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Biomedical subjects

M Nishio

Publications and source records attributed to M Nishio.

At least 235 records · Page 13Linked to original sources

[A case of pulmonary embolism probably induced by long term use of oral contraceptive].

We present a 53-year-old female with pulmonary embolism (PE), who had been taking oral contraceptive for 13 years. She was admitted to our hospital with upper abdominal pain and was found to be in shock. The diagnosis of PE was made from chest X-ray examination, electrocardiogram and pulmonary angiography. Pulmonary hypertension was observed on right heart catheterization, and an anticoagulant was administered. Multiple defects of the right pulmonary artery were detected on lung perfusion scan, and there were no significant findings on leg phlebogram. Home oxygen therapy was effective for the treatment of pulmonary hypertension and chronic hypoxemia which still persisted after her recovery from the acute stage. We are concerned that wide spread use of oral contraceptives will increase the incidence of PE in the near future in this country. We conclude that contraceptive users should be warned of their higher risk of PE, and that they should visit a clinic for examination.

Female↗

[Prospective randomized trials comparing hyperfractionated radiotherapy with conventional radiotherapy in stage III non-small cell lung cancer].

From September 1987 to August 1990, 36 patients with stage III non-small cell lung cancer were randomly assigned to 65 Gy in 26 fractions of 2.5 Gy each (conventional radiotherapy) or 71.5 Gy in 52 fractions of 1.375 Gy given twice a day (hyperfractionated radiotherapy). The overall time for both groups was 6.5 weeks. The groups were similar in terms of age, performance status, previous chemotherapy, stage IIIA and IIIB, and histopathology. The rate of complete response was 44.4% for hyperfractionation, and 16.7% for conventional fractionation. Overall survival rates at 24 months and 36 months were 50.0% and 21.8% for hyperfractionation, and 31.3% and 0% for conventional fractionation. Fever due to radiation pneumonitis occurred in seven of 18 patients with hyperfractionation (38.9%) and four patients with conventional fractionation (22.2%). No severe late toxicity has been observed in either group. We conclude that hyperfractionated radiotherapy in non-small cell lung cancer may improve survival without increasing severe toxicity.

Adult↗

A single-base-pair substitution abolishes D-amino-acid oxidase activity in the mouse.

Mutant ddY/DAO- mice lacking D-amino-acid oxidase (DAO) activity were examined for the cause of their lack of enzyme activity. Total RNA was extracted from the kidney of the ddY/DAO- mice and cDNA was synthesized. After cDNA encoding DAO was amplified by the polymerase chain reaction it was cloned into a plasmid and sequenced. Comparison of the DAO cDNA sequence with that of normal BALB/c mice revealed the presence of a single-base substitution (G----A) which causes a Gly-181----Arg substitution in the middle of the enzyme molecule. The mutant DAO cDNA was inserted into an expression vector and was expressed in transfected COS-1 cells. The transfected cells synthesized the DAO mutant protein, but they did not show DAO activity. In contrast, when cells were transfected with an expression vector carrying wild-type DAO cDNA, where the substituted base-pair was replaced by a normal base-pair, they showed DAO activity. These results indicate that the single base-pair substitution is the cause of the loss of DAO activity in the ddY/DAO- mice.

Animals↗

Molecular evolution of human paramyxoviruses. Nucleotide sequence analyses of the human parainfluenza type 1 virus NP and M protein genes and construction of phylogenetic trees for all the human paramyxoviruses.

The nucleotide sequences of the NP and M genes of human parainfluenza type 1 virus (HPIV-1) were determined. The NP gene was 1677 nucleotides long excluding polyadenylic acid. The NP gene contained a single large open reading frame (ORF), which encoded a polypeptide of 524 amino acids with a calculated molecular weight of 57,736. The M gene 1173 nucleotides long excluding the poly(A) tract and the sequence also contained a single large ORF which encoded a polypeptide of 348 amino acid with a molecular weight of 38,445, which was inconsistent with 28 kDa previously determined by SDS-PAGE. We aligned the deduced HPIV-1 NP and M protein sequences with 12 and 13 other paramyxoviruses, respectively, suggesting that a common tertiary structure was found in the NPs or Ms of HPIV-1, Sendai virus (SV), HPIV-3 and BPIV-3 and that other common structure was also maintained in these proteins of HPIV-2, SV 41 and 5, MuV, HPIV-4. Phylogenetic trees were constructed for the NP and M proteins of all the paramyxoviruses of which nucleotide sequences had been previously reported. Paramyxoviruses could be subdivided into two groups, i.e., PIV-1 group and PIV-2 group; the former group is composed of HPIV-1, SV, HPIV-3 and BPIV-3, and the latter group consists of HPIV-2, SV 41, SV 5, MuV, HPIV-4 A and HPIV-4 B.

