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Biomedical subjects

S Nagai

Publications and source records attributed to S Nagai.

At least 145 records · Page 8Linked to original sources

[A case report of thoracic outlet syndrome with acute arterial obstruction caused by abnormal first rib].

A 33-year-old male was transferred to our hospital because of coldness, numbness and pain in his right arm. Chest X-ray showed abnormal first ribs on both sides that were attached to the second ribs below the clavicles. Angiogram revealed an aneurysm of right subclavian artery, thrombus in the aneurysm and embolism to the brachial artery. Thrombectomy using a Fogarty catheter was done and the radial pulse recovered. Surgical resection of the abnormal first rib and thrombectomy was performed, because ischemic symptoms recurred in spite of anticoagulation and antiplatelet therapy. Acute arterial occlusion in patients with thoracic outlet syndrome is rare. The literature on arterial complications of thoracic outlet syndrome is reviewed.

Acute Disease↗

[Pharmacokinetic, bacteriological and clinical studies on cefozopran in neonates].

Cefozopran (CZOP) was administered to nine newborn patients with infections at a dose of 20 mg/kg twice or three times daily for 5 to 6 days to evaluate the efficacy, safety and pharmacokinetics of cefozopran. 1. Blood concentrations CZOP was intravenously given to 6 newborn patients by drip infusion at a dose of 20 mg/kg over 30 minutes. The maximum blood concentrations (Cmax) were 38.4 micrograms/ml in a patient aged 0 day, 37.7 and 54.3 micrograms/ml in two patients aged 1 day, 51.3 and 64.1 micrograms/ml in two patients aged 3 days and 51.0 micrograms/ml in a patient aged 5 days. Cmax was lower in the patient aged 0 day. The elimination half life (T 1/2) was 9.2 hours in the patient aged 0 day, 4.9 and 3.7 hours in the patients aged 1 day, 3.1 and 2.4 hours in the patients aged 3 days and 2.9 in the patient aged 5 days, showing a prolongation of T 1/2 in patients of lower age. 2. Urinary excretion Of the 6 patients given CZOP at a dose of 20 mg/kg by intravenous drip infusion over 30 minutes, urine was collected in 5 patients. The cumulative excretion rate within 6 hours after infusion was as low as 19.8% of dose in the patient aged 0 day. The rates were elevated as high as 46.3 and 57.0% of dose in the patients aged 1 day. In the patient aged 3 days, the recovery within 4 hours after infusion was 47.3%. It was 70.6% of dose within 6 hours after dosing in the patient aged 5 days. The urinary recovery within 6 hours after dosing increased with the advance of age. 3. Clinical results Efficacy was evaluable in 7 patients. Of them, 3 had suspected septicemia, 2 pneumonia, 1 intrauterine infection and 1 urinary tract infection. The clinical efficacy was judged "excellent" in all the evaluable patients. Neither adverse drug reactions of signs and symptoms nor abnormal alterations of the laboratory test values were recognized in the 9 patients evaluable for safety. These results suggest that CZOP is an effective and safe drug for treatment of infections in the newborns. As for the dosage and method of administration from the view of the pharmacokinetic data obtained, intravenous drip infusion of 20 mg/kg once or twice daily was considered to be sufficient for patients aged 0 day. For patients aged 1 to 7 days and those aged 8 days or elder, the administration of twice to 3 times daily and 3 to 4 times daily were considered to be sufficient, respectively.

Bacterial Infections↗

Isolation of cDNA clones of the rat mRNAs expressed preferentially in the prenatal stages of brain development.

For better understanding of the molecular mechanisms underlying the developmental processes of the mammalian brain, we isolated rat fetal brain-enriched (FBE) cDNA clones, whose corresponding mRNAs were expressed at least 5-fold more in the fetal brain than in the adult brain. Our modified differential screening procedure, which utilized a two-vector (pT7T3D and pBluescript) system and showed low background levels of colony hybridization for screening, efficiently identified 64 candidate FBE clones from a small number (475) of colonies in the fetal brain cDNA library. After subsequent second screening of the candidate FBE clones by Northern blot analysis, we successfully isolated 22 distinct FBE clones. The nucleotide sequence analysis of the 22 FBE clones revealed that 13 of them had no significant matches to the sequences reported in the databases, whereas 9 of them matched previously reported sequences (alpha-tubulin M alpha 1, beta-tubulin M beta 5, thymosin-beta 10, stathmin, beta-tubulin M beta 2, alpha-internexin, ferritin Lg chain, neuronatin and amphoterin), most of which have been shown to be down-regulated during brain development. We also found that the Northern blot analysis in the second screening could be replaced by cDNA library DNA-Southern blot analysis, in most clones corresponding to relatively abundantly expressed mRNAs. Thus, once the cDNA library is constructed, clone selection will be possible in such clones without the use of additional RNA or Northern blot in screening, allowing the analysis of small brain regions of interest.

