Search PubMed⌕ Search

Biomedical subjects

M Minami

Publications and source records attributed to M Minami.

At least 613 records · Page 34Linked to original sources

Abnormalities of third-order suppressor T cells in old (New Zealand black x New Zealand white) F1 mice.

The suppressor T cell (Ts) function of old NZW, NZB, C57BL/6 and (NZB X NZW) F1 [B/W)F1), mice to the 2,4-dinitro-1-fluorobenzene (DNFB) hapten was studied. Intravenous administration of dinitrophenyl (DNP) coupled syngeneic lymphoid cells (which normally induce DNP specific suppression) did not result in suppression of DNFB-specific contact hypersensitivity (CS) responses in old NZB or (B/W) F1 mice. Nevertheless, when spleen cells from these old mice were injected into young mice (either (B/W)F1 or A/Sn), strong suppression of the induction phase of CS responses was observed. In addition, effector phase suppressor activity was also observed when splenic cells from tolerized old (B/W) F1 donors were transferred into young (B/W)F1 mice during the effector phase of the CS response. In both cases, the significant cells in the transfer were I-J+ T cells. Thus, the old mice retained functional Ts1 and Ts2 suppressor cells. However, the suppressive activity of the old mice could be reconstituted with spleen cells from primed young mice, suggesting that they have a defect in the Ts3 subset. This was further supported by the finding that the significant cells from the primed young mice were I-J positive and cyclophosphamide-sensitive.

Aging↗

A genetically restricted suppressor factor that requires interaction with two distinct targets.

We have previously described a genetically restricted suppressor factor (TsF3) that suppresses the terminal phases of the contact sensitivity response. The activity of TsF3 is restricted by genes in the H-2 (I-J) and Igh complexes. This report analyzes the mechanisms responsible for these genetic restrictions. One cellular target of TsF3 is an I-J-bearing antigen-presenting cell population that is sensitive to low doses of cyclophosphamide. To elicit suppression I-J homology is required between this antigen-presenting cell population and the TsF3 donor. In contrast, the Igh-linked genetic restriction exists between TsF3 and an unprimed cell population present in the recipient. These findings suggest that under these experimental conditions TsF3 acts by bridging the APC with cells of the host. Finally, we demonstrated that nonspecific bystander or cognate suppression can be mediated by TsF3, provided specific antigen is present in the site of the ongoing T cell response.

Animals↗

Guanfacine and clonidine: the effects on adrenal medullary function in spontaneously hypertensive rats.

The effect of guanfacine on adrenal medullary function was investigated in anesthetized spontaneously hypertensive rats (SHR). This effect was compared with the clonidine-induced adrenal suppressant action. Sympathetic adrenal nerve activity and adrenal catecholamine secretion rate were determined and used for the analysis of adrenal medullary function. Intravenous administration of guanfacine (30-100 micrograms/kg) produced a decrease in both adrenal nerve activity and adrenal catecholamine secretion rate that paralleled a decrease in arterial blood pressure and heart rate. The ED50 of the guanfacine-induced decrease in adrenal nerve activity was 300 micrograms/kg, and the ED50 of clonidine was 30 micrograms/kg. This guanfacine dose produced decreases up to about 20% of the pretreatment values in both epinephrine and norepinephrine secretion rates from the adrenal medulla. Moreover, guanfacine produced a significant decrease of adrenal plasma flow rate. The adrenal plasma flow rate did not change significantly after clonidine administration. These findings suggest that the adrenal suppressant effect induced by guanfacine is predominantly due to its central action and that the vasoconstriction due to the peripheral action of guanfacine is partly related to its adrenal suppressant effect in SHR.

Adrenal Glands↗

[Effect of metoprolol on water drinking activity in Wistar Kyoto rats].

