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Biomedical subjects

S Nishimura

Publications and source records attributed to S Nishimura.

At least 145 records · Page 8Linked to original sources

Prolongation of canine epidural anesthesia by liposome encapsulation of lidocaine.

The purpose of our study was to produce a long-acting lidocaine by using a liposome that would entrap the drug. Egg yolk phosphatidylcholine and cholesterol were used as liposome materials. After epidural administration, the pharmacodynamics and pharmacokinetics of liposomal and free lidocaine were studied in 20 dogs. Two percent liposomal or free lidocaine (3.0 mL) was injected into the lumbar epidural space. Nerve blocking effects were estimated by measuring somatosensory evoked potentials. Recovery time from the epidural block in the liposomal lidocaine group (170 +/- 49.5 min) was approximately three times longer than that in the free lidocaine group (61 +/- 18.1 min). The areas under the drug concentration-time curves (AUC0-infinity) and time to maximal concentration (Tmax) in the liposomal lidocaine group were significantly larger than those in the free lidocaine group. These results suggest that the prolongation of epidural blockade by liposomal lidocaine is caused by a slow release of the drug from liposomes. The present study suggests that liposomal lidocaine can be used as a long-acting local anesthetic.

Amines

In vitro replication study of modified bases in ras sequences.

DNA templates containing a modified base (O6-methylguanine, 8-hydroxyguanine, xanthine or hypoxanthine) which was located in nucleotide sequences corresponding to the 12th or 61st codon of a ras gene were synthesized and deoxynucleotide incorporation opposite the lesions was investigated. The templates were replicated by Taq DNA polymerase, recombinant rat DNA polymerase beta and mouse DNA polymerase alpha-primase complex. Sequence analysis of the replicated products indicated selective incorporation of nucleotide(s) opposite a modified base, depending on the kind of base and of DNA polymerase. This system is very useful to obtain results of in vitro replication of modified bases in ras sequences.

Animals

A novel cDNA clone for acid invertase in tomato fruit.

The sequence of a novel cDNA clone, Aiv-1, for tomato acid invertase was similar to that of TIV1 (Klann et al., 1992) for the enzyme except for a unique intron-like insertion. It is considered that Aiv-1 is derived from either an alternatively spliced mRNA for an isozyme or a pre-mRNA of TIV1.

Amino Acid Sequence

[A 52-week dermal toxicity study of prednisolone farnesylate (PNF) gel in rats with a recovery period of 8 weeks].

The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.125, 0.5 and 2.0 mg/kg/day for 52 weeks, then the drug was withdrawn for 8 weeks to evaluate the reversibility. The results are summarized as follows: 1. In the PNF gel 2.0 mg/kg/day group, thinning of the skin at the application site, slightly retarded body weight gains, a tendency toward a decrease in the white blood cell count, an elevation of serum GOT and GPT activity, free fatty acid level, and a decrease in alpha 1-globulin fraction were observed. In the pathological examinations, decreased organ weights of the thymus, spleen and adrenal glands, and thinning of the skin were observed. Histopathological examination revealed atrophy of the thymus and zona fasciculata of the adrenal glands, thinning of the skin with atrophied skin appendages, and hepatocellular hypertrophy with hypertrophied uncleus in the perilobular zone. 2. In the PNF gel 0.5 mg/kg/day group, thinning of the skin at the application site and a decrease in alpha 1-globulin fraction were observed. Histopathologically, thinning of the skin atrophied skin appendages was observed. 3. In the PNF gel 0.125 mg/kg/day group, there were no toxic signs induced by the drug. 4. After the 8-week recovery period, the changes in the skin were observed in the 2.0 mg/kg/day group, but the severity was lowered. The other changes disappeared and so it was demonstrated that the changes were reversible. 5. Based on these results, it was concluded that the overt toxic dose of PNF gel was 0.5 mg/kg/day and the non-toxic dose was 0.125 mg/kg/day in the present study.

Administration, Cutaneous

Goodpasture's syndrome: a report of an autopsy case and a review of Japanese cases.

A 75-yr-old man was admitted because of acute renal failure. On the 9th hospital day, pulmonary hemorrhage occurred. He was treated with a bolus dose of methylprednisolone and plasma exchange, but died from respiratory failure on the 16th hospital day. Autopsy findings demonstrated marked intraalveolar hemorrhage and crescentic glomerulonephritis. Linear depositions of IgG along both alveolar and glomerular basement membranes (GBM) were shown by direct immunofluorescent studies. Circulating anti-GBM antibodies were demonstrated by indirect immunofluorescent techniques. This is a confirmatory case of Goodpasture's syndrome, which is rare in Japan. A review of the Japanese literature revealed some characteristics of Japanese cases.