Animals↗

Substance P-like immunoreactive substance in bronchoalveolar lavage fluids from patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis.

In order to find out whether substance P (SP) participates in the inflammatory and fibrotic processes of interstitial lung diseases or not, SP-like immunoreactive substance (SP-IS) concentrations in bronchoalveolar lavage (BAL) fluids from patients with idiopathic pulmonary fibrosis (IPF) and pulmonary sarcoidosis were measured using enzyme immunoassay (EIA). The mean SP-IS concentrations in BAL fluids from healthy nonsmokers and healthy smokers were 0.87 +/- 0.19 and 0.98 +/- 0.23 pg/ml, respectively. The mean SP-IS concentration in BAL fluids from patients with IPF was 1.15 +/- 0.39 pg/ml. The value of patients with IPF was significantly higher than that of healthy nonsmokers (p < 0.01). The mean SP-IS concentrations in BAL fluids from pulmonary sarcoidosis patients in stage I, stage II and stage III were 0.91 +/- 0.19, 0.96 +/- 0.35 and 1.00 +/- 0.29 pg/ml, respectively. No correlation was found between SP-IS concentration and pulmonary functions in IPF and sarcoidosis patients. The present results indicate that SP may be involved in the inflammatory process in IPF.

Adult↗

Expression of mRNA for a neuronal differentiation factor, TA2O, in developing rat brains.

In our previous study, a novel factor, TA2O, was isolated from NGlO8-l5 cells. The TA2O mRNA was increased by stimulation which also induced neuronal differentiation. Neuronal cells overexpressed with TA2O extended long neurites and stopped cell growth (Tohda et al., 1995, Neurosci. Res., 23: 21-27). We investigated the expression pattern of TA2O mRNA in developing rat brains to predict physiological roles of TA2O. TA2O mRNA began to increase between embryonic days 13 and 16. TA2O mRNA was observed mainly in neocortical, hippocampal and precerebellar neuroepithelium on embryonic day 16. Although the level of TA2O mRNA in the cerebral cortex was higher before birth than after birth, the level in cerebellar Purkinje cells increased gradually even after birth. The high expression level of TA2O mRNA in the hippocampus was maintained before and after birth. Thus, TA2O was expressed highly in brain regions in which neurons were changing morphologically and qualitatively, suggesting that TA2O may be involved in neuronal formation in vivo.

Animals↗

T cell receptor (TCR) V gene segment use in HLA-typed Japanese healthy subjects.

The expression of 13 different alpha and beta V gene segments of the T cell receptor for antigen (TCR) was examined, using V gene-specific MoAbs, on human peripheral blood T lymphocytes from 32 healthy Japanese subjects. In addition, to examine associations between TCR V gene products and HLA alleles, the HLA class I and class II types of all subjects were serologically determined. The reactivities of the anti-TCR V-specific MoAbs were, with some significant exceptions, similar to those previously described in healthy Caucasian subjects. We found a non-random V gene usage as well as a statistically significant bias of the expression of eight V beta gene products towards the CD4+ subpopulation, and a significant skewness in the usage of V alpha 12 towards the CD8+ population. Some subjects showed increased reactivities (above 10%) of certain MoAbs, mainly in the CD8+ subpopulation. We found no distinct correlation between any certain HLA class I or II allele and TCR V gene usage in the CD8+ or CD4+ subpopulations, respectively. In conclusion, the pattern of anti-TCR V-specific MoAb reactivities found in CD4+ and CD8+ subsets of peripheral blood lymphocytes of healthy Japanese subjects was in general found to match that previously described in healthy Caucasian subjects.

Adult↗

Heterogenous expression of the related MPB70 and MPB83 proteins distinguish various substrains of Mycobacterium bovis BCG and Mycobacterium tuberculosis H37Rv.

