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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 577 records · Page 32Linked to original sources
PubMed1996

mu-Opioid receptors inhibit dopamine-stimulated activity of type V adenylyl cyclase but enhance dopamine-stimulated activity of type VII adenylyl cyclase.

The introduction of D1A dopamine receptors and mu-opioid receptors into HEK 293 cells that were also transiently transfected with adenylyl cyclase cDNA imparted to dopamine and to mu-opioid receptor agonists the ability to modulate the activity of the expressed adenylyl cyclase. Dopamine added to cells expressing D1A receptors and type V adenylyl cyclase significantly stimulated type V enzyme activity. The concomitant addition of morphine produced a dose-dependent inhibition of dopamine-stimulated type V adenylyl cyclase activity. On the other hand, if the HEK 293 cells were transfected with cDNA for type VII adenylyl cyclase instead of the type V isoform, morphine stimulated this adenylyl cyclase activity beyond the stimulation produced by dopamine. Both the inhibitory and stimulatory effects of morphine were blocked by naloxone or pretreatment of the transfected HEK 293 cells with pertussis toxin. When expressed in the HEK 293 cells, the alpha subunit of transducin, which is considered to be the putative scavenger of the beta gamma subunits of G proteins, suppressed the stimulatory effect of morphine on type VII adenylyl cyclase. We also expressed the adenylyl cyclases in cells that were transfected with D1A receptor and G beta 1 and G gamma 2 cDNAs. Dopamine was more efficacious in stimulating type VII adenylyl cyclase activity in cells concomitantly transfected with the beta gamma subunit cDNAs than in cells not transfected with these G protein subunits. Transfection with beta gamma subunit cDNAs did not affect dopamine stimulation of type V adenylyl cyclase activity, and morphine-induced inhibition of type V adenylyl cyclase activity was still evident in cells cotransfected with the alpha subunit of transducin. These data support the contention that the effects on type VII adenylyl cyclase activity mediated through the G1/G(o) proteins may depend on the actions of the beta gamma subunits. The same is not the case for type V adenylyl cyclase. Our data demonstrate that both qualitative and quantitative responses to mu-opioid receptor stimulation depend on the isoform of adenylyl cyclase expressed in neurons or other cells of the body.

Adenylate Cyclase Toxin↗
PubMed1996

Sodium balance and hypertension in obese and fatty rats.

To investigate the role of sodium in obesity induced hypertension, Wistar fatty rats (WFR) were employed. This rat has the following characteristics: (1) hyperglycemia, (2) hyperinsulinemia, and (3) hypertriglycemia. Four percent sodium chloride with constant amount of food intake was administered to these rats from 8 to 16 weeks. During this period, body wt, food intake, water consumption, urine volume, systolic blood pressure, urinary excretion of sodium and potassium, urinary albumin excretion, plasma sodium and potassium, and plasma glucose and immunoreactive insulin (IRI) were measured before, and twice more during eight weeks. No remarkable changes were observed in plasma glucose level during these periods between the two groups. On the other hand, in group 1 IRI significantly increased compared with group 2. Mean blood pressure was increased from 110 +/- 5 to 130 +/- 8 mm Hg (P < 0.01). To ascertain whether this salt sensitivity relates to the abnormalities in pressure-natriuresis responses, the pressure-natriuresis (P-N) was characterized. The P-N curve in WFR was shifted to the right and its slope was flattened compared to its control Wistar lean rats. In conclusion, an excess of dietary sodium intake may contribute to an elevation of blood pressure in Wistar fatty rat with hyperglycemia and hyperinsulinemia. This salt sensitivity may change the abnormal pressure-natriuresis responses.

Animals↗
PubMed1996

[A case of recurrent multiple HCC after surgical resection showing regression by two TAEs using 5-FU and zinostatin stimalamer].

A-68-year-old man had hepatocellular carcinoma (HCC) in the area of S6 segment which was resected surgically. Three months after surgery, multiple recurrent lesions were found in both lobes of the liver. A transcatheter arterial embolization (TAE) with 5-FU and zinostatin stimalamer (SMANCS) was done. After TAE, the tumor mass disappeared in the right lobe and reduced to 10% in the left lobe. Although mass lesions remained unchanged for 3 months, the increased of AFP (143.9 ng/ml) was noticed after 4 months. Ten months after the second TAE with 5-FU and SMANCS, the disappearance of tumor masses was confirmed by diagnostic images.

