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Biomedical subjects

N Nagai

Publications and source records attributed to N Nagai.

At least 127 records · Page 7Linked to original sources
PubMed1995

IL-2 inhibits IL-4-dependent IgE and IgG1 production in vitro and in vivo.

Nippostrongylus brasiliensis (Nb) infection of mice induces IL-4 producing CD4+ T cells which stimulate polyclonal IgE and IgG1 production, providing a model system to study IL-4 action on B cells in vivo. B cell Ia expression and the proportion of IL-2R beta positive B cells were increased in Nb-inoculated mice, and B cells from these mice responded to IL-2 by prompt and marked cell growth. Injection of anti-IL-4 1 day after Nb inoculation substantially inhibited these responses, indicating that they were largely IL-4 dependent. Thus IL-4 acted as a polyclonal B cell activator in vivo and caused B cells to develop into IL-2 responsive cells. Furthermore, injection of IL-2 inhibited IgG1 and IgE production by Nb-inoculated mice. To understand the mechanism of this IL-2-mediated inhibition, we used an in vitro IgG1 and IgE induction system. B cells from Nb-inoculated mice displayed an increase in the capacity of IL-2 to inhibit lipopolysaccharide (LPS) plus IL-4-driven IgE and IgG1 production, indicating that B cells expressing IL-2R beta are highly sensitive to IL-2. This inhibition was principally dependent upon the direct action of IL-2 on B cells. However, partial abolition of IL-2 inhibitory action by anti-IFN-gamma treatment suggested that endogenous IFN-gamma released from IL-2-stimulated cells was also involved in this IL-2-mediated IgE and IgG1 inhibition. Northern blot analysis demonstrated that IL-2 inhibited IL-4 induction of germline and productive C epsilon transcripts in LPS-stimulated B cells. Digestion-circularization polymerase chain reaction analysis revealed IL-2 inhibited IL-4 induction of s mu-s gamma 1 rearrangement in LPS-stimulated B cells.

Animals↗
PubMed1995

Transthoracic visualization of pulmonary thrombus that mimicked left atrial thrombus. A case report.

A forty-five-year-old woman with an unusual case of primary pulmonary hypertension is presented. She showed a progressive dilatation of the pulmonary arteries and pulmonary thrombus over twenty-one years. Transthoracic echocardiography showed the presence of pulmonary arterial thrombus that mimicked left atrial thrombus. However, when the transducer was rotated clockwise to obtain the short-axis view, a thrombus was observed in the right pulmonary artery with spontaneous echo contrast. Although the visualization of pulmonary arterial thrombus by echocardiography has been quite limited, it would be worthwhile since patients with primary pulmonary hypertension may have enlarged pulmonary arteries, as observed in the present case.

Diagnosis, Differential↗
PubMed1995

Drug interactions between theophylline and H2-antagonists, roxatidine acetate hydrochloride and cimetidine: pharmacokinetic analysis in rats in vivo.

The effects of roxatidine acetate hydrochloride (Rox) on the pharmacokinetics of theophylline were compared to those of cimetidine in rats in vivo, Cimetidine or Rox was maintained at a steady state level using continuous infusion, then theophylline was injected into the rats as a bolus (7.5 mg/kg). Cimetidine showed competitive inhibition of theophylline elimination in vivo, with an inhibition constant (Ki) of 28.5 microM. Cimetidine significantly decreased the total body clearance and extended the plasma half-life of theophylline, but did not change its volume of distribution. In contrast, Rox did not significantly influence the pharmacokinetics of theophylline in rats. The in vivo animal model used in the present study for investigating the mechanism of the drug interaction showed good agreement with the results obtained in clinical and in vitro studies.

Animals↗
PubMed1995

Long-term follow-up of idiopathic ventricular arrhythmias in otherwise normal children.

