Biomedical subjects

T Aizawa

Publications and source records attributed to T Aizawa.

At least 19 recordsLinked to original sources

PubMed1992

Left ventricular filling abnormalities in non-insulin-dependent diabetes mellitus and improvement by a short-term glycemic control.

To determine whether left ventricular (LV) filling abnormalities in diabetes are associated with diabetic microangiopathy, and to evaluate the effect of a short-term glycemic control on the filling abnormalities, diastolic filling dynamics were assessed by pulsed Doppler echocardiography in 246 patients with non-insulin-dependent diabetics. Isovolumic relaxation time and the ratio of peak flow velocity of atrial filling wave to peak flow velocity of early filling wave (A/E) were significantly greater in diabetic patients than in age- and sex-matched control subjects. Diabetic patients with retinopathy had significantly greater isovolumic relaxation time and A/E values than those without retinopathy. A/E was significantly decreased 1 month after insulin treatment in those without, but not with retinopathy. It is concluded that LV diastolic filling is impaired in mildly hyperglycemic patients with non-insulin-dependent diabetes mellitus without severe complications, the abnormality being more intense in patients with retinopathy. A short-term glycemic control results in a marked decrease in abnormalities in patients without, but not with retinopathy.

Adult↗

PubMed1992

Degeneration in vitro of post-mitotic neurons overexpressing the Alzheimer amyloid protein precursor.

A pathological hallmark of Alzheimer's disease is the deposition of amyloid fibrils in the brain. The principal component of amyloid fibrils is beta/A4 amyloid protein, which can be generated by the aberrant processing of a large membrane-bound glycoprotein, the beta/A4 amyloid protein precursor (APP)3. To test whether overexpression of APP generates abnormally processed derivatives that affect the viability of neurons, we stably transfected full-length human APP complementary DNA into murine embryonal carcinoma P19 cells. These cells differentiate into post-mitotic neurons and astrocytes after exposure to retinoic acid. When differentiation of the APP cDNA-transfected P19 cells was induced, all neurons showed severe degenerative changes and disappeared within a few days. The degenerating neurons contained large amounts of APP derivatives that were truncated at the amino terminus and encompassed the entire beta/A4 domain. These results suggest that post-mitotic neurons are vulnerable to overexpressed APP, which undergoes aberrant processing to generate potentially amyloidogenic fragments.

Alzheimer Disease↗

PubMed1992

Expression of necdin, an embryonal carcinoma-derived nuclear protein, in developing mouse brain.

Necdin is a polypeptide sequence encoded by neural differentiation-specific mRNA derived from embryonal carcinoma cells. We have examined the expression of necdin and its mRNA in cultured cells and mouse brain by Northern blot analysis and immunohistochemistry. Among various established cell lines including neuroblastoma and glioma cells, only differentiated embryonal carcinoma cells (P19 and F9) expressed necdin mRNA. Necdin immunoreactivity was localized in the nuclei of differentiated neurons derived from P19 cells. Necdin mRNA was detected throughout brain regions of adult mouse; the relative abundances in the hypothalamus and midbrain were the highest, whereas those in the olfactory bulb and cerebellum were the lowest. In developing mouse brain, necdin mRNA was expressed during early periods of neuronal generation and differentiation, and the peak levels were attained during postnatal days 1-4. Necdin immunoreactivity was not detected in the neural stem cells on embryonic day 10, but was concentrated in the nuclei of brain cells, mostly neurons, at advanced stages of differentiation. The majority of differentiated neurons in the brain had necdin-immunoreactive nuclei on postnatal day 33. Thus, necdin may represent a valuable molecular marker for differentiated neurons both in vitro and in vivo.

Amino Acid Sequence↗

PubMed1992

Disappearance of thyrotropin-blocking antibodies and spontaneous recovery from hypothyroidism in autoimmune thyroiditis.