Aged↗
PubMed1996

[A case of rheumatoid factor-positive pachymeningitis].

We report a case of rheumatoid pachymeningitis involving the posterior fossa. A 71-year-old woman presented with headache, vertigo and dizziness. MRI demonstrated hypertrophic masses in the meninges of the left cerebellar tentorium, cerebellopontine angle and the fourth ventricle. Six months of treatment with betamethasone, prednisolone and azathioprine improved the patient's neurological status. Because an inappropriate immune process and systemic immune disease may cause idiopathic pachymeningitis, the performance of immunological studies for idiopathic cases is mandatory.

Aged↗
PubMed1996

Early recognition of patients with decreased methotrexate clearance following high-dose methotrexate infusion therapy.

The purpose of this study was to identify the patients with decreased methotrexate (MTX) clearance as early as possible after the start of high-dose methotrexate (HD-MTX) infusion. Fifty-six patients (age: 18 approximately 83 years) received a HD-MTX infusion (dosage: 1.9 approximately 3.8 g/m2) for 6 h. These patients were retrospectively divided into a low-clearance group and a high-clearance group based on the serum MTX concentration at 48 h (1 microM). Six out of the 56 patients showed decreased MTX clearance. The MTX concentrations in the low-clearance group were significantly higher than those in the high-clearance group even in earlier sampling times than at 48 h. The average MTX concentrations were 330 microM at 6 h, 72 microM at 12 h, and 16 microM at 24 h in the low-clearance group, and those in the high-clearance group were 210 microM, 18 microM, and 1.0 microM, respectively. The estimated elimination half-lives (t1/2) at 6 approximately 12 h and 12 approximately 24 h after the start of the infusion were also significantly longer in the low-clearance group (2.8 vs. 1.7 h and 5.0 vs. 2.8 h, respectively). Therefore, we proposed convenient criteria based on the mean + 1 S.D. of the high-clearance group: the concentration > 270 microM at 6 h and > 32 microM at 12 h; the t1/2 value > 2.1 h at 6-12 h. All 6 patients were recognized as belonging to the low-clearance group at an early stage after HD-MTX infusion by using our proposed criteria. These results indicate that patients with decreased MTX clearance could be identified within the first 12 h after the start of HD-MTX infusion. The factors influencing the prolonged elimination of MTX were also investigated. A significant decrease in renal function on day 2 was observed in the low-clearance group. The MTX level at 12 h and the estimated t1/2 values were significantly correlated with BUN, Scr and Clcr on the 2nd day after HD-MTX therapy, suggesting that an alteration in renal function occurs within 12 h of the HD-MTX infusion. The prolonged elimination of MTX could be attributable to this decrease in renal function.

Adult↗
PubMed1996

General pharmacology of recombinant human basic fibroblast growth factor.

