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Biomedical subjects

M Kudo

Publications and source records attributed to M Kudo.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Refractory idiopathic cold agglutinin disease successfully treated with intermittent high-dose cyclophosphamide].

A 56-year-old woman, who had been suffering from idiopathic cold agglutinin disease and treated unsuccessfully with prednisolone and cyclosporine A for 6 months, was referred to our hospital in November 1998. She was given methylprednisolone pulse therapy followed by low-dose cyclophosphamide, but her anemia did not improve. We then began administration of intermittent high-dose cyclophosphamide (1,200 mg/day, every 4 weeks), and this resulted in a dramatic increase of her hemoglobin level and improvement of her symptoms. She is currently receiving 500 mg of cyclophosphamide every 2 months and showing a good response. Intermittent high-dose cyclophosphamide therapy can be an effective treatment for refractory cold agglutinin disease.

Anemia, Hemolytic, Autoimmune↗
PubMed2000

Activation of the luteinizing hormone receptor following substitution of Ser-277 with selective hydrophobic residues in the ectodomain hinge region.

Glycoprotein hormone receptors are G protein-coupled receptors with ligand-binding ectodomains consisting of leucine-rich repeats. The ectodomain is connected by a conserved cysteine-rich hinge region to the seven transmembrane (TM) region. Gain-of-function mutants of luteinizing hormone (LH) and thyroid-stimulating hormone receptors found in patients allowed identification of residues important for receptor activation. Based on constitutively active mutations at Ser-281 in the hinge region of the thyroid-stimulating hormone receptor, we mutated the conserved serine in the LH (S277I) and follicle-stimulating hormone receptors (S273I) and observed increased basal cAMP production and ligand affinity by mutant receptors. For the LH receptor, conversion of Ser-277 to all natural amino acids led to varying degrees of receptor activation. Hydropathy index analysis indicated that substitution of neutral serine with selective nonpolar hydrophobic residues (Leu>Val>Met>Ile) confers constitutive receptor activation whereas serine deletion or substitution with charged Arg, Lys, or Asp led to defective receptor expression. Furthermore, mutation of the angular proline near Ser-273 to flexible Gly also led to receptor activation. The findings suggest the ectodomain of glycoprotein hormone receptors constrain the TM region. Point mutations in the hinge region of these proteins, or ligand binding to these receptors, could cause conformational changes in the TM region that result in G(s) activation.

Amino Acid Sequence↗
PubMed2000

Barbiturates inhibit K(+)-evoked noradrenaline and dopamine release from rat striatal slices--involvement of voltage sensitive Ca(2+) channels.

The cellular target site(s) for anaesthetic action remain unclear. In rat striatal slices we have previously demonstrated that K(+)-evoked noradrenaline (NA) and dopamine (DA) release is mediated predominantly via P/Q-type voltage sensitive Ca(2+) channels (VSCC). Using this model of Ca(2+) dependent transmitter release we have evaluated the effects of anaesthetic and non-anaesthetic barbiturates. Rat brain striatal slices were incubated in the absence and presence of barbiturate for 10 min at 37 degrees C. The slices were then incubated for 6 min with 40 mM KCl. All anaesthetic barbiturates produced a concentration-dependent inhibition of K(+)-evoked NA and DA release. Non-anaesthetic barbiturate, barbituric acid was ineffective. The pIC(50) for NA and DA release (thiopental: 4.90+/-0.13 and 5.00+/-0.10, pentobarbital: 4.39+/-0.07 and 4.43+/-0.14, phenobarbital: 3.85+/-0.08 and 3.59+/-0.10, respectively) correlated with lipid solubility (NA: r(2)=0.999, DA: r(2)=0.987). We therefore suggest that barbiturates inhibit catecholamine release via an interaction with P/Q VSCC further implicating this channel in anaesthetic action.

Anesthetics↗
PubMed2000

Biochemical and immunohistochemical demonstration of tissue kallikrein in the neuronal nuclei of the developing rat brains.

