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Biomedical subjects

M Kuroda

Publications and source records attributed to M Kuroda.

At least 127 records · Page 7Linked to original sources
PubMed1999

[Evaluation of chemotherapy with docetaxel and cisplatin in advanced non-small cell lung cancer].

Clinical study has been conducted to evaluate the efficacy of chemotherapy with docetaxel and cisplatin in six patients with advanced non-small cell lung cancer. Treatment schedule consisted of docetaxel 60 mg/m2 and cisplatin 80 mg/m2 on day 1 and repeated every 4 weeks. Eligible patients had histologically proven locally advanced or metastatic non-small cell lung cancer, PS < or = 2, age < or = 74, normal hematological, hepatic and renal functions and informed consent in writing. Six patients have been included; all were males, median age 64 (range 47-74), histology; adenocarcinoma 4, squamous cell carcinoma 2, stage III B 4, stage IV 2. Among these 6 patients, 3 PR (50%) were observed. Neutropenia was the most common adverse event (83%). The lowest granulocyte counts were most frequently seen on day 9.4 (range: 6-14). Non hematologic adverse events included alopecia (6 cases), general fatigue (5 cases), anorexia (5 cases) and emesis (3 cases). These events were recovered rapidly with no therapy. The results suggest that combination chemotherapy of docetaxel and cisplatin will be effective and safe under careful observation.

Adenocarcinoma↗
PubMed1999

[Cerebral venous thrombosis in minimal change nephrotic syndrome].

A 46-year old man presented with an eight-day history of edema and was found to be nephrotic, with a plasma albumin level of 1.1 g/dl and urine protein excretion of 13.3 g/24 hrs. The level of plasma creatinine was normal at 1.0 mg/dl. A finding of renal biopsy was consistent with minimal change glomerulopathy. On the 6th hospital day, he suddenly developed a severe headache and was noted to have bilateral papilledema. Lumbar puncture revealed an opening pressure of 250 mm of water. Magnetic resonance venography showed an irregular flow in the superior sagittal sinus and right transverse sinus, a finding consistent with thrombus. The diagnosis of cerebral venous thrombosis was made, and the patient was given both Warfarin 2 mg/day and prednisolone 60 mg/day. A complete recovery from nephrotic syndrome was achieved within eight weeks. Nephrotic syndrome causes a hypercoagulable state, leading to both venous and arterial thrombosis. The most common clinical features are renal vein thrombosis, femoral vein thrombosis, and pulmonary embolism, however, cerebral venous sinus thrombosis is rare in patients with nephrotic syndrome. It is important to be aware of this complication, since prompt treatment with anticoagulation and control of nephrotic syndrome can lead to a successful outcome.

Anti-Inflammatory Agents↗
PubMed1999

[Extraordinary high elevation of serum CA19-9 levels in an apparently healthy subject].

We studied the woman presenting extraordinarily high serum CA19-9 levels who did not have any disease that was known to result in elevation of the serum CA19-9 level. Her CA19-9 values in sera obtained by 16 determinations with the enzyme immunoassay (EIA) over a period of 7 years were from 820 U/ml to 1,310 U/ml (median 1,015 U/ml). The correlation was good between serum CA19-9 levels in this subject with the EIA and radio immunoassay (RIA). The molecular weight of CA19-9 was determined by high-performance liquid chromatography (TSK gel G4000 SWXL column). While the molecular weights of CA19-9 in each patient with pancreatic cancer, cholangioma, cholecystitis or pancreatitis that were used as controls, were greater than 1,000 kDa, the CA19-9 of this subject had the molecular weight of approximately 550 kDa. To further determine whether human immunoglobulin was involved in the elevation of CA19-9 in the serum of this subject, we investigated the effect of adding rabbit anti-human IgM, IgG and IgA sera to the serum of this subject, CA19-9 values were unaffected by these antisera. Thus, the data obtained from the absorption study indicated that an anti-idiotypic antibody against the anti-CA19-9 antibody is unlikely to be responsible for an elevation of CA19-9 in the serum of this subject.

Antibodies, Anti-Idiotypic↗
PubMed1999

Comparison of differential diagnostic capabilities of 201Tl scintigraphy and fine-needle aspiration of thyroid nodules.

