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Biomedical subjects

S Morikawa

Publications and source records attributed to S Morikawa.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Recent clinical aspect of tuberculin reaction].

The tuberculin reaction is the best known and most widely studied form of delayed hypersensitivity and is a clinically acceptable measure of cell mediated immunity. The reaction is characterized by a delayed response to antigenic challenge which is mediated by Th1 cells. This sort of reaction has been thought to form part of the body defenses against a number of infections and infestations. Currently, however, evidence is more favour of a dissociation between allergy and resistance. On the other band it is also evidence that the ability to respond to antimicrobacterial therapy parallel the strength of cell-mediated immune reactivity. Tuberculin test still possess the value as the diagnostic and prognostic parameters for tuberculosis.

Humans↗
PubMed1997

Involvement of hepatocyte growth factor in formation of bronchoalveolar structures in embryonic rat lung in primary culture.

To clarify the role of hepatocyte growth factor (HGF) in embryonic lung development, organoids from fetal rat lung were cultured in collagen gels with or without HGF antisense oligonucleotides. Cyst-like structures formed within 24 h in organoids isolated from fetuses after 14 days' gestation, but this was abolished by the oligonucleotide addition, apparently by interference with the endogenous expression of HGF. Electron microscopy revealed two types of structure: an alveolar type characterized by osmiophilic lamellar bodies in the cytoplasm and lumen, and a bronchial type consisting of epithelial cells bearing microvilli on their apical surfaces. HGF mRNA was detectable from day 14 in fetal lung by RT-PCR. Our results suggest that HGF plays, coordinately with its expression, a crucial role in the morphogenesis of both alveolar and bronchial epithelia in the rat fetal lung.

Animals↗
PubMed1997

T2*-weighted magnetic resonance imaging of cerebrovascular reactivity in rat reversible focal cerebral ischemia.

Cerebrovascular carbon dioxide (CO2) reactivity is an important hemodynamic index in cerebrovascular disease. In the present study T2*-weighted magnetic resonance image (T2* WI) was evaluated as a non-invasive method to investigate changes in CO2 reactivity. Fourteen rats were subjected to permanent or, 30 and 90 min of temporary middle cerebral artery occlusion. A series of T2* WIs and diffusion-weighted magnetic resonance images (DWI) was performed hourly under normo- and hypercapnic conditions. Triphenyltetrazolium chloride (TTC) staining of brain sections was obtained at the end of experiment to evaluate ischemic damage. During ischemia, a 4-6% signal increase upon hypercapnia was observed on T2* WI in the non-ischemic hemisphere, while no such reactivity was seen in the putamen and cortex ipsilateral to the MCA occlusion. After reperfusion, CO2 reactivity recovered in the putamen and cortex in the 30 min ischemia group and in the cortex alone of the 90 min ischemia groups. The areas with irreversible CO2 reactivity dysfunction coincidentally revealed no recovery on DWI and lack of TTC staining. The results indicate that T2* WI can be used to monitor changes in CO2 reactivity after various ischemic insults that may indicate tissue viability.

Animals↗
PubMed1997

Relationship between gluconeogenesis and phosphoenergetics in rat liver assessed by in vivo 13C and 31P NMR spectroscopy.

The relationship between the phosphoenergetic state and gluconeogenesis in the liver after ischemic damage was investigated using living rats. The ATP level was determined with in vivo 31P nuclear magnetic resonance spectroscopy, and gluconeogenesis was evaluated with in vivo 31C NMR spectroscopy using L-[3-13C]alanine as a tracer. These two measurements were alternated repeatedly. The rats were divided into three groups: without ischemia (group A); with 10 min ischemia (group B); and with 30 min ischemia (group C). ATP was depleted to 20% of the preischemic state after 10 min ischemia and this level was maintained during 30 min ischemia. After reperfusion, the ATP level was partially restored, but the recovery was smaller in group C. Infusion of [3-13C]alanine was started immediately after the reperfusion. In vivo 13C NMR disclosed changes in the alanine C3, glutamine/glutamate C2 and C3, glucose C1-6, and glycogen C1 signals in the liver. After 60 min infusion of [3-13C]alanine, the ATP level correlated negatively with the signal intensity of alanine (r = -0.664, p = 0.008) and positively with those of glucose and glyogen (r = 0.586, p = 0.023, and r = 0.643, p = 0.011, respectively). These results suggest that the ATP level participates in gluconeogenesis and glycogenesis in the liver. Such multinuclear in vivo NMR observations might uncover new aspects of the metabolic function of the liver in the in vivo state.

