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Biomedical subjects

H Bando

Publications and source records attributed to H Bando.

At least 109 records · Page 6Linked to original sources

Alternating chemotherapy with cyclophosphamide/adriamycin/vincristine (CAV) and cisplatin/etoposide (PVP) against small cell lung cancer. Eastern Shikoku Lung Cancer Chemotherapy Group.

Seventy-four confirmed small cell lung cancer (SCLC) patients received alternating combination chemotherapy with CAV and PVP. The CAV comprised of cyclophosphamide 800 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1 and vincristine 1.4 mg/m2 on day 1, administered every 3-4 weeks. The PVP comprised cisplatin 80 mg/m2 on day 1 and etoposide 75 mg/m2 on day 1-5 administered every 3-4 weeks. Of these 74 patients, 63 (85.1%) achieved complete or partial responses with 16 (21.6%) obtaining a complete response. The median survival time was 13.2 months: 10.4 months in patients with extensive disease (ED), 16.3 months in those with limited disease (LD). A three-year disease-free period was achieved in eight patients (11.2%: 4.8% with ED, 16.8% with LD). The median duration of response was 28.3 weeks: 20.1 weeks with ED and 44.0 weeks with LD. The most commonly encountered side effects were nausea, vomiting, alopecia and myelosuppression but all were tolerable. We consider CAV-PVP to be an effective combination regimen for treating SCLC.

Adult↗

Correlation between plasma levels of ACTH and cortisol in basal states and during the CRH test in normal subjects and patients with hypothalamo-pituitary disorders.

Using a new ACTH-immunoradiometric assay (IRMA), we measured plasma ACTH levels in the basal states and during CRH test in normal subjects and the patients with hypothalamo-pituitary disorders. The basal levels of plasma ACTH in 76 normal young (25-45 yr) and 140 elderly (60-85 yr) subjects were 23.1 +/- 13.6, and 17.5 +/- 11.2 pg/ml, respectively. The plasma ACTH levels were less than detection limit (5 pg/ml) in 3 patients with isolated ACTH deficiency, and less than 10 pg/ml in 6 of 7 patients with hypopituitarism. A significant correlation was observed between the basal levels of plasma ACTH and of cortisol in two age groups, with almost the same regression line, showing no age-related decline in the plasma levels of ACTH and cortisol. In 2 normal subjects and 2 patients with Cushing's disease, synchronized secretions of ACTH and cortisol were observed between 0800h and 1800h. In normal subjects and the patients with pituitary disorders, a significant correlation was observed between the Area Under the Curve's for plasma ACTH and cortisol during the CRH test. The correlation constant was higher in normal subjects, but lower in the patients with acromegaly, non-functioning pituitary tumor, and Cushing's disease in this order, suggesting low sensitivity of the pituitary-adrenal axis in these patients. These results suggest that the ACTH-IRMA kit provide reliable data for clinical investigation, and that the secretions of ACTH and cortisol correlate each other in basal states and during the CRH test in the patients with pituitary disorders as well as in normal subjects.

Adolescent↗

Sequencing analyses and comparison of parainfluenza virus type 4A and 4B NP protein genes.

The nucleotide sequences of the cDNA copies of the mRNA coding for the nucleocapsid proteins (NPs) of human parainfluenza viruses type 4A (PIV-4A) and type 4B (PIV-4B) were determined. The copy of PIV-4A NP mRNA contained 1885 nucleotides encoding a protein with a calculated molecular weight of 62,561. The same number of amino acids with a similar molecular weight (62,425) were predicted for the PIV-4B NP protein. Comparisons on the nucleotide sequence and the amino acid sequence of NP protein between these two subtypes revealed extensive homologies in the nucleotide sequence (87%) and in the amino acid sequence (93%). Furthermore, a conserved region with about 100 amino acids was observed between PIV-4s and other paramyxoviruses, Newcastle disease virus (NDV), Sendai virus, mumps virus (MuV), PIV-3, BPIV-3, measles virus (MV), and canine distemper virus (CDV), indicating a common ancestor for these nine viruses. Our data also indicated that the PIV-4 NP proteins were more closely related to MuV and NDV than to other parainfluenza viruses, PIV-3, BPIV-3, and Sendai virus. Interestingly, the NP protein homology between PIV-4s and the morbillivirus group, MV and CDV, was slightly higher than that between PIV-4s and the parainfluenza viruses, PIV-3, BPIV-3, and Sendai virus.

