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Biomedical subjects

M Munakata

Publications and source records attributed to M Munakata.

At least 91 records · Page 5Linked to original sources

Role of vasopressin in neurocardiogenic responses to hemorrhage in conscious rats.

Vasovagal reflexes, such as hypotension and bradycardia, are induced by rapid hemorrhage and mimic neurocardiogenic reflexes in mammals. We examined the role of vasopressin in the neurocardiogenic responses to mild, rapid hemorrhage (1 mL/100 g for 30 seconds) and severe hemorrhage (1 mL/100 g body wt for 30 seconds repeated three times at 11-minute intervals) in homozygous Brattleboro and Long-Evans rats. Mild, rapid hemorrhage induced severe bradycardia and hypotension only in Long-Evans rats. Exogenous vasopressin (1.85 pmol/kg per minute for 1 hour) restored both the bradycardic and hypotensive responses in Brattleboro rats. DDAVP, a vasopressin V2-receptor agonist (0.19 pmol/kg per minute for 24 hours), did not affect the cardiovascular responses to hemorrhage in Brattleboro rats, although it maintained urine production within normal limits. However, OPC-31260 (21.6 mumol/kg IV), a vasopressin V2-receptor antagonist, attenuated both the hypotensive and bradycardic responses to hemorrhage in Long-Evans rats. A vasopressin V1-receptor antagonist attenuated bradycardia and delayed the recovery of arterial pressure after hemorrhage but did not affect the hypotension that occurred immediately after hemorrhage in Long-Evans rats. Methylatropine also attenuated both the bradycardic and hypotensive responses induced by hemorrhage, but propranolol had no effect on the cardiovascular responses to hemorrhage in Long-Evans rats. The recovery of arterial pressure after repeated hemorrhage was less adequate in Brattleboro rats than in Long-Evans rats. Our results suggest that the neurocardiogenic responses to hemorrhage, especially hypotension, may be related to vasodilation induced by a V2-receptor-mediated mechanism and by the vagal reflex, both of which are substantiated by the existence of vasopressin. The coexistence of V1- and V2-receptor mechanisms may be necessary for the hypotensive response to hemorrhage. We found that a V2-receptor antagonist attenuated the hypotension mediated by the so-called neurocardiogenic reflex.

Acute Disease↗

Effects of intracerebroventricular administration of 6-hydroxydopamine on ouabain-like immunoreactivity in plasma and the hypothalamo-pituitary axis in rats.

OBJECTIVE: To examine the role of central mechanisms on the production and release of an ouabain-like factor, the effects of intracerebroventricular injections of 6-hydroxydopamine on the tissue content and on the plasma level of the ouabain-like factor were determined in rats. METHODS: The vehicle (0.1% ascorbic acid in 0.9% saline) and 6- hydroxydopamine (250 micrograms/rat) were injected into the left lateral ventricle in ether-anaesthetized Wistar rats. Hypothalamus, pituitary, adrenal and venous blood was sampled 24h and 7 days later. The procedure was repeated using another rat group 7 days later. Characteristics of immunoreactive ouabain-like factor were determined by a combination of high-performance liquid chromatography and a highly sensitive enzyme-linked immunosorbent assay for ouabain. The level of the ouabain-like factor in these tissues and in plasma extracts measured by the enzyme-linked immunosorbent assay was compared between the two groups receiving 6-hydroxydopamine and the vehicle. RESULTS: Twenty-four hours after the intracerebroventricular injections of 6-hydroxydopamine, the ouabain-like factor level in the pituitary, hypothalamus and plasma had decreased significantly, whereas the ouabain-like factor level in the adrenal had not changed. The content of noradrenaline in the hypothalamus was also decreased markedly 7 days later and the content of ouabain-like factor in the pituitary remained low. On liquid chromatography the elution pattern of the ouabain-like factor in plasma and in tissue extracts coincided with that of authentic ouabain. CONCLUSIONS: Intracerebroventricular treatments with 6-hydroxydopamine elicited decreases in ouabain-like factor contents in the pituitary, the hypothalamus and the plasma. These results suggest that the production and release of ouabain-like factor are closely associated with the brain, particularly the hypothalamus-pituitary axis, and that noradrenergic or dopaminergic neurons, or both, play a key role in this mechanism.

