Biomedical subjects

M Mizuno

Publications and source records attributed to M Mizuno.

At least 289 records · Page 16Linked to original sources

PubMed1994

The effect of B-HT 920, a dopamine D2 agonist, on bar-press feeding in the monkey.

Although the dopamine (DA) system has been shown to regulate food intake, the function of the DA receptor subtypes on behavior still remains to be elucidated. In the present study, we examined the effect of B-HT 920, a selective agonist of DA D2 receptors that preferentially affect presynaptic autoreceptors, on both food consumption and execution of a high fixed-ratio bar-press task for food reward in monkeys. Two kinds of bar-press task were used: 1) a cue-triggered bar-press task during the first 40 trials, and 2) a self-paced bar-press task in which the monkeys freely performed bar-press trials until they were satiated. A SC injection of B-HT 920 (25 micrograms/kg) increased food consumption in the home cage. The same facilitatory effect on food consumption was also observed in the operant task condition. During the cue-triggered bar-press task, however, both the latency of the bar-press responses to a cue light and the time required to complete the bar-press trials were prolonged after the injection of B-HT 920. The results suggest that the activation of D2 autoreceptors suppresses the operant food acquisition behavior and increases food consumption through an inhibition of the satiety mechanism rather than an activation of any hunger-related drive.

Animals↗

PubMed1994

Intracellular Na+ and K+ shifts induced by contractile activities of rat skeletal muscles.

The effects of direct and indirect electrical stimulation on intracellular potassium and sodium contents ([K]i and [Na]i, respectively) in rat soleus muscle (SOL) and extensor digitorum longus muscle (EDL) were investigated under in vivo conditions. The changes of [K]i and [Na]i contents in both muscles which were stimulated indirectly reached respective values at 30 min or 1 hr after the beginning of stimulation, whereas those of EDL stimulated with 60 Hz changed gradually through 2 hr stimulation. The shifts of [K]i and [Na]i in EDL occurred during the twitch contraction at considerably lower frequency stimulation (0.5-10 Hz), whereas those in SOL were observed during the tetanus contraction at high frequency stimulation (10-40 Hz). The difference of change in cationic shifts between EDL and SOL under low frequency stimulation was reduced by ouabain treatment, though the difference was still significant. When the muscles were indirectly stimulated 6000 times at 1, 5, 10 and 20 Hz, the cationic shifts in EDL were greater than those in SOL, extending over all frequencies. It was concluded that such a difference in ionic shift between contracting EDL and SOL may be primarily due to the difference in unidirectional ionic fluxes per stimulation and, secondly, to the difference in Na(+)-K+ pump activity.

Animals↗

PubMed1994

Congenital abnormal eye movement without gaze nystagmus.

Ten cases with congenital abnormal eye movements were reported. Eye movement abnormalities were confined to horizontal pursuit, OKN, and visual suppression. Horizontal saccade and VOR, and vertical eye movements were normal in most cases. Gaze nystagmus was not observed in any case. No serious lesion in the CNS concerning eye movements was detected. Although the cause of abnormal eye movements was not clear, congenital origin was postulated. Similar cases reported in the literature were discussed. These cases may be called "congenital nystagmus without gaze nystagmus."

Audiometry↗

PubMed1994

Pseudopregnancy-dependent accumulation of cholesterol sulfate due to up-regulation of cholesterol sulfotransferase and concurrent down-regulation of cholesterol sulfate sulfatase in the uterine endometria of rabbits.