Clinical characteristics and long-term prognosis of 163 children with ventricular arrhythmias without underlying heart diseases (78 with ventricular premature contractions (VPC group), 39 with ventricular couplets (CPLT group), and 46 with ventricular tachycardia (VT group)) were studied by Holter electrocardiographic monitoring (Holter ECG) and treadmill exercise testing. The age of the subjects at the initial examination was 8.9 +/- 3.4 years in the VPC group, 9.9 +/- 3.5 years in CPLT group, and 9.4 +/- 3.1 years in the VT group. The duration of the follow-up was 71.7 +/- 32.1 months in the VPC group, 65.9 +/- 32.8 months in the CPLT group, and 84.0 +/- 31.9 months in the VT group. VPC's disappeared during the follow-up period in 22 (28%) of the 78 children in the VPC group. CPLT's disappeared in 15 (38%) and VPC's disappeared in 9 (23%) of the 39 children in the CPLT group. In the 46 children in the VT group, VT disappeared in 30 (65%), and VPC's disappeared in 17 (37%). One child (2%) in the VT group died of heart failure due to drug-resistant sustained VT. The mean time until the disappearance of VPC's in the 163 patients was estimated to be 115.2 +/- 4.3 months. The mean time until the disappearance of VT in the 46 children in the VT group was estimated to be 89.0 +/- 4.9 months. Multivariate analysis of prognostic factors related to the disappearance of VPC's indicated that nighttime VPC's were significantly more likely to disappear (p = 0.018), and that symptomatic VT was significantly more likely to disappear than asymptomatic VT (p = 0.032), probably because more symptomatic cases received antiarrhythmic therapy. Ventricular arrhythmias in children without underlying diseases often disappeared, and the prognosis was generally favorable. However, appropriate treatment and follow-up were required in children with sustained VT, symptomatic VT, or VT with a high rate of VT.

Adolescent↗
PubMed1995

Histopathological features of atrophic thyroiditis with blocking type-TSH binding inhibitor immunoglobulins.

To investigate the histopathological features of atrophic thyroiditis (AT) with blocking type-TSH binding inhibitor immunoglobulins (TBII), the present morphological observations were carried out employing additional immunohistochemical procedures. Moreover, these were compared with examples of goitrous Hashimoto's thyroiditis showing negative TBII (HT). There exist apparent differences between AT and HT. In particular, significant follicular atrophy with epithelial flattening including decreased positive staining of the follicular epithelial cells for thyroglobulin in AT was characteristically observed. These results suggest that the mechanism for the development of hypothyroidism in AT with blocking type-TBII might be due to suppression of thyroid cell function through the inhibition of endogenous TSH stimulation by the blocking antibody with subsequent epithelial degenerative destruction.

Adult↗
PubMed1995

Two distinctive BMP-carriers induce zonal chondrogenesis and membranous ossification, respectively; geometrical factors of matrices for cell-differentiation.

A partially purified BMP preparation was combined with a fibrous glass membrane (FGM) or porous particles of hydroxyapatite (PPHAP), and then implanted subcutaneously into the backs of rats. As a control of these new carriers, a conventional carrier of insoluble bone matrix (IBM) was also used. These new geometrically different solid-state carriers induced tissues in quite different manners. FGM/BMP implants induced cartilage formation within the entire inner area of the membrane accompanied by a small amount of bone formation on the surface of the membrane. In contrast, PPHAP/BMP implants induced only bone within the pores of PPHAP without any detectable cartilage formation. Enzyme-linked immunosorbent assay revealed that the type II collagen content in FGM/BMP was six times higher than that in IBM/BMP, while there was no detectable type II collagen in PPHAP/BMP. The results were explained by the geometric properties of the two distinctive carriers.

Animals↗
PubMed1995

[New index for prediction of the patients prone to ventricular arrhythmias after acute myocardial infarction].