UNLABELLED: We assessed the ability of 201TI planar scintigraphy and fine-needle aspiration (FNA) biopsy to differentiate malignant from benign lesions by comparing the findings of these techniques with those of surgical histopathology for 107 patients with 109 thyroid nodules. METHODS: 201TI (74 MBq) was injected intravenously, and an early image and a delayed image were acquired after 10 and 120 min, respectively, for 10 min each. For 201TI planar scintigraphy, accumulation of the tracer in the nodules was visually scored and the nodules were grouped. Group A showed high activity in both early and delayed images. Group B revealed high activity in only the early image. Group C showed activity in the early image equal to that in normal tissues. Quantitative calculation of the washout rate was less than 0 in group CI and 0 or higher in group CII. Group D revealed low activity in the early image and variable activity in the delayed image. Three differential diagnosis methods were used for 201TI planar scintigraphy: method 1, in which only group A was considered malignant; method 2, in which both group A and group B were considered malignant; and method 3, in which groups A, B and CI were considered malignant. FNA results were assessed and classified by experienced pathologists. Two differential diagnosis methods were used for FNA: method a, in which malignancy was assigned to class IV (probably malignant or higher), and method b, in which malignancy was assigned to class III (possibly malignant or higher). RESULTS: Concerning 201TI methods 1, 2 and 3, sensitivity was 74.0%, 84.0% and 92.0%, respectively; specificity was 83.1%, 64.4% and 54.2%, respectively; and accuracy was 78.9%, 73.4% and 71.6%, respectively. For FNA, method a and method b had a sensitivity of 36.0% and 50.0%, respectively, and a specificity of 96.6% and 84.7%, respectively. The accuracy of both methods was 68.8%. For follicular lesions, sensitivity ranged from 80.0% to 90.0% for 201TI scintigraphy and from 10.0% to 30.0% for FNA. CONCLUSION: 201TI planar scintigraphy was found to be easier to use and more accurate than FNA in the differentiation of diagnosis of benign and malignant thyroid nodules based on visual scoring combined with quantitative evaluation.

Adolescent↗
PubMed1999

[Results of chemotherapy and salvage surgery for advanced testicular cancer].

Since 1980, 73 patients with advanced testicular cancer have been treated with chemotherapy and 43 patients received post-chemotherapy (salvage) surgery. The median age of all patients was 31 years old, ranging from 17 to 63 years. The histology of the primary testicular tumor was pure seminoma in 23 patients and non-seminoma in 50 patients. According to the Japan Urological Association classification, 38 patients were classified as stage II and 35 patients as stage III. As first-line chamotherapy, 52 patients were treated with PVB regimen (cisplatin, vinblastin, bleomycin), 16 patients with PEB (cisplatin, etoposide, bleomycin) and 5 patients with VAB-6 (vinblastine, actinomycin-D, bleomycin, cisplatin, cyclophosphamide). Thirty (41%) of the 73 patients achieved a complete response (CR) with chemotherapy alone and 63 (86%) achieved no evidence of disease (NED) with salvage treatment. As second-line chemotherapy, 16 patients were treated with PE (cisplatin, etoposide), or VIP (etoposide, ifosfamide, cisplatin) or VeIP (vinblastine, ifosfamide, cisplatin). One of the 16 patients achieved CR and 11 (69%) patients achieved NED. As salvage surgery, retroperitoneal lymphnode dissection (RPLND) was performed in 22 patients, RPLND with thoracotomy in 7 cases and thoracotomy alone in 4 cases. Necrosis was found in surgical specimens of 24 (56%) patients, mature teratoma in 6 (14%) and residual cancer in 13 (30%). Ninety-six percent and 100% of the patients with necrosis and mature teratoma survived with NED, respectively, but only 54% of the patients with residual carcinoma survived despite further treatment. Residual cancer was still found in 8 of the 32 (25%) marker normalized cases. Residual cancer could not reliably be predicted or discriminated from necrosis or mature teratoma by the prognostic criteria. Therefore, salvage surgery remains essential in the treatment of advanced testicular cancer.

Adolescent↗
PubMed1998

Cloning and sequencing of major capsid protein (mcp) gene of a vibriophage, KVP20, possibly related to T-even coliphages.