The uterine endometria of rabbits induced into pseudopregnancy by intramuscular injection of 17 beta-estradiol, followed by intravenous injection of human chorionic gonadotropin, expressed cholesterol sulfate at a significantly high concentration. The highest concentration of cholesterol sulfate was observed 4 days after the injection of gonadotropin for formation of the corpus luteum, being 10 times higher than that in nonpregnant endometria, and 15.2% of the total cholesterol in the endometrium was converted to the sulfated form, whose percentage in nonpregnant endometrium was 3.2%. However, no significant change in the concentration of gangliosides was observed during the period of pseudopregnancy. In the pseudopregnant endometria, the activity of cholesterol sulfotransferase, a cytosolic thiol enzyme, was increased thirtyfold over that in the nonpregnant endometria, whereas cholesterol sulfate sulfatase, a microsomal enzyme, exhibited approximately one-tenth of the activity in nonpregnant endometria. Arylsulfatase C, but not arylsulfatases A and B, exhibited the same change in activity as cholesterol sulfate sulfatase. Thus, the striking increase in cholesterol sulfate after induction of pseudopregnancy was found to be due to the activation of cholesterol sulfotransferase and the simultaneous inhibition of cholesterol sulfate sulfatase.

Animals↗

PubMed1994

Transfection-induced tumor necrosis factor-alpha increases the susceptibility of human glioma cells to lysis by lymphokine-activated killer cells: continuous expression of intercellular adhesion molecule-1 on the glioma cells.

To develop more effective adoptive immunotherapy, we transfected the human tumor necrosis factor-alpha (TNF-alpha) gene into human glioma cells (U251-SP), which were used as target cells. TNF-alpha is known to increase both the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of glioma cells and the susceptibility of glioma cells to lymphokine-activated killer (LAK) cell cytolysis. We compared the expression of ICAM-1 induced by TNF-alpha generated by the TNF-alpha gene-transfected cells with that induced by exogenously added TNF-alpha. When the TNF-alpha gene was transfected into U251-SP cells, the expression of ICAM-1 was detected on the cell surface from 3 days after the transfection and continued until at least 9 days. In contrast, it was expressed only transiently in the case of exogenously added TNF-alpha. Also, the cytolytic activity of LAK cells induced by transfection-induced TNF-alpha was significantly stronger than that induced by exogenously added TNF-alpha. The increased susceptibility was quenched by anti-ICAM-1 monoclonal antibody. These data indicated that continuous expression of ICAM-1 induced by TNF-alpha gene transfection of glioma cells resulted in higher cytolytic activity of LAK cells.

Antibodies, Monoclonal↗

PubMed1994

Functions of macrophages in human decidual tissue in early pregnancy.

PROBLEM: Roles of decidual macrophages (DMs) in the maintenance of early pregnancy was determined by comparing three of their functions, antigen presentation, immunoregulation, and lymphokine production, with those of peripheral monocytes (PMos) isolated from the same subjects. METHOD: The antigen-presenting capacity of DMs was examined by the one-way mixed lymphocyte reaction (MLR) in which accessory cell-depleted mononuclear cells isolated from pregnant women were used as responders. The effect of DMs on cellular immunity was investigated by inhibition tests of either one-way MLR or phytohemagglutinin stimulation. The production of interleukin-1 (IL-1) and prostaglandin E2 (PGE2) by DMs following lipopolysaccharide stimulation was examined. RESULTS: Addition of increasing concentrations of DMs to the culture resulted in a concentration-dependent proliferative response, as well as with PMos. In both assays, a stronger suppression was observed in the presence of DMs from normal pregnant women compared with PMos from the same subjects. DMs were found to secrete significantly lower levels of IL-1 alpha and IL-1 beta than PMos. No difference in PGE2 production was observed between DMs and PMos. CONCLUSIONS: These findings suggest that DMs present in human early decidual tissue have a capacity for allo-antigen presentation, a higher suppressive activity, and a lower capacity to produce IL-1 than their peripheral counterparts.

Abortion, Spontaneous↗

PubMed1994

Exercise-induced 31P-NMR metabolic response of human wrist flexor muscles during partial neuromuscular blockade.

