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Biomedical subjects

K Higashi

Publications and source records attributed to K Higashi.

At least 127 records · Page 7Linked to original sources
PubMed1996

Bone scintigraphy in detection of bone invasion by oral carcinoma.

Detecting osseous involvement is clinically important in the management of oral carcinoma. Thirty-one patients with osseous involvement due to oral carcinoma who underwent panoramic radiography and bone scintigraphy were evaluated retrospectively. Bone scintigraphy confirmed osseous involvement in all 31 (100%) of these patients. In 27 (87%) of 31 patients with osseous involvement, both the panoramic radiogram and bone scintigram were positive. In the remaining four patients (13%), bone scintigram was positive for mandibular or maxillary invasion, while panoramic radiogram was negative. There were no instances of an abnormal radiogram with a normal bone scintigram. These findings strongly suggest that bone scintigraphy is more sensitive than panoramic radiography in detecting osseous involvement of the mandible and maxilla due to oral carcinoma. Furthermore, bone scintigraphy was a critical pre-surgical in determining the extent of the osseous involvement.

Carcinoma, Squamous Cell↗
PubMed1996

Conductive deafness in aglossia.

Aglossia is a rare anomaly often accompanied with several congenital defects including varying degrees of limb deficiency, micrognathia and oral synechiae. We report on a girl with aglossia and persistent anterior buccopharyngeal membrane. Other anomalies observed on the patient were oesophageal atresia, hypoplastic epiglottis, ptosis of the left eyelid, and conductive deafness which is probably an additional symptom of this syndrome group.

Abnormalities, Multiple↗
PubMed1996

Inhibition of nucleolar function and morphological change by adriamycin associated with heat shock protein 70 accumulation.

Adriamycin (ADR) has been considered to target mainly DNA metabolism in the nucleus. Recently, we observed the nuclear translocation of heat shock protein 70 (HSP70) after ADR treatment. We examined which intranuclear changes might be related to this alteration of HSP70 localization. We found considerable alternations in the nucleolar morphology and function in ADR-treated tumor cells, i.e., a ring-shaped segregation of granular components of almost all nucleoli and a dramatic reduction of nucleolar 45S ribosomal precursor RNA biosynthesis in HeLa cells exposed to 100 microM ADR for 2 h. Concomitantly with these changes, HSP70 was concentrated into the nucleoli, as in the case of heat shock treatment. These results indicate a novel anticancer effect of ADR via the suppression of cellular protein biosynthesis, in addition to its effect on DNA.

Antibiotics, Antineoplastic↗
PubMed1996

Efficacy and side effects of intermittent recombinant interferon-alpha 2a in chronic aggressive hepatitis C: with or without initial daily administration.

To investigate the therapeutic effect and incidence of side effects of recombinant interferon-alpha 2a (IFN-alpha) in chronic aggressive hepatitis C under stratification by administration mode, a study was conducted by assigning patients to either group A (daily consecutive administration of 9 million units (MU) IFN-alpha for 2 weeks and, thereafter, 3 MU intermittently 3 times weekly for 22 weeks) or group B (exclusively intermittent administration; 9 MU IFN-alpha twice weekly or 6 MU IFN-alpha thrice weekly for 24 weeks). The 28 patients in group A received IFN-alpha for 24 weeks up to a total dose of 324 MU and the 53 patients in group B received the same for 24 weeks up to a total dose of 432 MU. When recovery was defined as the absence of hepatitis C virus (HCV)-RNA 6 months after the completion of treatment, the rate of recovery for group A was 32.1% and that for group B was 37.7%, the latter being higher but without significance. Side effects in groups A and B consisted of leucopenia occupying 14.3 and 7.5%, respectively, and thrombocytopenia occupying 42.9 and 11.3%, respectively; group B exhibited lower values for both side effects. No difference was detected between these groups in other side effects, including pyrexia, generalized malaise, arthralgia or psilosis. Intermittent administration from the outset permitted shortened duration of hospitalization and earlier rehabilitation. Intermittent administration of INF-alpha is required when treating patients with chronic hepatitis C showing lower leucocyte or platelet counts.