General pharmacological effects of recombinant human basic fibroblast growth factor (bFGF) were investigated. 1. Central nervous system: Basic FGF produced almost no effect on the general symptoms and behaviors of mice. Basic FGF did not influence the spontaneous motor activity, hexobarbital-induced anesthesia, electroshock seizure threshold, pentylenetetrazole-induced seizure in mice and normal body temperature and spinal reflex in rats up to a dose of 1 mg/kg (s.c., i.v.). As regards pain sensation, it inhibited the acetic acid-induced writhing at 1 mg/kg (s.c.). No abnormal waves were observed in spontaneous EEG of the rabbit up to 1 mg/kg (i.v.) of bFGF, but at 0.1 mg/kg it had a slight effect on the ratio of EEG levels and at 1 mg/kg induced an increase in rest period, disappearance in the period of fast wave sleep and a decrease in the period of deep sleep. 2. Somatic nervous system: Basic FGF did not influence the corneal reflex, twitch response of the skin and diaphragm-phrenic nerve preparations. 3. Autonomic nervous system and smooth muscle: Basic FGF showed little effects on the spontaneous movement of the isolated ileum, contraction induced by various agonists in isolated ileum, resting tension and noradrenaline(NA)-induced contraction of the aorta, resting tension and histamine-induced contraction of isolated trachea, spontaneous movement and 5-HT-induced contraction of isolated strips of stomach fundus, NA-induced contraction of isolated vas deferens of the rat up to the concentration of 10(-4) g/ml. Basic FGF augmented the tone of the isolated non-pregnant uterus at the concentrations of 10(-5) g/ml and above and inhibited or tended to inhibit the contractile tension of non-pregnant or pregnant uterus at 10(-4) g/ml, but it did not influence the spontaneous movement of the uterus, either the non-pregnant or pregnant, under in situ conditions even at a dose of 1 mg/kg (i.v.). Basic FGF did not influence the pupil size. 4. Respiratory and circulatory systems: Basic FGF had no effect on the isolated heart. The influence was not exerted on the heart rate for the isolated atria but slight inhibition of contractile force was observed at 10(-4) g/ml. In anesthetized dogs a decrease in blood pressure, a slight increase in heart rate and respiratory rate and a decrease in femoral blood flow were observed at 0.01 and 0.1 mg/kg (i.v.) of bFGF Similarly, a slight increase in heart rate and a slight decrease of blood pressure were observed at 1 mg/kg (s.c.) in conscious rats. 5. Digestive system: Administration of bFGF at 1 mg/kg did not result in changes in the transport capacity within the gastrointestinal tract (s.c., i.v.) and the secretion of the gastric juice (s.c.). 6. Urine output and electrolyte metabolism: Basic FGF produced a decrease in urinary Na+ excretion at 1 mg/kg (s.c.), and showed a tendency to increase in urinary volume at 0.01 and 0.1 mg/kg (i.v.). At 1 mg/kg (i.v.) urinary excretion of Na+ and Cl- was decreased significantly. It had no effect on the ability of rats to excrete PSP (phenol red) up to 1 mg/kg (s.c.). 7. Blood system: Basic FGF did not influence the coagulation time of the whole blood, prothrombin time and activated partial thromboplastin time of rats up to 1 mg/kg (s.c., i.v.). It did not influence the aggregation of rabbit platelets induced by collagen and ADP up to 10(-4) g/ml. Basic FGF at concentration of 10(-4) g/ml exhibited no hemolytic action. 8. Local action: Plantar subcutaneous injection of bFGF at above 0.005 mg/site induced edema by itself on and after the next day, and also reinforced carrageenin-induced edema from 1 day after injection. The results show that bFGF did not produce any acute effects on the somatic nervous system, autonomic nervous system, smooth muscle and blood system. In contrast, bFGF produced slight effects on the circulatory system, central nervous system and kidney function when injected systemically. Subcutaneous administration may produce edema at the s

Animals↗
PubMed1996

Visceral fat accumulation and vascular complications associated with VMH lesioning of spontaneously non-insulin-dependent diabetic GK rat.

OBJECTIVE: We have reported that ventromedial hypothalamic (VMH) lesions induced marked hyperglycemia and a distinct reduction in pancreatic insulin content during short-term observation in male Goto-Kakizaki (GK) rats, an animal model for non-insulin-dependent diabetes mellitus (NIDDM) (Metabolism 43: 32-37, 1994). We investigated the long-term effect of VMH lesions on glucose metabolism, pancreatic insulin content, abdominal fat distribution and vascular complications in male GK rats. DESIGN: Metabolic and histological examinations in male GK rats during 16 weeks after making VMH lesions were compared to those in sham operated GK or Wistar rats. SUBJECTS: Eleven 9-week-old male GK rats and 4 male Wistar rats. VMH-lesions were made in 6 GK rats and sham operation were performed on 5 GK rats and 4 Wistar rats as controls. MEASUREMENTS: Food intake, body weight, and plasma glucose, insulin and lipid levels at 2 weeks interval after operation. Urinary protein and albumin levels at 15 weeks after operation. Measurement of pancreatic insulin content, mesenteric fat and abdominal subcutaneous fat weights, and histological examinations of kidney and aorta were performed after 16 weeks. RESULTS: Although food intake increased in VMH-lesioned GK (GK-VMH) rats compared with that in sham-operated GK (GK-sham) rats, the body weight of GK-VMH rats was significantly less than that of GK-sham rats. Plasma glucose was markedly elevated in GK-VMH rats from 2 through 16 weeks after operation, while it was only mildly increased in GK-sham rats. Plasma insulin levels were higher in GK-VMH rats one week after operation and thereafter tended to be lower compared to those in GK-sham rats. Plasma triglyceride levels were significantly increased in GK-VMH rats. The insulin content of pancreas at 16 weeks after operation was markedly decreased in GK-VMH rats. VMH lesions caused a significant 1.2-fold increase in mesenteric fat weight and a 1.3-fold higher ratio of mesenteric fat weight to subcutaneous fat weight in GK rats compared with sham-operated rats at 16 weeks after operation. The urinary excretions of protein and albumin in GK-VMH rats were greater than those in GK-sham rats. Histological examinations of the kidneys in GK-VMH rats revealed that the glomerular basement membranes were thicker than those of GK-sham rats. The descending aorta in GK-VMH rats also showed morphologic changes in the intima characteristic of an early stage of atherosclerosis. CONCLUSION: Male GK-VMH rats may be a useful animal model for non-obese NIDDM with visceral fat accumulation, which develops typical diabetic complications, including both microangiopathy and macroangiopathy.