Amino Acid Sequence↗

Sequence determination of the hemagglutinin-neuraminidase (HN) gene of human parainfluenza type 2 virus and the construction of a phylogenetic tree for HN proteins of all the paramyxoviruses that are infectious to humans.

The nucleotide sequence of the hemagglutinin-neuraminidase (HN) gene of human parainfluenza type 2 virus (PIV-2) was determined. The PIV-2 HN gene was 2112 nucleotides excluding poly(A) tail. There was a single large open reading frame in the mRNA which encoded a protein of 571 amino acids with a calculated molecular weight of 63,262. Analysis of the deduced amino acid sequence revealed that there were fourteen potential glycosylation sites and a major hydrophobic region near the N-terminus, which would anchor the protein in the viral membrane. Comparisons of the HN protein sequences of PIV-2 with those of Simian virus 5 (SV5), Sendai virus (SV, parainfluenza virus type 1), human parainfluenza virus type 3 (PIV-3), type 4 (PIV-4), bovine parainfluenza virus type 3 (BPIV-3), mumps virus (MuV), and Newcastle disease virus (NDV) showed definite amino acid sequence relatedness, indicating a common ancestor for these viruses. Furthermore, statistical analysis of the protein sequences suggested a possible evolutionary relatedness among the paramyxoviruses. This is the first time that a phylogenetic tree has been constructed for all the parainfluenza viruses and mumps virus which are infectious to humans. In addition, amino acid sequences involved in hemagglutinating and neuraminidase activities of paramyxovirus were discussed.

Amino Acid Sequence↗

Antigenic and structural properties of a paramyxovirus simian virus 41 (SV41) reveal a close relationship with human parainfluenza type 2 virus.

Seven structural component proteins of a paramyxovirus simian virus 41 (SV41) were identified with the aid of monoclonal antibodies prepared against SV41 and human parainfluenza type 2 virus (PIV2). The nucleoprotein is antigenically very close to that of PIV2, while it is comparatively far from that of simian virus 5 (SV5). The hemagglutinin-neuraminidase (HN) protein showed no immunological relationship to either of the HN proteins of PIV2 or SV5. The amino acid sequence of the SV41 HN protein was deduced from the nucleotide sequence of its HN gene and revealed that the SV41 HN is unexpectedly close to the PIV2 HN (61.2% identity in amino acid sequence), while the SV5 HN showed only 48.3% identity with the PIV2 HN. The SV41 HN is also related to the SV5 HN (51.3% identity); thus, the SV41 HN is phylogenetically situated between the PIV2 and SV5 HNs. These results indicate that SV41 is the virus closest to PIV2 at present.

Amino Acid Sequence↗

Sequence analyses of the 3' genome end and NP gene of human parainfluenza type 2 virus: sequence variation of the gene-starting signal and the conserved 3' end.

