Biomedical subjects

M Homma

Publications and source records attributed to M Homma.

At least 217 records · Page 12Linked to original sources

PubMed1989

Export of an N-terminal fragment of Escherichia coli flagellin by a flagellum-specific pathway.

Flagellin and several other external components of the bacterial flagellum are thought to be exported, not by the general N-terminal signal peptide-dependent pathway, but by a flagellum-specific pathway involving a central channel in the flagellum itself. We have constructed a variety of mutant alleles of the Escherichia coli flagellin gene. Mutant flagellins with large internal deletions or truncations of their C-terminal region could still be exported, even though they could not assemble into filament. The most extreme example was a fragment containing only the N-terminal 183 residues of the 497-residue wild-type flagellin. This result suggests that the N-terminal region of flagellin contains a signal that enables the protein to be recognized and exported by the flagellum-specific pathway.

Amino Acid Sequence↗

PubMed1989

Transcriptional enhancement of the human gene encoding for a melanoma-associated antigen (ME491) in association with malignant transformation.

A cloned DNA fragment (lambda R31) containing the human gene for melanoma-associated ME491 antigen was transfected into mouse fibroblast cell lines and the antigen expression was studied. Our preliminary observation of higher expression of the antigen in more malignant Ltk- cells and weaker expression in less malignant NIH3T3 cells tempted us to investigate the antigen expression in Harvey(H)-ras-transformed NIH3T3 cells. It was observed that malignant transformation of the lambda R31-transfected NIH3T3 cells by H-ras oncogene enhanced the antigen expression to some extent. Northern blot analysis suggested that the enhancement occurred at the transcriptional level. Nucleotide sequence analysis of the 5'-regulatory region of the ME491 antigen gene in lambda R31 identified a number of consensus sequence motifs for binding of transcription factors such as Sp1, AP-2 and polyomavirus enhancer binding proteins 2 and 3. A consensus sequence motif for binding of AP-1, known as a ras-responsive element, was not found in that region. The significance and possible involvement of the transcription factors in the enhancement of ME491 antigen expression are discussed.

Animals↗

PubMed1989

Flagellar switch of Salmonella typhimurium: gene sequences and deduced protein sequences.

The fliG, fliM, and fliN genes of Salmonella typhimurium encode flagellar components that participate in energy transduction and switching. We have cloned these genes and determined their sequences. The deduced amino acid sequences correspond to proteins with molecular masses of 36,809, 37,815, and 14,772 daltons, respectively. None of the protein sequences are especially hydrophobic or look as though they correspond to integral membrane proteins, a result consistent with other evidence suggesting that the proteins may be peripheral to the membrane, possibly mounted onto the basal body M ring. The fliL gene, which immediately precedes fliM, is of unknown function; it encodes a protein with a deduced molecular mass of 17,082 daltons. The hydropathy profile of FliL indicates that it is likely to be an integral membrane protein with at least one spanning segment, near its N terminus. None of the four proteins exhibit consensus N-terminal signal sequences. Comparison of the fliL, fliM, and fliN sequences with the homologous ones in Escherichia coli reveals ranges of similarities of 77 to 95% at the amino acid level and 75 to 86% at the nucleotide level, with the majority (58 to 89%) of codon changes being synonymous ones.

Amino Acid Sequence↗

PubMed1989

L-, P-, and M-ring proteins of the flagellar basal body of Salmonella typhimurium: gene sequences and deduced protein sequences.