Kallikrein content and cellular localization in the prenatal, newborn and adult rat brains were determined by the enzyme-linked immunosorbent assay and immunohistochemistry. The content was the highest in the prenatal rats and highly predominant in the neuronal nuclei during the prenatal to newborn periods, whereas the immunoreactive kallikrein was mainly located around neuronal cell bodies and their processes in the adult rats. The preferential nuclear localization in the prenatal rat brains was further confirmed by the immunoblotting technique after the SDS-polyacrylamide gel electrophoresis of the lysate of the nuclei fractionated from the prenatal rat brains. The meaning(s) of this kallikrein localization in the neuronal nuclei at the prenatal and newborn stages is unknown. However, we would like to conclude that this enzyme plays an important role in the morphogenesis of brain by acting on the substance(s) in the neuronal nuclei at the developing stage.

Age Factors↗
PubMed2000

Immunohistochemical distribution of the endothelin-converting enzyme-1 in the rat hypothalamo-pituitary axis.

We prepared a rabbit polyclonal antibody against an endothelin converting enzyme-1 (ECE-1) to examine the distribution of ECE-1 in the hypothalamus and the pituitary of the rat. By the Western blot analysis, the antibody specifically recognized ECE-1 proteins in membrane fractions of the rat hypothalamus. Immunohistochemical staining revealed ECE-1 immunoreactivity in both cell bodies and axons in some hypothalamic neurons. The immunopositive cell bodies were located in the paraventricullar and supraoptic nuclei; immunopositive axons were distributed in the suprachiasmatic, paraventricullar (PVN), and supraoptic (SON) nuclei. However no immunoreactivity was detected in the posterior pituitary gland. The present results indicate that ECE-1 converts the endothelin-1 (ET-1) from precursor big ET-1 to mature ET-1 in the PVN/SON. The big ET-1 existing in the posterior pituitary gland is thought to be escaped from the converting by ECE-1 in the hypothalamus.

Animals↗
PubMed2000

Localization of mRNA for SHIP2, SH2 domain-containing inositol polyphosphate 5-phosphatase, in the brain of developing and mature rats.

The localization of mRNA for SHIP2, SH2 domain containing inositol 5-phosphatase SHIP isozyme, was examined by in situ hybridization histochemistry in the brain of developing and mature rats. SHIP2 mRNA was first detected in the ventricular germinal zone at embryonic stages. As the postnatal development proceeded, the expression signal was evident in cell of the white matters, presumptive oligodendrocytes, and no significant expression was seen in neurons throughout the development.

Aging↗
PubMed2000

Effects of extracellular matrix on phenotype modulation and MAPK transduction of rat aortic smooth muscle cells in vitro.

The transition of arterial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype may play an essential role in the formation of atherosclerotic and restenotic lesions. This process includes a prominent structural reorganization and allows cells to acquire the ability to migrate, proliferate, and secrete extracellular matrix components. According to Western blotting analysis and immunohistochemical and morphological observations, laminin not only retains SMCs in a contractile state but also possibly stimulates cells to transform a synthetic to a contractile phenotype at an early stage, mediated by P38 MAPK signal transduction. However, fibronectin promotes SMCs to transform from a contractile to a synthetic phenotype, mediated by the ERK MAPK signal pathway. The localization of smooth muscle alpha -actin, myosin heavy chain isoform SM2, and vimentin in explant-isolated rat SMCs was affected by a substrate of fibronectin and laminin and also by ERK MAP kinase inhibitor (PD098059) and P38 MAPK inhibitor (SB203580). Furthermore, vimentin may play a much more important role in differentiation than desmin in phenotype modulation in rat aortic smooth muscle cells.

Actins↗
PubMed2000

Mice overexpressing extracellular superoxide dismutase have increased resistance to global cerebral ischemia.