The study was undertaken to elucidate the effect of beta 1 adrenoceptor blocking agent, metoprolol, on water drinking activity in Wistar Kyoto rats (WKY). Both 7 day (10mg/kg/day) oral administration of metoprolol and propranolol did not produce any changes in the systolic blood pressure of WKY. However, metoprolol produced a significant decrease in heart rate in WKY. Neither the propranolol treated rats nor the control (non-drug group) rats showed any significant changes in heart rate. Heart rates were significantly changed in the metoprolol group as compared with the other two groups. This finding reconfirms that metoprolol has beta 1 selectivity. Drinking activity, an indicator of central nervous function, did not change after metoprolol administration. Power spectral analysis of water drinking activity did not reveal any changes in rhythm in respect to periodicity in the metoprolol group. Although water drinking activity is synchronized with urinary catecholamine and aldosterone excretion rates, urinary catecholamine and aldosterone excretion rates did not change after metoprolol administration. These findings suggest that it is the beta 1 adrenergic blocking action of a bradycardia-producing dose of metoprolol that prevented any change in water drinking behavior in WKY.

Aldosterone↗

[Clinical application of immuno-precipitation inhibition technique for determination of disopyramide in human plasma].

Immuno-precipitation Inhibition Technique (IPIT) method of determining disopyramide levels in human plasma was reevaluated in respect to factors affecting assay procedure, specificity and recovery. With this method only 20 microliters of plasma is required to obtain a rapid, sensitive and specific determination. Due to little intra-assay and inter-assay variation, the IPIT method is suitable for clinical determinations for disopyramide. Furthermore pharmacokinetic parameters calculated from the disopyramide concentrations coincided with the reported data determined by other methods. It was demonstrated, however, that precise temperature control and sample mixture are essential for accurate plasma disopyramide determination using this method.

Disopyramide↗

A postoperative long-term study of the deltoid contracture in children.

Sixty-eight children with contracture of the deltoid muscle (82 shoulders) were treated operatively. These cases showed a minimum angle of 25 degrees of abduction in the resting position. The postoperative course with a minimum follow-up of 5 years was analyzed in 40 cases (49 shoulders). Abduction contracture of the shoulder joint completely disappeared after surgery in 23 shoulders (47%), and winging of the scapula disappeared in 39 shoulders (78%). The angle of horizontal adduction was restored in 14 shoulders (41%) postoperatively. Contracture recurred in only three shoulders (6%).

Adolescent↗

[Effects of continuous pure tone stimulation on blood pressure, plasma norepinephrine and urinary norepinephrine concentration in stroke-prone spontaneously hypertensive rats].

The present study was undertaken to elucidate the effect of pure tone stimulation on sympathetic nerve activity in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were exposed to a pure tone stimulation of 4 KHz at 60 dB SPL tone burst which was interrupted at a frequency of one second and continued for one hour a day for either one 10 day course period or two 10 day course periods. Over a period of 10 days, Group A received one hour-long stimulation daily. Group B received the same type of stimulation for two separate 10 day course periods and Group C did not receive any tone stimulation. Group A and Group C did not show any significant changes in blood pressure, heart rate or body weight. However, an increase in urinary norepinephrine (NE) (p less than 0.02) which returned to pretreatment levels after tone stimulation was observed in Group A. Group B showed a significant increase in blood pressure as compared with Group A (p less than 0.02): the systolic blood pressure of Group B was 233.2 +/- 36.1 mmHg; the systolic blood pressure of the sex-age matched Group A was 193.0 +/- 25.7 mmHg. Group B displayed an increase in plasma NE concentration as compared with Group A (p less than 0.05). These findings demonstrated that the summation of two 10 day course pure tone stimulations produced a larger increase in blood pressure and plasma NE concentration than one 10 day course stimulation. These increase in blood pressure and plasma NE concentration occurred via an increase in sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

[The factors affecting plasma catecholamines concentration in rats and man].