Chronic Disease↗
PubMed1996

Cervical osteoplastic laminotomy using autogenous bone.

Cervical foraminotomies are performed from the fifth to the eighth cervical nerve roots on both sides. On the side with more marked radiculopathies the laminae are osteotomized to the full extent, but not so completely on the other side. The mass of laminae from C-3 to C-7 is lifted up using the incompletely severed side of the laminae as the fulcrum. The removed spinous processes of C-6 and C-7 are adjusted and fixed between the articular joints and the lifted laminae from C-4 to C-6. This procedure prevents extradural scar formation, there are no complications caused by foreign bodies, postoperative neuroimaging is possible because no metallic artifact is formed, and extensive decompression is achieved for the cervical cord and nerve roots.

Adult↗
PubMed1996

Hearing impairment in Engelmann disease.

There are several hyperostosis diseases of the skull that are accompanied by hearing impairment. In this article a case of Engelmann disease is presented. Currently > 130 cases of Engelmann disease are reported in literature. About 18% of these cases reported hearing impairment, but it is possible that this figure may be higher, because many of the authors concentrated on other aspects of the disease and made no reference to hearing loss in their reports. The etiology of deafness is the narrowing of the internal auditory canals cause by bony encroachment on nerves and vessels. This lends to progressive perceptive hearing loss and narrowing of the tympanic cavities. The result is fixation or adhesion of ossicle to tympanic walls, and narrowing of the bony part of auditory tubes, which causes serous otitis media.

Adolescent↗
PubMed1996

Decreased DNA topoisomerase II alpha expression and cold-sensitive growth in a mouse mammary cancer cell line resistant to etoposide and doxorubicin.

A mouse mammary carcinoma FM3A cell line resistant to the DNA topoisomerase (topo) II-targeting agent, etoposide (VP-16), FM3A/VP-2B, had a markedly reduced growth rate at a low temperature (33 degrees C). The cells had the following properties: (a) FM3A/VP-2B, which had 24-fold higher resistance to VP-16 than its parental line, FM3A, was cross-resistant to doxorubicin, but not to a camptothecin derivative, CPT-11. (b) Cold-resistant revertants from FM3A/VP-2B, R-6 and R-11, remained 8- to 9-fold more resistant to VP-16 and 2- to 3-fold more resistant to doxorubicin. (c) FM3A/VP-2B had one-fourth the level of topo II activity and one-third of the topo II alpha content and mRNA of FM3A. R-6 and R-11, however, had levels similar to FM3A. (d) FM3A/VP-2B and FM3A had a 3-base deletion at position 4170 on one allele on the topo II alpha cDNA, but expression of the wild-type and the deletion allele was not appreciably changed in both cell lines. Decreased topo II alpha expression might have led to the acquisition of drug resistance to etoposide in FM3A/VP-2B, and appeared to be linked with the cold-sensitive growth. We also present a corrected mouse topo II alpha cDNA sequence.

Amino Acid Sequence↗
PubMed1996

[Hemolytic anemia in association with viral hepatitis].

During 1968-1994, 48 patients who has a hemolytic anemia complicated with viral hepatitis were reported in Japan, 25 with acute hepatitis A, 10 with acute hepatitis B, 10 with some other viral hepatitis, and 3 with chronic hepatitis. It is suggested that there are four mechanisms that occur hemolysis in the patients with viral hepatitis. (1) In the individual who has predisposition to hemolytic anemia, viral infection accelerates the red cell destruction and hemolysis become obvious. (2) Directly, virus itself injures to the red cell membrane. (3) The serious liver failure and hypersplenism induce the hemolysis. (4) Autoimmune hemolytic anemia because of immunological abnormality caused by viral infection. In this review, the clinical characteristics of hemolytic anemia in association with viral hepatitis were reviewed.

