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Biomedical subjects

M Mizoguchi

Publications and source records attributed to M Mizoguchi.

At least 73 records · Page 4Linked to original sources
PubMed1997

Expression of neurofibromatosis 2 protein in human brain tumors: an immunohistochemical study.

The neurofibromatosis 2 (NF2) gene-encoded protein, named merlin, may function as a molecular linkage connecting cytoskeleton and plasma membrane. Merlin is thought to play a crucial role as a tumor suppressor not only in hereditary NF2-related tumors, but also in sporadic tumors such as schwannomas, meningiomas and gliomas. Using a merlin-expression vector system, we raised specific antiserum against merlin. We observed the intracellular distribution of merlin in cultured glioma cells, and further investigated merlin expression in 116 human brain tumors. Immunofluorescence microscopy revealed that merlin was localized beneath the cell membrane and concentrated at cell-to-cell adhesion sites, where actin filaments are densely associated with plasma membrane. By immunohistochemistry, none of the schwannomas from either NF2 patients or sporadic cases showed any immunoreactivity, while normal Schwann cells of cranial nerves were immunopositive. In meningiomas, merlin expression was frequently seen in the meningothelial subtype (8/10, 80%), but no expression could be detected in either the fibrous or the transitional variant. Most normal astrocytes were negative; however, reactive astrocytes often expressed merlin. Glioblastomas and anaplastic astrocytomas were found to be strongly positive, and focal positive staining was observed in fibrillary and pilocytic astrocytomas. Thus, the loss of merlin appears to be integral to schwannoma formation and the differential pathogenesis of meningioma subtypes. However, merlin alterations do not appear to play a critical role in either the tumorigenesis or malignant transformation of neoplastic astrocytes.

Brain Neoplasms↗
PubMed1997

Clinical, pathological, and etiologic aspects of acquired dermal melanocytosis.

To study the pathogenesis of acquired dermal melanocytosis (ADM), we reviewed the clinical, immunohistochemical, and ultrastructural features of 34 cases (female, 33, and male, 1) of ADM. The patients' ages at onset ranged from 8 to 51 years and averaged 26.8 +/- 12.7 years. There was a positive family history. Gray-brown macules were mostly recognized on the face. Not only active dermal melanocytes but also non-pigmented c-KIT- and TRP-2-positive immature melanocytes were detected in the dermis. Taken together those clinical and histological findings, activation of pre-existing immature melanocytes by sunlight, estrogen, and/or progesterone, and some other factors, may be the most likely mode of the development of ADM. Moreover, using cultured murine neural crest cells as a model of c-KIT-positive immature melanocytes, we confirmed that endothelin-1, which is produced and secreted by keratinocytes after UV-irradiation, affects melanocytes and accelerated melanogenesis.

Adult↗
PubMed1996

Assembly of hair keratins in transfected epithelial cells.

To define the interactions required for the filament assembly of differentiation-specific keratins, active copies of mouse hair keratin mHa1 and mHb4 genes were introduced into a rat kangaroo kidney epithelial cell line (PtK2) and a rat stratified squamous epithelial cell line (rat epidermal keratinocyte). In PtK2 transient transfectants, when introduced individually or in combination, mHa1 and mHb4 formed aggregates of ring-like structures of various sizes at the perinuclear region with no evidence of organization into a keratin network. These aggregates altered the distribution of the endogenous keratins and vimentin. In most of the cells carrying the ring-like structures of mHa1 and mHb4 around the nucleus, the endogenous keratin network collapsed and localized around the nucleus. Furthermore, the densely accumulated endogenous keratin surrounded the ring-like aggregates with partial co-localization. However, when transfected into the rat epidermal keratinocytes, mHa1 and mHb4 were able to co-localize with the well-developed cytoskeleton of endogenous keratins. These results showed that, in contrast to keratin pairs K5/K14 and K8/K18, the mHa1/mHb4 pair is unable to develop an extensive keratin network on its own and that there are possible differential abilities among these hair keratins and other keratins to form well-developed cytoplasmic networks.

Animals↗
PubMed1996

CDw49b/CD29 integrin complex mediates the differentiation of human endothelial cells into capillary-like structures in vitro.

We have investigated different beta-1 integrins (CDw49/CD29) on human umbilical vein endothelial cells (HUVEC) with regard to their roles in modifying the morphological structure of these cells on/in matrigel. The inhibition of matrigel-induced capillary formation by antibodies against subunits of beta-1 integrins was examined quantitatively using a digital analyzer. Antibodies to CDw49b and CD29 (common beta chain) caused a marked inhibition of capillary formation (up to 70%) in a dose-dependent manner, whereas antibodies to CDw49d, CDw49e and CDw49f were less inhibitory. We also examined the appearance of HUVEC cultured in matrigel. HUVEC suspended in matrigel for 24 h formed extended cell processes which connected, resulting in the formation of a capillary network. In contrast, fibroblasts cultured in matrigel showed only bipolar extensions without cell-cell contact. After 48 h in culture in matrigel, some HUVEC showed the capillary-unit of a lumen encircled by EC which may mimic the basic putative unit in the formation of capillaries. However, HUVEC pretreated with antibodies to CDw49b and CD29 failed to form significant processes and a hollow lumen. These phenomena may illustrate the importance of endothelial cell-basement membrane matrix interaction (through integrins, especially CDw49b/CD29 complex) occurring during differentiation of endothelial cells in angiogenesis.

