Interleukin-6 produced by renal-cell carcinoma cells and progression of multiple myeloma.
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Aged↗
Biomedical subjects
M Kawano
Publications and source records attributed to M Kawano.
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↗
A case of plasma cell leukemia superimposed on Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia.
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Blotting, Southern↗
Sialagogue-stimulated protein phosphorylation related to ornithine decarboxylase induction in cultured rat parotid explants.
Both beta-adrenergic (isoproterenol) and cholinergic (carbachol) sialagogues increase amylase secretion, ornithine decarboxylase activity and DNA synthesis in murine parotid gland in vivo and in vitro. These agonists enhanced the incorporation of labelled inorganic orthophosphate into parotid proteins in rat parotid explants cultured on siliconized lens paper floating on serum-free 199 medium. Analysis of the labelled proteins by SDS-PAGE and autoradiography revealed that isoproterenol enhanced the phosphorylation of four proteins with apparent molecular weights of 17, 20, 31 and 32 kDa and carbachol stimulated the phosphorylation of 31 and 32 K proteins. Isoproterenol-dependent ornithine decarboxylase induction and phosphorylation of the proteins were selectively suppressed by monensin but not by polymyxin B, whereas carbachol-dependent ornithine decarboxylase induction and protein phosphorylation were inhibited by polymyxin B but not by monensin. Neither monensin nor polymyxin B suppressed isoproterenol- or carbachol-stimulated amylase secretion. Time course experiments showed that sialagogue-stimulated protein phosphorylation preceded the increase of ornithine decarboxylase activity and had almost disappeared when it was maximal. Propranolol and atropine, antagonists of isoproterenol and carbachol, respectively, completely inhibited not only amylase secretion and ornithine decarboxylase induction but also protein phosphorylation stimulated by the corresponding agonists. These findings suggest that increased phosphorylation of specific proteins is associated with sialagogue-stimulated ornithine decarboxylase induction but not amylase secretion.
Amylases↗
Effects of transforming growth factor-beta 1 on growth of aortic smooth muscle cells. Influences of interaction with growth factors, cell state, cell phenotype, and cell cycle.
Transforming growth factor (TGF)-beta 1 may have different effects on cell proliferation depending on many conditions. This paper clarifies the effects of various conditions on the effect of TGF-beta 1 on proliferation of cultured rabbit aortic smooth muscle cells (SMC) and also the time of its action during the cell cycle. TGF-beta 1 at 10-10,000 pg/ml inhibited DNA synthesis of SMC in the G0 stage derived from normal media or atheromatous intima stimulated by either platelet-derived growth factor (PDGF), fibroblast growth factor, SMC-derived growth factor, or fetal bovine serum (FBS). TGF-beta 1 also inhibited the growth of SMC in the growing state stimulated by either PDGF or FBS. TGF-beta 1 was effective only when added to the culture within 2 h after stimulation of the G0 state SMC with PDGF. It also inhibited increase in transcription of the c-myc protooncogene on stimulation of SMC with PDGF. These data suggest that TGF-beta 1 inhibited proliferation of SMC irrespective of the cell phenotype, growth conditions, and growth factors present and that it exerted this inhibitory effect during the time of the G0/G1 transition.
Animals↗
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↗
Transcripts of simian virus 41 (SV41) matrix gene are exclusively dicistronic with the fusion gene which is also transcribed as a monocistron.
The complete nucleotide sequences of the matrix (M) and fusion (F) genes of simian virus 41 (SV41) were determined. Deduced amino acid sequences confirmed the close relationship of SV41 with human parainfluenza type 2 virus (PIV2). Analyses of noncoding regions between the F and the hemagglutinin-neuraminidase (HN) genes suggested the absence of the small hydrophobic gene, which is present between the F and the HN genes of simian virus 5 and mumps virus. It was striking that there was no apparent consensus gene end sequence between the M and the F genes and that the M gene was transcribed exclusively as a dicistron with the F gene. The number of monocistronic transcripts of the F gene was approximately half that of the dicistronic transcripts. However, the F protein of SV41 seemed to be efficiently translated, since viral multiplication and fusion from within were as efficient as in PIV2. These results suggest that the lack of a consensus gene end sequence resulted in the readthrough of viral RNA polymerases between the M and the F genes and that the initiation of F gene transcription could occur by newly entered polymerases independently of the polymerases that started the upstream M gene transcription.
Amino Acid Sequence↗
Glycolipids in rat cochlea.
In recent years, the functions of glycolipids have been intensively studied. Before the research of the roles of glycolipids in the inner ear, it seemed to be necessary to demonstrate the composition of glycolipids at first. Therefore, rat cochlea has been examined for glycolipid composition in the present study. Glycolipids extracted from 200 cochlea samples were separated into neutral and acidic glycolipid fractions. Each fraction was analyzed by thin-layer chromatography. The neutral glycolipid was almost exclusively galactosylceramide (cerebroside) with trace amounts of globoside and unidentified glycolipids. In acidic glycolipids, sulfated galactosylceramide (cerebroside sulfate) was most abundant. Of the gangliosides (sialic acid-containing glycolipids), ganglioside GM3 (51.8%) was the predominant component, and GM2 (6.0%), GM1 (8.8%), GD3 (10.7%), GD1a (8.7%), GD1b (5.9%), and GT1b (3.6%) were also detected. In addition to these, rat cochlea also contained several, minor, unidentified gangliosides. This pattern of the cochlear acidic glycolipids is very similar to that of the renal acidic glycolipids. This finding seems to be very interesting when considering that the toxic side effects of aminoglycosides occur only in the kidney and the inner ear.
Animals↗
The late waves of brainstem auditory evoked potentials in children with cerebrovascular diseases.
We examined brainstem auditory evoked potentials (BAEPs) in 28 children with cerebrovascular diseases and 38 normal control subjects and investigated the neuroanatomic correlations of the late waves (VI and VII) of the BAEPs. The patients included 19 patients with moyamoya disease and 9 with other cerebrovascular accidents. Wave VI was more consistently seen (only missing in 2 cases, 5%-2 ears, 3%) than wave VII (missing in 26 cases, 68%-40 ears, 53%) in the control group. Absent, depressed or prolonged wave VI correlated well with cerebral lesions involving internal capsule and basal ganglia, while wave VII had a less significant correlation with any cerebral lesions in children with cerebrovascular diseases.
Adolescent↗
Sequence characterization of the matrix protein genes of parainfluenza virus types 4A and 4B.
The complete nucleotide sequences of the matrix protein (M) genes of parainfluenza virus types 4A and 4B (PIV-4A and -4B) were determined from cDNA of the mRNA, and found to be 1548 bases in length, exclusive of poly(A) sequences. The sequences contained a large open reading frame of 1146 nucleotides encoding 362 amino acids. A high degree of identity (96.1%) was observed between the amino acid sequences of PIV-4A and PIV-4B M. These M sequences were compared with those of 10 other paramyxoviruses and a phylogenetic tree was constructed.
Amino Acid Sequence↗
Increased expression of the c-myc gene may be related to the aggressive transformation of human myeloma cells.