Adolescent↗
PubMed1996

Linear immunoglobulin A (IgA) bullous dermatosis of childhood: identification of the target antigens and study of the cellular sources.

A 4-year-old girl developed numerous tense blisters on the body. The blisters healed without scarring. Histopathological and immunofluorescence studies showed findings consistent with linear immunoglobulin A (IgA) bullous dermatosis of childhood. Immunoelectron microscopy revealed deposition of IgA in the lamina lucida of the basement membrane zone of the dermal-epidermal junction. Circulating IgA autoantibody was positive at the titre of 1 : 128 and recognized the antigens located on epidermal sites of 1 mol/l NaCl-split skin. Immunofluorescence staining of cultured normal human fibroblasts and cultured DJM-1 cells (derived from human squamous cell carcinoma of skin) with the patient's sera demonstrated that both of these cells synthesize the antigens in vitro, although fibroblasts produce the antigens more abundantly. When DJM-1 cells were injected intracutaneously into nude mice, the antigens recognized by the sera were present mainly around the tumour cell islands in a linear pattern, while the dermal-epidermal junction of mouse skin was negative, suggesting that epidermal cells may contribute directly to synthesis and deposition of the antigens at the basement membrane. By immunoprecipitation using cultured normal human fibroblasts, the patient's sera could precipitate at least two specific molecules at 100-kDa and 145-kDa molecular weight.

Animals↗
PubMed1996

Interaction of protein phosphatases and ethanol on phospholipase C-mediated intracellular signal transduction processes in rat hepatocytes: role of protein kinase A.

Phospholipase C (PLC)-mediated signal transduction processes in rat hepatocytes are subject to modulation by protein phosphatases (PPases) and protein kinases, including protein kinase A (PKA) and protein kinase C. Ethanol (EtOH) stimulates PLC activity in liver cells in the absence of hormones, and EtOH pretreatment inhibits the subsequent stimulation of PLC by hormonal stimuli. There is evidence that protein kinase activities are involved in these actions of EtOH. We investigated the effects of okadaic acid (OKA), a PPase inhibitor, and 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate (cpt-cAMP), a cell permeant cAMP analog that activates PKA, on EtOH-induced PLC activation. In addition, we studied the combined effects of cpt-cAMP and EtOH/OKA on vasopressin-induced PLC activation. PLC activation (cytosolic Ca2+ mobilization and inositol trisphosphate accumulation) induced by EtOH and vasopressin was inhibited by treatment with OKA, and was potentiated by cpt-cAMP. OKA treatment prevented the effect of cpt-cAMP. Pretreatment with EtOH caused inhibition of vasopressin-induced PLC activation. EtOH also decreased the enhancing effect of cpt-cAMP on the responses to vasopressin. The susceptibility to enhancement by cpt-cAMP plotted as a function of the initial rate of vasopressin-induced Ca2+ mobilization in EtOH-treated cells was similar to the pattern observed in OKA-treated cells. These data suggest that interactions of OKA and PKA on EtOH-induced PLC activation occurred at the level of G-protein, and indicate that EtOH may act as an inhibitory agent of PPase.

Animals↗
PubMed1996

Effect of glutathione on inositol 1,4,5-triphosphate-induced Ca2+ release in permeabilized hepatocytes from control and chronic ethanol-fed rats.

The effect of oxidized and reduced glutathione on inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ release from endoplasmic reticular Ca2+ stores was studied in digitonin-permeabilized hepatocytes from chronically ethanol-fed rats and pair-fed control animals. The fractional Ca2+ release induced by a subsaturating concentration of InsP3 was significantly enhanced in cells from ethanol-fed rats in the absence of a change in maximal InsP3-releasable Ca2+ pool size, and this difference was not affected by preincubation with reduced glutathione. Incubation with oxidized glutathione (1 mM) increased the efficacy of Ca2+ release by subsaturating concentrations of InsP3 in both control preparations and in cells from ethanol-fed rats. The shift in the InsP3 dose-response curve was not significantly different between the two preparations. These findings suggest that the enhanced efficacy of InsP3-induced Ca2+ release in hepatocytes from ethanol-fed rats is not caused by the oxidation of protein-bound thiol groups on the InsP3 receptor.