Adenosine Triphosphate↗
PubMed1997

Timing of insults causing abnormal outcome in preterm infants 1989-1992.

OBJECTIVE: The purpose of this study was to clarify the influence of timing of brain insults causing abnormal outcome in preterm infants. METHODS: One hundred and thirty-one preterm infants were examined. The timing of brain insult was estimated from EEG or clinical findings. Development was assessed until a corrected age of 48 months. RESULTS: 39% and 4% of infants, respectively, born before and after the 28-week time point subsequently died (P < 0.05). Abnormal development was observed in 16% of the first group and 13% of the second (N.S.). None of those born before 28 weeks showed intrauterine injuries while nine of the infants which were born after this time showed intrauterine injuries (P < 0.05). Fetal distress was noted in all infants suffering neonatal death born after 28 weeks. CONCLUSION: Intrauterine brain insult was concluded to be the cause of neonatal death or abnormal development in many infants born after 28 weeks.

Brain Injuries↗
PubMed1997

Human amniotic fluid motogenic activity for fetal alveolar type II cells by way of hepatocyte growth factor.

OBJECTIVE: To find out if hepatocyte growth factor (HGF) in amniotic fluid (HGF-AF) has a direct effect on fetal lung development, we investigated the effects of AF as well as recombinant human HGF (rhHGF) on proliferation, migration, and morphogenesis of fetal alveolar type II cells in vitro. METHODS: Amniotic fluid samples were obtained from 37 women at various gestational ages. Mitogenic, motogenic, and morphogenic activity was investigated by 5-bromo-2'-deoxyuridine incorporation, Boyden chamber assay, and culture in collagen-gels, respectively. RESULTS: The motility of AK-D cells was stimulated by AF from 14 to 31 weeks' gestation in proportion to the concentration of HGF-AF, and this effect was comparable to that observed with rhHGF. Furthermore, this activity was neutralized by anti-human HGF antibody. However, AF samples subsequent to 32 weeks had no motogenic influence despite the continued presence of immunoreactive HGF-AF. Neither increased DNA synthesis nor morphogenesis in response to AF was identified under the conditions used. CONCLUSION: The present study suggests that AF stimulates alveolar type II cell migration by way of HGF-AF in vitro.

Amniotic Fluid↗
PubMed1997

Acute 3-nitropropionic acid intoxication induces striatal astrocytic cell death and dysfunction of the blood-brain barrier: involvement of dopamine toxicity.

Mechanisms underlying the selective vulnerability of the lateral striatal area to the toxic effects of 3-nitropropionic acid (3-NPA) were investigated in rats. A single exposure to 3-NPA (20 mg/kg, s.c.) induced no deficits in behavior and histology, but subsequent injection produced motor symptoms, catalepsy, lip smacking, abnormal gait, paddling, rolling, opisthotonos, tremor, recombence, somnolence and so on, in 30% of the animals within a few hours. Diffusion-weighted magnetic resonance imaging of the brains revealed an area of high signal intensity in the bilateral striata. By this stage (within a few hours), striatal astrocytes had become swollen and disintegrated. Extravasation of immunoglobulin G was detected, indicating blood-brain barrier (BBB) dysfunction. Electron microscopy revealed edema and disorganization of structures inside the astrocytic end-feet around the branches of the lateral striatal artery. Neurons were less vulnerable than astrocytes to the 3-NPA injury. Treatment of the rats with D2 receptor agonist prior to exposure to 3-NPA attenuated the behavioral abnormalities and histological damage whereas pretreatment with D2 antagonist exacerbated these changes. The concentrations of extracellular dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC) were both increased in rats exposed to 3-NPA. In vitro imaging of astrocytes revealed a progressive increase in [Ca2+]i after superfusion with 3-NPA, and the 'ceiling' level was maintained even after extensive washing. DA superfusion also increased the astrocytic [Ca2+]i and this increase was reversible. Data indicate that 3-NPA-induced striatal damage was associated with astrocytic cell death and dysfunction of the BBB. Intracellular edema and extreme Ca2+ overload induced by the toxin were further aggravated by an increase in the level of DA activity. These factors acting either singly or in combination may trigger astrocyte destruction.