The effects of a depolarizing (decamethonium, DECA) and a nondepolarizing neuromuscular blocking agent (vecuronium, VECU) on the phosphorus-31 nuclear magnetic resonance (31P-NMR)-detected metabolic response to muscle contractions were studied separately in six healthy untrained males. Subjects who showed splitting of the P(i) peak during graded rhythmic forearm exercise without the drugs were selected. It was found that both drugs abolished the P(i) peak splitting during exercise. Despite a similar reduction in phosphocreatine (PCr) during exercise with each drug, a smaller increase in P(i) was observed with DECA than with VECU (P < 0.05). End-exercise muscle pH was higher with DECA (6.93 +/- 0.07) than with VECU (6.79 +/- 0.11) (P < 0.05). The PCr and P(i) recovery was two- and threefold faster with DECA than with VECU, respectively (P < 0.05). On the basis of the concept that depolarizing and nondepolarizing agents have a preferential effect on fast- and slow-twitch muscle fibers, respectively, the present results support the hypothesis that the NMR-observed splitting of the P(i) peak reflects the metabolic differences between the two major fiber types of human skeletal muscle.

Adenosine Triphosphate↗

PubMed1994

31P-NMR spectroscopy, rsEMG, and histochemical fiber types of human wrist flexor muscles.

The metabolic response to graded rhythmic forearm exercise determined by phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy was evaluated with respect to recruitment pattern of muscles and to fiber type composition of the nondominant arm in 14 untrained subjects. Rectified smoothed surface electromyography (rsEMG) over finger and wrist flexor muscles increased similarly and progressively at 30, 45, and 60% of maximal exercise intensity. On the basis of the 31P-NMR response pattern during exercise, subjects were separated into three groups: H group (n = 4), with a single high-pH P(i) peak; M group (n = 7), with two P(i) peaks reflecting two pH components; and L group (n = 3), with a single low-pH P(i) peak. The H group demonstrated a faster recovery of P(i) and phosphocreatine than the L group (P < 0.05). The M group displayed both types of P(i) recovery and an intermediate resynthesis rate of phosphocreatine. The M group had an even distribution of slow- and fast-twitch fibers in the flexor carpi radialis muscle, whereas subjects in the H and L groups possessed a predominance of slow- and fast-twitch fibers, respectively. The results suggest that during rhythmic forearm exercise the interindividual NMR variation in energy metabolism is related closely to fiber type composition of the muscle.

Adult↗

PubMed1994

Postcaloric nystagmus by positional change. 1. Study in normal subjects.

We investigated the postcaloric nystagmus related to positional change. Twenty-two healthy subjects were examined (experiment 1). A caloric test was carried out in the supine position. Following the cessation of the primary phase, the subject was reoriented to the upright position. An additional 10 subjects were also examined with other positional changes (experiment 2): following the cessation of the primary phase, the subject was reoriented to the lateral positions, irrigated-ear-up and irrigated-ear-down positions. As a control study, 6 subjects were examined without positional change (experiment 3). In 37 (84%) ears, postcaloric nystagmus was observed in the upright position. Furthermore, in 12 of 20 (60%) ears in the irrigated-ear-up position and in 13 of 20 (65%) ears in the irrigated-ear-down position, the horizontal component of postcaloric nystagmus was observed. Without positional change, no postcaloric nystagmus was observed. These findings indicate that caloric nystagmus is modified by an adaptive process and that postcaloric nystagmus as it relates to positional change might be attributed mainly to the vestibular adaptation.

Adolescent↗

PubMed1994

A possible role for stable microtubules in intracellular transport from the endoplasmic reticulum to the Golgi apparatus.