A large, tailed, prolate-headed vibriophage designated KVP20 was isolated from seawater. KVP20 was morphologically very similar to the previously described vibriophage, KVP40 (Matsuzaki, S., Inoue, T., Tanaka, S., 1998. Virology, 242, 314-318). However, they showed entirely different host specificities and could easily be differentiated from each other by their patterns of DNA restriction fragments. The major capsid protein (mcp) gene of KVP20 encoding the precursor of major capsid protein (pro-Mcp) was cloned and sequenced. The deduced amino-acid (aa) sequence of KVP20 pro-Mcp was compared with the reported aa sequences of KVP40 pro-Mcp, as well as of the equivalent proteins (gp23s) of coliphages T4 and RB49. There was 96.7, 57.5, and 55.2% homology to the corresponding proteins of KVP40, T4, and RB49, respectively. These data strongly suggest that the two vibriophages are closely related to each other and that they are both distantly, but definitely, related to coliphages T4 and RB49.

Amino Acid Sequence↗
PubMed1998

Cloning of mammalian Ire1 reveals diversity in the ER stress responses.

Cells modify their gene expression pattern in response to stress signals emanating from the endoplasmic reticulum (ER). The well-characterized aspect of this response consists of the activation of genes that encode protein chaperones and other ER resident proteins, and is conserved between mammals and yeast. In mammalian cells, however, ER stress also activates other pathways, including the expression of the transcription factor CHOP/GADD153 and its downstream target genes. ER stress is also linked to the development of programmed cell death, a phenomenon in which CHOP plays an important role. Here we report on the cloning of a murine homolog of yeast IRE1, an essential upstream component of the ER stress-response in yeast. The mammalian Ire1 is located in the ER membrane and its over-expression in mammalian cells activates both the endogenous ER chaperone GRP78/BiP and CHOP-encoding genes. Over-expression of a dominant-negative form of Ire1 blocks the induction of GRP78/BiP and CHOP in response to the ER stress induced by tunicamycin treatment. Over-expression of murine Ire1 also leads to the development of programmed cell death in transfected cells. These results indicate that a single upstream component, Ire1, plays a role in multiple facets of the ER stress-response in mammalian cells.

Adaptation, Biological↗
PubMed1998

An ultrastructural study of p75 neurotrophin receptor-immunoreactive fiber terminals in the reticular thalamic nucleus of young rats.

The reticular thalamic nucleus (RT) receives cholinergic fibers from both the basal forebrain and the brainstem. Recent studies have shown that the p75 neurotrophin receptor (p75NTR) is synthesized in cholinergic neurons in the basal forebrain but not in those in the brainstem. In this study, to identify cholinergic fibers originating from the basal forebrain, we used a monoclonal antibody against p75NTR (192-IgG) and characterized the ultrastructure of the immunoreactive fiber terminals in the rostral part of the RT in 3-week-old rats. Light microscopy revealed that p75NTR-immunoreactive fine fibers and varicosities were distributed throughout the nucleus. From electron micrographs, three types of labeled terminals were identified. The first type of labeled fiber terminals (63 out of 106) was consistently small, contained densely packed vesicles, and established asymmetrical synaptic contacts with heavy and bushy postsynaptic thickening on distal dendritic profiles; the second type (18 out of 106) established asymmetrical synaptic contacts with very slight postsynaptic thickening; and the third type (25 out of 106) of labeled terminals contained pleomorphic vesicles and established symmetrical synaptic contacts with more proximal dendritic surfaces than the first two types. In addition to the above, labeled dendritic profiles receiving non-labeled asymmetrical and symmetrical synaptic contacts were identified. These findings suggest that the basal forebrain cholinergic system establishes a variety of synaptic connections in the RT and influences cortical activity indirectly via thalamocortical pathways, as well as via direct projections to the cortex.

Animals↗
PubMed1998

Identification and cloning of two novel allergens from the lipophilic yeast, Malassezia furfur.

Two novel allergens, designated Mal f 2 and Mal f 3 according to the WHO/IUIS Allergen Nomenclature Subcommittee recommendation, were isolated from the lipophilic yeast Malassezia furfur cell extracts and the genes coding for those were cloned. Mal f 2 and Mal f 3 had apparent molecular weights of 21 kDa and 20 kDa, respectively, on SDS-PAGE under reducing conditions. The identified cDNA clone of Mal f 2 encoded an open reading frame of 177 amino acid residues. Fifty-one percent identity was found between the Mal f 2 and Mal f 3 sequences. Comparison of the Mal f 2 and Mal f 3 sequences with known protein sequences revealed that they had sequence homology with two peroxisomal membrane proteins of Candida boidinii and an Aspergillus fumigatus allergen, Asp f 3. In RAST, both Mal f 2- and Mal f 3-specific IgE antibodies could be detected in approximately 70 % of sera from M. furfur sensitized patients with atopic dermatitis.