Alcoholism↗
PubMed1996

Inhibitory effect of ethanol on hepatocyte growth factor-induced DNA synthesis and Ca2+ mobilization in rat hepatocytes.

Hepatocyte growth factor (HGF) is the most potent mitogen identified for hepatocytes and is thought to be an important growth factor in the regulation of liver regeneration. Its effects are mediated through a tyrosine kinase receptor, the product of c-met proto-oncogene. One of the downstream signaling processes activated by HGF is phospholipase C-gamma. HGF stimulation of liver cells causes formation of inositol 1,4,5-triphosphate, which releases Ca2+ from intracellular Ca2+ ([Ca2+]i) stores, and causes elevation of cytosolic Ca2+ levels. It is known that liver regeneration is inhibited by both acute and chronic ethanol (EtOH) treatment. We investigated the effect of EtOH on HGF-induced DNA synthesis and mobilization of [Ca2+]i in rat hepatocytes in primary culture. DNA synthesis was monitored by [3H]thymidine incorporation in primary cultures of hepatocytes 42 hr after stimulation with HGF. HGF concentration required for maximum DNA synthesis was 0.3 to 1 ng/ml, and DNA synthesis was inhibited by 100 mM EtOH at HGF concentrations in the range of 0.1 to 5 ng/ml. This inhibition was strongest (45 to 47% inhibition) at a low concentration of HGF (0.1 to 0.3 ng/ml) and decreased at an HGF concentration > 1 ng/ml. HGF-induced changes in [Ca2+]i were measured in single fura 2-loaded hepatocytes by fluorescence imaging techniques. The Ca2+ response induced by HGF (0.3 to 5 ng/ml) was inhibited by EtOH, with an EC50 of approximately 50 mM. Analysis of Ca2+ response patterns in individual cells indicated that EtOH suppressed the number of responsive cells and made Ca2+ responses more transient, but did not affect peak [Ca2+]i elevation; thus suggesting an inhibition at the level of phospholipase C-gamma-activation. These data indicate that inhibition by EtOH of the response of liver cells to HGF may contribute to the inhibitory effect of EtOH on liver regeneration.

Animals↗
PubMed1995

Possible correlation between DNA damage induced by hydrogen peroxide and translocation of heat shock 70 protein into the nucleus.

Oxygen radicals have been implicated as the causative agent in deleterious processes such as gene mutation, cellular transformation and cell death. Cellular response to DNA damage induced by hydrogen peroxide was examined in human amniotic cultured cells (WISH). The content of 8-hydroxydeoxyguanosine in nuclear DNA increased during the early period of exposure to hydrogen peroxide, that is, it peaked at 1 h in the cells treated with 1 mM hydrogen peroxide and then declined, but not to the control levels within 4 h. Interestingly, immunofluorescence staining of treated cells revealed that cytoplasmic hsp70 protein translocated transiently into the nucleus, which was most remarkable around 30 min after the addition of 1 mM hydrogen peroxide into the culture medium. On the other hand, the induction of hsp70 gene mRNA was not significant during the early period of treatment by 0.5 mM hydrogen peroxide and was occurred after 5 h. DNA damage induced by Adriamycin further supported the possible correlation between hydroxyl radical-mediated cleavage of DNA and nuclear translocation of hsp70 protein. These results suggest that preexisting hsp70 protein translocated into the nucleus to either protect chromatin DNA from further damage or to facilitate the repair of DNA damage in some unknown ways.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Induction of heat shock protein 70 and nucleolin and their intracellular distribution during early stage of liver regeneration.

