Biomedical subjects

H Yokoo

Publications and source records attributed to H Yokoo.

At least 37 records · Page 2Linked to original sources

PubMed2000

Post-translational reduction of cell surface expression of insulin receptors by cyclosporin A, FK506 and rapamycin in bovine adrenal chromaffin cells.

Long-term (>/=3 h) treatment of cultured bovine adrenal chromaffin cells with cyclosporin A (CsA) decreased cell surface (125)I-insulin binding by 62% in a concentration (IC(50)=18 microM)- and time (t(1/2)=16 h)-dependent manner, but did not change the K(d) value. FK506 (1 microM) or rapamycin (3 microM) treatment reduced (125)I-insulin binding. Western blot analysis showed that CsA treatment decreased insulin receptor (IR) beta-subunit level (t(1/2)=15 h) in membrane fraction, but did not alter total cellular levels of IR precursor and IR beta-subunit. Internalization rate of cell surface IR measured by using brefeldin A, an inhibitor of vesicular exit from the trans-Golgi network, was comparable between non-treated and CsA-treated cells. Thus, CsA, FK506 and rapamycin inhibit peptidyl prolyl cis-trans isomerase activities of cyclophilin and FK506-binding protein, and down-regulate IR presumably by reducing cell surface externalization of IR.

Animals↗

PubMed2000

alpha(1)-Adrenergic receptor subtypes in rat cerebral microvessels.

To identify alpha(1)-adrenergic receptor subtypes involved in the regulation of cerebral microcirculation, we studied alpha(1)-adrenergic receptor subtypes expressed in the rat cerebral microvessels. The microvessels were prepared from rat cerebral cortex by albumin flotation and glass bead filtration techniques. [(125)I]HEAT binding to the cerebral microvessels was displaced by low concentrations of 5-methylurapidil, a selective antagonist for alpha(1A)-receptors, and modified Scatchard analysis of the data revealed that half of alpha(1)-receptors is alpha(1A)-subtype, and that alpha(1B)- and/or alpha(1D)-receptors are also present. The K(i) value of the high-affinity component for 5-methylurapidil was 3.90+/-1.08 nM, which is comparable with the value obtained in the rat cerebral cortex (2.17+/-0.88 nM). Reverse transcription and polymerase chain reaction experiments showed that mRNAs of alpha(1A)- and alpha(1B)-receptors, but not alpha(1D)-receptors, were expressed in the cerebral microvessels. These results suggest that alpha(1)-receptors involved in the regulation of cerebral microvessel function are alpha(1A)- and alpha(1B)-receptor subtypes.

Adrenergic alpha-Antagonists↗

PubMed2000

Inhibition by neuroprotective drug NS-7 of nicotine-induced 22Na(+) influx, 45Ca(2+) influx and catecholamine secretion in adrenal chromaffin cells.

Adrenal Glands↗

PubMed2000

Adrenomedullin inhibits spontaneous and bradykinin-induced but not oxytocin- or prostaglandin F(2alpha)-induced periodic contraction of rat uterus.

In isolated rat uterine strips, adrenomedullin (AM) inhibited the spontaneous periodic contraction in a concentration-dependent manner (IC(50)=22.3+/-0.7 nM). The inhibitory effect of AM was prevented by either AM(22-52), a putative antagonist for AM receptors, or calcitonin gene-related peptide (CGRP)(8-37), a putative antagonist for CGRP receptors. AM also attenuated bradykinin (BK)-induced periodic uterine contraction, which was blocked by AM(22-52) or CGRP(8-37), whereas AM had no effect on the periodic contraction caused by oxytocin or prostaglandin F(2alpha) (PGF(2alpha)). RT-PCR analysis showed that mRNAs for calcitonin receptor-like receptor (CRLR), receptor-activity-modifying protein (RAMP)1, RAMP2 and RAMP3 were expressed in the rat uterus. These results demonstrate that AM selectively inhibits spontaneous and BK-induced periodic contraction via activating receptors for AM and CGRP.

Adrenomedullin↗

PubMed2000

Short- and long-term differential effects of neuroprotective drug NS-7 on voltage-dependent sodium channels in adrenal chromaffin cells.