Transgenic mice, which exhibit a fivefold increase in brain parenchymal extracellular superoxide dismutase (EC-SOD) activity, were used to investigate the role of EC-SOD in global ischemic brain injury. Halothane-anesthetized normothermic wild-type (n = 22) and transgenic (n = 20) mice underwent 10 min of near-complete forebrain ischemia induced by bilateral carotid artery occlusion and systemic hypotension (mean arterial pressure = 30 mm Hg). After 3 days of recovery, the brains were histologically examined. Other mice underwent autoradiographic determination of regional CBF 10 min prior to, during, and 30 min after forebrain ischemia. Histologic injury in the cortex and caudoputamen was minimal in both groups. The percentage of dead hippocampal CA1 neurons was reduced in the EC-SOD transgenic group (wild type = 44 +/- 28%; EC-SOD transgenic = 23 +/- 21%, mean +/- SD, P = 0.015). CBF was similar between groups prior to ischemia. The intraischemic blood flow was severely reduced in forebrain structures and was similar between groups. Blood flow at 30 min postischemia had recovered to 50-60% of baseline values in both groups. These results indicate that EC-SOD can play an important role in defining the magnitude of selective neuronal necrosis resulting from near-complete forebrain ischemia. This implicates involvement of extracellular superoxide anions in the pathologic response to global cerebral ischemia.

Animals↗
PubMed2000

Primary intracranial malignant schwannoma of trigeminal nerve. A case report with review of the literature.

The authors report a rare case of primary intracranial malignant schwannoma of the trigeminal nerve occuring in a 30-year-old woman without von Recklinghausen's neurofibromatosis (VRNF). The tumour arose from the intracranial part of the left trigeminal nerve, without skull base destruction. The tumour was partially removed operatively, followed by focal 50 Gy irradiation, but unfortunately the tumour showed rapid regrowth. A second operation was attempted, but she died of cerebral infarction soon after operation. Histologically, the original tumour was characterized by the presence of foci of extremely high cellularity, pleomorphism and mitosis in an otherwise typical benign schwannoma. Immunohistochemically, the tumour cells were positive for S-100 protein even in the atypical areas, suggesting the tumour to be of Schwann cell origin. However, the recurrent tumour was composed of undifferentiated spindle cells, which were negative for S-100 protein. Thus, it is possible to consider that the S-100 protein expression could reflect the degree of differentiation of Schwann cells. Furthermore, the postoperative irradiation might have exacerbated the malignant progression in the present case.

Adult↗
PubMed2000

Immunohistochemical localization of mitogen-activated protein kinase (MAPK) family and morphological changes in rat heart after ischemia-reperfusion injury.

The mitogen-activated protein kinase (MAPK) family is considered to be activated by stress, but the role of the MAPK family is still unknown in cardiac pathology. In the present study, not only the localization of MAPKs such as the extracellular responsive kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK (p38), but also ultrastructural changes were investigated in the ischemia-reperfusion model of Wistar rats. At 5, 10, 30, 60, and 180 min reperfusion after 30 min ischemia by occluding the coronary artery, the expression of these MAPKs was increased in blood vessels and cardiomyocytes by Western blotting and immunohistochemical methods. In addition, after ischemia reperfusion, various ultrastructural changes such as decreased glycogen granules, mitochondrial swelling, and myolysis were observed in the blood vessels and cardiomyocytes. These results suggest that protein kinases may regulate numerous biological processes, including the regulation of contraction and ion transport.

Animals↗
PubMed2000

Neurogenesis in the superior olivary complex in the rat.

In a previous paper we provided evidence that crossed projection neurons are generated earlier than uncrossed projection neurons in the lateral superior olive. The aim of the present study was to determine if other major nuclei of the superior olivary complex (SOC), the medial superior olivary (MSO), the superior paraolivary (SPN) and the medial trapezoid (MTB) nuclei, are distinguished by their neuronal constitutions of birthdates. Pregnant rats were injected intraperitoneally with 5-bromodeoxyuridine (BrdU), the thymidine analogue, to label the neurons on one of the embryonic (E) days E11-E16. When the progeny rats reached adulthood, the brains were processed for BrdU immunohistochemistry. The MSO was mostly composed of neurons generated on E12 (95%). The remaining neurons in the MSO completed their neurogenesis by E13. The SPN neurons were generated from E12 to E14 with a peak on E13 (80%). Regardless of the morphological heterogeneity, the SPN consisted of a single population of neurons in terms of neurogenesis. The MTB neurons were generated from E13 to E16 with a peak on E14 (73%). In contrast to the previous assumption, no topographical relationship existed between neurogenesis and tonotopicity within each nucleus of the SOC.