Aged

Acute renal failure following hypokalemic rhabdomyolysis due to chronic glycyrrhizic acid administration.

A 72-year-old man developed acute renal failure (ARF) following severe hypokalemic rhabdomyolysis. The hypokalemia was due to chronic glycyrrhizin (glycyrrhizic acid) administration. Although glycyrrhizin-induced hypokalemic rhabdomyolysis has been occasionally reported, the association of this type of rhabdomyolysis with ARF has not been described. In the present case, there was a sensitivity to glycyrrhizin the preceding renal insufficiency, and dehydration which was thought to have contributed to ARF. It should be recognized that elderly patients with such predisposing factors may be susceptible to a rapid deterioration of renal function after glycyrrhizin-induced hypokalemic rhabdomyolysis.

Acute Kidney Injury

Histopathological reactions of calcium phosphate cement.

Calcium phosphate cement (CPC) consisting of Ca4 (PO4)2O and CaHPO4 (2H2O) was recently developed. This study evaluated in vivo aspects of CPC and CPC mixtures compared to those of commercial hydroxyapatite (HP) and several endodontic materials: Grossman's cement (GC), calcium hydroxide-iodine paste (CHP) and gutta-percha plate (GP). Biocompatibility of subcutaneous implants in Donryu rats was evaluated after one month. Results showed very slight inflammatory reactions from CPC, CPC mixtures and HP. The materials were surrounded by thin fibrous connective tissues with a small number of lymphocytes and plasma cells. Severe inflammatory reactions were provoked by GC. Granulation tissues induced by CHP resembled those of pseudoxanthomatous granuloma. The GP material was encapsulated by relatively thick fibrous connective tissues with little inflammatory reactions.

Animals

Photosensitized formation of 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) in DNA by riboflavin.

Potosensitized formation of 8-hydroxyguanine in DNA by riboflavin was observed. A reaction mechanism involving guanine radical cation and hydration reaction was proposed. This hypothesis was confirmed by the incorporation of [18O]-atom within guanine moiety in isotopic experiments using [18O]-H2O. Photosensitized formation of oh8Gua by riboflavin was also observed in cellular DNA.

Animals

Azatyrosine inhibits neurite outgrowth of PC12 cells induced by oncogenic Ras.

An antibiotic, azatyrosine [L-beta-(5-hydroxy-2-pyridyl) alanine], specifically converts ras-, raf- or c-erbB2 (neu)-transformed NIH3T3 cells to apparently normal phenotype. The reversion induced by azatyrosine is permanent, and the phenotype of the revertant cells does not change even after prolonged culture in the absence of azatyrosine [N. Shindo-Okada, O. Manabe, H. Nagahara & S. Nishimura (1989). Mol. Carcinogen., 2, 159-167]. In the present study, we found that neurite outgrowth of PC12 cells induced by expression of either the ras or raf oncogenes was inhibited by addition of azatyrosine to the medium. Azatyrosine also inhibited neurite outgrowth induced by microinjection of oncogenic Ras protein into PC12 cells. The dose dependency was much the same for the two systems, inhibition of neurite outgrowth of PC12 cells and reversion of the transformed NIH3T3 cells. Microinjection of azatyrosine into the cells was as effective as addition to the medium, indicating that the target of azatyrosine is intracellular. In contrast, neurite outgrowth induced by nerve growth factor, which has been shown to be mediated by normal Ras [N. Hagag, S. Halegouna & M. Viola (1986). Nature, 319, 680-682], was found to be resistant to azatyrosine. Azatyrosine also showed no effect on neurite outgrowth induced by a membrane-permeant cyclic AMP analog through another pathway. These findings suggest that azatyrosine sensitivity is the result of abnormal signal transduction by oncogenic Ras. It was shown that azatyrosine also inhibited differentiation-associated growth arrest of PC12 cells induced by oncogenic Ras. In Ras-induced neurite outgrowth, the azatyrosine-sensitive process was found to be completed in the first 6-9 h, and is probably essential for the commitment of PC12 cells to differentiation rather than to growth.

Alanine

Nasal T-cell lymphoma associated with hemophagocytic syndrome. Immunohistochemical and genotypic studies.

A 53-year-old man with nasal T-cell lymphoma exhibited hemophagocytic syndrome as a terminal event. Immunohistochemical studies revealed that neoplastic cells were derived from T cells. Genotypic analysis of DNA samples that were obtained from the frozen tissue specimens demonstrated clonal rearrangements of the T-cell receptor beta-chain genes. No rearrangement was observed in the immunoglobulin heavy-chain gene. To our knowledge, only three cases of nasal T-cell lymphoma with hemophagocytic syndrome have been reported before the present case. All of these cases occurred in Oriental patients. The present report suggests the beneficial effect of high-dose glucocorticoid therapy on the prolongation of survival compared with that of the other three cases.