Amino Acid Sequence↗

Human blood monocyte activation by Nocardia rubra cell wall skeleton for productions of interleukin 1 and tumor necrosis factor-alpha.

Human blood monocytes were obtained from peripheral blood of healthy donors by counter-flow centrifugal elutriation. Functional integrity of monocytes for production of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) in response to Nocardia rubra cell wall skeleton (N-CWS) was examined by bioassay and enzyme immunoassay. Monocytes treated with N-CWS at more than 0.5 microgram/ml produced IL-1 and TNF-alpha extracellularly. Extracellular TNF activity appeared within 4 h, and maximally, 16 h after N-CWS stimulation, whereas longer time was needed for IL-1 activity to appear, the peak production being at 24 h. The neutralizing experiment also showed that anti TNF-alpha antibody did not affect IL-1 production by the monocytes treated with N-CWS, suggesting independency of IL-1 production of TNF-alpha. These results suggest that the therapeutic antitumor effect of N-CWS is due, in part at least, to the augmented production of these monokines.

Bacterial Proteins↗

Intracavitary brachytherapy combined with external-beam irradiation for squamous cell carcinoma of the thoracic esophagus.

During the 15 year period from 1974 to 1988, 277 patients with previously untreated, histologically confirmed, squamous cell carcinoma of the thoracic esophagus were treated with the Time Dose and Fractionation (TDF) factor of more than 99. Of these, 161 patients were treated with external beam irradiation combined with intracavitary brachytherapy. Intracavitary brachytherapy was done for all patients for whom insertion of an outer applicator 1 cm in diameter was possible and for whom a relatively good performance status was seen at completion of external beam irradiation. Except for mild radiation-induced esophagitis, no acute radiation injuries were noted. The early clinical effect of radiation upon the esophageal lesion was determined by esophagography and esophagoscopy, approximately 1 month after the combined radiotherapy; a complete response was observed in 86 (53.4%) of the 161 patients. Furthermore, after a 5 year follow-up, local control of esophageal cancer was found to have been successful in 51 (31.7%) of the 161 patients. The highest rate of local control was associated with the following criteria: Stage I, T1, tumor length less than 5 cm, and superficial or tumorous type of tumor. The 5-year actuarial survival rates were 43.3% for Stage I, 21.1% for Stage II, and 0% for both Stages III and IV. Benign radiation-induced esophageal ulcerations or strictures did develop in five of the long-term survivors, suggesting that the dosage is close to the maximal tolerance of the esophagus. We recommend that 1500-2000 cGy in two or three fractions is the optimal dosage for intracavitary radiation of the esophageal mucosa after external irradiation of 5500 cGy in 22 fractions for 5.5 weeks or 6000 cGy in 30 fractions for 6 weeks. We believe that intracavitary treatment of esophageal carcinoma is a highly effective and a safe therapeutic modality, not only as a palliative therapy, but also as a radical treatment for patients in Stages I and II.

Aged↗

Nucleotide sequence analysis of the simian virus 41 gene encoding the large (L) protein and construction of a phylogenetic tree for the L proteins of paramyxoviruses.

The complete nucleotide sequence of the simian virus 41 (SV41) large (L) protein gene was determined. The L gene spanned 6883 nucleotides including a putative trailer RNA, and the L mRNA contained a single large open reading frame encoding a polypeptide of 2269 amino acids. Dot-matrix comparisons under stringent conditions identified domains highly conserved among paramyxoviruses. Domain 3 is the most highly conserved, and has been hypothesized to be the RNA polymerase active site. A phylogenetic tree was constructed from the sequences of the L proteins of seven paramyxoviruses. SV41 was most closely related to human parainfluenza virus type 2 (HPIV-2), and SV41, HPIV-2 and SV5 form a subgroup. The intergenic sequences at the nucleocapsid protein-phosphoprotein and haemagglutinin-neuraminidase-L protein gene junctions, and the 5' trailer sequence of SV41 were also determined, and it was shown that the first 13 nucleotides of the 5' trailer sequence are complementary to those of the 3' leader sequence. The intergenic, and gene-start and -end sequences of SV41, HPIV-2 and SV5 are shown.