We cloned and determined the nucleotide sequences of cDNAs against nucleocapsid protein (NP) mRNA and the genomic RNA of human parainfluenza type 2 virus (PIV-2). The 3' terminal region of genomic RNA was compared among PIV-2, mumps virus (MuV), Newcastle disease virus (NDV), measles virus (MV), PIV-3, bovine parainfluenza type 3 virus (BPIV-3), Sendai virus (SV), and vesicular stomatitis virus (VSV), and an extensive sequence homology was observed between PIV-2 and MuV. Although no significant sequence relatedness was observed between PIV-2 and other viruses, the terminal four nucleotides were identical in the viruses compared, implying a specific role of these nucleotides on the replication of paramyxoviruses. A primer extension analysis elucidated the major NP mRNA initiation site with the sequence UCUAAGCC, which showed a moderate homology with the gene-starting consensus sequences of other paramyxoviruses. On the other hand, the NP mRNA was terminated at the nucleotide stretch AAAUUCUUUUU, and this sequence was conserved in all the PIV-2 genes, indicating that the oligonucleotides will form a part of the gene attenuation signal of PIV-2. Comparisons of NP protein sequence indicated a possible subgrouping of the paramyxoviruses into two groups, one of which is a group including PIV-2, PIV-4, MuV, and NDV, and another is a group including PIV-3, BPIV-3, and SV. This result supports an idea from our previous studies using polyclonal and monoclonal antibodies. Furthermore, our data indicated that the PIV-2 NP protein sequence was more closely related to MV and CDV than to other parainfluenza viruses, PIV-3 and SV.

Amino Acid Sequence↗

Complete nucleotide sequence of the matrix gene of human parainfluenza type 2 virus and expression of the M protein in bacteria.

The sequence of the M gene of human parainfluenza virus type 2 (PIV-2) has been determined. The sequence contained a large open reading frame with 1131 nucleotides encoding a protein with a calculated molecular weight of 42,312. Comparison of M protein sequence indicated that PIV-2 was more closely related to mumps virus and Newcastle disease virus than to other parainfluenza viruses, Sendai virus (SV), and parainfluenza virus type 3 (PIV-3), indicating a possible subdividing of the Paramyxovirus into two groups. This grouping is consistent with that obtained from analysis of the HN gene. Measles virus and canine distemper virus definitely belong to the subgroup composed of SV and PIV-3. No homology region was found in all the paramyxoviruses compared. However, a tertiary structure may be conserved in each subgroup of paramyxovirus. The M protein of PIV-2 was expressed in bacteria, and the product was recognized by a monoclonal antibody specific for the PIV-2 M protein. The bacterial-expressed protein, however, was heterogeneous and smaller in size.

Amino Acid Sequence↗

Molecular cloning and sequence analysis of human parainfluenza type 4A virus HN gene: its irregularities on structure and activities.

We cloned the cDNA of human parainfluenza type 4A virus (PIV-4A) HN gene by reverse-transcription of virus-specific mRNAs and genomic RNA, and determined the complete nucleotide sequence of the HN gene. The predicted HN protein sequence of PIV-4A showed significant relatedness with those of other paramyxoviruses, SV5, NDV, MuV, PIV-3, BPIV-3, indicating a common ancestor. The homologies between the viruses suggested that PIV-4A is more closely related to NDV, SV5, and MuV than to the parainfluenza viruses, PIV-3, bovine parainfluenza type 3 virus (BPIV-3), and Sendai virus (SV). Sixty amino acids were commonly conserved among the viruses, other than PIV-4A. Two of these amino acids were substituted in PIV-4A HN and are predicted to be located near the active site of the neuraminidase. The analysis of neuraminidase of PIV-4 revealed that the activity is hardly detectable, suggesting the significant effect of the substituted amino acid sites on neuraminidase activity.

Amino Acid Sequence↗

Terminal structure of a Densovirus implies a hairpin transfer replication which is similar to the model for AAV.

We cloned the complete sequence of Bombyx DNV (Ina isolate; Bm DNV-1) genome in a bacterial plasmid pUC 119 and determined the nucleotide sequences of both termini, resulting in elucidation of the nucleotide sequence of the complete genomic DNA of DNV. The complete sequence of the DNV DNA (5048 nucleotides) has inverted repeats of 225 nucleotides and the terminal 153 nucleotides are palindromic. The palindromes can fold back on themselves to form a hairpin structure but, unlike AAV, the small internal palindrome which forms a T-shaped conformation was not observed. End-label analysis demonstrated that the palindromic sequences at both termini can exist in either of two orientations (flip or flop) in virion DNA with different frequencies. These data suggest that the hairpin transfer model for AAV replication must be modified to explain the DNV replication. Additionally, a comparison study on the terminal structures of insect, human, and rodent parvoviruses allowed a prediction on the ancestral terminal structure of parvovirus genome.