Rat and human plasma catecholamines were measured simultaneously by HPLC-THI, HPLC-ECD and REA, and the three methods were compared. An attempt was also made to determine the factors affecting the estimated value of plasma catecholamine concentration. Our study showed that: Sensitivity and reproducibility to norepinephrine and epinephrine were identical in all three methods. One advantage of the REA method is that comparatively smaller sample volumes are required to produce similar results. Plasma dopamine concentration in peripheral blood samples was determined by the HPLC-ECD rather than the HPLC-THI method. Withdrawal of 5 ml of blood produced a significant increase in norepinephrine, epinephrine and dopamine in rat plasma. The catecholamine concentration in these cases was determined by the REA method. Plasma norepinephrine concentration did not increase with age in Wistar Kyoto rats. However, plasma norepinephrine concentration increased significantly with age in stroke-prone spontaneously hypertensive rats (SHRSP). Plasma norepinephrine concentration in male SHRSP was greater than that in female SHRSP. SHRSP-plasma norepinephrine concentrations rose in parallel to increases in blood pressure. The plasma norepinephrine concentration in SHRSP with cerebral hemorrhage rose significantly as compared with the plasma norepinephrine levels in SHRSP without cerebral bleeding. Because each method of determination of plasma catecholamine concentration has both merits and demerits, selection should be determined by sample size and amount of catecholamines in the plasma samples. Factors affecting the estimated value of plasma catecholamine concentration should be taken into consideration.

Animals↗

[A chronobiological study of behavioral changes in rats].

A chronobiological study of behavioral changes in Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke prone spontaneously hypertensive rats (SHRSP) was undertaken. Attention was focused on changes in ambulatory activity and drinking behavior using an Ambulo-Drinkometer, the effects of centrally acting antihypertensive drugs, and the relationship between behavioral changes and humoral factors. (1) The experiment was performed during a light-dark alternation cycle. Approximately 10 days were required for rats to acclimate to new cages. (2) Using power spectral analysis, a 24 hr periodicity was dominant in both sexes of WKY and SHRSP. A 120 hr periodicity was demonstrated in female SHRSP. This long periodicity may have been due to a female sexual rhythm. (3) Ambulatory activity of WKY and SHRSP tended to decrease with age. (4) After abrupt cessation of clonidine administration, an ambulatory ultradian rhythm was demonstrated. Guanfacine treated SHR showed less change in ambulatory ultradian rhythm than clonidine treated SHR. (5) Using a Drinkometer with attached metabolic cages, drinking counts, urinary volumes, urinary aldosterone and catecholamine excretion rates were higher during the dark phase than during the light phase. It was demonstrated that analysis of rhythmicities and measurement of behavioral amplitude are both needed in the study of behavioral pharmacology.

Acclimatization↗

The role of I-J and Igh determinants on F1-derived suppressor factor in controlling restriction specificity.

In the 4-hydroxy-3-nitrophenyl acetyl (NP) contact sensitivity system, the activity of third-order suppressor cells and their factors is restricted by H-2(I-J) and Igh linked genes. The present report analyzes the specificity of NP-specific Ts3 cells and factors derived from H-2 and Igh heterozygous (B6 X C3H)F1 mice. Two approaches were used. First, heterogeneous populations of F1 Ts3 cells were activated in vitro and then assayed in Ts3-depleted recipients which carried different combinations of H-2 and Igh alleles. The second approach was to hybridize the Ts3 cells and analyze the specificity of the F1-derived TsF3. The combined data demonstrated four functionally distinct populations of Ts3 cells. The activity of each population was restricted by a particular combination of H-2 and Igh haplotypes. Thus, Ts3 cells derived from F1 donors can demonstrate an apparent scrambling of H-2 and Igh restriction specificities. There was functional allelic exclusion of the H-2(I-J) and Igh determinants expressed on (B6 X C3H)F1 hybridoma-derived TsF3. Thus, TsF3 from each cloned hybridoma line expressed only one set of I-J and Igh determinants. Furthermore, there was a complete correlation between the I-J and Igh linked determinants expressed on TsF3 and the restriction specificity. In view of the recent findings on the molecular biology of the I-J region, an alternative interpretation of the role of I-J determinants on suppressor cells and factors is offered.

Animals↗

A mechanism responsible for the induction of H-2 restricted second order suppressor T cells.