MPB70 and MPB83 are homologous cross-reactive secreted mycobacterial proteins with very limited species distribution. The expression of these two proteins was compared between several substrains of Mycobacterium bovis BCG, virulent M. bovis and Mycobacterium tuberculosis H37Rv. A polyclonal antibody specific for MPB70 in Western blotting, and a monoclonal antibody, MBS43, found to be specific for MPB83 in ELISA and Western blotting, were used for the comparison. The previously established pattern of high- and low-producing substrains of BCG for MPB70 is only partially applicable for MPB83. MPB70 low-producing strains are also MPB83 low-producing, but the expression of MPB83 is much more variable than the expression of MPB70 in the MPB70 high-producing strains. Purified MPB83 (23 kDa) was found to be glycosylated. A band in SDS-PAGE at 1-2 kDa lower than that of purified MPB83 may represent unglycosylated MPB83. Furthermore, it was confirmed that purified MPB70 (22 kDa) is unglycosylated. There is cross-reactive antigen at 26 kDa. The MPB83 related antigen at 26 kDa was found to be the most abundant. These findings indicate greater heterogeneity between different substrains of BCG than previously realized. Virulent M. bovis produce and secrete large amounts of MPB70 and MPB83 while both these proteins occur in a far lower concentration in M. tuberculosis.

Antibody Specificity↗

Different percentages of peripheral blood gamma delta + T cells in healthy individuals from different areas of the world.

The frequency of gamma delta + T cells in the peripheral blood of 26 Turkish, 24 Swedish, 35 Japanese and 14 "Asian' (non-Japanese) healthy blood donors and healthy volunteers were investigated by flow cytometry. In the Turkish group, 9.3% (median value) of the CD3+ peripheral blood T cells expressed the gamma delta T cell receptor. A similar level of gamma delta + T cells was found in the non-Japanese "Asian' healthy volunteers (9.2%), while significantly lower values were detected in the Swedish (4.2%) and Japanese (4.5%) groups. These dramatic differences in normally occurring gamma delta + T cells in different groups of healthy individuals were further reflected by a low incidence of > 10% gamma delta + T cells in the Swedish (0/24) and Japanese (6/35) groups compared to the Turkish (12/26) and "Asian' (5/14) groups. The described gamma delta + T cell differences between distinct ethnic groups are thus likely to be a consequence of environmental factors, but additional genetic influences cannot be ruled out. The present study demonstrates the potential importance of the ethnic origin and environmental history of subjects examined in studies of gamma delta + T cells-disease relations.

Adolescent↗

Effects of nilvadipine (a dihydropyridine-type calcium entry blocker) on cerebral blood flow in acute experimental brain ischemia in rats.

The purpose of the present study was to examine the effect of nilvadipine (a dihydropyridine-type calcium entry blocker) on the cerebral circulation, experimental models of cerebral ischemia were used to measure abrupt changes in the cortical cerebral blood flow (CBF) at the 'penumbra' (the boundary region between the anterior cerebral artery (ACA) and the middle cerebral artery (MCA)). Left middle cerebral artery occlusion (MCAO) was performed in Sprague--Dawley rats, and then 8 or 16 micrograms kg-1 of nilvadipine was administered to two groups of the rats. The former group was referred to as the 8-MCAO(+) group (n = 8), and the latter group, the 16-MCAO(+) group (n = 8). To a control group (n = 8), only the solvent of nilvadipine was administered. After the administration in each group, CBF and the mean arterial blood pressure (MAP) were continuously measured for 60 min. The MAP in both the 8-MCAO(+) and 16-MCAO(+) groups was significantly lower than in the control group for 25 min after nilvadipine administration (Wilcoxon 2 sample test, p < 0.05). Also, the CBF in the 16-MCAO(+) group was significantly lower (about 20%) for 55 minutes than that in the control group. On the other hand, the CBF in the 8-MCAO(+) group three minutes after nilvadipine administration was not significantly lower than in the control group (Wilcoxon 2 sample test). Our findings confirmed that nilvadipine (8 micrograms kg-1) maintained CBF while lowering the blood pressure in the experimental model of acute cerebral ischemia.

Animals↗

Bronchiolitis obliterans with organizing pneumonia.

In 1955, Epler and Colby first described idiopathic bronchiolitis obliterans with organizing pneumonia. Davison and colleagues termed the entity cryptogenic organizing pneumonia. Clinically, the disease resembles a flu-like syndrome of acute or subacute onset. Other features include crackles, patchy infiltrates on chest radiograph, restrictive function, and decrease in diffusing capacity. Most cases of idiopathic bronchiolitis obliterans with organizing pneumonia (BOOP) respond dramatically to corticosteroids. However, some patients deteriorate rapidly. Differences between idiopathic or secondary BOOP and other interstitial lung diseases are vast. CT findings and bronchoalveolar lavage fluid lymphocytosis are helpful in differentiating BOOP from idiopathic pulmonary fibrosis.

Adrenal Cortex Hormones↗

Gene transduction into murine primitive hematopoietic cells with 2-gene retroviral vectors using a Transwell coculture system.

