endothelial cells damage. Changes in left pulmonary function including arterial oxygen tension, peak airway pressure, and pulmonary vascular resistance were recorded during reperfusion after the 2 hours of warm ischemia. RESULTS: Fibrinolytic activity and soluble thrombomodulin levels increased in the vessels of the ischemic lung, indicating endothelial cell injury. The increased fibrinolytic activity and the rise in soluble thrombomodulin were suppressed by the preadministration of tranexamic acid, resulting in remarkably improved pulmonary function during reperfusion. After 2 hours of reperfusion, the wet-to-dry weight ratios and histological studies showed reduced pulmonary edema in the group that had received tranexamic acid. CONCLUSION: These findings suggest that the fibrinolytic system is involved in the onset mechanism of ischemia-reperfusion injury through induced endothelial cell damage and increased vascular permeability.

Animals↗

Characterization of the bleomycin resistance determinant encoded on the transposon Tn5.

The transposon Tn5 carries a gene, ble, which confers resistance to bleomycin (Bm) and gives a survival advantage to its host cell. We found that the ble gene product, designated BLMT, is a binding protein with a strong affinity for Bm. BLMT quenched both the antibacterial and DNA-cleaving activities of Bm, when incubated with the antibiotic. An electron spin resonance spin-trapping analysis showed that BLMT inhibits the generation of Bm-induced hydroxyl radical, by trapping Bm but not the hydroxyl radical. Western blot analysis using an anti-BLMT monoclonal antibody revealed that BLMT is immunologically distinct from Bm-binding proteins from Streptomyces verticillus, Staphylococcus aureus and Streptoalloteichus hindustanus. Escherichia coli, transformed with a mutant ble having leucine instead of proline at N-terminal amino acid position 7, lost resistance to Bm, although the cell maintained the survival benefit. This suggests that the Bm resistance mediated by ble is independent of its ability to give a survival advantage to the host bacterium.

Acetyltransferases↗

The detection of a unique antigen associated with papillary thyroid carcinoma.

We produced antibodies against a thyroid papillary carcinoma homogenate (PCAb) and analyzed antigens recognized by this antibody using western blotting. Fifty-four thyroid tissue specimens and 6 control tissue specimens obtained from non-thyroid carcinoma (gastric tissue, colon and liver) were analyzed. Consequently, an antigen of 40 kDa in size was found in 16 of 16 (100%) of papillary thyroid carcinoma from primary lesions and in 2 of 2 (100%) papillary thyroid carcinoma from metastatic foci, whereas it was not detected in thyroid tissue samples from follicular carcinoma, anaplastic carcinoma, follicular adenoma, adenomatous goiter, Graves' disease and normal thyroid tissues. The reactivity of thyroglobulin antiserum (TgAb) to this 40 kDa antigen was tested by western blotting and showed that TgAb did not appear to recognize the 40 kDa antigen. Moreover PCAb, after treatment with Tg, still reacted with this 40 kDa antigen. Therefore, this 40 kDa antigen might be different from Tg. Furthermore, to inspect the structure of this antigen, the effect of some chemicals and enzymes such as 2-mercaptoethanol, sodium dodecyl sulfate, ethanol and protease on the reactivity of PCAb to the 40 kDa antigen were analyzed. The results of these experiments suggested that this 40 kDa antigen may have a peptide structure. To our knowledge, the finding reported here represents the first demonstration of the protein specifically present in papillary thyroid carcinoma. Further investigations should elucidate the characteristics of this antigen and may contribute to definitive diagnosis of thyroid carcinoma as well as improving the understanding of the mechanisms involved in developing the thyroid carcinoma.

Antigens, Neoplasm↗

Characteristics of brain injury-derived neurotrophic peptide-binding sites on rat brain synaptosomes and neurons in culture.