Animals↗
PubMed1997

Increased mitochondrial damage by lipid peroxidation in trophoblast cells of preeclamptic placentas.

Lipid peroxides and their related free radicals have been implicated in the pathogenesis of placental dysfunction in preeclampsia. Recent studies suggest that the placenta is a source of the increased lipid peroxides in the maternal circulation of women with preeclampsia. We examined intracellular localization of 4-hydroxy-2-nonenal (HNE: a major aldehydic product of lipid peroxidation)-modified proteins in human placentas by immunohistochemistry, and immunoblotting. The trophoblast layer of the chorionic villi showed intense immunoreactivity for HNE-modified proteins in 4 of 12 preeclamptic placentas, whereas no staining was observed in 12 normal placentas. Immunoblotting revealed that three immunoreactive proteins with apparent molecular mass of 110 kDa, 75 kDa, and 70 kDa were localized in the mitochondrial fraction. The present results indicate that the damage to mitochondrial proteins by lipid peroxidation by products and subsequent dysfunction of trophoblasts contribute to the pathophysiology of preeclampsia.

Aldehydes↗
PubMed1997

The effects of halothane and isoflurane on the phosphoenergetic state of the liver during hemorrhagic shock in rats: an in vivo 31P nuclear magnetic resonance spectroscopic study.

We studied the effects of halothane versus isoflurane on the phosphoenergetic state and intracellular pH (pHi) of the rat liver using in vivo 31P nuclear magnetic resonance (NMR) spectroscopy during and after hemorrhagic shock. Seventeen rats were anesthetized with 1 minimum alveolar anesthetic concentration of halothane or isoflurane. The mean arterial blood pressure was reduced to 40 mm Hg and maintained at this level for 45 min by withdrawing blood from the common carotid artery. The shed blood was then returned slowly. In vivo 31P NMR spectra were consecutively collected throughout the study. The phosphoenergetic state of the liver was evaluated from the changes in adenosine triphosphate (ATP) and inorganic phosphate (P(i)) levels. pHi was calculated from the chemical shifts of P(i) and alpha-ATP peaks. During hemorrhagic shock, beta-ATP decreased to 35% and 45%, and P(i) increased to 300% and 230% of their initial values in the halothane and isoflurane groups, respectively. Intracellular acidosis was more severe in the halothane group. The recoveries of beta-ATP and P(i) were better in the isoflurane group. Halothane showed a more detrimental effect than isoflurane on the hepatic phosphoenergetic level during and after hemorrhagic shock.

Acidosis↗
PubMed1997

Generation of monoclonal antibodies against a feline CD antigen (CD4) expressed by a recombinant baculovirus.

We attempted to establish a system to generate monoclonal antibodies (mAbs) recognizing CD antigens on lymphocytes of domestic animals using the expressed CD antigens by a baculovirus expression system. For this purpose, we selected feline CD4 (fCD4) antigen and expressed it in an insect cell line (Sf9 cells). To obtain mAbs, BALB/c mice were immunized with feline peripheral blood mononuclear cells (fPBMCs) or Sf9 cells expressing the fCD4 (Sf-fCD4 cells), and then hybridomas secreting antibodies were screened by indirect immunofluorescence assay against the opposite antigens of Sf-fCD4 cells or fPBMCs, respectively. Five mAbs recognizing the fCD4 were obtained in total. The system established here might be useful to obtain mAbs recognizing CD antigens of domestic animals.

Animals↗
PubMed1997

[Investigation of the usefulness of CYFRA 21-1 as a tumor marker in squamous cell carcinomas of the head and neck].