BACKGROUND: Hypothyroidism may result from the production of antibodies that block the actions of thyrotropin. How often these thyrotropin-blocking antibodies are a cause of hypothyroidism and whether their production may cease, causing hypothyroidism to disappear, have not been extensively studied. METHODS: We determined the frequency with which thyrotropin-blocking antibodies were present in 172 hypothyroid patients with goitrous autoimmune thyroiditis (Hashimoto's disease) and 64 hypothyroid patients with atrophic autoimmune thyroiditis (idiopathic primary hypothyroidism). For 6 to 11 years we then followed 21 of these patients who were found to have thyrotropin-blocking antibodies. They received levothyroxine therapy for 3.5 to 8 years, after which it was discontinued. At frequent intervals during this time we measured the patients' serum concentrations of thyroxine, triiodothyronine, thyrotropin, and thyrotropin-blocking antibodies (measured as immunoglobulins that inhibit thyrotropin binding and immunoglobulins that inhibit thyrotropin bioactivity). RESULTS: Thyrotropin-blocking antibodies were detected in 9 percent of the patients with goitrous autoimmune thyroiditis and in 25 percent of those with atrophic autoimmune thyroiditis. Among the 21 patients studied serially while receiving levothyroxine, thyrotropin-blocking antibodies disappeared in 15 (group 1), 7 of whom had goiter initially, and persisted in 6 (group 2), none of whom had goiter initially. Levothyroxine therapy was subsequently discontinued in these 21 patients. Six of those in group 1 (four with goiter) remained euthyroid (mean follow-up after discontinuation of therapy, 2.1 years), and nine became hypothyroid again within 3 months. All six patients in group 2 remained hypothyroid. CONCLUSIONS: Hypothyroidism in some patients with autoimmune thyroiditis may be due to thyrotropin-blocking antibodies. The production of thyrotropin-blocking antibodies may subside, producing remissions of hypothyroidism. Chronic autoimmune thyroiditis may therefore cause transient as well as permanent hypothyroidism.

Adult↗

PubMed1992

Silent myocardial ischemia in patients with non-insulin-dependent diabetes mellitus as judged by treadmill exercise testing and coronary angiography.

Patients with diabetes were compared with nondiabetic control subjects, with respect to the prevalence of silent myocardial ischemia, by means of treadmill exercise testing and coronary angiography. Results of treadmill exercise testing showed ischemic ST depression in 41 of the 132 diabetic patients (mean age 61 +/- 4 years) and in 42 of the 140 nondiabetic control subjects (mean age 60 +/- 8 years) (31% vs 30%, p = NS). Coronary angiography was performed in 36 of 41 diabetic patients and 34 of 42 nondiabetic control subjects with positive results of treadmill exercise tests, who gave their consent. Among "treadmill-positive" subjects, diabetic patients had a prevalence of silent myocardial ischemia that was 2.2 times higher than that in nondiabetic control subjects (p less than 0.05). Diabetic patients who received insulin had a 2.6 times higher prevalence of silent myocardial ischemia than those who did not (p less than 0.05). Similarly diabetic patients with retinopathy has a 2.5 times higher prevalence of silent myocardial ischemia than those without it (p less than 0.05).

Aged↗

PubMed1992

Alteration of renal function in hyperthyroidism: increased tubular secretion of creatinine and decreased distal tubule delivery of chloride.

In 77 untreated patients (16 males and 61 females, aged 12 to 65 years) with hyperthyroid Graves' disease, and in 107 control subjects (36 males and 71 females, aged 13 to 78 years), blood urea nitrogen (BUN), serum creatinine (Scr) levels, and BUN to Scr ratios (BUN/Scr) were determined. In 53 patients, the determinations were performed before treatment and after restoration of euthyroidism by treatment with an antithyroid drug. In addition, in seven untreated patients and seven normal subjects, renal clearances of creatinine (Ccr), urea nitrogen (Cun), inulin (Cin), and p-aminohippurate (CPAH) were also determined. The distal tubule delivery of chloride (DTD) and the distal fractional chloride reabsorption (DFCR) were also measured in these subjects: DTD = (CH2O + Ccl)/Cin x 100, and DFCR = CH20/(H20 + Ccl) x 100, where CH20 and Ccl stand for clearances of H2O and chloride, respectively. BUN was significantly elevated, while Scr was significantly depressed, in untreated patients with hyperthyroid Graves' disease. Accordingly, the BUN/Scr was markedly elevated. Restoration of euthyroidism accompanied the normalization of all these abnormalities. Ccr and Cun were significantly elevated, but Cin (glomerular filtration rate [GFR]) was slightly, but insignificantly, elevated in the patients. As a result, the ratios Ccr/Cin and Cun/Cin were significantly greater in the patients than in controls (Ccr/Cin, 1.42 v 1.00; Cun/Cin, 0.92 v 0.68). The amounts of urinary creatinine and urea nitrogen (UN) excretion were decreased and increased, respectively, and DTD was significantly depressed, but DFCR was unchanged in the patients. We conclude that BUN is elevated, Scr is depressed, and the BUN/Scr is increased in hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Induction of granule release by intracellular application of calcium and guanosine-5'-O-(3-thiotriphosphate) in human eosinophils.