The flgH, flgI, and fliF genes of Salmonella typhimurium encode the major proteins for the L, P, and M rings of the flagellar basal body. We have determined the sequences of these genes and the flgJ gene and examined the deduced amino acid sequences of their products. FlgH and FlgI, which are exported across the cell membrane to their destinations in the outer membrane and periplasmic space, respectively, both had typical N-terminal cleaved signal-peptide sequences. FlgH is predicted to have a considerable amount of beta-sheet structure, as has been noted for other outer membrane proteins. FlgI is predicted to have an even greater amount of beta-structure. FliF, as is usual for a cytoplasmic membrane protein of a procaryote, lacked a signal peptide; it is predicted to have considerable alpha-helical structure, including an N-terminal sequence that is likely to be membrane-spanning. However, it had overall a quite hydrophilic sequence with a high charge density, especially towards its C terminus. The flgJ gene, immediately adjacent to flgI and the last gene of the flgB operon, encodes a flagellar protein of unknown function whose deduced sequence was hydrophilic and may correspond to a cytoplasmic protein. Several aspects of the DNA sequence of these genes and their surrounds suggest complex regulation of the flagellar gene system. A notable example occurs within the flgB operon, where between the end of flgG (encoding the distal rod protein of the basal body) and the start of flgH (encoding the L-ring protein) there was an unusually long noncoding region containing a potential stem-loop sequence, which could attenuate termination of transcription or stabilize part of the transcript against degradation. Another example is the interface between the flgB and flgK operons, where transcription termination of the former may occur within the coding region of the latter.

Amino Acid Sequence↗

PubMed1989

In vivo responsiveness to glucocorticoid correlated with glucocorticoid receptor content in peripheral blood leukocytes in normal humans.

Dexamethasone loading tests (0.1 mg dexamethasone/kg, iv) were performed in 18 normal males to evaluate the individual responsiveness to glucocorticoid. There were inter-individual differences in increase in peripheral blood polymorphonuclear leukocyte count, decrease in peripheral blood lymphocyte count, and increase in plasma free fatty acids levels after dexamethasone injection. In addition, there was a significant correlation between the maximum increase in polymorphonuclear leukocytes and the maximum decrease in lymphocytes (r = 0.7514, p less than 0.0003). Simultaneous measurements of glucocorticoid receptor content by whole-cell assay revealed that glucocorticoid receptor content in polymorphonuclear leukocytes linearly correlated with that in the corresponding lymphocytes (r = 0.9482, p less than 0.0001). There were also significant correlations between the maximum increase in polymorphonuclear leukocytes and glucocorticoid receptor content in polymorphonuclear leukocytes (r = 0.7239, p less than 0.0007), and between the maximum decrease in lymphocytes and glucocorticoid receptor content in lymphocytes (r = 0.7703, p less than 0.0002). These results suggest that individual differences are preserved both in glucocorticoid responsiveness and in glucocorticoid receptor content in peripheral blood leukocytes in normal humans.

Adolescent↗

PubMed1989

[A case of anti-phospholipid antibody syndrome presenting chorea as an initial manifestation].

A 20 year old female patient with anti-phospholipid antibody syndrome who presented chorea as an initial symptom is described. At the age of 14, she noticed involuntary movements of upper and lower extremities bilaterally. The CT scan revealed the presence of low density areas in the right caudate nucleus and left putamen. The result of the laboratory tests included antibodies to nuclear antigens (positive FANA and anti-DNA), prolonged PT and APTT, biological false positive for syphilis. Her serum contained antibodies to cardiolipin and phosphatidylserine as demonstrated by specific ELISA assay method. The clinical diagnosis of chorea was made and haloperidol was administered with partial symptomatic improvements. The patient reported here is the first well documented case of anti-phospholipid antibody syndrome presenting chorea as an initial manifestation in the Japanese literature.

Adult↗

PubMed1989

Distinct antitumor mechanisms of recombinant interleukin-2 on recombinant interleukin-2-activated killer-sensitive and -resistant murine tumors.