Adipose Tissue↗
PubMed1996

Distribution of Fv-4 resistant gene product in Friend leukemia virus-resistant Fv-4r mouse strain.

Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We demonstrated previously that the Fv-4 resistant (Fv-4r) gene product, Fv-4r env antigen, is released from Fv-4r-bearing BALB/c-Fv-4Wr (C4W) mouse-derived cells into serum in vivo and binds to cells expressing surface receptors for ecotropic MuLV, thereby protecting them from infection with Friend leukemia virus (FLV) by receptor interference. This unique resistance mechanism against retroviral infection might provide a possible therapeutic model system of human retroviral infection such as AIDS. To further investigate the Fv-4r gene action in vivo, we examined the distribution and character of Fv-4r env antigen in serum and systemic organs from C4W mice. The Fv-4r env antigen was immunohistochemically localized to the lympho-hematopoietic cells and exocrine glandular cells, such as those of the salivary gland and pancreas. Using immunoprecipitation followed by Western blotting, we determined two types of gp70-related Fv-4r env antigen in the serum of C4W mice, showing molecular weights of either 70-75 kDa and 80-85 kDa. When thymocytes from Fv-4 susceptible gene (Fv-4r)-bearing C3H mouse were mixed with C4W mouse serum, the 70-75k Da molecule of the C4W serum dominantly bound to C3H thymocytes and thus contributed to receptor interference function. Using immunoelectron microscopy, Fv-4r env antigen was mainly localized to the cell surface membrane of thymic lymphoid cells, while acinar cells of the salivary gland possessed Fv-4r env antigen in the endoplasmic reticulum (ER) as well as on the cell surface membrane. These data indicate that several glandular organs, as well as lymphohematopoietic organs of C4W mice, may contribute to the production of cell-free Fv-4r env antigen, resulting in protection of cells from infection with FLV by receptor interference.

Animals↗
PubMed1996

[Retroperitoneal ganglioneuroma: a case report].

We experienced a case of ganglioneuroma. A 37-year-old man was admitted to our hospital for right flank pain. Computed tomography (CT) showed a low density mass near the upper pole of the right kidney. Selective renal arteriography did not demonstrate any tumor vessels in the right kidney. An endocrinological study revealed high values of noradrenaline and dopamine in urine. Under the preoperative diagnosis of a retroperitoneal tumor or right adrenal tumor, tumor resection was performed. The tumor was found in the retroperitoneal space on surgical exploration. The histopathological diagnosis was ganglioneuroma.

Biomarkers, Tumor↗
PubMed1996

[Unresectable gastric cancer followed by remarkably effective tumor disappearance and good quality of life for 10 months after CDDP/5'-DFUR combination chemotherapy--a case report].

A 40-year-old woman was admitted to the hospital because of dysphagia and severe anemia (Hb 4.5 g/dl). She was diagnosed as having an advanced gastric cancer, which was unresectable because of liver metastasis, esophageal invasion and paraaortic lymph node metastasis. Combination chemotherapy with CDDP/5'-DFUR was started. CDDP of 80 mg/m2 was administered twice every 4 weeks by a 24-hour drip infusion method, and oral 5'-DFUR of 1,400 mg/m2 was administered for 4 days prior to the first administration of CDDP. Then, 5'-DFUR of 500 mg/m2 was given every day except for 7 days after the first administration of CDDP. Her performance status before the chemotherapy was 3, and improved to 1 a month after the first administration of CDDP. The patient was discharged very much improved on the 45th day after the first administration of CDDP. The side effect was nausea but tolerable. Six months after the first administration, her cancer disappeared on X-ray films, endoscopic and CT examinations. Her PS improved to 0, and she has remained alive with a good QOL for 10 months after the second administration of CDDP.