Recently late potential (LP) has been evaluated using signal averaged electrograms in order to predict the patients prone to the ventricular arrhythmias such as ventricular tachycardia (VT) or ventricular fibrillation (VF). However, the predictive accuracy was not satisfactory in clinical use. Therefore some new approach was expected. We tried to find a new index to predict the susceptibility to ventricular arrhythmias using frequency analysis by fast Fourier transformation technique (FFT). Fragmented electrograms are elucidated to be present through QRS complex beside the terminal portion of QRS and ST segment by Cain et al. Eighty-seven body surface electrograms were analyzed by FFT, and the power spectral distribution of specific band width of 25-50 Hz was evaluated. Late potential was also obtained by ordinary technique. The patients after acute myocardial infarction were classified into 5 groups according to Lown's grade; group 1 (grade 0.1), group 2 (grade 2), group 3 (grade 3,4A) and group 4 (grade 4B, non sustained VT), and group 5 (grade 4B, sustained VT/VF). The body surface distribution of 25-50 Hz were classified into 3 types; type A (almost equal two maxima), type B (unequal two maxima) and type C (single maximum). Types A & B were frequently observed, but type C was never seen in high risk group (group 4 and 5). Predictive accuracy of VT/VF was 89.2% by type A and 66.7% by LP. The combination of the two criteria improved the predictive accuracy of VT/VF up to 92.9%.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Surface Potential Mapping↗
PubMed1995

Clinical evaluation of human granulocyte colony-stimulating factor in chemotherapy for ovarian cancer.

The clinical evaluation of human granulocyte colony-stimulating factor (G-CSF) in 38 patients treated with chemotherapy for ovarian cancer stage III was investigated among 3 groups. G-CSF was not given in group A (19 courses), was administered from day 5 of chemotherapy in group B (53 courses), and was given when the WBC count decreased to below 2,000/mm3 in group C (29 courses). The time to nadir was significantly shorter in group B compared with groups A and C and revealed 10 days for the WBC count and 11 days for the neutrophil count (p <0.01), with mean nadir values of 2,896/mm3 and 982/mm3 respectively, and so the count of WBC and neutrophil have been kept during the course. The effect of G-CSF was not modified by age, body weight or the number of chemotherapy courses in groups B and C. These results demonstrate that early treatment with G-CSF may allow increased intensity of chemotherapy by using greater doses or by shortening of the interval between cycles.

Adolescent↗
PubMed1994

Mazindol enhances glucose uptake by rat skeletal muscle.

The pharmacological action of mazindol (5-hydroxy-5-p-chlorophenyl-2,3-dihydro-5-imidazo[2,1-a]isoindo l) was examined by studying its effect on glucose uptake by rat tissues using radiolabelled 2-deoxy-D-glucose. The following results were obtained. (1) The rate constant (Ki) of net tissue 2-deoxy-D-glucose uptake increased in the cerebral cortex (4.7-fold, P < 0.05), the hypothalamus (4.6-fold, P < 0.05), heart (4.0 fold, P < 0.05) and skeletal muscles (gastrocnemius, 5.7-fold, P < 0.01; soleus, 4.7-fold, P < 0.05), but not in epididymal adipose tissue in vivo 90 min after intragastric administration of mazindol (20 mg/kg). (2) This increase in Ki values of net tissue 2-deoxy-D-glucose uptake was not observed after addition of mazindol to the diet (40 mg/100 g of diet) for 4 days. (3) Mazindol (16.7 ng/ml to 16.7 micrograms/ml) stimulated 2-deoxy-D-glucose transport into sarcolemmal vesicles of the gastrocnemius muscle in vitro (1.6-1.8-fold, P < 0.05) and this stimulation was blocked by cytochalasin B (10 microM). These findings suggest that mazindol stimulates glucose transport into skeletal muscles by acting on glucose transporters in the sarcolemmal membrane, and suggest that mazindol may stimulate glucose transport into the brain and heart by a similar mechanism.

Animals↗
PubMed1994

Permissive effect of VIP on the hyperglycemic response induced by 2-deoxy-D-glucose.