The intracellular transport of secretory proteins involves at an early stage the formation of vesicles from transitional elements of the endoplasmic reticulum (ER) containing these proteins and the transfer of these vesicles to the cis-face of the Golgi apparatus. We propose that the latter transfer process does not occur by random diffusion, but is instead mediated by tracking along stable microtubules. To test this proposal, we have carried out double immunoelectron microscopic labeling experiments on frozen sections of HepG2 hepatoma cells secreting the protein human serum albumin (HSA). By a cycloheximide treatment protocol, the stage during which the transfer of newly synthesized HSA from the ER to the Golgi apparatus occurs in vivo was determined. Sections of the cells were then double immunolabeled using primary antibodies to HSA and to glu-tubulin, the latter specifically detecting stable microtubules. We observed a significantly high frequency of HSA-containing structures between the ER and the Golgi apparatus with which stable microtubules were closely associated. These results support the proposal that stable microtubules may play a critical role in directing the transfer process from the ER to the Golgi apparatus.

Biological Transport, Active↗

PubMed1994

Immunoelectron microscopic localization of MHC class 1 and 2 antigens on bile duct epithelial cells in patients with primary biliary cirrhosis.

We studied the distribution of class 1 and class 2 major histocompatibility complex (MHC) antigens on bile duct epithelial cells in liver from patients with primary biliary cirrhosis (PBC) by an immunohistochemical method using monoclonal antibodies to HLA-ABC products and HLA-D subregion products (HLA-DR, -DP, -DQ). By light microscopy, the expression of MHC class 1 antigens (HLA-ABC antigens) was enhanced in PBC compared with controls. While negligible staining of MHC class 2 antigens was detected on the bile duct in controls, de novo expression of MHC class 2 antigens, as well as the coexpression of HLA-DR, HLA-DQ, and HLA-DP antigens on the bile duct epithelial cells, was observed in PBC. By electron microscopy, HLA-ABC and HLA-DR antigens were present preferentially along the basolateral domain of the cell surface of the bile duct epithelial cells and on the membrane of the endoplasmic reticulum in the cytoplasm, suggesting that these MHC antigens are synthesized by the bile duct epithelial cells in PBC. The distribution of these MHC antigens on the basolateral surface of the bile duct epithelial cells, where they are easily accessible to immunocytes, supports the idea that MHC-restricted cytotoxic T lymphocytes are involved in the bile duct injury in PBC.

Adult↗

PubMed1994

Distribution of complement regulatory proteins, decay-accelerating factor, CD59/homologous restriction factor 20 and membrane cofactor protein in human colorectal adenoma and cancer.

To clarify the events related to complement-mediated immune responses in human colorectal cancers, we immunohistochemically examined the distribution of decay-accelerating factor (DAF), CD59/homologous restriction factor 20 (HRF20), membrane cofactor protein (MCP) and terminal complement complex (TCC) in human colorectal adenomas and cancers, and then compared the findings with their distribution in normal colonic mucosa. In the normal mucosa, TCC was not present on epithelial cells. Whereas DAF and CD59/HRF20 were present only occasionally on the apical surfaces of normal epithelial cells, MCP was diffusely distributed on the basolateral surfaces of most epithelial cells of the colon. These findings suggest that MCP has a primary role in the regulation of complement activation on these cells. In adenoma cells, the expression of both DAF and CD59/HRF20 was enhanced. In cancer cells, the expression of CD59/HRF20 and MCP was diminished, whereas DAF expression was markedly enhanced. Since DAF was frequently stained in the lumen of the cancer glands, it was suggested that DAF was released into the colonic lumen in patients with colorectal cancer.

Adenoma↗

PubMed1994

Immunohistochemical analysis of epithelial cell proliferation in normal-appearing rectal mucosa of patients with colorectal adenoma and cancer using an in vitro labeling method with bromodeoxyuridine.