It has been demonstrated that CYFRA 21-1 (ELISA kit), which recognizes the soluble cytokeratin 19 fragment, is useful for assessing circulating tumor antigens in sera of patients with lung cancer. In this study, we compared the clinical significance of this new marker with the established squamous cell carcinoma antigen (SCC Ag), using sera from patients with head and neck malignant disease, healthy controls, and supernatants of established cell lines derived from squamous cell carcinomas and adenocarcinomas. The subjects were: Group A, 39 patients with malignant disease of the head and neck. Group B, 11 patients considered to be tumor-free after treatment. Group C, 67 patients with benign disease or healthy volunteers. Culture supernatants: 11 cell lines established from squamous cell carcinomas and adenocarcinomas. Serum levels of CYFRA 21-1 and SCC Ag of group A were significantly higher than those of group C. This finding suggests that CYFRA 21-1 is useful as a tumor marker as well as SCC Ag. CYFRA 21-1 and SCC Ag levels of patients in group A at the early and progressive stages of disease were comparable to the levels in group C. Both tumor markers are therefore useful for diagnosis of in the early stage of cancer. We attempted to set a cut-off level of CYFRA 21-1. The sensitivity of CYFRA 21-1 is higher than that of SCC Ag, especially in patients in the early stage of the disease. This finding indicates that the CYFRA 21-1 is preferable to SCC Ag as a tumor marker for the diagnosis of patients even in the early stages of malignant disease. The levels of CYFRA 21-1 in culture supernatants derived from tumor cell lines are higher than those of SCC Ag in all cell lines. The levels of CYFRA 21-1 are measurable, with levels varying with the cell line. There appears to be no correlation between the level of CYFRA 21-1 and the character of the cell lines, but this issue remains to be further investigated.

Adult↗
PubMed1997

Assembly of JC virus-like particles in COS7 cells.

JC virus lacks an appropriate cell line to support virus replication. The establishment of a JC pseudovirus assembly system could play an alternative role for a virus culture system. COS7 cells and a transfer vector, pcDL-SR alpha 296, were used to express JC viral structural genes. VP231-SR alpha, which encodes VP2/VP3 and VP1, but lacks 137 bp of the 5'-terminus of agnogene, showed both efficient nuclear migration and quantitative expression of the major capsid protein VP1. JC pseudovirus assembly was observed in the nucleus of VP231-SR alpha transfected cells. Evidence of JC pseudovirus assembly is presented. The further utilization of this system, which includes a study for the viral morphogenesis, serological diagnosis, as well as the potential application for gene transfer vector, is discussed.

Animals↗
PubMed1997

Synergistic antitumor effects of human interferon-beta and interferon-gamma on human gastric adenocarcinoma cells.

The combined effects of different classes of interferon (IFN) on human gastric adenocarcinoma cell line HPE-GAC-2 (GAC-2) were investigated in vitro. Synergistic effects of IFN-beta and -gamma, causing cell death, were observed in a dose-dependent manner. IFN-gamma modulated the sensitivity of GAC-2 cells to the cytocidal effect of IFN-gamma. The modulatory effect was independent of the cytostatic or cytocidal activity of IFN-beta since brief contact with IFN-beta did not influence the growth kinetics of the cells and was effective in modulate the cellular sensitivity to IFN-gamma. A brief pretreatment of the cells with IFN-alpha or-beta resulted in a variable level of modulation, whereas coculture of the cells with IFN-beta or -alpha and IFN-gamma had a similar cytotoxic effect indicating a different level of activity induced by IFN-alpha and -beta with the common type I receptor. These results suggest that IFN-beta-induced modulation was receptor-mediated. Phase contrast microscopy showed evidence of apoptotic cell death induced by one or more IFN agents. The morphological changes included chromatin condensation and nuclear fragmentation which were apparent at as early as 6 hr of culture with a high concentration of IFN(s). Our results indicate that IFN-beta and IFN-alpha enhance the in vitro apoptotic effects of IFN-gamma against GAC-2 tumor cells.

Adenocarcinoma↗
PubMed1996

Immunomodulatory effect of recombinant human superoxide dismutase (SOD) on human B lymphocyte function in vitro.

Recent investigations demonstrate that B lymphocytes possess an oxygen-generating system which is similar to the phagocytic NADPH-oxidase system. Reduction of nitroblue tetrazolium by stimulated tonsillar B cells is inhibited by superoxide dismutase (SOD). However, the biological significance of the superoxide-generating property of B cells remains to be explored. In this study, we examined the immunomodulatory effect of a recombinant human SOD (rh-SOD) on the activation of human B lymphocytes in vitro. A supplement of rh-SOD in the B cell culture increased the proliferation of unstimulated B cells in the presence of SAC, but not of SAC-preactivated B cells in the presence of cytokines such as IL-2 or IL-4. In addition, rh-SOD enhanced the immunoglobulin generation by B cells at the terminal stage of differentiation. Inactivation of the enzymatic activity of SOD by treatment with anti-SOD antibody abrogated the enhancing effects. These data suggest that the superoxide-generating system in B cells may be involved in the cellular activation process.

Antibodies↗
PubMed1996

Glucose and energy metabolism in rat liver after ischemic damage assessed by 13 C and 31 P NMR spectroscopy.