Amino Acid Sequence↗

Sequence analysis of the large (L) protein of simian virus 5.

The complete nucleotide sequence of the large (L) protein gene of simian virus 5 (SV5) was determined from cDNA of the genomic RNA and mRNA, and found to be 6804 bases in length, exclusive of a poly(A) tract. The sequence contained an open reading frame of 6765 nucleotides encoding 2255 amino acids. Results of dot matrix comparisons of the L protein of SV5 with those of human parainfluenza type 3 virus and Sendai virus indicated that there are five conserved domains, and that each domain contains characteristic sequence(s). The L protein of SV5 was detected in purified virions using antiserum directed against an oligopeptide corresponding to the N-terminal region.

Amino Acid Sequence↗

Antigenic diversity of human parainfluenza virus type 1 isolates and their immunological relationship with Sendai virus revealed by using monoclonal antibodies.

Fifty-six monoclonal antibodies (MAbs) directed against human parainfluenza virus type 1 (hPIV-1) were prepared in order to identify the structural proteins of hPIV-1, to examine the immunological relationship between hPIV-1 and Sendai virus (SV), and to determine the antigenic diversity of clinical isolates of hPIV-1. In addition, 41 MAbs characterized previously and directed against SV were used for immunological comparison of SV and hPIV-1 isolates. Of the MAbs against hPIV-1, two reacted with phospho (P) protein, 11 with nucleocapsid protein (NP), 24 with haemagglutinin-neuraminidase (HN) protein and 19 with fusion (F) protein. With the aid of MAbs against hPIV-1 and those against SV showing cross-reactivity with hPIV-1, the structural proteins of hPIV-1 were identified; p83, p56, p34, gp74 and gp60 of hPIV-1 were identified as the P, NP, M, HN and F proteins, respectively. The MAbs against the P protein and NP of hPIV-1 showed limited cross-reactivity with SV, whereas they had high reactivity with clinical isolates of hPIV-1. Interestingly, one MAb against the NP of hPIV-1 lacked reactivity with clinical isolates which were isolated in the 1970s and 1980s. The MAbs against the HN of hPIV-1 also exhibited quite limited reactivity with SV and the clinical isolates; two groups of HN-specific MAbs showed almost no reactivity with the clinical isolates from the 1970s and 1980s, similarly to the NP-specific MAb. However, anti-HN MAbs belonging to the two groups showing specific activities (neuraminidase inhibition and haemolysis inhibition) reacted with almost all clinical isolates. On the other hand, although anti-F protein MAbs had limited reactivity with SV, they showed reactivity with almost all hPIV-1 isolates. The MAbs against the P, NP, M, HN and F proteins of SV also showed limited cross-reactivity with the clinical hPIV-1 isolates, and this reactivity was independent of the time and place of isolation, except for that of the F protein. These results confirm that although hPIV-1 is related to SV, it is antigenically distinct from it.

Antibodies, Monoclonal↗

Fusion regulation proteins on the cell surface: isolation and characterization of monoclonal antibodies which enhance giant polykaryocyte formation in Newcastle disease virus-infected cell lines of human origin.

Newcastle disease virus (NDV)-infected HeLa and FL cells showed small polykaryocytes at about 24 h postinfection, while the addition of anti-FL-cell rabbit, rat, or mouse serum to the NDV-infected cells gave rise to giant polykaryocytes at 15 h postinfection. We isolated three monoclonal antibodies (MAbs) (4-5-1, 6-1-13, and 7-2-1) capable of enhancing giant polykaryocyte formation in NDV-infected HeLa cells. These MAbs immunoprecipitated gp80 or gp135, which were detected mainly on the surface of HeLa cells. A functionally intact F protein was essential for antibody-enhanced cell fusion, and hemagglutinating (receptor-binding) activity of HN protein was involved in the fusion at an early stage; that is, the MAbs enhanced NDV-mediated syncytium formation. These molecules were considered to have the ability to regulate NDV-mediated cell fusion and thus were designated fusion regulation protein (FRP)-1 (gp80) and FRP-2 (gp135). Anti-FRP MAbs enhanced the susceptibility of cells to fusion activity of NDV. Anti-FRP-1 MAbs reacted with a molecule on the surface of every cell derived from humans and monkeys but showed no cross-reactivity with mouse or hamster cells. FRP-2 could be detected in limited cell lines of human origin.

Animals↗

Effect of pentazocine on the cytotoxicity of cortisone-resistant lymphocytes from mouse thymus.

