G-CSF levels during spontaneous recovery from drug-induced agranulocytosis.
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Agranulocytosis↗
Biomedical subjects
N Ohsawa
Publications and source records attributed to N Ohsawa.
Sensitive chemiluminescent immunoassay for human granulocyte colony-stimulating factor (G-CSF) in clinical applications.
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Adolescent↗
Origin of the rhythmical fluctuations in the animal without a natural heartbeat.
In order to analyze the origin of the rhythmical fluctuations in the cardiovascular system, an artificial heart, which does not have rhythmical periodicities such as altering heart rate and cardiac function, was utilized in chronic animal experiments with adult goats. Two pneumatically actuated ventricular assist devices were implanted as a total biventricular bypass under general anesthesia, and then the natural heart was electrically fibrillated to constitute the biventricular bypass type of complete prosthetic circulation model. All hemodynamic data were recorded under awake conditions and were calculated in the computer system by spectral analysis methods. In the power spectrum of the arterial blood pressure of the animal with the artificial heart, the Mayer wave peak and respiratory wave peak were clearly observed, and spectral analysis including the coherence function suggests that the Mayer waves originated from the peripheral vascular resistance and the respiratory waves probably originated from the periodicities of the pulmonary circulation. These fluctuations in the circulatory system influenced the arterial baroreflex system and transfer to the sympathetic outflow through the central baroreflex system, which suggests that rhythmical fluctuations in hemodynamic parameters originate at least in part from these vascular periodicities.
Animals↗
Familial unresponsiveness to thyrotropin by autosomal recessive inheritance.
Unresponsiveness to TSH has been identified and sufficiently studied in only three patients. We report siblings with this defect as the first documentation of familial occurrence. A 26-yr-old woman was diagnosed with congenital hypothyroidism during infancy. The thyroid was atrophic, and thyroid function tests without T4 replacement showed serum free T4 levels below 3 pmol/L, serum TSH of 125 mU/L, and serum thyroglobulin below 5 mg/L. 123I scintigram showed decreased uptake (5% at 24 h), but normal shape at the correct position in the neck. Autoantibodies against thyroglobulin, thyroid peroxidase, and TSH receptor in serum were not detected. The amount of cAMP released into FRTL-5 cell culture in the presence of TSH from the patient was not different from that released by the same amount of TSH from normal subjects, suggesting that TSH bioactivity in our patient was normal. The brother of the patient also had congenital hypothyroidism, and the data on his thyroid function was similar to that for his sister. There was a consanguineous marriage in the parents of the siblings, and the mother of the patients had a normal serum free T4 level, but slightly increased serum TSH and thyroglobulin levels, indicating subclinical hypothyroidism. The possible pathogenesis of TSH unresponsiveness in our patients includes a mutation in the TSH receptor gene, abnormality in transcription-regulating factor, abnormality in GTP-binding protein, and/or inhibition of the action of cAMP. The family history of the patients suggests that the mode of inheritance in TSH unresponsiveness is autosomal recessive.
Adult↗
Effects of exercise and pacing loads on myocardial amino acid balance in patients with normal and stenotic coronary arteries, with special reference to branched chain amino acids.
Arterial and coronary sinus differences (A-S) of alanine, glutamate, isoleucine, leucine, valine and phenylalanine were measured in 7 control subjects and 12 patients with coronary artery disease (CAD) at rest and during exercise, and in 8 controls and 21 CAD patients at rest and during pacing. Lactate, great cardiac vein flow and oxygen were also measured. However, none of these parameters distinguished CAD from controls. Changes in alanine and glutamate during each load were, for the most part, consistent with previous studies, i.e., a greater release of alanine and uptake of glutamate was observed in the ischemic group. A-S of isoleucine, leucine and valine showed significant positive correlation to that of alanine (r = 0.59, r = 0.89, r = 0.77, respectively, during exercise, and r = 0.57, r = 0.65, r = 0.72, respectively, during pacing). A-S of isoleucine, leucine and valine showed significant positive correlations to each arterial concentration during exercise (r = 0.54, r = 0.62, r = 0.63, respectively), but not during pacing. Although none of the uptakes of the branched chain amino acids (BCAA) were significant, the mean A-S of each BCAA was positive at rest in both controls and CAD, and declined during each load. A-S of leucine was significantly smaller in CAD than in controls during exercise (0.7 +/- 7.0 vs 6.8 +/- 4.1 mumol/l, p < 0.05) and those of leucine and valine were significantly smaller in CAD patients with ischemic electrocardiographic change than in those without electrocardiographic change during pacing (0.1 +/- 5.9 vs 6.1 +/- 5.5, p < 0.05; -3.1 +/- 10.1 vs 9.9 +/- 6.8 mumol/l, p < 0.01, respectively). These results suggest that BCAA, especially leucine and valine, tend to be taken up by human myocardium physiologically and show characteristic changes under myocardial stress similar to those seen with alanine and glutamate.
Adult↗
[Effects of repeated restraint stress at 30-minute intervals during 24-hour on serum testosterone, LH and glucocorticoids levels in male Japanese monkeys (Macaca fuscata)].