Animals↗
PubMed2000

Design and synthesis of potential inhibitors of the ergosterol biosynthesis as antifungal agents.

A series of azolylmethyloxolane derivatives with modified sterol side-chain structures, designed as potential dual functional inhibitors of cytochrome P450 14alpha-demethylase (14DM) and delta24-sterol methyltransferase (24-SMT) based on the common characteristic features of 24-aminosterols and azole antifungal agents, were synthesized and evaluated for their antifungal activities and inhibitory activities of 14DM and 24-SMT. Among these compounds, imidazolylmethyloxolane derivatives 28a and 28b showed potent in vitro antifungal activities comparable to those of itraconazole. However, the in vitro bioactivities have not been linearly translated into in vivo protection data for some unknown reasons.

Administration, Oral↗
PubMed2000

Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders.

Omenn syndrome was recently found to be caused by missense mutations in RAG1 or RAG2 gene that result in partial V(D)J recombination activity. Although the clinical hallmarks of the disease are well defined, there have been several cases with clinical findings similar to, but distinct from Omenn syndrome. The data on immune functions and RAG gene mutations of such cases are limited. We described five Japanese infants from four unrelated families, including two cases of Omenn syndrome and three cases of related disorders. Sibling cases with typical Omenn phenotype were found to be compound heterozygotes of R396C and L885R mutations in RAG1. The former has been reported in European cases and may constitute a hot spot. The latter is a novel missense mutation. Infants with related disorders exhibited erythroderma, eosinophilia, hypogammaglobulinaemia, decreased number of B cells and skewing to Th2, and their lymph node specimens showed architectural effacement, lymphocyte depletion and histiocytic hyperplasia, each of which is seen characteristically in Omenn syndrome. However, in these cases serum IgE levels were low or undetectable. We found no mutation in RAG genes except for a K820R substitution in RAG1, which was regarded to be a functional polymorphism, in two of these cases. Our study suggests that RAG missense mutation may be a genetic abnormality unique to Omenn syndrome with characteristic clinical and laboratory findings. Variations of Omenn syndrome, or related disorders, may represent a different type of immunodeficiency, distinct from abnormalities in lymphoid-specific recombinase activity.

Apoptosis↗
PubMed2000

Mutations in the WUSCHEL gene of Arabidopsis thaliana result in the development of shoots without juvenile leaves.

The vegetative growth of Arabidopsis thaliana can be divided into two phases. The transition from the juvenile (early) phase to the adult (later) phase is associated with changes in several morphological features of leaves, such as the shape of leaf blades, the number of trichomes and patterns of venation. In a screening of mutants with altered morphological identities of leaves, we found one which we named juvenile leafless and misshapen shoot apical meristem (jam). The mutation represented a new allele of the WUSCHEL (WUS) gene, and, in its presence, plants produced no juvenile leaves. Analysis of the morphology of mutant plants revealed that all the rosette leaves had characteristics of adult leaves. The formation of the first rosette leaf in the wus(jam) mutant was markedly delayed, and occurred at the almost same time as formation of the third or fourth leaf in wild-type plants. In the wild-type, these leaves correspond to the first adult leaves. Analysis by RT-PCR showed that transcripts of WUS accumulated in shoot apices and roots, but not in cotyledons and leaves. The present results suggest that the WUS gene controls the morphological traits of rosette leaves either directly or indirectly. In view of the predicted function of the WUS gene, namely maintenance of stem cells within the shoot apical meristem, we suggest that the lack of juvenile leaves in the mutant might have been caused by interruption of leaf initiation during the juvenile phase or by halting of an entire process of formation of juvenile leaves.

Arabidopsis↗