Antibodies, Monoclonal↗
PubMed1996

Differential expression of CD44 variants among meningioma subtypes.

Aims/background-CD44 is a widely distributed cell surface molecule which has numerous isoforms generated by alternative splicing. The diverse functions related to the CD44 variants (CD44v) have been reported in various physiological and pathological conditions. The pattern of expression of CD44v among meningioma subtypes was investigated to ascertain whether CD44 variants play a role in a variety of biological processes, such as epithelial differentiation and extracranial metastasis.Methods-Twenty three meningiomas were studied immunohistochemically using novel antibodies directed against CD44 isoforms. Six of the 23 samples were analysed by reverse transcription polymerase chain reaction (RT-PCR), followed by Southern blotting with CD44v specific probes.Results-In meningothelial, fibrous and anaplastic meningiomas, a standard form of CD44 was detected by RT-PCR and was homogeneously expressed in tumour cells when studied immunohistochemically. CD44v was not detected in these subtypes. In secretory meningiomas, however, CD44v isoforms were strongly expressed in the cell clusters that produce secretory granules and also accumulated in the granules. The population of tumour cells immunopositive for CD44v was similar to that which stained with antibodies directed against carcinoembryonic antigen, epithelial membrane antigen and ezrin. On RT-PCR with Southern blotting, only the secretory type showed high level expression of CD44v.Conclusions-CD44v in meningiomas is expressed in relation to tumour cell differentiation towards the epithelial type.

Journal Article↗
PubMed1995

Effects of monoclonal anti-c-kit antibody (ACK2) on melanocytes in newborn mice.

Previous studies indicate that c-Kit is required for postnatal melanocyte development. To understand the precise mechanisms of c-Kit dependence, we studied melanocyte development in newborn C57BL/6 mice by means of peritoneal injection of a monoclonal anti-c-Kit antibody (ACK2), which blocks c-Kit functions. The mice were injected once or more with ACK2 at various intervals after birth. In experiment 1, skin samples were examined on day 10 post-partum and in experiment 2 they were examined daily until day 10 post-partum. We studied melanocytes in the hair follicles, epidermis, and dermis by light and electron microscopy with dopa reactions and immunohistochemistry. Epidermal melanocytes in untreated mice were dopa negative and c-Kit positive on day 0 post-partum but became dopa positive soon thereafter. In ACK2-treated mice, the earlier the mice received ACK2 injections after birth, the fewer melanocytes they had, not only in the epidermis, but also in follicles. In these mice, melanocytes that had undergone apoptosis in the dermis and the follicles were detected ultrastructurally. Some appeared to have produced tyrosinase, because they had dopa-positive melanosomes. These results suggest that melanocytes in newborn mice are c-Kit dependent and undergo apoptosis when c-Kit receptors are blocked by ACK2 in the early days after birth. During this c-Kit-dependent period, melanocytes differentiate from dopa negative to positive and migrate from the epidermis to hair follicles.

Animals↗
PubMed1995

Leser-Trélat sign associated with Sézary syndrome.

A 74-year-old Japanese male had developed generalized erythroderma and rapid growth of multiple verrucous lesions over the entire surface of his face, trunk, and extremities three months before he was seen. Histologically seborrheic keratoses were revealed. Laboratory examinations showed peripheral leukocytosis with atypical lymphocytes and high levels of IgE and IgG. On the basis of these clinical and histopathologic findings, we diagnosed the patient as having Leser-Trélat sign associated with Sézary syndrome. The erythroderma subsided after administration of oral predonisone, and no new formations of seborrheic keratosis were observed. However, because of subsequent aggravation of the generalized erythroderma, we administered chemotherapy. Six months after the initial examination, lung cancer was found, and the patient subsequently died of respiratory and renal failure.

Aged↗
PubMed1995

[Growing skull fracture: a case report].

An 18-day-old male baby who had fallen from his mothers arms and hit his head on the floor was admitted to our hospital. On admission, the patient was crying, but no weakness was noted in the extremities. A small fluctuant protrusion was visible in the right parietal region. The plain skull X-ray film revealed a wide linear fracture in the parietal bone. Computed tomography (CT) showed swelling of the right hemisphere and a traumatic subarachnoid hemorrhage. At 41 days old, the subcutaneous fluid collection had increased in volume and the width of the linear skull fracture was also enlarged as shown on the X-ray film. CT and magnetic resonance imaging (MRI) revealed a large cyst herniating through the wide parietal bone defect. There was also an enlarged right lateral ventricle and a torn dural margin in the brain. The cranioplasty with dural plasty was performed on the 43rd day of ago under the diagnosis of growing skull fracture of the right parietal bone. The postoperative course was uneventful, without seizure or weakness. In order to diagnose growing skull fracture, especially to show the relationship between the fracture, torn dura matter, the ventricle and the contused brain, MRI was very helpful combined with CT and plain skull X-rays. Cranioplasty with dural repair was considered the essential procedure for the treatment of such growing skull fractures.