To identify diffuse mucosal changes which may precede the development of colorectal cancer and a possible indicator for detecting high-risk populations, we immunohistochemically studied cell-cycle events in crypts of normal-appearing rectal mucosa of patients with colorectal adenoma and cancer using an in vitro labeling method with bromodeoxyuridine (BrdU). Biopsy specimens of endoscopically normal-appearing rectal mucosa were obtained during colonoscopy from 20 patients with colorectal adenocarcinoma, 20 with adenoma, and 15 without apparent colorectal diseases. The specimens were incubated with BrdU in vitro, and labeled S-phase cells were identified immunohistochemically using a monoclonal antibody to BrdU. Modification of the BrdU-labeling pattern in the normal appearing rectal mucosa, such as the presence of BrdU-labeled cells at the mucosal surface or in the upper one-fifth of the crypt column, was observed in 15 of the 20 patients with adenocarcinoma, 17 of the 20 patients with adenoma and 6 of the 15 controls. This upward shift in the frequency of proliferating cells in the crypt was significantly higher in the patients with colorectal adenoma and cancer than in the controls, and may be used to identify subjects at high risk for colorectal cancer.

Adenoma↗

PubMed1994

Chronic hepatitis C complicated by Coombs-negative hemolytic anemia during interferon treatment.

Autoimmune hemolytic anemia is an autoimmune diseases which is reported to be caused by interferon treatment. A 33-year-old male with chronic hepatitis C developed Coombs-negative hemolytic anemia, probably due to administration of interferon-alpha 2b. This is, to our knowledge, the first report of chronic hepatitis C complicated by Coombs-negative hemolytic anemia during interferon treatment.

Acute Kidney Injury↗

PubMed1994

Serial transcranial Doppler flow velocity and cerebral blood flow measurements for evaluation of cerebral vasospasm after subarachnoid hemorrhage.

Serial transcranial Doppler (TCD) and cerebral blood flow (CBF) examinations were performed in 73 patients with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysm to evaluate cerebral vasospasm. Twenty-six (35.6%) of the 73 patients developed ischemic neurological symptoms associated with cerebral vasospasm, which were reversible in all except four patients (5.5%) who demonstrated low-density areas associated with vasospasm on computed tomographic scans. In general, the flow velocities in the middle cerebral arteries began to increase soon after onset of SAH, reaching the maximum between days 8 and 10, subsequently decreasing gradually. There was no significant difference in the highest value and the time course of flow velocities between symptomatic vasospasm and asymptomatic vasospasm patients. Patients with symptomatic vasospasm demonstrated two typical time courses of flow velocities: rapid increases in flow velocities that preceded the clinical manifestations of vasospasm (16 patients, 61.5%), and no rapid increases in flow velocities despite the presence of ischemic symptoms (10 patients, 38.5%). In the latter, angiograms demonstrated vasospasm in segments distal to those evaluated by TCD examination. These results showed that the degree of cerebral vasospasm cannot be assessed only by the absolute flow velocities. CBF was measured two to 10 (mean 4.7) times within 3 weeks of SAH using the 133Xe intravenous injection method. The CBF value remained stable even during the period of major risk of vasospasm. However, the CBF was significantly lower in patients with symptomatic vasospasm on days 8, 9, 10, 13, 14, and 15, when compared with patients without symptomatic vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Retroviral transfer of herpes simplex thymidine kinase gene into glioma cells causes targeting of gancyclovir cytotoxic effect.

The thymidine kinase (tk) gene of herpes simplex virus type 1 (HSV-1) was transduced into three glioma cell lines (T98, U251MG, T9) using a retrovirus vector. The supernatants of viral producer cell line PA317/LTRNL was used for infection and three transduced cell lines (T98/LTRNL, U251MG/LTRNL, T9/LTRNL) were established. The toxicities of the anti-herpetic drugs, acyclovir and gancyclovir, were evaluated in vitro. The cytotoxicities of acyclovir and gancyclovir to the HSV-1 tk gene-transduced cells increased 100-1000 fold compared to the non-transduced parental cell lines. The cytotoxic effect of gancyclovir was higher than that of acyclovir, requiring a concentration of less than 0.31 microM to obtain 50% inhibition. Deoxyribonucleic acid analysis of the gancyclovir-treated cells demonstrated fragmentation, suggesting that apoptosis is involved in the mechanism of cell death. The HSV-1 tk gene-transduced cells were co-cultured with parental cells and treated with gancyclovir. More than 95% of cells were killed in a mixture ratio of 1:1, suggesting that the "bystander effect" operated in this system. Selective transduction of HSV-1 tk gene into glioma cells using a retroviral vector and treatment with gancyclovir is a promising therapy for patients with malignant glioma.