Our previous work demonstrated a simultaneous induction of Hsp70 and nucleolin mRNA during the prereplicative stage of hepatocytes after partial hepatectomy [Ohmori, H. et al. (1990) Exp. Cell Res. 189, 227-232]. In the present study, changes of intracellular localization of these proteins were examined. Nucleolin, which mainly localized in the nucleus, increased with time and accumulated in the nucleolus around 12-18 h after partial hepatectomy. Hsp70 protein also increased slightly around 6-12 h after the operation. In accordance with this increase, immunohistochemical staining revealed that almost all nuclei of hepatocytes became Hsp70-positive, although Hsp70 was seen to be dispersed throughout the nucleoplasm and nucleolus at all times examined. Next, we isolated a cDNA clone of ribosomal protein (S-17) and examined its behavior. Induction of S-17 mRNA was observed to be essentially similar to that of nucleolin mRNA in regenerating rat liver, although inductions of histone H2A and H4 occurred at a later time, that is, in parallel with DNA synthesis. Furthermore, we observed a simultaneous induction of Hsp70 and nucleolin mRNA by serum-stimulation after serum-depletion in HeLa and IAR-20 (rat) culture cells. These results suggest that the induction of Hsp70, in addition to nucleolin, was not fortuitous but may be involved in the early events of liver regeneration.

Animals↗
PubMed1995

Alterations of expression of the cytoskeleton after immortalization of human fibroblasts.

Human diploid fibroblasts (HDF) have a limited in vitro lifespan of population doubling level (PDL) 50-70. The molecular mechanism underlying cellular senescence and immortalization is not thoroughly understood. It has been reported that the cytoskeleton has diverse functions and may have a role in growth regulation through association with other cellular components. To shed light on the relationship between functions of the cytoskeleton and senescence or immortalization, we investigated the alterations in gene expression after immortalization and measured the amounts of mRNAs for talin, vinculin, alpha-actinin, tropomyosin 1 (TM1), vimentin, lamin A and C, and alpha-tubulin by slot blot and Northern blot analyses. We found that the mRNAs for vinculin and vimentin were reduced and the mRNA for lamin A was increased in immortalized cells. We also studied the cytoskeletal protein levels and their intracellular distributions by Western blot analysis and immunostaining. Most of the proteins studied behaved in a way similar to the mRNAs through senescence and immortalization. Vinculin, tropomyosins and vimentin showed their altered distributions in immortalized cells.

Cell Line↗
PubMed1995

Relationship between the anchor structure of the galactosyl ligand for liposome modification and accumulation in the liver.

Liposomes which have been modified with (8-hexadecanoylamido-3,6-dioxaoctyl)-beta-D-galactose (Gal-t-pa), a straight chain palmitoyl derivative, and are composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (CH), and dicetyl phosphate (DCP) at a ratio of 10:10:1, showed the same accumulation in the liver as the control liposome. Also, liposomes which have been modified with [8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl]-beta-D-gal actoside (Gal-t-psa) showed remarkable accumulation in the liver. The accumulation of liposomes modified with galactose derivatives in the rat liver differed markedly according to the anchor structure. To clarify the cause of this finding, we produced [3H]inulin entrapped [14C]Gal-t-pa modified double label liposomes and evaluated changes in their rat plasma concentration, distribution in the organs, and the in vitro interaction with rat plasma. [14C]Gal-t-pa on the liposome surface bound to serum albumin and was released, resulting in no accumulation in the liver. In addition, sialic acid palmitoyl derivatives and glucuronic acid palmitoyl derivatives behaved similarly. As with the galactose derivatives, they also bound to serum albumin, being released from liposomes. These results suggest that adequate attention should be paid to the anchor structure of the ligand, in order to incorporate a recognition element into liposomes for transport to cells.

Animals↗