We previously obtained evidence that in rats the neurons in the suprachiasmatic nucleus (SCN) receiving retinal neural inputs may be involved in the regulation of glucose metabolism. In this study we examined whether the SCN neurons containing vasoactive intestinal peptide (VIP)-like immunoreactive substance (VIP neurons) are involved in its regulation. We found that the hyperglycemic and hyperglucagonemic responses to intracranial injection of 2-deoxy-D-glucose (2DG) were synergistically enhanced by intracranial administration of VIP, and that these responses were significantly suppressed by treatment with anti-VIP antibody. These results suggest that VIP has a permissive effect on the hyperglycemic and hyperglucagonemic responses to 2DG, and thus that the VIP neurons in the SCN are probably involved in the regulation of glucose metabolism.

Analysis of Variance↗
PubMed1994

Variability in absorption lag time of pyridoxal phosphate under fasting and pre- and post-meal conditions.

Inter-individual variations in the absorption lag time of pyridoxal phosphate were determined after administration of an enteric-coated tablet (EC) or a plain capsule (PC) to 113 healthy volunteers under fasting, pre-meal, and post-meal conditions. The absorption lag time of pyridoxal phosphate was assessed from the urinary excretion of 4-pyridoxic acid after administration of EC and PC. Significantly larger lag times after administration of both formulations were observed under post-meal conditions than under pre-meal conditions (0.477 +/- 0.315 h versus 0.081 +/- 0.086 h for PC and 1.995 +/- 1.345 h versus 1.064 +/- 1.327 h for EC), indicating that the mean gastric emptying rates of both a solution and a tablet were delayed after food intake. The lag time for PC showed little inter-individual variation with (0-1.2 h) or without food (0-0.25 h), whereas that for EC showed markedly large inter-individual variation, from 0.25 to 2.63 h (median, 1.5 h) in the fasting condition, from 0.25 to > 5.5 h (median 0.25 h) under pre-meal conditions, and from 0.25 to > 5.5 h (median 1.25 h) under post-meal conditions. The effect of food on the gastric emptying rate of a solution appears to be almost uniform, whereas that for a tablet is so unpredictable that a reliable absorption rate for an enteric-coated tablet cannot be expected, particularly under pre- and post-meal conditions.

Absorption↗
PubMed1994

Circadian rhythms and energy metabolism with special reference to the suprachiasmatic nucleus.

The role of the hypothalamic suprachiasmatic nucleus (SCN) was examined in rats and obtained following results: (a) The time-dependent (light > dark) hyperglycemic response to intracranial injection of 2-deoxy-D-glucose (2DG) disappeared in rats with bilateral lesions of the SCN, in rats on weeks 4-6 after surgical blinding, and in congenitally blind (hereditary microphthalmic) rats; (b) The hyperglycemia induced by electrical stimulation of the SCN was not observed in weeks 4-8 after surgical blinding; (c) Change in the blood glucose concentration after insulin injection into the SCN was eliminated by SCN lesions; (d) Alterations in activity of autonomic efferents to peripheral organs on light exposure disappeared after SCN lesions; (e) SCN lesions decreased the blood glucagon level and increased the blood insulin level; (f) SCN lesions decreased protein intake, and glucagon increased it; (g) Increases in the plasma renin activity and vasopressin concentration after water-deprivation were suppressed in hereditary microphthalmic rats with abnormal SCN. These findings suggest that the SCN is involved in the mechanism of blood glucose and body fluid intake as well as that of circadian rhythm.

Animals↗
PubMed1994

Immunohistochemical demonstration of tenascin and fibronectin in odontogenic tumours and human fetal tooth germs.