The roles of Ca and G proteins in granule release from human eosinophils were examined by use of a patch-clamp technique in single cells. The morphologic changes and the release of eosinophil peroxidase (EPO) from single cells were simultaneously observed. In addition, the expression of small molecular weight guanine nucleotide binding protein (small G protein) mRNA (smg p25A [rab 3] and smg p21 [rab 1]) was investigated. The intracellular application of Ca, 10 mumol/L, and guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), 100 mumol/L, induced fusion of EPO containing granules with the surface membrane, which was associated with a marked increase in membrane capacitance. Ca alone caused a rapid granule release at an early stage of cell dialysis, but most granules still remained in a cluster. GTP-gamma-S alone caused a gradual degranulation. Northern blot analysis revealed the definite expression of smg p21 mRNA with no appreciable expression of smg p25A. These results provide direct evidence of granule fusion by intracellular application of Ca and GTP-gamma-S. In addition, Ca dependent proteins and G proteins act cooperatively in granule release, and these proteins likely regulate the different processes of degranulation. Furthermore, a protein, encoded by smg p21, may be involved in the granule release process in human eosinophils.

Calcium↗

PubMed1992

Abnormal molecular weight profile of urinary protein in rats with streptozotocin-induced diabetes.

A quantitative analysis of the molecular weight (MW) profile of urinary protein by SDS-PAGE was performed in streptozotocin (STZ)-injected, non-ketotic diabetic rats (DM group), diabetic rats receiving dipyridamole (DM-DIP group), normal rats (C group) and STZ-injected rats with near-normal glycemia due to insulin treatment (DM-INSULIN group). In the DM group, decrease of a small MW protein (SMWP) (MW 19.5 k) was found at 2.5 weeks, and an increase of larger MW proteins (LMWP) (MW 68 [albumin], 55 and 29 k) together with a decrease of SMWPs (MW 19.5 and 15 k) was found at 15 weeks, as compared to the C group: the MW profile of urinary protein in the DM-INSULIN and C groups was indistinguishable. At 15 weeks, creatinine clearance (Ccr) was significantly depressed and an increase in the mesangial matrix with electron dense deposits was evident in the DM group. The urinary protein abnormalities were partially corrected and the reduction of Ccr was absent in the DM-DIP group with no effect on glomerular morphology. STZ-induced diabetes in rats is accompanied by a reduction of urinary SMWP, and a subsequent increase of LMWP and depression of Ccr: dipyridamole ameliorates urinary protein abnormalities and prevents the reduction of Ccr.

Animals↗

PubMed1992

Increase of serum somatomedin C in hyperthyroid patients with pregnancy.

In thyrotoxic women with pregnancy, serum somatomedin C (SmC) concentration was markedly elevated (mean +/- SD 13.57 +/- 4.66 U/ml) compared to thyrotoxic women without pregnancy (1.24 +/- 1.09 U/ml), non-pregnant euthyroid women previously treated for hyperthyroidism (0.87 +/- 0.30 U/ml), normal subjects with pregnancy (6.08 +/- 3.36 U/ml) and pregnant euthyroid women previously treated for hyperthyroidism (5.98 +/- 1.52 U/ml). Since SmC/growth hormone ratio was significantly more in thyrotoxic pregnant women than in normal pregnant women and euthyroid pregnant women previously treated for hyperthyroidism, and since human placental lactogen (HPL), human chorionic gonadotropin (HCG) and prolactin (PRL) do not crossreact with SmC antibody, it is suggested that excess thyroid hormone during pregnancy results in excessive hepatic somatomedin C production.

Adult↗

PubMed1992

Differential effects of body weight, hyperinsulinemia and oral glucose load on serum C-peptide/insulin molar ratio.