The antitumor mechanism of recombinant human interleukin-2 (rIL-2) was studied using two murine tumor systems. Meth 8 tumor cells were easily lysed in vitro by rIL-2-activated killer (AK) cells, which mainly consisted of Thy1.2+, Lyt2.2+, L3T4- T cells, and asialo GM1+ natural killer (NK) cells; on the other hand, X5563 tumor cells were only slightly lysed in vitro by AK cells under the same conditions. One of these two tumors was inoculated i.d. into C3H/HeN mice and then rIL-2 (5 X 10(4) J.U./mouse/day) was repeatedly injected s.c. For AK-sensitive Meth 8-bearing mice, rIL-2 therapy starting 1 day after tumor inoculation was more effective for the growth than the therapy starting 7 days later and the therapeutic effect was abrogated by in vivo treatment with anti-asialo-GM1 serum. In contrast, for mice bearing AK-resistant X5563 tumor cells, delayed administration starting on day 7 or later was more beneficial than earlier administration on day 1 or 4. This treatment schedule resulted in complete tumor regression in a dose-dependent manner including significant inhibition of metastases in the spleen and/or lymph nodes. These therapeutic effects of rIL-2 on X5563 were not seen in T-depleted mice with anti-mouse thymocyte serum but were found in NK-depleted mice upon treatment with anti-asialo-GM1 serum. The results of these studies showed that the growth of AK-sensitive Meth 8 tumor was inhibited by AK cells, while the growth and metastases of AK-resistant X5563 tumor was inhibited by tumor-specific T cells, which were generated after tumor development and activated by rIL-2 therapy, rather than AK cells.

Animals↗

PubMed1989

[A case of ankylosing spondylitis complicating Crohn's disease].

A 20-year-old man, who had suffered from ankylosing spondylitis for about 1 year, was admitted to our hospital due to melena and syncope. Physical examination revealed tenderness of abdomen and sacroiliac joint, and decreased spinal mobility. X-ray examination showed sacroiliitis and squaring of vertebral bodies. RA test and RAHA, negative; CRP, strongly positive; HLA-B 27 positive. Intestinal barium enema revealed skipping longitudinal fissure at terminal ileum, and a biopsy specimen of the colon revealed non-caseating granuloma. The association of ankylosing spondylitis and Crohn's disease has widely been known in Europe and United States; but this is the first case reported in detail in Japan, where incidences of both diseases were much lower than those found in Caucasians.

Adult↗

PubMed1989

[A case of systemic lupus erythematosus with urticarial vasculitis].

A 37-year-old woman with SLE who presented with urticarial vasculitis is reported. Skin biopsy revealed presence of polymorphonuclear and mononuclear leukocyte infiltration, nuclear dust, extravasation of red blood cells and fibrinoid necrosis of small vessels which are characteristic features of leukocytoclastic vasculitis. In the literature, 49 cases with similar skin lesion have been reported under various terminologies including unusual SLE related syndrome, hypocomplementemia with cutaneous vasculitis and arthritis, urticarial vasculitis or hypocomplementemic vasculitic urticarial syndrome. Approximately 50% of these cases fulfilled the revised criteria for SLE. It is suggested that these cases represent a unique group of patients with characteristic skin manifestations and polyarthritis mediated by immune complex, and closely relate to SLE.

Adult↗

PubMed1988

Monoclonal antibodies to the thyrotropin receptor bind to a 56-kDa subunit of the thyrotropin receptor and show heterogeneous bioactivities.

Four monoclonal antibodies to the thyrotropin (TSH) receptor were established by fusing human peripheral lymphocytes of patients from Graves' disease with a human myeloma cell line. Of two antibodies with TSH-binding inhibitory immunoglobulin activity (TBII), one inhibited TSH stimulation of adenylate cyclase and another stimulated adenylate cyclase. These antibodies showed competitive and noncompetitive modes of binding inhibition, respectively. Of the other two antibodies without TBII activity, one stimulated adenylate cyclase and the other inhibited TSH stimulation of adenylate cyclase. Of the two antibodies, which inhibited TSH stimulation of adenylate cyclase, one with TBII activity inhibited stimulation of adenylate cyclase by stimulating antibody with TBII activity, but another without TBII activity inhibited stimulation by both stimulating antibodies with or without TBII activity. These inhibitory antibodies did not influence the stimulation of adenylate cyclase by Forskolin and guanosine 5'-(beta,gamma-imido)triphosphate compounds which are known to affect other parts of the receptor-adenylate cyclase system than the receptor unit. Four antibodies with heterogeneous potencies to the TSH receptor reacted with glycoproteins extracted from thyroid membranes. One stimulating antibody without TBII activity also interacted with the glycolipid fraction of the membrane preparation, and the binding decreased after desialylation or deglycosylation of the membrane components. In order to identify the binding sites of these monoclonal antibodies, receptor proteins interacting with antibodies were visualized by Western blot analysis and by the label transfer cross-linking method. All of these antibodies with different characteristics reacted with a 56-kDa molecule.