The mechanism by which I-J restrictions were imposed on second-order suppressor cells (Ts2) was analyzed. The induction of Ts2 cells requires presentation of an inducer suppressor factor by a specialized population of factor-presenting cells. The I-J phenotype of this factor-presenting population controls the H-2 restriction of the Ts2 cells. The splenic cells responsible for presenting inducer factor appear to be of macrophage or dendritic cell lineage. Several homologies exist between the mechanism responsible for the induction of H-2-restricted suppressor and helper T cells. Thus, the I region products on specialized presenting cells determine the specificity and genetic restrictions of the T cell. In an H-2 heterozygous F1 animal, two distinct populations of cells can be induced, one specific for each parental H-2 heplotype. Furthermore, the data suggest that the suppressor cells also bear receptors for self H-2 products. The ramifications of these observations for the suppressor cell cascade are discussed.

Animals↗

Analysis of T cell hybridomas. IV. Characterization of inducible suppressor cell hybridomas.

The Ts3 subset of suppressor cells is generated after antigen priming, but, in order to express suppressor activity these cells require an additional activation step involving triggering with specific suppressor factors (TsF2). This report characterizes two cloned hybridoma cell lines (pTs3 hybridomas) that represent this stage of Ts3 cell differentiation. These hybridoma cells could be specifically activated with TsF2 to release another antigen-specific suppressor factor (TsF3) within 6 h. The inducible feature of these cells permitted analysis of the signals necessary for Ts3 activation. Antigen was not required for activation. Only TsF2 factors derived from antiidiotypic second-order suppressor cells could activate pTs3 hybridoma cells. There were stringent genetic restrictions on the ability of Ts2 to activate pTs3 cells. Triggering of pTs3 required corecognition of two determinants on the TsF2 molecular complex, i.e., the I-J and Igh-related idiotypic determinants. Thus, although pTs3 cells could absorb TsF2 from an I-J-mismatched source, these pTs3 were not activated by the allogeneic TsF2. For activation to occur, the H-2 (I-J) and Igh complexes of the TsF2 donor had to match those of the strain from which the pTs3 cells were derived. Mixing two distinct TsF2, one derived from an H-2-matched source and the other from an Igh-matched source, failed to activate pTs3 cells. Once activated, the pTs3 cells released a suppressive material that was indistinguishable from the TsF3 factors previously characterized in this system. Finally, the activation of the pTs3 cells apparently does not induce the de novo synthesis of TsF3 since the suppressive activity could be extracted from nonactivated pTs3 cells. Thus, the inducible pTs3 hybridomas represent a mature stage in the differentiation cycle of Ts3 cells and provide a means for studying the nature of the specific signals required for Ts3 activation.

Animals↗

Analysis of T cell hybridomas. III. Distinctions between two types of hapten-specific suppressor factors that affect plaque-forming cell responses.

The ability of two cloned T cell hybridomas and their products to specifically suppress the in vitro plaque-forming cell (PFC) response to the 4-hydroxy-3-nitrophenyl acetyl hapten (NP) was studied. Supernatant from one hybridoma (TS1) was shown to suppress in the induction but not the effector phase of the immune response. Supernatant from the TS1 hybridoma was capable of inducing second-order (TS2) effector-phase suppressor cells in vitro but did not suppress the response of anti-I-J plus C-treated responder cells. In contrast, supernatant from a second hybridoma (TS3) was capable of suppressing PFC responses when added either in the induction or the effector phase of the response. TS3 supernatant was unable to induce effector-phase suppressor cells but was capable of suppressing the response of anti-I-J plus C-treated responder cells. In addition, specific suppressor factors isolated from supernatants of the TS1 and TS3 hybridomas were shown to bind to NP, bear NPb idiotypic and I-J-encoded but not immunoglobulin-constant region determinants. The factor secreted by the TS3 hybridoma appears to act directly on B cell targets. Mild reduction of this factor results in two separable moieties, only one of which binds NP. Reconstitution experiments suggest that both chains are required for function. The collective data indicate that these hybridomas represent cells from first- and third-order suppressor T cell populations described previously in contact sensitivity and in vitro PFC systems. The implications of the ability of these hybridoma products to affect both T and B cell-mediated immune responses are discussed.

Animals↗

Plasma norepinephrine concentration and plasma dopamine-beta-hydroxylase activity in patients with congestive heart failure.