Animals↗

[Three siblings with interstitial pneumonia].

Patient 1: A 64-year-old woman was admitted for further examination after reticulonodular shadows were found on a chest X-ray film. Idiopathic interstitial pneumonia (IIP) was diagnosed. Patient 2: The 60-year-old sister of patient 1 was admitted for further examination after reticulonodular shadows were found on a chest X-ray film. IIP was diagnosed. About half a year later, her proximal interphalangeal joints had become swollen and the result of a rheumatoid hemagglutination test was positive. Therefore, the pneumonia was suspected to have been caused by a collagen-vascular disease (CVD), rheumatoid arthritis. Patient 3: The 64-year-old brother of patient 1 was examined. A chest X-ray film revealed reticulonodular shadows that were strongly suggestive of IIP. The remaining three siblings were examined. In a 62-year-old sister, the chest X-ray film was normal, but the level of anti-nuclear antigen was elevated. The fact that the level of this antigen was high in these four siblings and that the 60-year-old sister later suffered from rheumatoid arthritis suggested the presence of a factor predisposing to CVD in these siblings. The interstitial pneumonia in these siblings may have been related to CVD.

Arthritis, Rheumatoid↗

[Pulmonary nitric oxide synthase isoform expression and their functional significance].

Nitric oxide (NO), discovered as an endothelium derived relaxing factor, is generated during conversion of L-arginine to L-citrulin by nitric oxide synthase (NOS). Now, genes for three isoforms of NOS (nNOS, eNOS, and iNOS) have been cloned and pulmonary expressions of these NOS isoforms have been studied extensively. Localization of these NOS isoforms in the lung and their functional roles are discussed.

Animals↗

[Idiopathic interstitial pneumonia and TNF gene restriction fragment length polymorphism].

Tumor necrosis factor alpha (TNF alpha) and lymphotoxin (TNF beta) are cytokines with numerous similar immunoregulatory effects. In pulmonary fibrosis, TNF alpha/beta appears to play a critical role in the regulation of the fibroproliferative response. The human TNF alpha/beta genes are located between the HLA-B and the HLA-DR region. In man 5.5 kb and 10.5 kb of TNF alpha/beta restriction fragment length polymorphic (RFLP) bands have recently been identified by means of enzyme NcoI. TNF alpha/beta production is reported to be correlated to the NcoI RFLP. In some collagen diseases, a decreasing frequency of the 10.5 kb band is reported. The two allele NcoI RFLP of the TNF alpha region, yielding bands of 5.5 kb and 10.5 kb, was investigated in normal Japanese subjects and patients with IIP. The frequency of these bands was not different between normal subjects and patients with IIP. However, in female patients, the frequency of the 5.5 kb band was significantly increased compared with those in the male patients and normal subjects. The increase of this band may have some relation to the pathogenesis of idiopathic interstitial pneumonia.

Female↗

[Emergency surgical salvage for a type A early thrombosed aortic dissection complicated cardiac tamponade in a 80-year-old-patient].

A 80-year-old woman underwent emergency operation for a type A early thrombosed aortic dissection associated with cardiac tamponade. Her preoperative chest CT (not enhanced) showed high density area in the false lumen that indicated early thrombosis and the projection of true lumen at antero-left-lateral portion of ascending aorta that means "ulcer-like projection" called on aortogram. After the relief of the cardiac tamponade by pericardiocenthesis, we emergently performed the graft replacement of the ascending aorta under the extracorporeal circulation combined with selective cerebral perfusion. Her postoperative course was uneventful and satisfactory.

Acute Disease↗

[Inappropriate preservation of myocardium by topical cooling with iced slush].