Adenylyl Cyclases↗

PubMed1988

The AI/RHEUM knowledge-based computer consultant system in rheumatology. Performance in the diagnosis of 59 connective tissue disease patients from Japan.

AI/RHEUM is a knowledge-based computer consultant system for the diagnosis of rheumatic diseases. Its diagnostic accuracy was evaluated using information that was supplied by Japanese rheumatologists on 59 patients with connective tissue diseases. The diagnoses of the AI/RHEUM model were in full or partial agreement with those of the Japanese rheumatologists in 54 of 59 cases (92%). Preliminary evaluation of the criteria tissue disease showed a sensitivity of 90% and a specificity of 96%.

Artificial Intelligence↗

PubMed1988

Pyloric stenosis in a patient with progressive systemic sclerosis.

A 64-year-old Japanese woman with progressive systemic sclerosis (PSS) who developed severe pyloric stenosis is described. The conservative treatments brought only the temporary symptomatic relief, and pyloroplasty became necessary. No ulcerative lesions or tumors were found in the resected stomach or duodenum specimens implicated for stenosis. The histological examinations revealed edema and replacement fibrosis in the pyloric ring. The possible mechanisms of pyloric stenosis are discussed.

Female↗

PubMed1988

Single amino acid change at the cleavage site of the fusion protein is responsible for both enhanced chymotrypsin sensitivity and trypsin resistance of a Sendai virus mutant, TR-5.

A trypsin-resistant mutant of Sendai virus, TR-5, which was obtained by passaging the wild-type (wt) virus in the presence of chymotrypsin followed by plaque purification, also had an enhanced susceptibility to activation by chymotrypsin. A trypsin-sensitive revertant, TSrev-58, derived from TR-5 had a decreased susceptibility to chymotrypsin and was susceptible to trypsin to the same degree as the wt virus. Based on the facts that TR-5 had an amino acid change (Arg----Ile) at residue 116 of the fusion (F) protein, which is the cleavage site for trypsin in the wt virus F protein, and that this change had reverted in TSrev-58, it was concluded that the above amino acid change was responsible for both the enhanced chymotrypsin sensitivity and the trypsin resistance of TR-5. In this paper, the cleavage site of the F protein of TR-5 by chymotrypsin was determined in comparison with those of the wt virus and TSrev-58. The cleavage sites were not different among these viruses, being located between residues 114 (Gln) and 115 (Ser), the two residues at the N-terminal side of the trypsin cleavage site. A possible reason for the increased susceptibility of TR-5 to chymotrypsin is discussed.

Amino Acid Sequence↗

PubMed1988

Identification and characterization of the products of six region III flagellar genes (flaAII.3 through flaQII) of Salmonella typhimurium.

A portion of flagellar region III of the Salmonella typhimurium genome has been cloned and shown to contain six genes: flaAII.3, flaAIII, flaS, flaR, flaQI, and flaQII. Of these, all but flaQI were known to exist from mutant studies; the former flaQ has been renamed flaQII. The genes were shown by minicell analysis to encode proteins with apparent molecular masses of 28, 48, 15, 46, 17, and 37 kilodaltons, respectively. The presence of a flagellar-gene-specific promoter in the vicinity of flaQI was established by testing expression of the plasmid-encoded tetracycline resistance gene in artificial constructions. In minicell preparations, the flaAII.3 and flaR products were found principally in the cytoplasmic fraction; the rest were found principally in the membrane fraction. A comparison between the homologous genes of S. typhimurium and Escherichia coli confirmed that their genomic organizations were similar and that their products had similar molecular masses and isoelectric points.