Amino Acids↗

Sequence of the fusion protein gene of human parainfluenza type 2 virus and its 3' intergenic region: lack of small hydrophobic (SH) gene.

cDNA clones representing the fusion (F) gene of human parainfluenza virus type 2 (PIV-2) were isolated from cDNA libraries constructed from virus-specific mRNA and genomic RNA, and the complete nucleotide sequence of the F gene was determined. The F gene is 1854 nucleotides long and encodes one long open reading frame of 551 amino acids. The cleavage site for activation of the precursor Fo protein is Thr-Arg-Gln-Lys-Arg. The F gene of PIV-2 is most closely related to those of simian virus 5 (SV5) and mumps virus (MuV). Interestingly, although the HN glycoprotein of PIV-2 shows no relatedness to the HA glycoprotein of measles virus (MV), a distinct homology is found in the F proteins of PIV-2 and MV. As concerns F proteins, paramyxoviruses can be divided into two subgroups; that is, PIV-2, SV5, and MuV belong to one group, and HPIV-1, SV, and PIV-3 belong to the other group. Newcastle disease virus (NDV) and MV are intermediate. Coding regions for small hydrophobic (SH) proteins have been found between the HN and F genes of SV5 and MuV, which are the viruses most closely related to PIV-2. However, such a gene could not be detected in two different strains of PIV-2.

Amino Acid Sequence↗

Sequence analysis of the phosphoprotein (P) genes of human parainfluenza type 4A and 4B viruses and RNA editing at transcript of the P genes: the number of G residues added is imprecise.

We cloned and sequenced the cDNAs against genomic RNAs and mRNAs for phosphoproteins (Ps) of human parainfluenza virus types 4A (PIV-4A) and 4B (PIV-4B). The PIV-4A and -4B P genes were 1535 nucleotides including poly(A) tract and were found to have two small open reading frames, neither of which was apparently large enough to encode the P protein. A cluster of G residues was found in genomic RNA and the number of G residues was 6 in both PIV-4A and -4B. However, the number of G residues at the corresponding site in the mRNAs to the genomic RNA was not constant. Three different mRNA cDNA clones were obtained; the first type of mRNA encodes a larger (P) protein of 399 amino acids, the second type encodes V protein of 229 or 230 amino acids, and the third type encodes the smallest protein (156 amino acids). Comparisons on the nucleotide and the amino acid sequences P and V proteins between these two subtypes revealed extensive homologies. However, these homology degrees are lower than that of NP protein. The C-terminal regions of the P and V proteins of PIV-4s could be aligned with all other Paramyxoviruses, PIV-2, mumps virus (MuV), simian virus 5 (SV 5), Newcastle disease virus (NDV), measles virus (MV), canine distemper virus (CDV), Sendai virus (SV), and PIV-3. On the other hand, the P-V common (N-terminal) regions showed no homology with MV, CDV, SV, and PIV-3. Seven phylogenetic trees of Paramyxoviruses were constructed from the entire and partial regions of P and V proteins.

Amino Acid Sequence↗

Sequence analysis of P gene of human parainfluenza type 2 virus: P and cysteine-rich proteins are translated by two mRNAs that differ by two nontemplated G residues.