Animals↗

PubMed1994

Liposomal transfection of human gamma-interferon gene into human glioma cells and adoptive immunotherapy using lymphokine-activated killer cells.

The authors evaluated the effect of liposomal transfection of human gamma-interferon (HuIFN-gamma) gene into human glioma cells and lymphokine-activated killer (LAK) cells, alone and in combination. An HuIFN-gamma gene inserted in a eukaryotic expression vector was entrapped in liposomes bearing positive surface charges. Liposomal gene transfection induced production of HuIFN-gamma and its secretion in culture medium of human glioma cell lines (SK-MG-1 and U-251 MG). At 4 days after transfection, the cells produced 10 to 50 U/ml of HuIFN-gamma in the medium, whereby the major histocompatibility complex (MHC) class I and II antigens, as well as intercellular adhesion molecule-1 (ICAM-1), were induced on the glioma cell surface. The growth-inhibiting effect of transfection-induced HuIFN-gamma was much stronger in comparison with control cultures exposed to 500 U/ml of exogenously added HuIFN-gamma. In addition, 20% to 40% growth inhibition was obtained in the glioma cells when they were treated with LAK cells alone at a 5:1 ratio of effector to target cells. Liposomal transfection of HuIFN-gamma gene into human glioma cells combined with immunotherapy using LAK cells was more effective than either technique alone. The reinforcement of growth inhibition in the case of combined therapy was quenched by anti-ICAM-1 monoclonal antibody, but not by anti-MHC class I or II monoclonal antibodies. These results suggest that the combined effect of liposomal transfection of HuIFN-gamma gene plus LAK cells into human glioma cells is a potentially useful therapy for malignant glioma, and that the mechanisms of the reinforcement of growth inhibition are closely related to the expression of ICAM-1 on the glioma cell surface.

Cell Adhesion Molecules↗

PubMed1994

Cause of failure of lactation in mouse mammary tumor virus/human transforming growth factor alpha transgenic mice.

Transgenic female mice bearing human transforming growth factor-alpha (TGF alpha) cDNA under the control of the mouse mammary tumor virus enhancer/promoter became pregnant but failed lactation. TGF alpha mRNA was detected in the mammary glands of these mice by the reverse transcriptase-polymerase chain reaction. By the use of collagenase-dissociated mammary epithelial cells, the binding of prolactin to its receptor was determined before and after parturition. At the end of pregnancy, the binding in TGF alpha transgenic (TGF alpha [+]) mice was small and its amount was comparable to that in the TGF alpha negative (TGF alpha [-]) mice. On the day of parturition, prolactin binding in TGF alpha (+) mice increased approximately 1.9-fold (insignificant), while that in TGF alpha (-) mice elevated over 5.3-fold (P < 0.01). The binding sites per cell were also higher in TGF alpha (-)mice. Radioimmunoassay of prolactin suggested that in TGF alpha (+) mice the low level of prolactin binding after parturition was not due to masking effect of serum prolactin. Among six TGF alpha (+) mice assayed, one mother with the highest prolactin binding activity (3.7-fold increase) initiated lactation, but the others did not. As there was little difference between groups in the growth and synthesis in the mammary glands, it was concluded that the failure of lactation in TGF alpha (+) mice is principally due to the lack of elevation of mammary prolactin receptor after parturition. At present, the role of TGF alpha in this process is obscure; however, TGF alpha was revealed not to interfere with the binding of prolactin to the receptor.

Animals↗