In cultured bovine adrenal chromaffin cells, NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride], a newly-synthesized neuroprotective drug, inhibited veratridine-induced (22)Na(+) influx via voltage-dependent Na(+) channels (IC(50)=11.4 microM). The inhibition by NS-7 occurred in the presence of ouabain, an inhibitor of Na(+),K(+) ATPase, but disappeared at higher concentration of veratridine, and upon the washout of NS-7. NS-7 attenuated veratridine-induced (45)Ca(2+) influx via voltage-dependent Ca(2+) channels (IC(50)=20.0 microM) and catecholamine secretion (IC(50)=25.8 microM). Chronic (>/=12 h) treatment of cells with NS-7 increased cell surface [(3)H]-STX binding by 86% (EC(50)=10.5 microM; t(1/2)=27 h), but did not alter the K(D) value; it was prevented by cycloheximide, an inhibitor of protein synthesis, or brefeldin A, an inhibitor of vesicular transport from the trans-Golgi network, but was not associated with increased levels of Na(+) channel alpha- and beta(1)-subunit mRNAs. In cells subjected to chronic NS-7 treatment, (22)Na(+) influx caused by veratridine (site 2 toxin), alpha-scorpion venom (site 3 toxin) or beta-scorpion venom (site 4 toxin) was suppressed even after the extensive washout of NS-7, and veratridine-induced (22)Na(+) influx remained depressed even at higher concentration of veratridine; however, either alpha- or beta-scorpion venom, or Ptychodiscus brevis toxin-3 (site 5 toxin) enhanced veratridine-induced (22)Na(+) influx as in nontreated cells. These results suggest that in the acute treatment, NS-7 binds to the site 2 and reversibly inhibits Na(+) channels, thereby reducing Ca(2+) channel gating and catecholamine secretion. Chronic treatment with NS-7 up-regulates cell surface Na(+) channels via translational and externalization events, but persistently inhibits Na(+) channel gating without impairing the cooperative interaction between the functional domains of Na(+) channels.

Animals↗

PubMed2000

Effects of macrophage-colony-stimulating factor deficiency on the maturation of microglia and brain macrophages and on their expression of scavenger receptor.

Macrophage-colony-stimulating factor (M-CSF) regulates the survival, proliferation and differentiation of the mononuclear phagocyte lineage. Osteopetrotic (op/op) mice defective in producing functional M-CSF were used in order to investigate the role of M-CSF on the development of microglia and brain macrophages and the expression of scavenger receptor (SR). Adult op/op and littermate mice at 10-47 weeks of age were investigated by immunohistochemistry with a panel of monoclonal antibodies (F4/80, Mac-1, anti-major histocompatibility complex (MHC) class II and anti-SR), electron microscopy and reverse transcriptase-polymerase chain reaction (RT-PCR). Microglia were weakly immunolabeled with F4/80 and Mac-1 in op/op and littermate mice, but the number of microglia in op/op mice was reduced in the cerebrum, cerebellum and brainstem compared with that of normal littermates. The numbers of Mac-1-positive microglia in op/op mice was 39% (pons) and 30% (cerebellar cortex) lower than that in normal littermates (P<0.05). In addition, the microglia cell processes in op/op mice were often shorter than those in control mice. In op/op and littermate mice, both MHC class II and SR were present in perivascular cells and macrophages of the leptomeninx and choroid plexus. Ultrastructurally, perivascular cells appeared to be immature, since their cytoplasm was narrow and contained few inclusion bodies compared with those of control mice. Reverse transcriptase-polymerase chain reaction showed a weak expression for SR mRNA in the brains of op/op mice as well as littermate mice. These results indicate that microglia are partly dependent on M-CSF for their proliferation and differentiation and that M-CSF has no significant effect on the expression of SR in the physiological brain. The study also suggests that M-CSF affects the maturation of perivascular cells at the ultrastructural level.

Animals↗

PubMed2000

A novel monoclonal antibody that recognizes human perivascular cells of the central nervous system under a specific immune reaction.