We cloned and sequenced the cDNAs against genomic RNA and mRNA for phosphoprotein (P) of human parainfluenza type 2 virus (PIV-2). cDNA clone from genomic RNA was 1439 nucleotides in length excluding poly(A) and was found to have two small open reading frames encoding proteins of 233 and 249 amino acids. Two different mRNA cDNA clones were obtained; that is, one mRNA contained a smaller reading frame coding 225 amino acids, V protein, and the other mRNA contained a larger reading frame coding 395 amino acids, P protein. Both mRNAs had G cluster in coding frame. The former mRNA contained seven G residues, and two extra G residues were inserted in the latter mRNA. Ten cDNA clones from the genomic RNA were identical and were composed of seven G residues, indicating that genomes analyzed here were a homogeneous population. Therefore, V protein is encoded by faithfully copied mRNA and P protein is translated from mRNA in which two additional G residues are nontemplately inserted immediately after seven genomically encoded G residues. The V and P proteins are amino coterminal proteins and have different C termini. The C terminus of V protein is cysteine-rich and bears some resemblance to metal-binding protein of the zinc finger-type motif. P protein sequence of PIV-2 showed high homologies with SV 5 (40.4%) and mumps virus (35.5%), and a moderate homology with Newcastle disease virus (20.6%). On the other hand, very little homology was found between PIV-2 and other paramyxoviruses including Sendai virus, PIV-3, and measles virus. The cysteine-rich region in V protein was found to be highly conserved in PIV-2, SV 5, and measles virus, suggesting that V protein of paramyxoviruses plays important roles in transcription and/or replication. The predicted cysteine-rich V protein was detected in virus-infected cells using antiserum directed against an oligopeptide specific for the predicted V polypeptide.

Amino Acid Sequence↗

Antiviral effect of 6-diazo-5-oxo-L-norleucine, antagonist of gamma-glutamyl transpeptidase, on replication of human parainfluenza virus type 2.

The antiviral effects of 6-diazo-5-oxo-L-norleucine (L-DON) on the replication of human parainfluenza virus type 2 (HPIV-2), mumps and vesicular stomatitis viruses were studied. L-DON suppressed growth of these viruses and, in particular, HPIV-2 in four cell types. L-DON was not toxic to the cells at the active dose and did not significantly inhibit cellular macromolecular synthesis. The L-DON-sensitive step of HPIV-2 replication was considered to be relatively early. The NP, P and M proteins were, although at a low level, clearly detectable in HPIV-2-infected Vero cells treated with L-DON, whereas the HN and F proteins were scarcely detected by either immunostaining or immunoprecipitation, indicating that L-DON mainly decreased the amounts of viral glycoproteins. Furthermore, Northern blot hybridization showed that secondary transcription of virus RNA was also inhibited.

Animals↗

Immunological relationships of simian virus 41 (SV41) to other paramyxoviruses and serological evidence of SV41 infection in human populations.

Antigenic relationships of simian virus 41 (SV41) to other paramyxoviruses were examined by immunoprecipitation of isotope-labelled SV41-infected cell lysates with specific antisera. SV41 is closely related to the group comprising human parainfluenza virus 2 (HPIV-2), simian virus 5 (SV5), parainfluenza virus 4 and mumps virus. Slight cross-neutralization was detected between SV41, HPIV-2 and SV5. Anti-SV41 activities were detected in 21 of 1116 human serum specimens, indicating that a proportion of the human population is infected with SV41. The haemagglutinin-neuraminidase of SV41 was preferentially immunoprecipitated by anti-SV41 positive sera.

Animals↗

[A case of intrapulmonary lymph node simulating small carcinoma of the lung].

A 48-year-old male was admitted for further examination of a coin lesion with a diameter of 8 mm seen on chest X-ray. The patient was a heavy smoker and his serum level of CEA was elevated to 29.8 ng/ml. Since the broncho-fiberscopic examination was not able to yield a definitive diagnosis, an operation was performed as lung cancer was suspected. According to the histological examination, the small nodule was diagnosed as an intrapulmonary lymph node with anthracosis and silicotic nodules. A review of the limited number of case reports shows that men are more prone to intrapulmonary lymph nodes, and that the patients were all smokers but not necessarily with occupational experience of exposure to silica.

Carcinoma, Small Cell↗

Incomplete replication of human parainfluenza virus type 2 in mouse L929 cells.

Human parainfluenza virus type 2 (HPIV-2) was tested for its ability to replicate in murine L929 cells. L929 cells were non-permissive for replication of HPIV-2. Interferon produced endogenously played no role in its incomplete replication. The mechanism by which growth of HPIV-2 was suppressed in L929 cells was studied. Synthesis of virus-specific polypeptides, particularly glycoprotein(s), was suppressed in HPIV-2-infected L929 cells. The HN mRNA could scarcely be detected in virus-infected L929 cells.