Gene Rearrangement, beta-Chain T-Cell Antigen Rece

[Role of polymorphonuclear leukocytes (PMN) and active oxygen species in hyperthermia--enhancing effect of G-CSF on superoxide generation from PMN].

We examined in vitro the effect of G-CSF and temperature on superoxide (O2-) generation by Cypridina luciferin analog (CLA) dependent chemiluminescence. PMN significantly generated O2- at the concentration of G-CSF 25 ng/ml or more at 37 degrees C within the range of 0.1 from 1,000 ng/ml. O2- generation from PMN was remarkably enhanced, stimulated by opsonized zymosan (OZ) and phorbol myristate acetate (PMA), at 41 degrees C as compared with 37 degrees C. O2- generation was enhanced with the addition of 25 ng/ml of G-CSF at 41 degrees C as compared to without it at 41 degrees C. A significant enhancement of O2- generation from PMN was observed at 25 ng/ml G-CSF and 41 degrees C.

Granulocyte Colony-Stimulating Factor

[A case of common carotid artery stenosis due to hanging].

We report a case of a 50-year-old woman with traumatic dissection of the right common carotid artery secondary to attempted suicidal hanging. Initial examination showed marks of strangulation on the neck, facial edema, and multiple conjunctival petechiae accompanied by difficulty in breathing and loss of consciousness. She gradually recovered except for her left upper limb weakness. Rehabilitation, with a diagnosis of left brachial plexus injury, was started. Two years later, she occasionally felt numbness of the left upper extremity. On her second admission, a bruit was heard on the right side of her neck. Neurological examination did not reveal any change. CT scan showed atrophic changes. Angiography demonstrated approximately 80% stenosis of the right common carotid artery which was thought to be responsible for the attacks of numbness. Right carotid endarterectomy was performed. Histological findings revealed dissection of the medial layer of the arterial wall. Complaints of numbness disappeared postoperatively, and angiography showed good patency at a follow-up examination. We conclude that the stenosis of the common carotid artery was not due to atherosclerosis but due to the dissection as a result of hanging.

Brachial Plexus

[Reactive histiocytosis during initial remission induction therapy for acute myeloblastic leukemia].

Six of 14 patients with acute myeloblastic leukemia (AML) complicated reactive histiocytosis during initial remission induction therapy. All six patients had a high fever without signs of infection during initial chemotherapy, and periods of myelosuppression were prolonged. Histiocytes with a mature appearance, some of which phagocyted erythrocytes, thrombocytes or neutrophils, increased in the bone marrow. All of 3 patients tested showed high serum levels of ferritin. Two of 3 patients treated with 125 mg/day methylprednisolone achieved complete remission. In the remaining 3 patients, one patient achieved complete remission, but the others died of fungal pneumonia or sepsis. Thus, reactive histiocytosis is one of the severe complications in patients with AML undergoing chemotherapy.

Adult

Comparison of diagnosis and treatment of Sjögren's syndrome in Japan and United States.

Today, as with western countries, diagnosis and treatment of Sjögren's syndrome (SS) patients in Japan are carried out by a team effort. The clinical manifestations of Japanese SS patients are quite similar also. There are, however, several minor modifications in the diagnosis and treatment of SS patients in Japan, which are presented in this article.

Humans

[Pharmacokinetic, bacteriological, and clinical studies on panipenem/betamipron in children].

Pharmacokinetic, bacteriological and clinical studies were performed on panipenem/betamipron (PAPM/BP) in children. The results are summarized as follow: 1. Twelve patients with various bacterial infectious diseases were treated with PAPM/BP. Each dose was 20 mg/20 mg/kg, administered 3 times daily, in 30-minute intravenous drip infusion. Treatments were continued for 5-22 days. Clinical efficacies of PAPM/BP in 12 patients with bacterial infections (1 with suspected sepsis, 5 with pneumonia, 1 with acute maxillary sinusitis, 2 with acute otitis media, 1 with cervical abscess and 2 with urinary tract infection complexed type) were evaluated as excellent in 7, good in 4 and fair in 1, with an efficacy rate of 91.7%. Seventeen causative organisms found in 10 patients (Haemophilus influenzae in 4, Branhamella catarrhalis in 3, Streptococcus pneumoniae in 2, Pseudomonas aeruginosa in 2, Staphylococcus aureus in 1, alpha-Streptococcus in 1, Corynebacterium sp. in 1, Peptostreptococcus micros in 1 and Klebsiella pneumoniae in 2) were eradicated except 2 strains (S. aureus and P. aeruginosa) from 1 patient (patient No. 2). No adverse reactions were observed in any of the 12 patients. 2. MICs of PAPM were examined against 22 clinical isolates (H. influenzae 5, B. catarrhalis 3, alpha-Streptococcus 3, S. pneumoniae 2, Corynebacterium sp. 2, S. aureus 1, P. aeruginosa 1, P. micros 1, Enterobacter cloacae 1, Escherichia coli 1, Group D Streptococcus 1 and Staphylococcus epidermidis 1) from children with bacterial infections. PAPM showed a good antibacterial activity comparable to the activity of cefoperazone (CPZ) against S. pneumoniae strains relatively tolerant to penicillins. However, the activity of PAPM against H. influenzae was somewhat weaker than that of CPZ. 3. Pharmacokinetic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections

Significance of increased lung thallium uptake during adenosine thallium-201 scintigraphy.