Topical cooling with iced slush has been applied as a conventional myocardial preservation in open heart surgery. However, there might be several disadvantages due to topical cooling with iced slush which melted to be liquid, because of membrane integrity decreased during ischemia. To understand more detailed mechanism of deterioration for myocardium by immersion in some liquid during ischemia, we subjected isolated crystalloid perfused rabbit hearts to a 30 minute of ischemia with immersion in Krebs-Henseleit (K-H) solution (I), K-H+hexamethlyamiloride which was Na+/H+ channel blocker (II) and histidine containing cardioplegia (HBS) designed to accelerate anaerobic glycolysis by a proton buffering (III), followed by a 30 minute of reperfusion. These groups were compared to the hearts hanging in air during ischemia (control). Phosphocreatine (PCr), ATP and intracellular pH were measured by 31 PNMR in group I, II, III. Developed pressure (Dev P) and diastolic pressure (EDP) with a intracavitary balloon were also evaluated with monitoring of 2 mmHg diastolic contracture during ischemia. Dev P declined to 46%, 54% of preischemic value in group I and group II, respectively, although % recovery of control heart was 74% after ischemia-reperfusion process. Diastolic function was severely deteriorated in group I and II, as compared to control heart. ATP and intracellular pH showed a similar decline as PCr in group I and II which was not seen in group III during ischemia. HBS prevented the deterioration of PCr, ATP and intracellular pH during ischemia along with excellent recovery of myocardial function. We therefore conclude that 1) significant deterioration of myocardium occurs with ischemia if the heart preserved in Krebs-Heseleit solution and the mechanism of injury by immersion in liquid on the heart appears to be due to proton accumulation caused by intracellular acidification and loss of high energy phosphate.

Animals↗

[Evaluation of the factor XIIa assay kit].

The assay for activated coagulation factors has recently been considered to be a useful tool for detecting hypercoagulable state. Measurement of activated factor XI and alpha 1 antitrypsin complex developed by us is the only one measure for detecting contact phase hypercoagulation. The ACTIVATED FACTOR XII kit (Shield Diagnostics) has recently been commercially available, and the reference range was reported in the instruction manual. However, because the recovery rate of purified factor XIIa (XIIa) in normal pooled plasma by this assay kit was strikingly decreased, the effects of inhibitors in plasma, such as low molecular weight serine proteinase inhibitor (diisopropyl fluoro-phosphate, DFP), the specific inhibitor for XIIa (corn trypsin inhibitor, CTI), the main inhibitor for XIIa (C1 inhibitor, C1I) were examined. These three inhibitors and XIIa were incubated for 18 hours, then the XIIa levels of these complexes and the recovery rate in the normal pooled plasma were assayed by this assay kit. The recovery ratios in the normal pooled plasma were; DFP-XIIa 82%, CTI-XIIa 63%, and C1I-XIIa 0%, XIIa without inhibitor 7%. These results suggest that this XIIa kit does not reflect the levels of complexed form of XIIa and inhibitors in plasma samples.

Adult↗

[Usefulness of the preoperative MRI for diagnosis and operative method in a case of cor triatriatum].

A case was 6-year-old female diagnosed as the cor triatriatum. The magnetic resonance imaging synchronized at R wave on the electrocardiogram was performed in order to see the abnormal septum in the left atrium. In the horizontal view, the abnormal septum that divides the left atrium into the accessory left atrial chamber and the true left atrium, was well visualized. This septum lied on the vertical portion. Operation was carried out with the approach through the accessory chamber and the fibromuscular membrane were excised. Preoperative imaging of the MRI was useful and helpful for us to reach to a decision of the surgical approach in this patient.

Cardiac Surgical Procedures↗

[Meanings of the clinical parameters of airway hyperresponsiveness].

Clinically, threshold concentrations of agonist causing 20% decrease in FEV1 (PC20 FEV1) or 35% decrease in airway conductance (PC35Gaw) are usually used as parameters of airway hyperresponsiveness. In this session, what do these parameters mean was discussed based on theoretical analysis, experimental data and clinical observations. Theoretically, using these parameters, it seems very difficult to distinguish whether hyperresponsiveness is due to the change in sensitivity or maximum responses. Experimental and clinical observations suggest that these parameters are affected by multiple factors, for example, genetic vs. acquired factors and functional vs. structural factors. There may be differences in the degree of contributions of each factors on clinical parameters of airway responsiveness between asthmatics and control, and mild and chronic severe asthma. Clinically, considering such differences may be important in interpreting the changes of these parameters.