Pentazocine and its related compounds were examined for their effect on the cytotoxicity of cortisone-resistant lymphocytes (CR lymphocytes) against Ehrlich carcinoma cells. The following compounds were used: pentazocine, naloxone, levallorphan, eptazocine and morphine. CR lymphocytes were obtained from the thymus or spleens of mice injected i.p. with hydrocortisone acetate (125 mg/kg) 2 days before harvesting the lymphocytes. The mixture of tumor cells and CR lymphocytes was inoculated s.c. into mice after incubation in the presence or absence of 10 microM drugs. Five weeks after inoculation, the percentage of mice developing a solid tumor among the recipients given the pentazocine-treated cell mixture of tumor cells and thymic CR lymphocytes was significantly smaller than the percentage in recipients given the cell mixture treated with or without other drugs (percent tumor takes: 21% and about 80%, respectively). Splenic CR lymphocytes did not show any cytotoxic effect, irrespective of the drug treatment. The pretreatment of CR lymphocytes or Ehrlich cells with 10 microM pentazocine did not affect the cytotoxicity of thymic and splenic CR lymphocytes. The proportion of the lymphocyte-conjugated tumor cells was significantly increased when the mixture of CR lymphocytes and tumor cells was incubated in the presence of pentazocine. The present results indicate that the cytotoxicity of thymic CR lymphocytes is enhanced by pentazocine possibly through the increase in the proportion of the lymphocyte-conjugated tumor cells but enhanced not by the other drugs.

Animals↗

Idiopathic acute eosinophilic pneumonia.

A previously healthy young man presented with acute respiratory distress, high fever and bilateral ground-glass appearance on chest radiograph. Bronchoalveolar lavage analysis demonstrated significant eosinophilia (72%) with no evidence of infection. The transbronchial lung biopsy showed that the walls of bronchioli and alveolar septa were markedly infiltrated with eosinophils. The patient rapidly improved with corticosteroid therapy. This case exemplifies the recently described idiopathic acute eosinophilic pneumonia. Similar cases published in the Japanese literature were reviewed and discussed.

Acute Disease↗

[A case of Wegener's granulomatosis complicated by hypopituitarism].

A 71-year-old male complaining of chest pain was admitted to our hospital. A single cavitary mass shadow was observed on chest X-ray films. Urinalysis revealed microscopic hematuria. CT examination demonstrated a tumorous shadow in the maxillary sinus. The diagnosis of Wegener's granulomatosis was histologically established by biopsy specimens from the nasal mucosa which showed necrotizing vasculitis and granuloma with fibrinoid degeneration. He was treated with combination therapy of prednisolone and cyclophosphamide. The abnormal shadows on chest X-ray and in the maxillary sinus on CT improved rapidly, but the patient developed progressive weight loss and complained of cold intolerance, weakness and dysphagia. Serum T3, T4 and TSH were found to be reduced. Anterior pituitary function tests showed reduction of TSH, GH and ACTH responses, which was probably due to irreversible vasculitis.

Aged↗

[Interpeak components of event-related potentials--comparison between normal and schizophrenic groups].

Event-related potentials (ERPs) during a two-tone discrimination task were recorded in 85 normal subjects and 110 schizophrenic subjects. We divided ERPs into 4 interpeak components. We named them A, A', B and B'. A is the component from the stimulus point to n100 peak. A' is the one from n100 peak to p200 peak. B is the one from p200 peak to n200 peak. B' is the one from n200 peak to p300 peak. Their latency was named Al, A'l, Bl, and B'l respectively. Their amplitude was also named Aa, A'a, Ba and B'a respectively. Bl and A'l of the schizophrenic group were both significantly longer than those of the normal group. B'a of the schizophrenic group was significantly smaller than that of the normal group. Interrelations between interpeak components of the normal group were examined statistically. Regarding latency, a significant negative correlation was seen between Al and A'l, and also between Bl and B'l. Regarding amplitude, a significant positive one was seen between Aa and A'a, and also between Ba and B'a. Interrelations between Al and A'l, Bl and B'l, Aa and A'a, and Ba and B'a of the schizophrenic group were the same as those of the normal group. These negative correlations in latency suggest that n100 peaks and n200 peaks have 'jitter'. A combination of interpeak components is supposed to reflect a higher function of the brain. There was a significant negative correlation between (A + A')l and (B + B')l in the normal group, but there was not a significant one between them in the schizophrenic group. The schizophrenic group is supposed to have a certain abnormality in a higher function of the brain. Our result suggests that we may possibly be able to associate an abnormal focus around p200 peak with some symptoms and signs of schizophrenia.