To determine the relationship of lung 201Tl activity during adenosine scintigraphy to the presence and extent of coronary artery disease, we investigated 132 subjects comprising 4 groups: 36 normal volunteers, 19 patients with angiographically normal coronaries, 29 patients with single-vessel (greater than 50% luminal stenosis) and 48 patients with multivessel coronary artery disease. Lung activity was quantified relative to maximal myocardial activity in both an early anterior planar image (pretomography) and the unprocessed tomographic image in the anterior projection. A good correlation was found for the lung-to-heart ratio assessed by planar and tomographic imaging (r = 0.83, p less than 0.0001), but the ratio was higher with planar imaging. The lung-to-heart ratio in the planar images was significantly higher in patients with multivessel disease compared to those with single-vessel disease (p less than 0.05) or volunteers and subjects with normal coronary arteries combined (p less than 0.001). A lung-to-heart ratio of greater than 0.45 in the planar images (upper 95% confidence limit for the normal subjects) was found in 6 (21%) single-vessel disease and 17 (35%) multivessel disease patients. Patients with elevated lung thallium activity during adenosine infusion had more hypoperfused myocardial segments (p = 0.007), more segments with redistribution (p = 0.04) and larger initial perfusion defect size (p = 0.04) than those with normal lung activity. Thus, evaluation of lung activity during adenosine thallium scintigraphy provides supplementary information regarding the severity of coronary artery disease and extent of myocardial hypoperfusion.

Adenosine

[Changes in dementia after shunt surgery for normal pressure hydrocephalus].

In order to investigate the pathogenesis of normal pressure hydrocephalus (NPH), dementia was analyzed with regard to the characteristic preoperative picture, the time when dementia improved, and what aspect of dementia was improved, retrospectively. Twenty seven patients of NPH were divided into two groups; young adult group: patients under 64 years old and geriatric group: patients above 65 years old. We found that the only difference found between these two groups was severity in dementia grading, higher in geriatric group. Postoperative course or complications did not differ. Dementia in NPH was not an essential impairment of intellectual ability, but was characterized by the subset symptoms of dementia, such as decrease in spontaneity and interest, slowness and paucity of thought and action. Improvement of memory followed postoperative recovery of these subset symptoms which was observed at earliest three days after shunt surgery. We postulate that recovery of dementia in NPH is associated with not only a decrease in intracranial pressure but also an improvement in the microcirculation of the brain or an improved metabolism.

Adult

[Pharmacokinetic, bacteriological and clinical studies on meropenem in children].

Pharmacokinetic, bacteriological and clinical studies on meropenem (MEPM) were performed in children. The results are summarized as follows: 1. A total of 16 patients was treated with MEPM. Each dose was 20 mg/kg, and administration was made 3 times daily using 30-minute intravenous drip infusion for 5-28 days. Clinical efficacies of MEPM in 16 patients with bacterial infections (1 with purulent meningitis, 1 with suspected subdural abscess, 2 with suspected sepsis, 4 with pneumonia, 1 with acute maxillar sinusitis, 2 with cervical abscess, 1 with acute gastroenteritis, 2 with skin soft tissue infection and 2 with urinary tract infection) were evaluated as excellent in 7 patients, good in 8 patients and fair in 1 patient with an efficacy rate of 93.8%. Fourteen causative organisms found in 11 patients (Streptococcus pneumoniae in 4, Branhamella catarrhalis in 3, Staphylococcus aureus in 3, Group B Streptococcus in 1, Escherichia coli in 3) were all eradicated. No adverse reactions were observed in any of the 16 patients. 2. MICs of MEPM against 6 clinically isolated bacteria (B. catarrhalis 2, S. pneumoniae 3 and S. aureus 1) from children with bacterial infections were examined. MEPM showed good antibacterial activities. 3. Pharmacokinetic studies: Peak plasma concentrations of MEPM averaged 43.07 micrograms/ml (37.20-46.30 micrograms/ml) at dose of 20 mg/kg administered by 30-minute drip infusion. In the first 8 hours after administration, the urinary excretion rates of MEPM averaged 39.9% of the administered dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent