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Biomedical subjects

K Iwatsuki

Publications and source records attributed to K Iwatsuki.

At least 73 records · Page 4Linked to original sources
PubMed1999

Interleukin-15 is not a constitutive cytokine in the epidermis, but is inducible in culture or inflammatory conditions.

The regulation in the skin of interleukin-15 (IL-15), a potent modulator of T-cell-mediated immune responses, is not fully understood. We investigated the levels of IL-15 and its mRNA produced by epidermal and cultured keratinocytes and found that normal keratinocytes did not constitutively express IL-15 in the epidermis, but in culture began to produce the cytokine. Some epidermal keratinocytes expressed IL-15 in inflammatory conditions associated with infiltration of neutrophils and eosinophils. IL-15 was detected only in the cell lysates, not in the supernatants of cultured keratinocytes. Dexamethasone (10(-5)-10(-6) M) markedly inhibited IL-15 mRNA expression by normal and transformed keratinocytes in a range of pharmacological concentrations. IFN-gamma (200 and 400 U/ml) slightly increased the IL-15 message level in a squamous cell carcinoma cell line, HSC-5, in a dose-dependent fashion, whereas no significant change was observed in cultured normal human keratinocytes. Our data indicate that IL-15 is not a constitutive cytokine in epidermal keratinocytes but is inducible.

Antineoplastic Agents↗
PubMed1999

Cytophagic histiocytic panniculitis improved by combined CHOP and cyclosporin A treatment.

In a 31-year-old Japanese man with cytophagic histiocytic panniculitis (CHP) remission was achieved by a combination of combined chemotherapy CHOP and cyclosporin A treatment. He was admitted to our hospital in January 1994 with recurrent high fever of 40.2 degrees C and tender and violaceous subcutaneous nodules on his trunk, arms and legs. He developed pancytopenia, hemorrhagic diathesis, liver dysfunction. Histological examination of the biopsied subcutaneous nodule revealed a lobular panniculitis with fat necrosis and a massive infiltration of histiocytes phagocytosing nuclear debris. He was treated initially with 40 mg/day prednisolone. However, following a reduction in prednisolone dosage, his symptoms reappeared. CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy was then initiated. Three courses of CHOP treatment alleviated his symptoms and cyclosporin A was used to maintain his condition for 15 months. His medication was then discontinued and he has been in complete remission for 10 months. Combined treatment of cyclosporin A and CHOP combined chemotherapy was shown to be effective for this patient with severe CHP.

Adult↗
PubMed1999

[Use of Ommaya CSF reservoir for refractory chronic subdural hematoma].

Ten patients with refractory chronic subdural hematoma were the subjects of this paper. All patients had severe diseases influencing the clinical course of chronic subdural hematoma, such as cerebral infarction, liver cirrhosis, thrombocytopenia, severe parkinsonism, severe heart disease, and spino-cerebellar degeneration. They were first treated in a usual manner; irrigation and drainage of the hematoma cavity. After recurrence of the hematoma, an Ommaya CSF reservoir was put into place and whenever the volume of the hematoma increased the reservoir was punctured. Postoperatively, 7 patients returned to the same conditions as they had before the onset. However, one patient died of myocardial infarction and 2 patients with parkinsonism could not maintain the condition they had before the onset of their disease, resulting in their partially dependent state. Complications were minor bleeding in one patient and an occlusion of the reservoir in another patient. By using this method reoperation was unnecessary, and the patients were able to move early in the post-operative period. This method was suitable for refractory chronic subdural hematoma with severe disease influencing its clinical course.

Aged↗
PubMed1999

[Choroid plexus metastasis of renal cell carcinoma causing intraventricular hemorrhage: a case report].

We report a rare case of choroid plexus metastasis of renal cell carcinoma causing intraventricular hemorrhage. A 75-year-old female was admitted to our hospital for SAH. Preoperative examination evoked suspicion of an anterior communicating aneurysm as a cause of SAH. Furthermore, there were lesions on the tuberculum sellae and in the left trigone of the lateral ventricle, which were enhanced by Gd-DTPA on MRI. The patient was operated on via the pterional approach on December 3, 1996, but no aneurysm was found. She underwent total removal of the tuberculum sellae mass, which was postoperatively proved to be a meningioma by histological examination. The intraventricular tumor was supposed to be a meningioma, but it was not treated surgically. Two months later, the patient presented hematuria and was diagnosed as having a right renal cancer and underwent right nephrectomy on March 18, 1997. However, postoperatively, disturbance of consciousness continued. A CT scan revealed intraventricular hemorrhage around the tumor in the trigone of the lateral ventricle on March 21. An emergency operation for tumor and clot removal succeeded in improving the patient's condition. Histological examination of the tumor revealed clear-cell type renal cell carcinoma. Solitary choroidal plexus metastasis from renal cell carcinoma is quite rare: only 5 cases have been reported. But only our case was accompanied by intraventricular hemorrhage. Renal cell carcinomas are divided into two types: a slowly progressive type and a rapidly progressive type. Four cases among the reported 5 cases were the slowly progressive type, and our case was regarded as being of the same type.

Aged↗
PubMed1998

Molecular analysis of the nucleocapsid protein of recent isolates of canine distemper virus in Japan.

We analyzed the molecular properties of the nucleocapsid protein (NP) of canine distemper viruses (CDV), isolated between 1992 and 1995 in Japan. Four CDV field isolates (Yanaka, Ueno, Hamamatsu, and Adachi strains) obtained were antigenically identical. Sequence analysis of entire region of the NP gene of a field isolate, the Yanaka strain, revealed that the NP gene contained 1683 nucleotides and was 93.2% homologous with a laboratory strain, the Onderstepoort strain. The deduced amino acid sequence contained 523 amino acids and was 95.2 and 99% homologous with those of the Onderstepoort and a virulent strain, A75/17 strain, respectively. Since most of the diversities in amino acid sequence occurred in two domains, at the N'- and the C'- termini, we further sequenced 3'-terminal regions of the remaining three field isolates. Based on the sequences, the new CDV isolates had one cluster that distinguished them from the laboratory strain.

Amino Acid Sequence↗
PubMed1998

Different growth properties in response to epidermal growth factor and interleukin-6 of primary keratinocytes derived from normal and psoriatic lesional skin.

Epidermal growth factor (EGF) family members and its receptor (EGFR) are thought to have an important role in the proliferation of epidermal keratinocytes. In this report, we investigated the EGF/EGFR system in primary keratinocytes derived from normal and psoriatic lesional skin. EGF elicited the growth of both normal human keratinocytes (NHKs) and psoriatic lesional keratinocytes (PLKs). Interleukin-6 (IL-6) potentiated the EGF-dependent growth of NHKs, but has no observable effect on PLKs, while IL-6 itself showed no growth-stimulating activities in both cell types. Immunodetection and in situ hybridization analyses revealed that IL-6 induces EGFR expression in NHKs in a time- and dose-dependent manner. This EGFR expression decreased reversibly to an undetectable level when IL-6-treated NHKs were re-cultured in IL-6-free conditions. On the other hand, PLKs expressed high levels of EGFR even when unstimulated and the expression level was not affected by IL-6 stimulation. These results suggest that the EGF/EGFR system is involved in the growth of NHKs and PLKs and that IL-6 potentiates NHK growth partly through the induction of EGFR. The different EGFR regulatory system may contribute to the pathogenesis of psoriasis.

Adult↗
PubMed1998

Increase in jugular levels of polymorphonuclear neutrophil elastase in patients with acute cerebral infarction.

To elucidate the involvement of activated polymorphonuclear neutrophil (PMN) proteolytic activity in the pathophysiology of cerebrovascular stroke, we measured internal jugular venous and femoral arterial levels of PMN elastase in 6 patients with acute stroke from the day onset (day 0) to 7 days after onset (day 7). Two patients with cerebral infarction demonstrated markedly elevated of PMN elastase in the jugular blood (730 and 1320 micrograms l-1, respectively), but not in the blood (203 and 205 micrograms l-1, respectively) on day 2. Both patients manifested signs of hemorrhagic infarction early on day 2. On day 4, the increased levels of jugular elastase returned to the normal range (< 250 micrograms l-1 in both patients. In contrast, none of the 4 patients with intracerebral hemorrhage demonstrated increased levels of PMN elastase in either the jugular or the arterial blood from days 0 to 7. The present study demonstrated a temporary but significant increase in jugular PMN elastase in patients with cerebral infarction, especially shortly after hemorrhagic infarction.

Acute Disease↗
PubMed1998

Molecular cloning and characterization of a new member of the rat placental prolactin (PRL) family, PRL-like protein H.

The rat placental PRL family consists of molecules structurally similar to PRL and GH, and to date nine members have been identified. In the course of investigating late stage specific placental PRL family expression by differential display, we have isolated a complementary DNA encoding a new molecule that is highly homologous to PRL-like protein C (PLP-C) and PLP-D, and named this molecule PLP-H. The complementary DNA encoded a mature protein of 239 amino acids, including a 31-amino acid signal sequence. Sequence comparison between PLP-H and other members of the placental PRL family showed that PLP-H is highly homologous to PLP-C and PLP-D (78% and 67% homology at the amino acid level, respectively). Expression of PLP-H was similar to that of PLP-C and PLP-D; PLP-H messenger RNA (mRNA) first appeared on day 14 of pregnancy, and its expression increased until term. RT-PCR analysis showed that PLP-H as well as PLP-C and PLP-D are expressed in all rat strains examined, confirming that PLP diversity is not due to strain differences. In situ hybridization analysis indicated that PLP-H mRNA is specifically expressed in spongiotrophoblast cells and in trophoblast giant cells of the placental junctional zone. Differentiated Rcho-1 cells also expressed PLP-H mRNA, whereas undifferentiated Rcho-1 cells did not. PLP-H seems to exist as a secretory protein because its N-terminal sequence is identical to that of GH/PRL-like molecule secreted from placental explants. PLP-H contains two putative N-glycosylation sites and eight cysteine residues, of which six are highly conserved in the placental PRL family. We prepared a recombinant protein for PLP-H together with PLP-D using a COS7 transfection system. Purified PLP-H showed two bands with molecular masses of 27 and 29 kDa. Only the 27-kDa protein was detected after N-glycosidase treatment, indicating that PLP-H is a glycoprotein. PLP-H and PLP-D did not stimulate the proliferation of Nb2 lymphoma cells or the phosphorylation of Janus kinase-2 and signal transducer and activator of transcription-5. These data indicate that PLP-H and PLP-D are nonlactogenic hormones. Thus, we have cloned a new member of the PLP subfamily, PLP-H, which has features in common with PLP-C and PLP-D.

Amino Acid Sequence↗
PubMed1998

Molecular identification of a recent type of canine distemper virus in Japan by restriction fragment length polymorphism.

Restriction fragment length polymorphism analysis was used to differentiate recent field viruses of canine distemper virus (CDU) from vaccine strains. Virus genomes were amplified by using reverse transcriptase-polymerase chain reaction in part of the haemagglutinin gene. After digestion with EcoRV, the PCR products of recent field isolates were cut into two fragments that differ from the uncut form of old strains including all of vaccine strains. This method could be applied to fresh or stored brains, spleens and peripheral blood mononuclear cells of infected dogs. This molecular approach is useful for determining the causative agent of postvaccinated CDV infection.

Animals↗
PubMed1998

The nucleotide and predicted amino acid sequence of the fusion protein of recent isolates of canine distemper virus in Japan.

Analysis of the molecular properties of fusion (F) proteins of field isolates of canine distemper virus (CDV) by immunoprecipitation analysis revealed an identical molecular mass of F protein of 3 field isolates as well as the Onderstepoort laboratory strain. Sequencing showed that the F gene of a field isolate (the Yanaka strain) shared 90.1% and 95.7% identities with the Onderstepoort strain at nucleotide and amino acid levels, respectively. All of the 13 cysteine residues and 4 potential asparagine-linked glycosylation sites were completely conserved amongst these strains. These results indicate that the F proteins is much less heterogeneous than that observed in the hemagglutinin proteins of CDV.

Amino Acid Sequence↗
PubMed1998

[Clinical application of FdUrd to meningeal dissemination of malignant tumors].

A clinical trial of intrathecal chemotherapy with FdUrd was performed in sixteen patients with meningeal dissemination of malignant tumors. Twelve of the sixteen patients responded to intrathecal FdUrd chemotherapy (1-5 micrograms/dose) through an Ommaya reservoir placed in the lateral ventricle: complete response, 2; partial response, 10; progressive disease, 4. Only slight nausea was observed in two patients and dull headache in one patient. No other systemic side effects such as myelosuppression or liver dysfunction were observed in any patients. Moreover, no delayed side effects such as marked brain atrophy or leukoencephalopathy developed during the course of this intrathecal chemotherapy despite over thirty consecutive intrathecal administrations. In conclusion, intrathecal FdUrd proved to be safe and effective for the treatment of meningeal dissemination of malignant tumors.

Adenocarcinoma↗
PubMed1997

STAT5 activation correlates with erythropoietin receptor-mediated erythroid differentiation of an erythroleukemia cell line.

Interaction between erythropoietin (EPO) and its membrane receptor induces the proliferation and differentiation of erythroid progenitors. EPO has been shown to activate the JAK2-STAT5 pathway in various hematopoietic cell lines, although the physiological role of this pathway is unclear. We have previously shown that epidermal growth factor activates a chimeric receptor bearing the extracellular domain of the epidermal growth factor receptor linked to the cytoplasmic domain of the EPO receptor, resulting in proliferation of interleukin-3-dependent hematopoietic cells and erythroid differentiation (globin synthesis) of EPO-responsive erythroleukemia cells. In the present study, we introduced various deletion and tyrosine to phenylalanine substitution in the cytoplasmic domain of the chimeric receptor and expressed these mutant chimeras in an EPO-responsive erythroleukemia cell line, ELM-I-1. Mutant chimeric receptors retaining either Tyr343 or Tyr401 could activate STAT5, judged by tyrosine-phosphorylation of STAT5 and induction of CIS, a target gene of STAT5. These mutants were able to induce erythroid differentiation. However, a chimeric receptor containing both Y343F and Y401F mutations could not activate STAT5 nor induce erythroid differentiation. Thus, Tyr343 or Tyr401 of the EPO receptor are independently necessary for erythroid differentiation as well as STAT5 activation. Moreover, exogenous expression of dominant-negative STAT5 suppressed EPO-dependent erythroid differentiation. These findings suggest that STAT5 plays an important role in erythroid differentiation through the EPO receptor cytoplasmic domain.

Animals↗
PubMed1997

Species-specific beta-N-acetylgalactosaminylation of serum IgG proteins.

Lectin blot analysis of bovine, goat, human, rabbit and mouse serum immunoglobulin G (IgG) samples revealed that Wisteria floribunda agglutinin (WFA) binds to the heavy chains of bovine, goat and human serum IgG proteins but not those of the rabbit and mouse proteins. WFA-positive light chain bands were also detected in bovine, goat and human serum IgG samples only after the filters were treated with Arthrobacter ureafaciens sialidase. The WFA-binding to these IgG proteins was abolished by treatment of the filter with sialidase and then beta-N-acetylhexosaminidase or N-glycanase prior to incubation with the lectin. WFA-agarose column chromatography of the oligosaccharides released by hydrazinolysis from the IgG samples followed by reduction with NaB3H4 revealed that 0.15, 0.09 and 0.07% of the total oligosaccharides from bovine, goat and human serum IgG samples bind to the column, respectively. Partial characterization of WFA-positive bovine IgG oligosaccharides by Bio-Gel P-4 column chromatography suggested that the major oligosaccharide is of non-fucosylated biantennary complex-type. These results indicate that beta-N-acetylgalactosaminylation occurs to N-linked sugar chains of heavy and light chains of IgG proteins in a species-specific manner.

Animals↗
PubMed1997

Molecular and phylogenetic analyses of the haemagglutinin (H) proteins of field isolates of canine distemper virus from naturally infected dogs.