The relationship between plasma norepinephrine (NE), epinephrine (E) and dopamine-beta-hydroxylase activity (DBH) was studied in 90 cardiac patients (New York Heart Association [NYHA] classes I-IV), 85 healthy control subjects and 18 competitive skiers. The cardiac patients in NYHA classes III and IV had significantly higher NE (p less than 0.001) and lower DBH (p less than 0.001) levels than the controls, whereas the skiers had significantly lower NE (p less than 0.001) and higher DBH (p less than 0.05) levels than the controls. Seven cardiac patients in whom successful cardiac surgery was performed had decreased NE (p less than 0.001) and increased DBH (p less than 0.02), as well as significantly improved NYHA cardiac status (p less than 0.001). These findings demonstrate an inverse relationship between NE and DBH in a population of athletes, normal subjects and cardiac patients; the same inverse relationship holds for these patients when sequential studies are done after a change in cardiac status.

Adolescent↗

Determination of anaerobic threshold for assessment of functional state in patients with chronic heart failure.

The use of anaerobic threshold in assessment of aerobic capacity was evaluated in 34 normal subjects and 47 patients with various kinds of chronic heart disease. Anaerobic threshold was determined as the oxygen consumption (VO2) at which a linear relationship between pulmonary ventilation (VE) and VO2 was lost during progressive treadmill exercise. Anaerobic threshold determined in this manner was validated with that determined by blood lactate measurements in eight normal subjects and nine cardiac patients (r = .962, p less than .001). Thereafter, anaerobic threshold was determined only by respiratory measurements. In symptom-limited, maximal exercise, anaerobic threshold was reached well before maximal effort and corresponded to 70% of maximal VO2 both in normal subjects and cardiac patients. Anaerobic threshold decreased as age progressed in normal subjects (r = - .70, p less than .001). Anaerobic threshold in cardiac patients was lower than that in the normal subjects and decreased progressively as New York Heart Association functional classification advanced (normal, 32.95 +/- 6.17 ml/min/kg; class I, 22.78 +/- 3.74; class II, 16.99 +/- 3.66; class III, 12.97 +/- 2.76; p less than .01 between each group other than between class II and class III). Anaerobic threshold in cardiac patients correlated poorly with other objective indices, e.g., cardiomegaly (r = -.54, p less than .001) and rise in pulmonary wedge pressure (r = -.64, p less than .001). At anaerobic threshold, cardiac patients subjectively graded the work load as light (13%), light-to-moderate (27%), moderate (30%), and moderate-to-heavy (28%). Thus determination of anaerobic threshold by respiratory measurements is a safe, accurate, and objective method to measure aerobic capacity in cardiac patients and in normal subjects.

Adult↗

[Plasma bradykinin concentration in patients with cardiovascular diseases].

The present study was undertaken to quantify the circulating kinins in patients with various cardiovascular diseases using a newly developed radioimmunoassay technique and to evaluate this method in terms of its clinical application. For the determination of bradykinin (BK), this assay uses a rabbit anti-serum which has been injected with kallidin. This assay shows good specific activity, recovery and reproducibility. In order to avoid the formation of kinin as well as to block its inactivation, human blood samples were collected with a polypropylene syringe containing an inhibitor mixture (EDTA, trasylol, 1-10-phenanthroline, soybean trypsin inhibitor, polybrene). 1) The plasma BK concentration in normal human subjects, in patients with essential hypertension, effort angina and other cardiac diseases were 12.2, 9.2, 8.0 and 14.0 pg/ml, respectively. 2) Thirty min after captopril (12.5 mg, p.o.) administration, blood pressure and pulmonary wedge pressures decreased, and cardiac output increased accompanied with increases in plasma renin activity, plasma BK concentration and plasma norepinephrine concentration. 3) During the cold pressor test, both plasma BK concentration and blood pressure increased in the normal human subjects, whereas plasma BK levels decreased and blood pressure increased in the patients with hypertension. This radioimmunoassay for plasma BK determination makes it possible to measure plasma BK concentration in patients with various cardiac diseases.

Adult↗