Perivascular cells or fluorescent granular perithelial cells of the central nervous system are newly recognized members of monocyte/macrophage populations. In this study a monoclonal antibody, GP-3, that labels proteinous lysosomal antigen of human perivascular cells, has been established. It selectively label the cells in foamy-macrophage infiltrating diseased areas, such as Wallerian degeneration and contusion, without significant reaction to the cells in normal areas, infiltrating macrophages or microglia. These findings suggest that the perivascular cell is an independent cell type and the antigen molecule is fairly specific to perivascular cells and plays an unknown role in immune-nervous system interaction.

Adult↗

PubMed2000

Cerebellar basket cells of Creutzfeldt-Jakob disease: immunohistochemical and ultrastructural study.

To elucidate possible abnormalities of cerebellar basket cells of Creutzfeldt-Jakob disease (CJD), seven sporadic cases were examined neuropathologically. Recently, parvalbumin-positive, GABAergic cerebral interneurons have been demonstrated to show early, selective loss in CJD, and the phenomenon is postulated as a cause of characteristic neurological symptoms of CJD. In this study, however, we demonstrated that the basket cells, cerebellar counterparts, were resistant even in patients with severe brain atrophy, and their processes showed intense argyrophilia and immunopositivity to phosphorylated neurofilament. They can newly be listed as CJD-resistant neurons similar to those of the hippocampus and brainstem nuclei. The mechanism to escape cell loss is of great interest, and there might be unknown factors modulating susceptibility within parvalbumin-positive neuronal subgroups. Furthermore, one case showed abnormal positivity with hematoxylin, crystal violet and pyronin in the basket cells. The pyronin positivity was reduced after ribonuclease digestion, suggesting that the causative substance was composed of RNA. Ultrastructurally, the fibers contained free ribosomes and amorphous electron-dense deposits. To our knowledge, such a finding has also not been previously reported.

Aged↗

PubMed2000

Retroperitoneal epithelioid angiomyolipoma leading to fatal outcome.

Epithelioid angiomyolipoma (AML) is a newly established variant of AML, characterized by monomorphous epithelioid cells that show HMB-45 immunopositivity, and it often displays aggressive behavior. To date, they have mostly appeared in the kidneys; however, the present autopsy case of a 43-year-old female without the stigmata of tuberous sclerosis complex had a huge retroperitoneal mass, accompanied by involvement of the regional lymph nodes. Histopathologically, the tumor was composed of round, polygonal or short spindle-shaped monomorphous cells with abundant eosinophilic cytoplasm and large nuclei with frequent multinucleation. Mitotic figures were scattered. Mature fat cells and thick-walled abnormal blood vessels were totally absent. Immunohistochemically, the tumor cells were reactive with HMB-45 and alpha-smooth muscle actin antibodies. In spite of curative surgery and repeated radio- and chemotherapy, the tumor continued to grow and brought about the patient's death 4 years after the initial symptoms. At autopsy, the peritoneal cavity was filled with the tumor mass exceeding 5.5 kg. Histopathological features were essentially the same as those of biopsy samples, but the cellular pleomorphism and emperipolesis were more easily identified. This report calls attention to this unusual manifestation of AML in the retroperitoneum and the importance of distinguishing it from sarcomas and/or paragangliomas.

Adult↗

PubMed2000

Protein kinase C-alpha and -epsilon down-regulate cell surface sodium channels via differential mechanisms in adrenal chromaffin cells.