Asthma↗

Normal sympathetic vasomotor and cardiac parasympathetic activities in patients with primary aldosteronism: assessment by spectral analysis.

The role of the autonomic nervous system in hypertension due to mineralocorticoid excess remains unclear. To address this issue, we performed power spectral analysis of blood pressure (BP) and RR interval oscillations in 20 patients with primary aldosteronism (PA), 54 patients with essential hypertension (EH) and 45 normotensive (NT) subjects. Blood pressure and the degree of organ damage were similar between PA and EH groups. Age did not differ between the three groups. The Mayer wave power spectrum (MWP) of BP (approx. 0.1 Hz), an index of sympathetic vasomotor tone, was smaller in patients with PA than in patients with EH either while subjects were supine (systolic/diastolic; 3.9 +/- 3.2 (SD)/1.5 +/- 1.3 vs. 5.5 +/- 4.2/2.1 +/- 1.6 mmHg2, P < 0.05 for both) or standing (7.6 +/- 6.6/3.0 +/- 3.0 vs. 17.7 +/- 23.7/7.2 +/- 8.3 mmHg2, P < 0.05 for both). Supine respiratory-related power spectrum (RRP) of the RR interval (approx. 0.25 Hz), an index of cardiac parasympathetic tone, was greater in patients with PA than in patients with EH (545 +/- 574 vs. 302 +/- 464 ms2, P < 0.01). The MWP of BP and the RRP of the RR interval were similar between patients with PA and NT subjects. Adrenalectomy reduced the 24-h mean BP (-18 mmHg for systolic BP, P < 0.001; -12 mmHg for diastolic BP, P < 0.01) and increased the 24-h mean heart rate (+8 bpm, P < 0.001). Furthermore, the diastolic MWP increased mildly (+32%, P < 0.05) and the RRP of the RR interval decreased dramatically (-75%, P < 0.01) following adrenalectomy. These results suggest that both vascular sympathetic and cardiac parasympathetic regulatory systems have minor roles in the maintenance of hypertension in patients with PA. The autonomic nervous system contributes more to the maintenance of BP following than prior to adrenalectomy. This information may be useful for the management of hypertension still persists after removal of adrenal adenoma.

Adenoma↗

Three cases of idiopathic interstitial pneumonia with bullae seen in schoolteachers.

We encountered three patients with chronic interstitial pneumonia with many bullae in the lower lung fields whose lifetime occupation was teaching school. Pathological examination of autopsy lungs of these patients revealed interstitial pneumonia and multiple bullae throughout the lungs, including the lower lobe. Since blackboard chalk has been used as a popular writing material among teachers in Japan, the mineral contents in the lungs of two of the three cases and four control cases with idiopathic interstitial pneumonia (IIP) (whose occupations were not teaching) were analyzed. The amount of deposition of total dust, inorganic dust, non-SiO2 inorganic dust, and calcium was significantly higher in the lungs of two schoolteachers compared with those of the control lungs. The amount of free silica in case 1 and alpha-quartz in case 3 were also significantly higher than in the controls. Two thirds of the chalk produced in Japan is still made from gypsum and involves small amounts of silica and other minerals, in addition to calcium. These findings indicated the deposition of chalk in the lungs of these patients with interstitial pneumonia and multiple bullae.

Blister↗

The effect of graded calcium infusions on rhythmic blood pressure oscillations in normal man.