The present study aims at expressing a reporter gene in hematopoietic cells in vivo by introducing it into primitive hematopoietic cells with a 2-gene retroviral vector. Various constructs of retroviral vectors containing the human IL-2 receptor alpha chain gene (TAC) as the reporter and the neomycin phosphotransferase gene (neo) as a selectable marker were engineered, and the effectiveness of these vectors for expression of the reporter gene was evaluated after transfection into the packaging cell line GP + E86. It was found that the highest levels of reporter gene expression were attained with constructs ordered 5' long terminal repeat (LTR)-TAC-internal promoter-neo-3' LTR. In experiments investigating the expression of a reporter gene in hematopoietic cells, we used the Escherichia coli beta-galactosidase gene (lacZ) instead of TAC, because a very sensitive detection method was available for lacZ. For transduction of hematopoietic progenitors, packaging cell lines producing recombinant viruses were cultured in a Transwell hung into a Dexter-type bone marrow (BM) culture. The BM cells were selected with G418, and transferred into irradiated recipient mice. LacZ enzyme activity was detectable in the peripheral blood lymphocytes (PBL) of recipients taken 8 wk after reconstitution.

Animals↗

[BCG vaccination to Mycobacterium leprae infection in mice].

BCG vaccine (Tokyo strain) was given in BALB/cA mice intradermally 1 or 3 months before Mycobacterium leprae (M. leprae) challenge as modified Shepard's method. The vaccine dosage was 10(7-8) or 10(6). The BCG gave good protection in both dosages and both challenges against M. leprae infection. Lymphocytes proliferations of BCG-vaccinated splenocyte cultures in response to M. leprae lysate or BCG components (hsp65, 38 kD, 30 kD or 12 kD protein) were tested, and potent proliferative responses were seen in the cultures with M. leprae lysate and hsp65. Furthermore, gamma-IFN productions were positive in the cultures with M. leprae lysate or hsp65, but negative with other antigens. The production of gamma-IFN with hsp65 was never inhibited with polymyxin B, but inhibited with IL-10. These results show that BCG (Tokyo strain) is a useful vaccine for M. leprae infection in mice, and one of the components of BCG, hsp65, may be a effective antigen component for protection of M. leprae infection inducing Th1 type cytokine.

Animals↗

Effective isolation of MPB64 from a large volume of culture filtrate of Mycobacterium bovis BCG Tokyo.

MPB64, a secretory protein of Mycobacterium bovis BCG Tokyo, was isolated from a culture filtrate of the bacteria in Sauton synthetic medium harvested on day 8. The protein was isolated by five steps; (i) concentration of the culture filtrate by cutting the molecules smaller than 5 kDa with the Millipore Pellicon Cassette system, (ii) affinity separation by a Phenyl Sepharose CL-4B column, (iii) separation with a DEAE-Sepharose CL-6B column with 3 M urea, (iv) separation with a Sephacryl S200HR column, and (v) separation with a DEAE-Sepharose column without urea. MPB64 in each fraction was determined by comparing the band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with that of standard MPB64. The specificity of isolated MPB64 was tested by immunoblotting with anti-MPB64 antibody. The potency of isolated MPB64 in eliciting skin reaction in the BCG-sensitized guinea pigs was the same to that of standard MPB64. The method described herein is an improved one for isolating MPB64 from a large volume of culture filtrate of M. bovis BCG Tokyo. The technique should be applicable to isolation of other mycobacterial secretory proteins.

Antigens, Bacterial↗

[Chest wall reconstruction using polyester mesh].

From January 1987 through December 1994, we performed chest wall reconstruction using the polyester mesh in 15 patients with lung cancer, 11 with empyema after open drainage, 8 with chest wall tumor and 1 with radiation dermatitis and costal chondritis. Twenty five patients were resected 3 or more ribs. Chest wall defects were reconstructed with the polyester mesh covered with Gore-Tex soft tissue patch. Twenty two cases passed more than a year without signs of infection and follow-up averaged 27.6 months. Polyester mesh was removed due to bronchial fistula (3 cases), deformities (3 cases) and abscess formation (1 case). In these cases, polyester mesh was well incorporated and had no foreign body change. In conclusion, the polyester mesh seems to be a dependable prosthetic material for chest wall reconstruction.

Adult↗

[Flow cytometric analysis of the DNA content of resected non-small cell lung cancer with reference to long-term follow-up].