Adult↗

[Mechanism of attention in sleep--the changes of waveforms of event-related potentials in sleep].

Since attention has such a close correlation with arousal level, the influence of sleep on the waveforms of event related potential (= ERP) must be studied in advance for evaluating attentiveness of human mental activity. ERP, which odd-ball paradigm was used to elicit, was examined in 9 adult and healthy subjects from arousal to sleep. And ERP during a whole night was also examined in 5 of them to study the relation of the waveforms of ERP and sleep stages including a stage of rapid eye movement. As a result, there were some clear differences between the waveforms of the rare and frequent stimuli, and with change of sleep stages the differences also changed. Remarkable increase of amplitude and prolongation of latency of P200 and N200 were found in the waves of target stimuli in stage I. Activities of both components were connected with each other like a complexed component and preceded by the change of P300 activities. The waveforms of target stimuli in stage II had same kind of components with those of arousal stage. There were increased P200, N200, P300 activities and subsequent large negative activity which we called N3. These components were not clear in the waveforms of non-target stimuli. But P300 and N3 components were disappeared gradually during stage III. The averaged waveforms in stage III accompanied with 14-16 Hz fast wave suggested that they were identical with K-complex of sleep EEG. Add to this result, the habituation usually observed on P200 and N200 of nontarget stimuli in arousal let us to think that they are also identical with orienting reflex by rare and novel stimuli of external events (Sokolov). According to the result of examination changing the probability of target stimuli (20%----50%----80%), the waves of target stimuli in stage II were dependent on the probability of rare stimuli as well as in arousal stage. The dependence on probability was thought to reflect an automatic processing of selecting stimuli by orienting reflex in sleep. Another 3 subjects were examined of auditory evoked response in sleep with the same stimuli and without a task of counting numbers of rare stimuli. In stage II, however, they showed the waveforms by rare stimuli just like those by rare and target stimuli of 9 subjects. Then, it was supposed that attentiveness for external stimuli might be existent in sleep and changeable with sleep stages.

Adult↗

Characterizations of the human parainfluenza type 2 virus gene encoding the L protein and the intergenic sequences.

We cloned and determined the nucleotide sequences of cDNAs against genomic RNA encoding the L protein of human parainfluenza type 2 virus (PIV-2). The L gene is 6904 nucleotides long including the intergenic region at the HN-L junction and putative negative strand leader RNA, almost all of which is complementary to the positive strand leader RNA of PIV-2. The deduced L protein contains 2262 amino acids with a calculated molecular weight of 256,366. The L protein of PIV-2 shows 39.9, 28.9, 27.8 and 28.3% homologies with Newcastle disease virus (NDV), Sendai virus (SV), parainfluenza type 3 virus (PIV-3) and measles virus (MV), respectively. Although sequence data on other components of transcriptive complex, NP and P, suggested a closer relationship between PIV-2 and MV, as concerns the L protein, MV is closely related to another group as SV and PIV-3. From analysis of the alignment of the five l proteins, six blocks composed of conserved amino acids were found in the L proteins. The L protein of PIV-2 was detected in purified virions and virus-infected cells using antiserum directed against an oligopeptide corresponding to the amino terminal region. Primer extension analyses showed that the intergenic regions at the NP-P, P-M, M-F, F-HN and HN-L junctions are 4, 45, 28, 8 and 42 nucleotides long, respectively, indicating that the intergenic regions exhibit no conservation of length and sequence. Furthermore, the starting and ending sequences of paramyxoviruses were summarized.

Amino Acid Sequence↗

Growth properties and F protein cleavage site sequences of naturally occurring human parainfluenza type 2 viruses.

The growth properties of 24 clinical isolates of PIV-2 obtained from six independent areas in Japan were examined using Vero and primary monkey kidney cells. These viruses could be subdivided into three groups on the basis of the ability of syncytium formation on the two primate cell systems. The distinct correlation between the F protein cleavability and the fusogenic effect was observed in Vero cells, and the importance of consecutive basic residues in the F protein cleavage site for efficient cleavage was suggested by the sequence analyses of their F genes. On the other hand, in PMK cells, their fusogenic activities could not be directly attributed to the F cleavability, fusion peptide sequence, and replication efficiency, indicating that unidentified structural features play an important role in cytopathic activities of naturally occurring PIV-2s.

Amino Acid Sequence↗