Glucose and energy metabolism in rat liver after ischemic damage was investigated by in vivo 31P NMR spectroscopy, 1H-detected 13C NMR spectroscopy, and in vitro 13C NMR spectroscopy using [1-13C]glucose as a tracer. Arterial ketone body ratio (AKBR; acetoacetate/beta-hydroxybutylate) and oxygen consumption of isolated mitochondria were also examined to evaluate hepatic function. The rats were divided into three groups: (A) without ischemia, (B) 10-min ischemia, and (C) 30-min ischemia. ATP was almost depleted at 10 min of ischemia and recovered after reperfusion, but the recovery was not complete. The recovery after 30-min ischemia was smaller than that after 10-min ischemia. [13C]Glucose was infused immediately after the reperfusion, and in vivo 1H-detected 13C NMR demonstrated sequential glucose incorporation into the liver. However, the incorporation depended on the blood sugar levels and did not reflect hepatic function. In vitro 13C NMR disclosed the glycogen C-1 signal in the nonischemic group and alanine C-3 and lactate C-3 signals in the ischemic groups. The intensity of glycogen was correlated positively (r = 0.648, P = 0.002) and those of alanine and lactate were correlated negatively (r = -0.831, P < 0.005 and r = -0.710, P = 0.005, respectively) to the ATP levels as measured by in vivo 31P NMR. These results suggested that ATP level participates in glycogenesis and gluconeogenesis in the liver. The AKBR and oxygen consumption of isolated mitochondria were the highest in the 10-min ischemia group, which might reflect mitochondrial compensatory response to the decreased ATP level.

Animals↗
PubMed1996

Laminoplasty with foraminotomy for coexisting cervical myelopathy and unilateral radiculopathy: a preliminary report.

STUDY DESIGN: An assessment was made of the efficacy of a combined laminoplasty and foraminotomy operation for patients with coexisting myelopathy and unilateral radiculopathy. The procedure was done in 17 patients. OBJECTIVES: The patients were followed with lateral flexion and extension radiographs, computed tomography scans, and an assessment system specially designed to qualitatively evaluate the patients' neurologic status. Follow-up period averaged 4 years (range, 2.1-9.3 years). SUMMARY OF BACKGROUND DATA: Excellent-to-good results were obtained for 76% (13 of 17) of the patients without any significant functional compromise based on the radiographs. Sixteen nerve roots were decompressed with a less than 25% foraminotomy, whereas eight were decompressed by a 25%-50% foraminotomy without serious neurologic damage, except for one patient. The neurologic results appeared unrelated to the extent of foraminotomy. METHODS: A refined procedure for combined laminoplasty and foraminotomy was reviewed retrospectively in terms of neurologic outcome and radiographic data. RESULTS: The present series is small, and results are not comparable directly with other methods. The procedure appears effective for myelopathy and radiculopathy. This procedure is applicable to patients with myelopathy and coexisting nerve root impingement anterolaterally or in the neural foramen. CONCLUSION: The combined laminoplasty and foraminotomy operation may provide greater neurologic improvement in patients with coexisting myelopathy and unilateral radiculopathy, while maintaining cervical spine stability after surgery.

Adult↗
PubMed1996

Acute focal cerebral ischemia in rats studied by diffusion-weighted magnetic resonance imaging--an experimental study.

BACKGROUND: Temporary occlusion of the cerebral artery is occasionally repeated during neurosurgical operations, but the safety of such a procedure remains to be studied further. METHOD: We studied early changes and reversibility of focal cerebral ischemia and the cumulative effects of repeated ischemic insults in rats using magnetic resonance imaging (MRI). RESULTS: Diffusion-weighted magnetic resonance images (DWI) and determination of signal intensity ratio (SIR) proved to be a valuable measure of studying early changes and reversibility of transient focal cerebral ischemia and cumulative adverse effects of repeated ischemic insults. DWIs showed marked intensity changes shortly after focal cerebral ischemia, while T2-weighted images failed to show hyperintensities until 2.5 hours after the onset of permanent ischemia. The critical period of ischemia in this model was 60 minutes. However, 20 minutes ischemia, when repeated twice with 60 minutes reperfusion in between, showed irreversible damage. CONCLUSION: Repeated insults of focal regional cerebral ischemia may cause irreversible tissue damage even if each ischemic period is less than the critical one.

Animals↗