Animals↗

Isolation and characterization of monoclonal antibodies to human parainfluenza virus type 4 and their use in revealing antigenic relation between subtypes 4A and 4B.

Eighty monoclonal antibodies (MAbs) against parainfluenza virus type 4(PIV-4) were isolated and characterized. Of 50 MAbs against PIV-4A, 14 reacted with the nucleocapsid (NP) protein, 11 with the hemagglutinin-neuraminidase (HN) glycoprotein, 6 with the fusion (F) glycoprotein, and 19 with the matrix (M) protein. With the aid of the PIV-4A and PIV-2 specific MAbs showing cross-reactivity with PIV-4B, the structural proteins of PIV-4B were identified. gp72, p65, gp65, gp55, p53, and p40 of PIV-4B were assigned to HN, NP, Fo, F1, P, and M proteins, respectively. Based on the results, specificities of the MAbs against PIV-4B were determined. Of 30 hybridoma clones against PIV-4B, 13 clones were found to produce antibodies against the NP protein, 7 against the HN protein, and 10 against the F protein. Epitope mapping of these MAbs was performed with competitive binding assays in ELISA. According to their biological activities, the MAbs against the HN protein of either PIV-4A or 4B could be divided into three groups. The first group showed high hemagglutination inhibition (HI), hemolysis inhibition (HLI), and neutralizing (NT) activities. The second group showed high NT activity, but could not block hemagglutination. The final group showed a lower level of all activities. The MAbs against the F protein of PIV-4A and against PIV-4B were divided into two groups. Some MAbs against the F protein had high titer of NT, suggesting that the F protein had neutralizing-related epitopes. Antigenicity of the NP protein was highly conserved among subtypes of PIV-4. On the other hand, the MAbs against the HN and the F proteins showed high reactivity with the homologous subtype viruses, but low reactivity with the heterologous subtype viruses, indicating that the external glycoproteins exhibited antigenic variations between two subtypes of PIV-4. When the immunological interrelationship among various paramyxoviruses was analyzed. PIV-4 was found to be antigenically related to PIV-2, SV 5, and mumps virus.

Animals↗

Extensive antigenic diversity among human parainfluenza type 2 virus isolates and immunological relationships among paramyxoviruses revealed by monoclonal antibodies.

A panel of 128 monoclonal antibodies (MAbs) directed against hemagglutinin-neuraminidase (HN), fusion (F), matrix (M), and polymerase (P) proteins, and nucleoprotein (NP) of the Toshiba strain of human parainfluenza type 2 virus (PIV2) was prepared to examine the antigenic relationships among clinical isolates of PIV2 and among paramyxoviruses by indirect enzyme-linked immunosorbent assays. The HN proteins of 18 clinical isolates of PIV2 showed extensive antigenic diversity: 23 of 33 anti-HN MAbs showed no or limited reactivity to many isolates, while other structural proteins were antigenically well conserved. Some anti-HN MAbs recognizing conserved epitopes of the isolates exhibited two types of neutralizing activity, that is, these antibodies inhibited viral infectivity through attachment inhibition or fusion inhibition. This result also showed the presence of a potential third function of the HN protein which might affect the fusing activity of the F protein besides the hemagglutinating and neuraminidase activities. Many of the anti-NP and anti-P MAbs reacted with simian virus 41 (SV41) and simian virus 5 (SV5), whereas a few reacted with mumps virus or PIV4. Two of 6 anti-F MAbs reacted with SV41. None of the 128 MAbs showed reactivity with PIV1, PIV3, Newcastle disease virus (NDV), and measles virus. This result confirmed antigenic proximity of SV5 and SV41 to PIV2 and revealed comparatively restricted immunological relatedness among PIV2, PIV4, and mumps virus.

Antibodies, Monoclonal↗