We measured the cellular DNA content of paraffin-embedded tumor specimens by flow cytometry from 340 cases of resected non-small cell lung cancer, and investigated the correlation of DNA content and prognosis of these cases with long-term follow-up. These 340 cases were divided into some populations according to pathological stage, histologic type, surgical curativity and N factor, and we compared the prognosis of DNA diploidy cases and DNA aneuploidy cases in each population. DNA aneuploidy cases had a significantly less favorable prognosis than DNA diploidy cases in population of stage I adenocarcinoma, stage IIIA non-small cell lung cancer and N2 cases among stage IIIA non-small cell lung cancer, all after curative operation. But in other populations, there was no significant difference in prognosis between DNA diploidy cases and DNA aneuploidy cases. In conclusion, DNA ploidy pattern is a prognostic factor for survival in patients with stage I adenocarcinoma and N2 cases of stage IIIA non-small cell lung cancer.

Adenocarcinoma↗

[Pulmonary typical carcinoid with metastases to pulmonary hilar, and mediastinal lymph nodes].

A 50-year-old woman was admitted to our hospital complaining of recurrent bloody sputum and hemoptysis. Chest X-ray films showed an infiltrative shadow in the left lower lung field. Chest computed tomograms showed a nodular tumor shadow near the left B8 and this tumor shadow was found between A8 and A9 by pulmonary arteriography. Bronchoscopic examination revealed a red coagulum in the left B8 and cytologic examination of broncho alveolar lavage fluid revealed atypical squamous cells. With a clinical diagnosis of squamous cell carcinoma of the lung, a left lower lobectomy with hilar and mediastinal lymph node dissection was done. A milk-white tumor was found in the lower lobe of the resected lung. The pathological diagnosis of the resected tissue specimen was carcinoid, accompanied by pulmonary, hilar, and mediastinal lymph node metastases. Reduced immunofluorescence by Chromogranin A and serotonin staining were further evidence that the tumor was atypical. This case is very interesting in that the tumor metastasized to the lung and lymph nodes, even-though it was pathologically typical.

Carcinoid Tumor↗

[Pharmacokinetic, bacteriological and clinical studies on cefozopran in neonates and premature infants. A study of cefozopran in the perinatal co-research group].

The following results were obtained in pharmacokinetic, bacteriological and clinical investigations of a cephem antibiotic for injection, cefozopran (SCE-2787, CZOP), administered to neonates and premature infants. 1. Pharmacokinetics (1) Half-lives (T 1/2's) of CZOP in 0-day-old (less than 24 hours after birth) neonates and premature infants were longer than those in 1-day-old or older infants. When half-lives were compared between 0-day-old neonates and 0-day-old premature infants, longer half-lives were observed in premature infants. (2) When CZOP was intravenously administered to 1-day-old or older neonates and premature infants at a dose of 20 mg/kg, no differences were noted in blood concentrations between neonates and premature infants from 30 minutes to 6 hours after administration as well as T 1/2's. (3) Blood concentration of CZOP administered at doses of 10, 20 and 40 mg/kg were dose-dependent. (4) Urine excretion rates of CZOP administered to 1-day-old or older neonates and premature infants were approximately 30 to 60% in the first 6 hours after administration. Urine excretion rates in 0-day-old neonates and premature infants were low. 2. Clinical results (1) Of a total of 136 cases to which CZOP was administered, clinical efficacy evaluation was possible in 96 cases, and safety evaluation in 132 cases. (2) The clinical efficacy rates were 78.6% (22/28) in 28 cases in which causative organisms were detected (Group A), and 97.1% (66/68) in 68 cases in which no such organisms were detected (Group B), with the total efficacy rate (Groups A and B) of as high as 91.7% (88/96). (3) Bacteriological evaluations were made with 33 strains isolated from the 28 cases of Group A. Elimination rates for Gram-positive and Gram-negative bacteria were 88.2% (15/17) and 92.3% (12/13), respectively, with the total elimination rate of 90.0% (27/30). No microbial substitution was noted. (4) As an adverse reaction, diarrhea was noted in one case (0.8%). Abnormal laboratory test values were noted in 15 cases (12.3%) including eosinophilia, elevated GPT, and elevated gamma-GTP. All of these abnormalities were transitory, and none of them critical. As a result of above pharmacokinetic and clinical investigations, CZOP is considered to be highly useful in the treatment of indicated infections in neonates and premature infants. It appears that 20 mg/kg of CZOP can be administered by intravenous injection or intravenous drip infusion to neonates and premature infants aged 0-day (less than 24 hours after birth) once or twice daily, to those aged 1 (24 or more hours after birth) to 7 days twice or three times daily, and to those aged 8 or more days three to four times daily, and that the dose can be increased up to 40 mg/kg in cases of critical or intractable infections.

Bacterial Infections↗