In cultured bovine adrenal chromaffin cells, our [3H]saxitoxin ([3H]STX) binding, immunoblot, and northern blot analyses specified protein kinase C (PKC) isoform-specific posttranscriptional and posttranslational mechanisms that direct down-regulation of cell surface Na channels. Immunoblot analysis showed that among 11 PKC isoforms, adrenal chromaffin cells contained only conventional (c)PKC-alpha, novel (n)PKC-epsilon, and atypical (a)PKC-zeta. Treatment of adrenal chromaffin cells with 100 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) or 100 nM phorbol 12,13-dibutyrate (PDBu) caused a rapid (<15 min) and sustained (>15 h) translocation of PKC-alpha and -epsilon (but not -zeta) from cytosol to membranes, whereas a biologically inactive 4alpha-TPA had no effect. Thymeleatoxin (TMX), an activator of cPKC, produced similar membrane association of only PKC-alpha at 100 nM, with the potency of TMX being comparable with those of TPA and PDBu. Treatment with either 100 nM TPA or 100 nM TMX reduced cell surface [3H]STX binding to a comparable extent at 3, 6, and 12 h, whereas TPA lowered the binding to a greater extent than TMX at 15, 18, and 24 h; at 15 h, Gö6976, a specific inhibitor of cPKC, completely blocked TMX-induced decrease of [3H]STX binding while preventing by merely 57% TPA-induced decrease of [3H]STX binding. Treatment with 100 nM TPA lowered the Na channel alpha-subunit mRNA level between 3 and 12 h, with its maximum 52% fall at 6 h, and it was accompanied by a subsequent 61 % rise of the beta1-subunit mRNA level at 24 h. Gö6976 failed to prevent TPA-induced reduction of the alpha-subunit mRNA level; TMX did not change the alpha- and beta1-subunit mRNA levels throughout the 24-h treatment. Brefeldin A, an inhibitor of vesicular exit from the trans-Golgi network, augmented TPA- and TMX-induced decrease of [3H]STX binding at 1 and 3 h. Our previous and present studies suggest that PKC down-regulates cell surface Na channels without altering the allosteric gating of Na channels via PKC isoform-specific mechanisms; cPKC-alpha promotes Na channel internalization, whereas nPKC-epsilon decreases the alpha-subunit mRNA level by shortening the half-life of alpha-subunit mRNA without changing its gene transcription.

Adrenal Glands↗

PubMed2000

Up-regulation of cell surface insulin receptor by protein kinase C-alpha in adrenal chromaffin cells: involvement of transcriptional and translational events.

Our previous study showed that treatment of cultured bovine adrenal chromaffin cells with phorbol 12, 13-dibutyrate (PDBu) or 12-O-tetradecanoylphorbol 13-acetate (TPA) caused a rapid (<15 min) and persistent (>15 h) translocation of both conventional (c) protein kinase C-alpha (PKC-alpha) and novel PKC-epsilon (but not atypical PKC-zeta) from cytosol to membranes, whereas thymeleatoxin (TMX) increased the similar but selective membrane association of only cPKC-alpha. In the present study, chronic (>/=12 h) treatment of chromaffin cells with PDBu raised cell surface (125)I-insulin binding without altering the K(D) value; it developed in a concentration (EC(50) = 1.9 nM)-and time (t(1/2) = 14.6 h)-dependent manner, reaching its maximum 115% increase at 48 h. Either TPA (30 nM) or TMX (EC(50) = 6.4 nM) also increased (125)I-insulin binding by 97 or 88%, whereas the biologically inactive 4alpha-TPA had no effect. The increasing effect of PDBu (30 nM for 24 h) on (125)I-insulin binding was significantly blocked, even when H7, an inhibitor of PKC, was added at 8 h after the initiation of PDBu treatment. Concurrent treatment with brefeldin A, an inhibitor of vesicular transport from the trans-Golgi network, cycloheximide, an inhibitor of protein synthesis, or 5,6-dichlorobenzimidazole riboside, an inhibitor of RNA synthesis, abolished the PDBu-induced increment of (125)I-insulin binding. Western blot analysis, using antibody against the beta-subunit of the insulin receptor, showed that treatment with PDBu (30 nM) or TMX (EC(50) = 2.3 nM) increased levels of insulin receptor precursor (approximately 190 kDa; t(1/2) = 7.1 h) and insulin receptor beta-subunit (t(1/2) = 15.4 h), causing their almost maximum 52 and 59% rises, respectively, at 24 h. Northern blot analysis revealed that PDBu or TMX increased levels of insulin receptor mRNAs by approximately 35% as soon as 3 h, producing its monophasic peak approximately 76% increases at 24 h. All of these increasing effects of PDBu and TMX on (125)I-insulin binding and insulin receptor beta-subunit and insulin receptor mRNA levels were entirely prevented by simultaneous treatment with Gö6976, a selective inhibitor of cPKC. These results suggest that long-term activation of cPKC-alpha up-regulates the density of the cell surface insulin receptor via transcriptional/translational events.