Allergens↗
PubMed1998

Identification of novel stress-induced genes downstream of chop.

CHOP (GADD153) is a small nuclear protein that dimerizes avidly with members of the C/EBP family of transcription factors. Normally undetectable, it is expressed at high levels in cells exposed to conditions that perturb protein folding in the endoplasmic reticulum and induce an endoplasmic reticulum stress response. CHOP expression in stressed cells is linked to the development of programmed cell death and, in some instances, cellular regeneration. In this study, representational difference analysis was used to compare the complement of genes expressed in stressed wild-type mouse embryonic fibroblasts with those expressed in cells nullizygous for chop. CHOP expression, in concert with a second signal, was found to be absolutely required for the activation by stress of a set of previously undescribed genes referred to as DOCs (for downstream of CHOP). DOC4 is a mammalian ortholog of a Drosophila gene, Tenm/Odz, implicated in patterning of the early fly embryo, whereas DOC6 encodes a newly recognized homolog of the actin-binding proteins villin and gelsolin. These results reveal the existence of a novel CHOP-dependent signaling pathway, distinct from the known endoplasmic reticulum unfolded protein response, which may mediate changes in cell phenotype in response to stress.

3T3 Cells↗
PubMed1998

Standard transport channels of X-ray beamlines at SPring-8.

SPring-8 is constructing most of its beamlines using a combination of standardized components. The structures of the beamlines are also standardized according to the light-source characteristics. Specifications of components as well as the unified method of assembly and alignment are described.

Journal Article↗
PubMed1998

Fabrication of silicon crystals for a pin-post water-cooling system at SPring-8.

An internally cooled crystal with pin-post structure was fabricated using sand-blasting methods and Au-diffusive bonding techniques. Test operation at an undulator beamline of SPring-8 showed that the crystal possessed sufficient cooling capability for radiation from the SPring-8 standard in-vacuum undulator. The remaining problem was how to suppress the strain on the surface induced by bonding and water pressure.

Journal Article↗
PubMed1998

Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development.

Chemokines and their receptors are important in cell migration during inflammation, in the establishment of functional lymphoid microenvironments, and in organogenesis. The chemokine receptor CXCR4 is broadly expressed in cells of both the immune and the central nervous systems and can mediate migration of resting leukocytes and haematopoietic progenitors in response to its ligand, SDF-1. CXCR4 is also a major receptor for strains of human immunodeficiency virus-1 (HIV-1) that arise during progression to immunodeficiency and AIDS dementia. Here we show that mice lacking CXCR4 exhibit haematopoietic and cardiac defects identical to those of SDF-1-deficient mice, indicating that CXCR4 may be the only receptor for SDF-1. Furthermore, fetal cerebellar development in mutant animals is markedly different from that in wild-type animals, with many proliferating granule cells invading the cerebellar anlage. This is, to our knowledge, the first demonstration of the involvement of a G-protein-coupled chemokine receptor in neuronal cell migration and patterning in the central nervous system. These results may be important for designing strategies to block HIV entry into cells and for understanding mechanisms of pathogenesis in AIDS dementia.

Animals↗
PubMed1998

CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum.

Cellular stress, particularly in response to toxic and metabolic insults that perturb function of the endoplasmic reticulum (ER stress), is a powerful inducer of the transcription factor CHOP. The role of CHOP in the response of cells to injury associated with ER stress was examined in a murine deficiency model obtained by homologous recombination at the chop gene. Compared with the wild type, mouse embryonic fibroblasts (MEFs) derived from chop -/- animals exhibited significantly less programmed cell death when challenged with agents that perturb ER function. A similar deficit in programmed cells death in response to ER stress was also observed in MEFs that lack CHOP's major dimerization partner, C/EBPbeta, implicating the CHOP-C/EBP pathway in programmed cell death. An animal model for studying the effects of chop on the response to ER stress was developed. It entailed exposing mice with defined chop genotypes to a single sublethal intraperitoneal injection of tunicamycin and resulted in a severe illness characterized by transient renal insufficiency. In chop +/+ and chop +/- mice this was associated with the early expression of CHOP in the proximal tubules followed by the development of a histological picture similar to the human condition known as acute tubular necrosis, a process that resolved by cellular regeneration. In the chop -/- animals, in spite of the severe impairment in renal function, evidence of cellular death in the kidney was reduced compared with the wild type. The proximal tubule epithelium of chop -/- animals exhibited fourfold lower levels of TUNEL-positive cells (a marker for programmed cell death), and significantly less evidence for subsequent regeneration. CHOP therefore has a role in the induction of cell death under conditions associated with malfunction of the ER and may also have a role in cellular regeneration under such circumstances.