Alteration and abnormal expression of the c-myc oncogene were investigated in human multiple myeloma. Human myeloma cells were highly purified (more than 95%) from bone marrow aspirates in 14 cases of advanced multiple myelomas and one case of plasma cell leukaemia. Southern blotting revealed that a rearranged configuration of c-myc gene was found in only one case of them, but this was a novel truncation of the gene in its coding exon II; a rearranged 3.4 kb band was detected by digestion with Xba I using c-myc exon II probe, but no rearranged band was found using exon III probe. In this case, the truncated c-myc allele was not transcribed; normal sized (2.4 kb) c-myc mRNA was markedly expressed, but no aberrant mRNA was detected. On the other hand, by Northern blotting, the nine cases, including the case with the rearranged c-myc gene, showed increased expression of normal sized (2.4 kb) c-myc mRNA. Elevated c-myc mRNA expressions were well related to the in vitro proliferation (3H-TdR uptake), but not to IL-6 response. Interestingly, extremely high expressions of c-myc mRNA were detected in two cases of aggressive myelomas, including the case with the rearranged c-myc gene, and in one of plasma cell leukaemia. These two cases of aggressive myelomas were the ones who showed the markedly high 3H-TdR uptakes, and had the common clinical features with the formation of an extramedullary mass and very short survival. These results suggest that the activation of c-myc gene could induce high proliferative activities and the subsequent aggressive transformation of myeloma cells.
Blotting, Northern↗
The natural history of screening detected IgA glomerulonephritis in children.
The clinical course of 43 children with IgA glomerulonephritis detected by mass urine screening was followed for a mean period of 8.1 years. Histological findings were graded according to the severity of glomerular and tubulointerstitial lesions. There was no correlation in the severity of histological grade and clinical outcome between subjects with microscopic hematuria and those with microscopic hematuria and proteinuria nor between those with and without one or more episodes of macroscopic hematuria during the follow-up period. None of the 35 children with proteinuria less than or equal to 1 g/m2/day had severe histological findings or developed renal impairment. In contrast, the 8 children with proteinuria greater than 1 g/m2/day had moderate and severe histological findings. Four of these 8 children developed hypertension or renal insufficiency during the follow-up period. Our study indicates that the outcome of screening detected IgA glomerulonephritis in children correlates with the level of proteinuria and the severity of renal pathology.
Adolescent↗
Pheochromocytoma with pyrexia and marked inflammatory signs: a paraneoplastic syndrome with possible relation to interleukin-6 production.
Pheochromocytoma can cause several paraneoplastic syndromes. We report a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs along with an elevated serum interleukin-6 (IL-6) level. All of these abnormalities disappeared and serum IL-6 became undetectable by removal of the tumor. In addition, immunohistochemical analysis revealed the presence of IL-6 in the tumor cells. It is suggested that pyrexia and the elevation of acute phase proteins can be a paraneoplastic syndrome with pheochromocytoma, and that the elaboration of IL-6 from pheochromocytoma may play an important role in the development of the syndrome.
Adrenal Gland Neoplasms↗
[A clinical study on the patients with otolaryngological diseases in Koshiki Islands].
One hundred and sixty four ENT patients were observed at the Kashima village hospital located on the remote, isolated islands (Islands of Koshiki), Kagoshima prefecture, during two years of April 1987 to March 1989. They were composed of the following conditions; 1. Of the 164 individuals, 46 cases, showing 28.1% were admitted from the other inconvenient districts. 2. About a half of all the patients with acute infectious diseases might be treated by their home doctors. 3. The patients required operative care were contained in the individuals with chronic inflammatory diseases. 4. Most of the cases with acute otitis in summer were caused by naked diving to catch the fishes in these islands. 5. The incidence of the chronic ENT diseases such as perceptive hearing disturbances including the presbyacusis, chronic otitis media, chronic sinusitis, and laryngopharyngeal paresthesia in order, were the same as one of the previous reports in the other remote isolated islands. All the general practitioners worked in the remote isolated islands should be necessary to have a special training of fundamental knowledges and clinical skills in otolaryngology.
Adolescent↗
[Hyperthermic treatment in patients with benign prostatic hypertrophy].