Adrenal Medulla↗

PubMed1999

Olfactory bulb dysplasia: a novel subtype of neuronal migration disorder.

We present a novel subtype of neuronal migration disorder found in a case of Pena-Shokeir phenotype, in which the deformation sequence originated from neurogenic fetal akinesia. The autopsied brain showed dysplastic features of dentate and olivary nuclei as well as a bilaterally enlarged olfactory bulb with abnormal laminar structures. The laminar structures comprised four layers: (1) a superficial layer without glomeruli, (2) a neuronal cell layer containing neurons simulating mitral cells, (3) a sparse cell layer enriched with tangential neuronal fibers, and (4) a reticular layer showing a mottled appearance with the accumulation of fine reticular neurites intermingled with granule cells. To our knowledge, these malformed laminar changes have never been reported, and we propose the term olfactory bulb dysplasia.

Autopsy↗

PubMed1999

Intranuclear inclusions of meningioma associated with abnormal cytoskeletal protein expression.

We describe a case of meningothelial meningioma with a large number of intranuclear inclusions. Morphologically, these are divided into cytoplasmic inclusions and nuclear vacuoles. The cytoplasmic inclusion has a limiting membrane with cell organelles and filaments. Inclusions of this type are generally eosinophilic, like the cytoplasm. However, there are many inclusions that are more eosinophilic than the cytoplasm or that have a ground-glass appearance. Some of them may contain fine or coarse granules. On the other hand, the nuclear vacuole lacks a limiting membrane and appears empty. In most of the inclusions of this type, there is a faintly basophilic substance in the margin. Generally, the cytoplasmic inclusions are as immunopositive as cytoplasm with vimentin, but some of these cytoplasmic inclusions are more reactive. Under the electron microscope, abnormal aggregation of intermediate filaments is recognized in the cytoplasmic inclusions. It is considered that a strong reaction of cytoplasmic inclusions with vimentin immunostaining is due to abnormal aggregation of intermediate filaments. The present study distinctly demonstrates abnormal localization of intermediate filaments in the cytoplasmic inclusions, and it is suggested that the cytoskeleton participates in the evolution of the cytoplasmic inclusions.

Aged↗

PubMed1999

Fatal cervical spondyloarthropathy in a hemodialysis patient with systemic deposition of beta2-microglobulin amyloid.

Destructive spondyloarthropathy is a serious complication in patients with end-stage renal disease. We report a case of fatal cervical spondyloarthropathy in a patient on hemodialysis who presented with severe pain in the cervical area. Magnetic resonance imaging (MRI) of the cervical spine showed a soft tissue mass at the cervico-occipital hinge with spinal cord compression and destructive lesions of the cervical vertebrae. The patient became quadriplegic during the MRI procedure and died a few days later. Postmortem examination showed deposition of beta2-microglobulin in the cervico-occipital hinge. A unique feature of this case was the documented presence of systemic beta2-microglobulin amyloid deposits involving the spleen that to our knowledge has not been reported previously. Clinical suspicion and early detection of lesions caused by dialysis-related amyloidosis (DRA) may help to prevent significant morbidity and mortality in long-term dialysis patients.

Amyloidosis↗

PubMed1999

Esophageal undifferentiated carcinoma displaying marked chondroid differentiation at metastatic foci.

A report of an unusual esophageal tumor in an 81-year-old man is presented. The primary tumor was diagnosed as undifferentiated carcinoma at biopsy and had disappeared after irradiation treatment. However, multiple metastases were noted in the brain, lungs, kidneys, adrenals and spleen at autopsy. Histologically, metastases showed marked cartilaginous metaplasia as demonstrated by light microscopy, histochemical and immunohistochemical studies, although the initial biopsy sample did not possess chondroid matrix. Furthermore, an apparent transition could be traced from carcinomatous to chondroid cells, suggesting that the chondroid cells were derived from carcinoma cells. The carcinomatous area partially showed both squamous and glandular differentiation, although they were poorly differentiated. A retrospective immunohistochemical study that used a panel of antibodies suggested a phenotypic relevance between primary and metastatic tumors.