Serum C-peptide immunoreactivity (CPR)/immunoreactive insulin (IRI) molar ratio was determined in 136 subjects without renal, hepatic and thyroid disorders, at fasting, and during the initial period of 75 g-oral glucose tolerance test. The subjects were divided into 4 groups based on their body weight and age; Group A, young (< 55 years) and normal body weight (body mass index [BMI, kg/m2] < or = 25) subjects; Group B, young and overweight (BMI > 25) subjects; Group C, aged (> or = 55 years) and normal body weight (BMI < or = 25) subjects; Group D, aged and overweight subjects. Fasting CPR/IRI ratio and absolute CPR level negatively correlated in Groups B and D but not in A and C. After oral glucose load with elevation of insulin, CPR/IRI ratio invariably declined in all groups and significant negative correlation between CPR/IRI and CPR was found in Groups A, B and D but not in C. Slope of the regression lines obtained for correlation between CPR/IRI ratio and CPR were significantly steeper at fasting compared to the post-stimulation phase. CPR/IRI ratio is affected by hyperinsulinemia and oral glucose load but not by obesity alone. Assuming that CPR/IRI ratio reflects hepatic extraction of insulin, the insulin clearance at fasting is progressively reduced with increasing insulin secretion in overweight subjects: failure to detect such phenomenon in normal body weight subjects may be due to a narrower CPR range in this population. Insulin metabolism at fasting and during glucose stimulation is likely to be regulated by distinct factors.

Aged↗

PubMed1992

A compact centrifugal pump for cardiopulmonary bypass.

A majority of the cardiopulmonary bypass (CPB) systems still utilize bulky roller pumps. A direct-drive small centrifugal pump intended for second-generation CPB pump has been developed. The pump has a 50 mm diameter impeller and provides a 6 L/min flow at 3,000 rpm against 300 mm Hg. A flexible drive shaft allows us to separate the pump head from the console resulting in easier manipulation. An in vitro study showed that the pump generated less hemolysis (index of hemolysis = 0.0011, comparable to the value for Bio-medicus BP-80). To improve blood flow around the shaft-seal region and to reduce thrombus formation around the shaft, six holes were drilled through the impeller. In biventricular bypass experiments using calves, our pump demonstrated excellent antithrombogenicity and durability for 48 h. And the compact and atraumatic centrifugal pump system showed excellent performance and easy manipulation under actual CPB conditions in animal.

Animals↗

PubMed1992

Development of an atraumatic small centrifugal pump for second-generation cardiopulmonary bypass.

A small and light direct-drive centrifugal pump has been developed for cardiopulmonary bypass. In the development process, blood compatibility studies including a hemolysis study, an in vitro fluid dynamic performance study, and in vivo durability and feasibility studies were performed. The centrifugal pump with a 50 mm diameter impeller resulted in almost the same index of hemolysis value as did a Bio-Medicus centrifugal pump. Heat dissipation from the motor was prevented by using a flexible drive cable. Forty-eight-hour sealing durability around the driving axis was accomplished by using a fluoro-rubber V-ring that connected to the hard chrome-plated stainless steel. In vitro and in vivo performances of the pump were satisfactory. Thrombus formation behind the impeller was prevented by using a holed impeller that generated blood flow from the back to the surface of the impeller. Elimination of air during priming procedures was also easier with this modification. This centrifugal pump has one-quarter of the priming volume, size, and weight of magnetically coupled centrifugal pump systems.

Animals↗

PubMed1992

Role of adrenal androgens in the development of arteriosclerosis as judged by pulse wave velocity and calcification of the aorta.

To evaluate the role of adrenal androgens in the development of arteriosclerosis, serum dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), aortic calcification and pulse wave velocity (PWV) were measured in 69 males and 119 females without overt cardiovascular disease. The steroids decreased with age in both sexes, and the reduction was significantly steeper in younger (< or = 40 years) than in older (> 40 years) subjects only in females. When adjusted for age, the steroids were significantly lower in subjects with aortic calcification than in those without it, and the PWV was significantly slower in the latter. Adrenal androgens appear to retard the development and/or progression of arteriosclerosis.

Adolescent↗

PubMed1992

Exacerbation of latent heart failure by mild hypocalcemia after parathyroidectomy in a long-term hemodialysis patient.

A 60-year-old uremic patient treated with hemodialysis for 13 years developed acute hypotension during hemodialysis and overt heart failure subsequently in a period of relatively mild hypocalcemia after parathyroidectomy. Blood pressure during hemodialysis was maintained by continuous calcium infusion alone. Cardiomegaly was improved by normalization of serum calcium. The cardiac complication is considered to be exacerbation of the underlying myocardial dysfunction by the acute decline of serum calcium which might be a feature of the 'hungry bone' syndrome. Latent myocardial dysfunction might be exacerbated by only mild hypocalcemia after parathyroidectomy in long-term hemodialysis patients.

Heart Failure↗

PubMed1992

Airway epithelial cells enhance eosinophil survival.