Bacterial Proteins↗

PubMed1988

Cell-mediated immunity induced in mice after vaccination with a protease activation mutant, TR-2, of Sendai virus.

Our previous study has shown that, although a trypsin-resistant mutant of Sendai virus, TR-2, replicates only in a single cycle in mouse lung with a negligible lesion, the animal acquires a strong immunity against lethal infection with wild-type Sendai virus, suggesting that TR-2 could be used as a new type of live vaccine (M. Tashiro and M. Homma, J. Virol. 53:228-234, 1985). In the present study, we investigated the immunological response elicited in TR-2-infected mice, particularly with respect to cell-mediated immunity. Analyses of cytotoxic activities of spleen cells with 51Cr release assays revealed that Sendai virus-specific T lymphocytes (CTL), in addition to natural killer activity and antiviral antibodies, were induced in DBA/2 and C3H/He mice infected intranasally with TR-2. Proteolytic activation of the fusion glycoprotein F was required for the primary induction of CTL, though not necessarily for stimulation of natural killer and antibody responses. Memory of the CTL induced by TR-2 was long-lasting and was recalled in vivo immediately after challenge with wild-type Sendai virus. In contrast to TR-2, immunization with inactive split vaccine failed to induce the CTL response, but it elicited a high titer of serum antibody and a low level of natural killer activity.

Animals↗

PubMed1988

Pneumopathogenicity in mice of a Sendai virus mutant, TSrev-58, is accompanied by in vitro activation with trypsin.

The pneumopathogenicity of a trypsin-sensitive revertant of Sendai virus, TSrev-58, which was derived from a trypsin-resistant mutant, TR-5, was examined in mice. In comparison with TR-5, the revertant had a single amino acid substitution at residue 116 (Ile----Arg) on F protein, which was the cleavage site, and had the same trypsin sensitivity as the wild-type virus. However, TSrev-58 still had a single amino acid difference from the wild-type virus at residue 109 (Asn----Asp) (M. Itoh, H. Shibuta, and M. Homma, J. Gen. Virol. 68:2939-2943, 1987). Nevertheless, the present study revealed that TSrev-58 had the same pneumopathogenicity in mice as the wild-type virus. This result indicates that the activating protease of Sendai virus present in the lungs of mice is quite similar to trypsin and also that the in vitro trypsin sensitivity of Sendai virus can be a good marker of pneumopathogenicity in mice.

Amino Acid Sequence↗

PubMed1988

Coexistence of CREST syndrome and primary biliary cirrhosis. Serological studies of two cases.

Two patients with characteristic features of CREST syndrome and primary biliary cirrhosis are reported. Sera of both patients contained autoantibodies to centromere and mitochondrial antigens. Immunodiffusion analysis identified the specificities of precipitating antibodies to mitochondria of the first case as anti-M-A and M-C, and of the second case as anti-M-A and M-B antibodies. Simultaneous occurrence of 2 marker antibodies in an individual patient indicates that the 2 patients reported here have CREST syndrome and primary biliary cirrhosis, both of which are considered as a distinct clinical entity.

Aged↗

PubMed1987

Hypertrophic osteoarthropathy, cutaneous vasculitis, and mixed-type cryoglobulinemia in a patient with nasopharyngeal carcinoma.

We describe a 27-year-old woman with a primary nasopharyngeal carcinoma who developed hypertrophic osteoarthropathy and cutaneous vasculitis. Her serum contained antibodies to Epstein-Barr virus and U1 RNP antigens. Cryoproteins isolated from her serum contained antibodies to U1 RNP and a protein with a molecular weight of 32 kd which reacted specifically with antibodies to U1 RNP. HLA typing revealed HLA-B7 and DR1; these have been reported to be increased in Japanese patients with rheumatic diseases who have autoantibodies to U1 RNP. These findings indicate that some features of the paraneoplastic syndrome in this patient might have been caused by immune complexes, part of which were formed by specific autoantibodies produced under genetically controlled conditions of immune responsiveness.

Adult↗