Aged↗

PubMed1999

Pigmented squamous cell carcinoma with dendritic melanocyte colonization in the external auditory canal.

A case of pigmented squamous cell carcinoma (SCC) with dendritic melanocyte colonization in the external auditory canal is reported and the previous cases are reviewed. A 65-year-old Japanese female was referred with a 7-year history of otitis. The patient also had a darkly pigmented 9 x 8 mm nodule in the external auditory canal. Microscopically, the tumor was SCC, but in some areas melanin pigments were found in the cytoplasm of the tumor cells. The tumor was thus diagnosed as pigmented SCC. As well as the tumor cells, dendritic-shaped cells colonized the tumor parenchyma and were immunohistochemically defined as melanocytes. The authors believe this is the first case of pigmented SCC with dendritic melanocyte colonization in the external auditory canal.

Aged↗

PubMed1999

Protein kinase C and the opposite regulation of sodium channel alpha- and beta1-subunit mRNA levels in adrenal chromaffin cells.

Our previous [3H]saxitoxin binding and 22Na influx assays showed that treatment of cultured bovine adrenal chromaffin cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) or phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C (PKC), decreased the number of cell surface Na channels (IC50 = 19 nM) but did not alter their pharmacological properties; Na channel down-regulation developed within 3 h, reached the peak decrease of 53% at 15 h, and was mediated by transcriptional/translational events. In the present study, treatment with 100 nM TPA lowered the Na channel alpha-subunit mRNA level by 34 and 52% at 3 and 6 h, followed by restoration to the pretreatment level at 24 h, whereas 100 nM TPA elevated the Na channel beta1-subunit mRNA level by 13-61% between 12 and 48 h. Reduction of alpha-subunit mRNA level by TPA was concentration-dependent (IC50 = 18 nM) and was mimicked by PDBu but not by the biologically inactive 4alpha-TPA; it was prevented by H-7, an inhibitor of PKC, but not by HA-1004, a less active analogue of H7, or by H-89, an inhibitor of cyclic AMP-dependent protein kinase. Treatment with cycloheximide, an inhibitor of protein synthesis, per se sustainingly increased the alpha-subunit mRNA level and decreased the beta1-subunit mRNA level for 24 h; also, the TPA-induced decrease of alpha-subunit mRNA and increase of beta1-subunit mRNA were both totally prevented for 24 h by concurrent treatment with cycloheximide. Nuclear run-on assay showed that TPA treatment did not alter the transcriptional rate of the alpha-subunit gene. A stability study using actinomycin D, an inhibitor of RNA synthesis, revealed that TPA treatment shortened the t(1/2) of alpha-subunit mRNA from 18.8 to 3.7 h. These results suggest that Na channel alpha- and beta-subunit mRNA levels are differentially down- and up-regulated via PKC; the process may be mediated via an induction of as yet unidentified short-lived protein(s), which may culminate in the destabilization of alpha-subunit mRNA without altering alpha-subunit gene transcription.

Adrenal Medulla↗

PubMed1999

Colorectal polyps with extensive absorptive enterocyte differentiation: histologically distinct variant of hyperplastic polyps.

BACKGROUND: The histologic classification of colorectal polyps is well established. However, practicing pathologists may still occasionally encounter colorectal polyps that are difficult to classify. We studied 6 colorectal polyps that showed uncommon histologic features that have not been described in the English language literature. MATERIALS AND METHODS: The polyps were studied using standard hematoxylin-eosin stain, mucin histochemistry, and electron microscopy. RESULTS: The 6 polyps we studied showed extensive papillary and villous structures with alternating villi and crypts. The villi were lined by well-differentiated absorptive cells, whereas the crypts were lined by immature glandular cells, thus mimicking the histology of the small intestinal mucosa. CONCLUSIONS: These polyps appear to represent a variant of the hyperplastic polyp, in as much as cellular maturation (immature glandular cells differentiate into the mature surface absorptive cells) is the essential feature distinguishing hyperplastic polyps from adenomas.

Aged↗