Guinea pig and human eosinophils were co-cultured with or without epithelial cells (controls). Eosinophil survival was enhanced in the presence of the cultured epithelial cells in a number-dependent fashion. Further, supernatants from cultured epithelial cells also enhanced eosinophil survival. Both a monoclonal antibody to GM-CSF and indomethacin inhibited these epithelial-cell-mediated effects, and GM-CSF and PGE2 were shown to prolong eosinophil survival. These findings indicate that airway epithelial cells can enhance eosinophil survival. It is suggested that the mechanism may involve GM-CSF and PGE2 generation.

Animals↗

PubMed1992

Differential effects of nifedipine on plasma atrial natriuretic peptide in normal subjects and hypertensive patients.

The physiology of atrial natriuretic peptide (ANP) secretion was studied in normotensive subjects and hypertensive patients both young and old. Basal plasma ANP concentration was least in young normotensives, intermediate in old normotensives and young hypertensives, and highest in old hypertensives. Nifedipine, a known stimulator of ANP secretion, acutely increased plasma ANP in young and old normotensive subjects but not in young hypertensive patients and half of the old hypertensive patients. Increase in serum ANP level in response to nifedipine did not augment its hypotensive effect. However, the increase of aldosterone in response to nifedipine-induced rise in plasma renin activity (PRA) seemed to be suppressed by elevated ANP.

Adult↗

PubMed1992

Mastoparan-induced hormone release from rat pancreatic islets.

Mastoparan, a tetradecapeptide purified from wasp venom, stimulates insulin and glucagon release by rat pancreatic islets in a dose-related manner. In perifusion experiments, mastoparan produces monophasic hormone release, which ceases within 10 min of removal of the peptide. After exposure of the isles to mastoparan, glucose-induced insulin release is clearly retained. In incubation experiments, mastoparan-induced insulin release is greatly blocked by pretreatment of the islets with pertussis toxin or neomycin (inhibitor of phosphoinositide turnover) or by lowering the ambient temperature to 17 C. Pretreatment of the islets with nifedipine (calcium channel blocker), H-7 (inhibitor of A- and C-kinase), somatostatin, or divalent cation-free medium does not affect the response to mastoparan. Pretreatment with parabromophenacylbromide (phospholipase-A2 inhibitor) does not block the response induced by a high concentration of (58 microM) mastoparan. The peptide does not stimulate insulin synthesis during 30 min of incubation. Mastoparan raises the cytosolic free Ca2+ concentration, measured by fura-2, in isolated islet cells at normal (1.9 mM) and very low (6.5 microM) extracellular Ca2+ concentrations. Intravenous administration of mastoparan in rats causes a significant elevation of both insulin and glucagon. Together with the previous data, we conclude that mastoparan stimulates islet hormone release through a temperature-dependent process mediated by pertussis toxin-sensitive GTP-binding protein(s). Activation of phospholipase-C and liberation of intracellular Ca2+ are likely to be coupled to exocytosis. Ca2+ influx through the Ca2+ channel and protein kinase-A and -C appear not to be involved in mastoparan's hormone-releasing action. Phospholipase-A2 may be involved in the hormone release induced by low, but not high, concentrations of the peptide.

Animals↗

PubMed1992

[Pharmacological studies of nutritive and tonic crude drugs on fatigue in mice].

The aim of the present study was to clarify acute anti-fatiguing effects of three crude liquid drug preparations (S1-S3), containing almost the same amounts of Ginseng Radix, Epimedii Herba and Agkistrodon Japonicae, with each differentially containing an additional 11, 13 or 15 crude drugs. After preloading forced swimming or tetrabenazine (TBZ: 50, 100 mg/kg, i.p.), each of the S1-S3 preparations applied orally (0.1 ml/10 g) significantly increased the duration times of swimming together with decreased total duration times of immobility during swimming. These effects peaked 60 min postinjection with the following decreasing order of effectiveness: S3 > S2 > S1. The same order of efficacy was also found for increased locomotor activity and decreased durations of swimming immobility after TBZ. After pretreatment with 200 mg/kg TBZ preparations S1-S3 also increased the numbers of jumping on a hot plate with greatly reduced latency. Without preloading the forced swimming, S1-S3 did not have any effect on jumping and its latency, but both S2 and S3 significantly, but more weakly, as compared to those after its preloading, decreased the immobility times. These results indicate that these crude preparations may cause tonic effects and so far tested, these effects seem to be more effective on subjects fatigued with physical and/or mental works than an normal subjects.

Administration, Oral↗