The distribution of tenascin and fibronectin (plasma fibronectin) was studied immunohistochemically in ameloblastomas, ameloblastic fibromas and ameloblastic carcinomas, as well as in tooth germs using monoclonal antibodies. Tenascin is an extracellular matrix molecule that was shown to be enriched in the embryonic mesenchyme surrounding the budding epithelium in various organs, including the tooth. Tenascin was strongly expressed in the basement membrane zone of the ameloblastomas and in the early tooth germ and the dental lamina, but not in the dental follicle. The expression of tenascin in the ameloblastic fibroma was seen in the basement membrane of the epithelial islands throughout the stromal tissues. There were clear differences in fibronectin expression in the follicular ameloblastoma and ameloblastic carcinoma. The results suggest that tenascin and fibronectin are involved in epithelial mesenchymal interactions of the tooth germ and in odontogenic tumours.

Ameloblastoma↗
PubMed1994

A transient increase of phenylalanine ammonia-lyase transcript in kinetin-treated tobacco callus.

In tobacco cell culture (Nicotiana tabacum L. "Bright Yellow" T-13), phenylalanine ammonia-lyase (PAL) activity was induced in response to an exogenously added kinetin. RNA blot hybridization analysis showed that a single species of PAL transcript 2.9-kb in size was detected using the PAL cDNA cloned from kinetin-treated cells. The cellular content of this transcript increased transiently (2.5-fold) 4 h after the addition of kinetin followed by an increase in PAL enzyme activity at 16 h.

Adenine↗
PubMed1994

Somatic afferent regulation of plasma immunoreactive glucagon in anesthetized rats.

We examined the neural mechanisms of the effect of noxious and innocuous mechanical stimulation of various segmental skin areas on the plasma glucagon concentration. Experiments were performed using chloralose- and urethane-anesthetized rats, ventilated artificially. The cutaneous stimuli of two different modalities, noxious and innocuous mechanical stimuli by pinching and brushing, were delivered to various segmental areas including the face, forelimb for forepaw, abdomen, and hindlimb or hindpaw. Blood samples were collected from the femoral artery, and plasma glucagon was measured by radioimmunoassay. Cutaneous pinching for 3.5 min of the face, forepaw, abdomen, or hindpaw increased the plasma immunoreactive glucagon (IRG), and the increase was larger following pinching of the abdmen or hindpaw than pinching of the face or forepaw. Brushing for 3.5 min of the face, forelimb, abdomen, or hindlimb did not significantly affect the plasma IRG. The increase in plasma IRG following skin pinching was abolished when both parasympathetic vagal and sympathetic nerves to the pancreas were bilaterally severed. The increase in plasma IRG was not abolished after bilateral severance of either the parasympathetic vagal or sympathetic nerves alone. These findings indicate that excitation of cutaneous nociceptive afferent information from the various spinal segments can regulate glucagon secretion from the pancreas as a reflex response, whose efferent limb is dually composed of both sympathetic and parasympathetic nerves.

Anesthesia↗
PubMed1994

Somatic afferent regulation of cytotoxic activity of splenic natural killer cells in anesthetized rats.

The effects of non-noxious and noxious mechanical stimulation of the skin on cytotoxic activity of splenic natural killer (NK) cells and splenic blood flow were examined in anesthetized rats. Bilateral brushing of the body surface between the lateral chest and hindlimb for 30 min did not significantly influence cytotoxic activity of splenic NK cells, splenic blood flow or splenic sympathetic efferent nerve activity. Bilateral pinching stimulation of the skin of the hindpaws for 30 min reduced cytotoxic activity of splenic NK cells and splenic blood flow to 67 +/- 8 and 82 +/- 3% of the control values, respectively. Pinching the hindpaws for 30 min increased splenic sympathetic efferent nerve activity to 143 +/- 15% of control. Electrical stimulation (10 V, 10 Hz) of the splanchnic nerve for 20 min produced a decrease in the cytotoxic activity of splenic NK cells and splenic blood flow. The hindpaw pinching-induced suppression of cytotoxic activity of NK cells was abolished after surgical transection of the splenic sympathetic nerve or the spinal cord at the cervical level. These results indicate that the suppression of cytotoxic activity of NK cells and splenic blood flow following noxious pinching stimulation is a supra-spinal reflex response mediated via the splenic sympathetic nerve.

Afferent Pathways↗