Hyperthermic treatment was performed in 31 patients with benign prostatic hypertrophy (BPH). Eight patients of them had a urethral catheter because of urinary retention. The prostate was heated trans-rectally to 43-45 degrees C. The treatment consisted of 10 sessions of 60 min. each. To evaluate this treatment, the following parameters were determined before, during and one week after the last hyperthermia session: subjective symptoms score, and residual urine volume, uroflowmetry and transrectal ultrasound of the prostate as objective data. Symptoms score improve in all patients. Of 8 patients with a catheter, the catheter could be removed from 4 patients. There was no significant change in prostate volume, but significant decreases of residual urine volume, and increases of maximum flow rate and mean flow rate were observed. No adverse reactions were seen. Judging from the above results, this treatment is considered to be useful for patients with BPH.
Aged↗
Induction of ornithine decarboxylase by sialagogues in a human parotid gland adenocarcinoma cell line.
Ornithine decarboxylase in a human parotid gland adenocarcinoma cell line was induced by both cholinergic (carbachol) and beta-adrenergic (isoproterenol) sialagogues. The enzyme protein level, measured with anti-peptide antiserum, as well as the enzyme activity, was found to be high in unstimulated cells and to increase approximately 2-fold on stimulation, while the mRNA level increased 3-4 fold, as revealed by Northern hybridization. The rise in activity was completely blocked by the simultaneous addition of antagonists or actinomycin D. These results suggest that receptor-mediated stimulation of ornithine decarboxylase activity by sialagogues involves alterations in the level of mRNA and that the proliferative responses of human parotid cells to these sialagogues resemble those of the murine parotid gland.
Adenocarcinoma↗
Biological effects of recombinant erythropoietin, granulocyte-macrophage colony-stimulating factor, interleukin 3, and interleukin 6 on purified rat megakaryocytes.
The biological effects of recombinant hematopoietic factors, which are considered to stimulate megakaryocytopoiesis in vitro or in vivo, were studied utilizing purified rat megakaryocytes. Recombinant human erythropoietin (rhEPO), recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF), and recombinant murine interleukin 3 (rmIL-3) stimulated both [3H]thymidine and [3H]leucine incorporation into purified rat megakaryocytes. In contrast, recombinant human interleukin 6 (rhIL-6) did not stimulate [3H]thymidine uptake but did increase [3H]leucine incorporation into purified rat megakaryocytes. These in vitro data suggest that DNA synthesis in megakaryocytes may be regulated by EPO, GM-CSF, and IL-3, and that protein synthesis is stimulated by EPO, GM-CSF, IL-3, and IL-6 in vitro.
Animals↗
Effect of glucocorticoids on the biologic activities of myeloma cells: inhibition of interleukin-1 beta osteoclast activating factor-induced bone resorption.
Regulatory effects of glucocorticoids (dexamethasone) on myeloma cells as well as bone resorption in multiple myeloma were investigated. Glucocorticoids significantly inhibited proliferation of myeloma cells, and decreased the messenger RNA (mRNA) expressions of interleukin-6 (IL-6) and secretory type immunoglobulin G (IgG). The inhibitory effects of glucocorticoids on myeloma cell proliferation could be due to the decreased expression of IL-6 mRNA, decreased IL-6 production, and thus suppression of autocrine growth by IL-6, which is an autocrine growth factor for myeloma cells as reported previously (Nature 332:83, 1988). Glucocorticoids also inhibited M-protein secretion by decreasing the levels of secretory type Ig mRNA. On the other hand, because IL-1 beta rather than lymphotoxin is considered to be a major osteoclast activating factor (OAF) produced by myeloma cells, and glucocorticoids decreased the expression of IL-1 beta mRNA and markedly suppressed the bone resorbing activity induced by IL-1 beta OAF in 45Ca-release bone resorption assay, it is suggestive that glucocorticoids could inhibit bone resorption induced by IL-1 beta OAF in multiple myeloma. Therefore, from these data it is concluded that glucocorticoids could be more effective chemotherapeutic agents in multiple myeloma than we expected, especially with regards to the inhibitory effects on proliferation and M-protein secretion from myeloma cells, as well as bone resorption by myeloma cells.
Blotting, Northern↗