Craniotomy↗
PubMed1994

Suppressive effect of intravenous immunoglobulins on the activity of interleukin-1.

In order to study the effect of human immunoglobulin preparations for intravenous use (IVIg) on the production and activity of interleukin-1 (IL-1) derived from monocytes, we treated cultured monocytes with IVIg and examined the lymphocyte-activating factor (LAF) activity of IL-1 in the culture supernatants. The results showed that IVIg suppressed the activity from most healthy adults and some febrile children with acute respiratory disease or Kawasaki disease. Further studies revealed that intact Ig (whole molecular Ig) did not suppress the mRNA expression of IL-1 alpha or IL-1 beta in mononuclear cells, that intact Ig and pepsin-digested Ig inhibited the LAF activity of recombinant IL-1 (rIL-1) and also that intact Ig contains immunoglobulin (probably anti-IL-1 antibody) which binds with rIL-1 by dot blotting using biotin-streptavidin. These results suggest that IVIg suppresses neither IL-1 synthesis nor the release of IL-1 from monocytes but does neutralize IL-1 alpha and IL-1 beta activity by binding IL-1 proteins as an anti-IL-1 antibody.

Adult↗
PubMed1994

Interleukin 8 in Behçet's disease.

Activated peripheral polymorphonuclear leukocytes (PMNs) and infiltration of PMNs into the lesions are characteristic findings of Behçet's disease (BD). A variety of cytokines, including interleukin 8 (IL-8), have been shown to activate PMNs. To investigate the role of IL-8 in the development of BD lesions, IL-8 production in vivo and in vitro was examined in 25 BD patients. IL-8 levels measured by ELISA in the non stimulated culture supernatants of peripheral mononuclear cells (MNCs) were higher in patients with active BD than in those with inactive BD or normal controls. Without LPS stimulation, IL-8 mRNA expression in incubated MNCs detected by Northern blot analysis was higher in active BD patients than in controls. Polarization assay confirmed the accelerated activity of PMN isolated from patients with active BD. However, these PMNs did not respond to IL-8 as strongly as to FMLP (an exogenous stimulator); a possible reason is that the PMNs of these patients are constantly exposed to IL-8 in vivo. Immunohistochemically, MNCs, endothelial cells and fibroblasts in BD lesions were positively stained by anti-IL-8 antibody. These data indicate that the production of IL-8 may be accelerated in inactive BD and that IL-8 may play an important role in the pathogenesis of BD.

Adult↗
PubMed1994

Pathogenesis of mucocutaneous lesions in Behçet's disease.

Behçet's disease (BD) is characterized by recurrent oral aphthae, skin lesions, eye lesions, and genital ulceration. To determine the pathogenesis of BD, we performed histological and immunohistochemical studies of these mucocutaneous lesions, an assay of neutrophil activity, and HLA typing. Dense dermal or subcutaneous infiltrations of polymorphonuclear cells (PMN) without leukocytoclastic vasculitis were found in 28 of 57 lesions. Immunohistochemically, deposits of C3 on the vessels were found in 12 of 31 lesions. Deposits of immunoglobulin were not found except for one of IgM. C3 deposits and PMN infiltrations were significantly related (p < 0.05). PMN activity by polarization was enhanced; however, the results did not show a significant relationship with the PMN infiltrations or the C3 deposits. The incidence of HLA-B51 was significantly high in BD, but no significant relationship was found between HLA-B51 and the results of other examinations. These results suggest that the pathogenesis of BD lesions differs from that of collagen diseases and that C3 deposits on the vessels may play an important role in the development of mucocutaneous lesions where PMN have mainly infiltrated.

Adolescent↗
PubMed1994

Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in Behçet's disease.

Increases in the number and activity of peripheral polymorphonuclear neutrophils (PMNs) is often found in Behçet's disease (BD), indicating that PMN may play an important role in the pathogenesis of this disorder. It has recently been reported that G-CSF and GM-CSF, a family of hematopoietic growth factors, enhance PMN activity. To explore the role of these two CSFs in BD, we first examined the chemotactic response of PMNs to these CSFs by performing a polarization assay. PMN response to G-CSF in BD patients was lower than that in controls, while PMN response to GM-CSF was similar in patients and controls. However, PMNs from BD patients showed an enhanced chemotactic response to N-formyl-L-methionyl-leucyl-phenylalanine. Thus, it is speculated that the PMNs of the patients might have already been activated in vivo by G-CSF and thus could not respond further to this agent in vitro. We examined G-CSF and GM-CSF mRNA expressions in peripheral mononuclear cells stimulated with LPS, PMA, and Con A by Northern hybridization. G-CSF mRNA expression levels in BD patients were higher than in the controls, while GM-CSF mRNA expression levels were lower than in the controls. We also examined the serum levels of the two CSFs by ELISA and EIA. However, all levels of the two CSFs in both patients and controls were not detectable, except in the case of one BD patient in the active stage of the disease, who showed high levels of G-CSF, but not of GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Behcet Syndrome↗