Animals↗
PubMed1998

Rapid purification and molecular modeling of AaIT peptides from venom of Androctonus australis.

As recombinant viruses expressing scorpion toxins are moving closer toward the market, it is important to obtain large amounts of pure toxin for biochemical characterization and the evaluation of biological activity in nontarget organisms. In the past, we purified a large amount of Androctonus australis anti-insect toxin (AaIT) present in the venom of A. australis with an analytical reversed-phase column by repeated runs of crude sample. We now report 20 times improved efficiency and speed of the purification by employing a preparative reversed-phase column. In just two consecutive HPLC steps, almost 1 mg of AaIT was obtained from 70 mg crude venom. Furthermore, additional AaIT was obtained from side fractions in a second HPLC run. Recently discovered insect selective toxin, AaIT5, was isolated simultaneously from the same venom batch. It shows different biological toxicity symptoms than the known excitatory and depressant insect toxins. AaIT5 gave 100% mortality with a dose of less than 1.3 micrograms against fourth-instar tobacco budworms Heliothis virescens 24 h after injection. During the purification process, we implemented mass spectrometry in addition to bioassays to monitor the presence of AaIT and AaIT5 in the HPLC fractions. Mass spectrometric screening can unambiguously follow the purification process and can greatly facilitate and expedite the downstream purification of AaIT and AaIT5 eliminating the number of bioassays required. Further, electrospray ionization was compared with matrix-assisted desorption/ionization and evaluated as a method of choice for mass spectrometric characterization of fractions from the venom purification for it provided higher mass accuracy and relative quantitation capability. Molecular models were built for AaIT5, excitatory toxin AaIT4, and depressant toxin LqhIT2. Three-dimensional structure of AaIT5 was compared with structures of the other two toxins, suggesting that AaIT5 is similar to depressant toxins.

Amino Acid Sequence↗
PubMed1998

Vecuronium dose requirement and pupillary response in a patient with olivopontocerebellar atrophy (OPCA).

PURPOSE: Olivopontocerebellar atrophy (OPCA), a variant of spinocerebellar degeneration (Shy-Drager syndrome), is a systemic degenerative disorder affecting the neurons of multiple nuclei. We investigated the sensitivity to vecuronium and the pupillary responses to various stresses in a patient with OPCA. CLINICAL FEATURES: A 65-yr-old woman with a six-month history of OPCA underwent a left upper lobectomy for lung cancer under propofol-N2O anaesthesia. She had symptoms of dysarthria, bulbar palsy, cerebellar ataxia, Parkinsonism, myosis, pyramidal signs and muscular atrophy of the distal extremities. A cumulative dose-response curve for vecuronium was constructed, and pupillary changes in response to various noxious stimuli were evaluated with concomitant recording of the Spectral-Edge-Frequency 90% (SEF90; the frequency below which 90 percent of the EEG power is located). The dose-response curve for vecuronium and the estimated ED50 value (the 50% blocking dose of vecuronium) in this patient with OPCA were almost identical with those of five ASA I-II patients (27 micrograms.kg-1 vs 31 micrograms.kg-1). The pupil size and the SEF90 did not change after tracheal intubation or surgical stimulation in this patient, while in the control subjects (n = 3), these measures increased in response to both stresses. CONCLUSIONS: The absence of pupillary and SEF90 responses to noxious stimuli suggests a sensitivity to propofol and/or central autonomic dysfunction in patients with OPCA. Although the dose requirement of vecuronium in this patient was similar to that of the control patients, the effects of neuromuscular blockers may vary depending on the severity of muscle atrophy.

Aged↗