This study was designed to determine whether calcium contributes to the regulation of rhythmic oscillations in blood pressure. Six normal subjects received sequential 1-h infusions of calcium gluconate (1.5, 3.0 and 4.5 mg calcium/kg/h) during continuous blood pressure (Finapres) monitoring. The plasma ionized calcium ([Ca2+]) concentration increased from 4.6 +/- 0.07 mg/dl to 5.97 +/- 0.20 mg/dl (p < 0.01) with infusion. The mid-frequency (0.07-0.14 Hz, Mayer wave) power spectrum of diastolic blood pressure was depressed slightly following the first dose but increased significantly following the final dose (p < 0.05). The high-frequency (0.15-0.40 Hz) power spectrum of systolic blood pressure decreased following the first dose (p < 0.05) and subsequently remained low. The low-frequency (0.02-0.6 Hz) power spectrum was not affected. These results demonstrate that graded hypercalcaemia affects blood pressure oscillations in man. Our data suggest that the amplitude of the Mayer wave, a clinical marker of sympathetic vascular tone, is modulated in part by calcium.

Adult↗

Effects of vasopressin V1 and V2 receptor antagonists on the development of salt-induced hypertension in Dahl rats.

To determine whether the vasopressor and antidiuretic actions of arginine vasopressin (AVP) may participate in the development of salt-induced hypertension, we examined the long-term effects of AVP V1 and V2 receptor antagonists on blood pressure (BP) in Dahl-Iwai salt-sensitive (DS) and salt-resistant (DR) rats. From age 7 weeks, DS and DR rats were fed a diet containing 8% NaCl, alone (control group); 8% NaCl and 1% OPC-21268 (V1 antagonist-treated group); or 8% NaCl and 0.05% OPC-31260 (V2 antagonist-treated group). The pressor response to AVP was significantly inhibited in DS rats treated with OPC-21268. Urinary volume and water intake were significantly increased by administration of OPC-31260; this increase was greater in DR rats than in DS rats. Indirect BP measurements obtained using tailcuff plethysmography showed that DS but not DR rats developed hypertension when fed high-salt diets. However, chronic treatment with either OPC-21268 or OPC-31260 did not alter the course of hypertension in DS rats, despite the effective blocking actions of these antagonists. This finding also was confirmed by direct BP measurements. Our results indicate that even if AVP plays a role in salt-induced hypertension peripheral blockade of either subtype of AVP receptors does not prevent the development of hypertension in DS rats.

Analysis of Variance↗

Dual mechanisms of GABAA response inhibition by beta-lactam antibiotics in the pyramidal neurones of the rat cerebral cortex.

1. The effects of beta-lactam antibiotics on the gamma-aminobutyric acid (GABA)-induced Cl- current were investigated in pyramidal neurones freshly dissociated from the rat frontal cortex by the use of a nystatin-perforated patch recording mode under voltage-clamp conditions. 2. The GABA-induced inward current increased in a concentration-dependent manner with an EC50 of 6.7 x 10(-6) M at a holding potential of -40 mV. The GABA response was accompanied by an increase in the membrane conductance and reversed at near the Cl- equilibrium potential. 3. All beta-lactams (penicillin, imipenem, aztreonam and cefotiam) inhibited the 10(-5) M GABA-induced response in a concentration-dependent manner with an IC50 and Hill coefficient of 1.3 x 10(-3) M and 0.64 for penicillin, 9.6 x 10(-4) M and 0.83 for imipenem, 2.5 x 10(-3) M and 9.99 for aztreonam, and 2.9 x 10(-4) M and 1.03 for cefotiam. 4. Imipenem inhibited the GABA-response competitively while penicillin inhibited the same response in a noncompetitive fashion. 5. The inhibitory action of imipenem showed no voltage-dependency, whereas the effect of penicillin was voltage-dependent. 6. It is thus proposed that some classes of beta-lactams, including imipenem may have a mechanism that is different from penicillin and competitively affects the GABAA receptor.

Animals↗

Beta 2 adrenergic receptor gene restriction fragment length polymorphism and bronchial asthma.