Brain injury-derived neurotrophic peptide is the fragmental 13-mer peptide of the novel neurotrophic factor which was extracted and purified from Sponge Gelform made of gelatin implanted at the mechanically-induced injury site in neonatal rat brains. Brain injury-derived neurotrophic peptide supports survival of septal cholinergic and mesencephalic dopaminergic neurons in culture, and rescues hippocampal neurons in culture from glutamate neurotoxicity. Here we studied the binding characteristics of brain injury-derived neurotrophic peptide to synaptosomes from normal adult rat brains and neurons in culture from neonatal rat brains. [125I]Asp-[Tyr11]-brain injury-derived neurotrophic peptide binding to rat brain synaptosomes was specific and saturable. Equilibrium binding studies revealed that [125I]Asp-[Tyr11]-brain injury-derived neurotrophic peptide bound to 1.1 pmol/mg protein with a Kd (dissociation constant) of 0.17 microM in hippocampal synaptosomes and to 2.0 pmol/mg protein with a Kd of 0.38 microM in septal synaptosomes. [125I]Asp-[Tyr11]-brain injury-derived neurotrophic peptide could bind to a subpopulation of hippocampal neurons in culture from embryonic rat brains. Affinity cross-linking with the carboxyl-reactive cross-linking reagent 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide-HCl and [125I]Asp-[Tyr11]-brain injury-derived neurotrophic peptide produced radiolabeled bands corresponding to 100,000, 50,000 and 40,000 mol. wt molecules on hippocampal neurons in culture. These results suggest that the 13-mer sequence of brain injury-derived neurotrophic peptide plays a crucial role in expressing the neurotrophic properties of the factor.

Animals↗

Role of the endogenous prostaglandin E2 in human lung fibroblast interleukin-11 production.

Interleukin-11 (IL-11) is known to be a member of the interleukin-6 (IL-6)-type cytokine family. IL-11 is likely to be a major determinant of immune regulation in acute and chronic inflammatory lung diseases, although it is not directly linked with specific disease processes. It has already been shown that although unstimulated human lung fibroblasts did not produce significant amounts of IL-11, the addition of interleukin-1 alpha (IL-1 alpha) and/or transforming growth factor-beta (TGF-beta) stimulated fibroblasts dose-dependently to produce IL-11. Northern blot analysis showed that these stimulators also upregulated IL-11 mRNA expression. As it has been previously reported that IL-1 and TGF-beta stimulate prostaglandin E2 (PGE2) release from lung fibroblasts, we investigate here the role of endogenous PGE2 and the direct effects of the two inhibitors of prostaglandin synthesis, indomethacin and dexamethasone, on IL-11 production by human lung fibroblasts. The addition of indomethacin, a cyclo-oxygenase inhibitor, resulted in significant suppression of IL-11 production and mRNA expression in lung fibroblasts. There was no detectable effect of PGE2 alone on IL-11 levels; however, the suppression of IL-11 production by indomethacin was almost completely reversed by addition of PGE2. In contrast, suppression of IL-11 production by indomenthacin was not reversed by addition of thromboxane B2 and carbocyclic thromboxane A2. In addition, dexamethasone completely suppressed IL-11 production and downregulated IL-11 mRNA. These results suggest that endogenous PGE2 acts as an autocrine stimulus for IL-11 production by human lung fibroblasts activated by IL-1 alpha and TGF-beta.

Anti-Inflammatory Agents↗

Syndrome of inappropriate secretion of antidiuretic hormone associated with amyotrophic lateral sclerosis in respiratory failure.

A 65-year-old man who had muscle weakness and dysarthria was admitted for investigation of motor neuron disease. He had lost 12 kg of weight in 6 months. Neurological findings disclosed upper and lower motor neuron disturbances with normal sensory nerve function, and needle electromyography showed a neurogenic pattern. Laboratory findings on admission demonstrated dilutional hyponatraemia due to an excessive secretion of antidiuretic hormone (ADH). Based on these findings, the patient was diagnosed as having the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with amyotrophic lateral sclerosis (ALS). During the night of first hospital day, the patient complained of severe dyspnoea, and mechanical ventilation was commenced. Following the mechanical ventilation, plasma ADH levels and serum sodium concentration were normalized. We propose that respiratory failure secondary to the atrophy of respiratory muscle might be responsible for the development of SIADH.

Aged↗