We isolated three strains of canine distemper virus (CDV)--the Ueno, Hamamatsu, and Yanaka strains--from dogs in Japan and analysed the molecular properties of their haemagglutinin (H) proteins. Immunoprecipitation of all three strains with a monoclonal antibody revealed H proteins with molecular masses of 84 kDa, which differs from the molecular mass (78 kDa) of the H protein of the Onderstepoort vaccine strain. However, after tunicamycin treatment immunoprecipitation identified H proteins of identical molecular mass (68 kDa) for all three field isolates and the vaccine strain. Sequence analysis showed nine potential sites for asparagine-linked glycosylation in the H proteins of the new isolates, in contrast to four in the H protein of the Onderstepoort strain. Thus, variation in glycosylation of the H proteins of the isolates and the vaccine strain may cause differences in antigenicity of the viruses. Sequences of the H genes showed that the new Japanese isolates have 99% identity with each other, 95% with other European and American isolates (from seals, a German dog, a ferret and large felids) and 90% with the vaccine strain. Phylogenetically, the new Japanese isolates form one cluster which is separate from recent European or American isolates, all of which are distinct from vaccine strains.

Amino Acid Sequence↗
PubMed1997

CD56-positive (nasal-type T/NK cell) lymphoma arising on the skin. Report of two cases and review of the literature.

Several authors have reported cases of patients with malignant lymphoma with unique characteristics, designated nasal-type T/NK cell lymphoma, which expresses the natural killer (NK) cell marker and shows frequent extra-nodal involvement and poor prognosis. We report 2 cases of this type of lymphoma which were CD56-positive and showed a histopathologically angiocentric pattern with cutaneous and subcutaneous tumorous lesions. Patient 1 had extensive invasion of skin, underlying skeletal muscle, spleen and bone marrow, and died of sepsis 34 months after onset. Patient 2 had multiple subcutaneous nodules and invasion to mammary gland, lung, lymph node and spleen at the time of her first visit. She died of a rapid invasion of lymphoma cells to the liver 5 months after onset. Both patients showed similar immunophenotypes of tumor cells (CD2+, CD3-, CD4-, CD8-, CD20-, CD56+) and germ line configuration of the heavy chain of immunoglobulin (JH), T-cell receptor C beta-1 subunit DNA and T-cell receptor J gamma subunit DNA. Epstein-Barr virus early regions RNA was demonstrated in the nuclei of tumor cells of both patients with in situ hybridization. The histopathological examination of the skin lesions of both patients revealed the features of angiocentric lymphoma. The detection of CD56 in the tumor cells of cutaneous lymphomas should be routinely performed for the early diagnosis of this type of lymphoma with extremely poor prognosis.

Antigens, CD↗
PubMed1997

Expression of the nucleocapsid protein gene of the canine distemper virus.

We constructed a cDNA clone of canine distemper virus (CDV) encoding an entire nucleoprotein (NP) gene, by means of the reverse transcription-polymerase chain reaction (RT-PCR). The cloned NP gene was inserted into the eucaryotic expression vector, pRVSV. After transfection of the plasmid into Vero cells, we examined the expression of CDV-specific NP antigen by means of indirect immunofluorescence assay (IFA) and Western blotting, using various antibodies against NP of CDV and an antiserum against NP of measles virus. The CDV-NP specific antigen was detected in the nuclei of the cells transfected with pRV-ON, by means of IFA with antibodies specific to the NP.

Animals↗
PubMed1997

[Treatment of metastatic brain tumors from lung cancer: analysis of performance status between treatment methods].

Retrospective analysis was performed in 280 patients; 112 surgical cases and 168 non-surgical cases to determine which of three treatments, alone or in combination provides more prolonged improvement of performance status (PS: Karnofsky score) in patients with metastatic brain tumors from lung cancer. The treatments under scrutiny were surgical removal of metastatic brain tumor (S), radiation therapy (R) and chemotherapy (C). KS in the group treated with S or C showed a significantly better result than that in the non-S group or non-C group during the two-year observation period. However, R group showed no significant improvement in KS compared to that in the non-C group during the two-year period. During the first year after admission, two subgroups of S plus R and R alone showed most rapid decrease in KS. However, subgroups of S plus C and S plus R and C showed better results than other subgroups. In analyzing the changes in KS over the short period from admission to one month after treatment had been completed, the non-S group showed a significant decrease in KS, while the S group showed a slight increase in mean KS. The subgroup of R alone showed the greatest decrease in KS. Thus, retrospective analysis showed that surgical removal of a metastatic brain tumor led to improved KS for a short period and chemotherapy was useful in prolonging the duration of better Q.O.L.

Antineoplastic Combined Chemotherapy Protocols↗