BACKGROUND: Beta 2 adrenergic dysfunction may be one of the underlying mechanisms responsible for atopy and bronchial asthma. The gene encoding the human beta 2 adrenergic receptor (beta 2ADR) has recently been isolated and sequenced. In addition, a two allele polymorphism of this receptor gene has been identified in white people. A study was carried out to determine whether this polymorphism is functionally important and has any relation to airways responsiveness, atopy, or asthma. METHODS: The subjects studied were 58 family members of four patients with atopic asthma. Restriction fragment length polymorphism (RFLP) with Ban-I digestion of the beta 2ADR gene was detected by a specific DNA probe with Southern blot analysis. Airways responses to inhaled methacholine and the beta 2 agonist salbutamol, the skin prick test, and serum IgE levels were also examined and correlated to the beta 2ADR gene RFLP. In addition, measurements of cAMP responses to isoproterenol in peripheral mononuclear cells were performed in 22 healthy subjects whose genotype for beta 2ADR was known. RESULTS: A two allele polymorphism (2.3 kb and 2.1 kb) of the beta 2ADR gene was detected in the Japanese population. Family members without allele 2.3 kb (homozygote of allele 2.1 kb) had lower airways responses to inhaled salbutamol than those with allele 2.3 kb. The incidence of asthma was higher in those without allele 2.3 kb than in those with allele 2.3 kb. The beta 2ADR gene RFLP had no relation to airways responses to methacholine and atopic status. cAMP responses in peripheral mononuclear cells of the subjects without allele 2.3 kb tended to be lower than those of the subjects with allele 2.3 kb. CONCLUSIONS: These results suggest that Ban-I RFLP of the beta 2ADR gene may have some association with the airways responses to beta 2 agonists and the incidence of bronchial asthma.

Adolescent↗

Can interstitial pneumonia as the sole presentation of collagen vascular diseases be differentiated from idiopathic interstitial pneumonia?

We prospectively followed 68 patients diagnosed as idiopathic interstitial pneumonia (IIP) over a period of 1-11 years. Thirteen patients (19%) subsequently developed systemic manifestations of collagen vascular diseases (CVD) and were diagnosed as having had interstitial pneumonia as the sole presentation of CVD (CVD-IP). Compared with the 55 IIP patients, the 13 CVD-IP patients were relatively younger, predominantly female, and had a lower incidence of dust inhalation in their history. They also had a higher erythrocyte sedimentation rate, higher incidence of the x-ray finding of discoid atelectasis in the lower lung fields, and a better prognosis than the IIP patients. However, these features did not clearly distinguish the two groups. We conclude that the patients clinically and/or histologically defined as suffering from IIP cannot be distinguished from CVD-IP patients before systemic signs of CVD appear in the latter group.

Adult↗

Dairy farmers have increased methacholine bronchial responsiveness independent of sensitization to mold antigens.

Patients with farmer's lung disease (FLD) and dairy farmers have nonspecific bronchial hyperresponsiveness. To examine the factors determining bronchial hyperresponsiveness among dairy farmers, we studied airway functions, airway responses to inhaled methacholine, serum total IgE levels, and antigen-specific IgE levels in 37 dairy farmers and 11 local control subjects. The 37 dairy farmers consisted of three groups; 12 farmers with episodes of FLD (FLD group), 13 farmers with serum antibody to Micropolyspora faeni (MF) and/or Thermoactinomyces vulgaris (TV) but without episodes of FLD (Ab(+) group), and 12 farmers without serum antibodies to MF and TV and without episodes of FLD (Ab(-) group). Pulmonary function tests showed small airways disorders among farmers (each of the three groups versus control subjects; p < 0.05). Methacholine provocation test, utilizing PD35Grs (a cumulative dose of methacholine that induces 35% reduction in respiratory conductance [Grs]), showed bronchial hyperresponsiveness in each group of dairy farmers compared with that in control subjects (Log PD35Grs, mean +/- SEM: 1.22 +/- 0.18, 1.00 +/- 0.17, and 1.20 +/- 0.20, respectively, versus 2.10 +/- 0.09; p < 0.001). However, there was no statistically significant difference in bronchial responsiveness among the three groups of dairy farmers. In addition, there was no significant difference in serum total IgE levels and specific IgE antibodies among the four groups. These results suggest that the bronchial hyperresponsiveness to methacholine among dairy farmers is not due to past episodes of FLD or sensitization to MF and/or TV, but is possibly due to the occupational environment of dairy farming.

Antibodies, Bacterial↗