Adult↗
PubMed1996

Clinical application of visual evoked fields using an MRI-linked whole head MEG system.

We have demonstrated anatomo-functional correlation of the brain visual function using an MRI-linked whole-head magnetoencephalography system. Visual evoked magnetic fields (VEFs) due to pattern reversal stimuli were measured in seven healthy subjects and 13 patients with intracranial structural lesions. Full-field stimuli evoked the most prominent peak around 100 ms latency (P100m) as a two-dipole pattern over the occipital area in all of the normal subjects and four patients with mild and partial hemianopsia. In five patients with homonymous hemianopsia due to unilateral occipital lesion, a single-dipole pattern of the P100m appeared over the normal occipital area only. In four patients with bitemporal hemianopsia due to pituitary tumors, a single-dipole pattern of the P100m appeared only over the ipsilateral occipital area to the stimulated eye. Using current dipole models, P100m sources were localized at the lateral bottom of the calcarine fissures. Although human occipital lobes are known to be morphologically variable, our results indicate excellent correlation of the cortical anatomy and human visual function. Full-field stimuli, requiring no strict visual fixation, are especially useful for clinical application. A clear two-dipole pattern in the normal VEFs enables us to compare two hemispheric activities.

Adult↗
PubMed1996

Analysis of diffuse parenchymal liver disease by liver scintigrams: differential diagnosis using neuro and fuzzy.

In colloid liver scintigraphy, diagnosis of diffuse parenchymal liver disease such as chronic hepatitis or cirrhosis is evaluated by size and distortion of the liver, distribution of tracer in the liver, size and activities of tracer in the spleen, visualization of the bone marrow and so on. It is not difficult to read a scintigram which shows a typical pattern of normal, chronic hepatitis and cirrhosis; however in some cases it is difficult to distinguish normal or chronic hepatitis and chronic hepatitis or cirrhosis visually. Therefore, we tried to use fuzzy inferences to perform differential diagnosis in chronic hepatitis (CH), severe fibrosis (SF) and liver cirrhosis (LC). First, five features in colloid liver scintigrams were measured or evaluated visually. These features were liver size index (left lobe/right lobe), splenomegaly, the degree of visualization of the bone marrow, liver deformity, and distribution of tracer in the liver. Having fuzziness in these data, certain characteristics of these features were considered to be fuzzy sets and thus could be expressed in membership functions. Fuzzy inference was carried out using these data and fuzzy rules. Using fuzzy inference, differential diagnosis in LC could be performed up to 100%, but those of CH and SF could not be performed sufficiently. Using neural network CH, SF and LC could be diagnosed up to 63%, 80%, and 88%, respectively. But fuzzy inference had the merit to evaluate the degree of disturbance by the center of gravity of the resulting membership function. Therefore by combining neural network and fuzzy inference, CH, SF, and LC could be differentiated to the degree 77%, 80%, and 100%, respectively.

Chronic Disease↗
PubMed1996

[Airway hyperresponsiveness and airway mucosal permeability].

The relationship between airway mucosal permeability and airway hyperresponsiveness was examined with tachykinins, their selective antagonists, and superoxide dismutase in male Hartley guinea pigs. In animals with ozone-induced airway inflammation, airway hyperresponsiveness and mucosal permeability increased concurrently but there was a time lag before the increase in airway vascular permeability. To study the role of tachykinins in the increases in mucosal permeability and in hyperresponsiveness, we used a neurokinin-receptor antagonist, CP-96345, and a neurokinin-2 receptor antagonist, SR-48968. CP-96345 had no significant effect, but SR-48968 reduced the increase in airway mucosal permeability; their effects on airway hyperresponsiveness were the opposite of their effects on airway permeability. Tachykinins themselves, both substance P and neurokinin A, significantly increased airway mucosal permeability. Superoxide dismutase, a scavenger enzyme of superoxide, reduced the ozone-induced airway hyperresponsiveness. These data suggest that the factors causing airway hyperresponsiveness differ from those that influence mucosal permeability, but it is possible that these pathophysiologic conditions are caused by the same substances or processes.

Animals↗