We investigated effects of frequent blood collections under the compulsory restraints on serum testosterone, LH and glucocorticoids in adult male Japanese monkeys. Blood samples were withdrawn from three animals at 30-min intervals and two animals at 4-hr intervals during 24 hr. Serum testosterone and LH were measured by a radioimmunoassay, and glucocorticoids was determined by a competitive protein binding assay. Sampling at 4-hr intervals during 24 hr revealed diurnal changes in serum testosterone and glucocorticoids. Levels of testosterone were high throughout the night and low at the day time, conversely serum glucocorticoids were high levels in the morning and low in the evening. On the other hand, 30-min intervals sampling, serum testosterone levels decreased and glucocorticoids levels increased, respectively, immediately after the start of blood sampling. And then, low in testosterone and high in glucocorticoids levels were continually maintained. But serum LH levels had the pulsatile pattern and did not change markedly during 24 hr. After ACTH administration in five animals, serum glucocorticoids levels increased markedly and also testosterone levels increased slightly, but LH levels did not change. These data indicated that the every 30-min restraint stress caused the increment of glucocorticoids levels and the suppression of testosterone levels, but did not affect the serum LH levels. The increased glucocorticoids might inhibit the testicular steroidogenesis, without suppressing the LH secretion from the pituitary.
Animals↗
Nutritional status of antioxidant vitamins (A, E, and beta-carotene) in elderly Japanese.
The nutritional status with respect to vitamins A and E, and beta-carotene was examined in elderly Japanese subjects in two institutions at Osaka and Kyoto. Only the plasma vitamin E level has been determined in the majority of previous investigations. In this study, vitamin E levels were determined in red blood cells (RBCs), platelets (PLT), mononuclear cells (MN), polymorphonuclear cells (PMN), and buccal mucosal cells (BMC), using HPLC with electrochemical detection. Alpha-tocopherol levels in plasma and RBCs did not differ between elderly and young adults, while those in PLT, MN, and BMC were lower in the elderly. Thus, the vitamin E status of elderly Japanese individuals appears to be inadequate of the cellular levels. The daily vitamin E intake of the elderly subjects was below the recommended dietary allowance for the Japanese population. Plasma levels of retinol and beta-carotene were also assessed. The vitamin A status did not differ between elderly and young adults on the basis of the levels of retinol and retinol-binding protein (RBP). The daily intake of retinol (as retinol equivalent) by the elderly subjects was more than 2,000 IU. With respect to beta-carotene, there was a large sex difference (female > male), which was more prominent in the young adults and became smaller in the elderly. This sex difference was partly attributable to a difference in plasma total lipids. No clear age-related trend was noted.
Adult↗
[Three cases of herpes simplex virus type 2 myelitis--detection of HSV2 DNA in cerebrospinal fluid].
Polymerase chain reaction (PCR) technique has been successfully used to detect herpes simplex virus (HSV) from patients with HSV encephalitis. By PCR assay capable of differentiating HSV1 and 2, we detected HSV 2 DNA in cerebrospinal fluid (CSF) from patients with HSV myelitis and discussed the clinical findings. Three cases of HSV myelitis (a 49-year-old female, two 38- and 44-year-old males) were studied. All cases were characterized by transverse myelopathy of the thoracic cord, and two patients had recurrence. In all cases HSV1 antibodies were significantly elevated in serum and CSF. We used 500 microliters of CSF for PCR, and prepared one common upstream primer and two type specific downstream primers for HSV1 and HSV2. Using three primers simultaneously different sizes of PCR products were amplified from HSV1 and HSV2 DNA. PCR products subjected to electrophoresis on 1.2% agarose and stained with ethidium bromide. Still more southern blot hybridization was performed to detect DNA by 35S-end-labelled oligonucleotide prove. HSV2 DNA was amplified from CSF in all cases by PCR, and HSV2 DNA was detected at both first and second episode in two relapsing myelitis. No case of relapsing myelitis by HSV2 has been reported. The PCR technique is useful for diagnosis of HSV1 and 2 myelitis, and its would suggest that some patients of idiopathic myelopathy could be due to HSV2 myelitis and HSV2 myelitis may not be rare.
Adult↗
[Tissue variability of androgen receptor gene in bulbospinal muscular atrophy--comparison of the number of CAG repeats between muscles and peripheral blood leukocytes].
We investigated an expansion of CAG repeats in exon 1 of androgen receptor gene in skeletal muscle tissue obtained from the patients with various neuro-muscular disorders (5 BSMA, 33 patients with amyotrophic lateral sclerosis, 3 patients with spinal progressive muscular atrophy and 2 patients with hereditary motor sensory neuropathy), by polymerase chain reaction (PCR) amplification according to LaSpadas' description. These muscle tissues had been stored at -70 degrees C freezer during 7 years. We also studied the tissue variation of CAG repeats size between muscles and peripheral blood leukocytes in 4 patients with BSMA. And we confirmed the increased number of CAG repeats in all 5 BSMA except for other patients with neurogenic muscular atrophy. In the 4 BSMA patients, we subcloned the PCR products from muscles tissues and peripheral blood leukocytes, and we determined the number of CAG repeats by sequencing. The repeats of them were 43-51, and all BSMA patients showed the same number of CAG repeats in muscles tissues and peripheral blood leukocytes. The CAG repeats fragment of BSMA may be stable region in frozen storage state for 7 years, and we didn't recognized the somatic variation at least between muscles tissues and peripheral blood leukocytes.
Adenosine↗
Growth-inhibitory action of an estrogen-chlorambucil conjugate (KM2210) in human breast cancer cell line MCF-7: its relation to reduction of estrogen receptor and transforming growth factor-alpha secretion.
We investigated the effects of a benzoate of an estradiol-chlorambucil conjugate (KM2210) and chlorambucil on growth, estrogen receptor, and secretion of transforming growth factor (TGF)-alpha in the hormone-dependent human breast cancer cell line MCF-7. In the presence of 10(-10)-10(-6) M KM2210, the estrogen-induced growth of MCF-7 was completely inhibited. Inhibited growth of MCF-7 treated with 10(-8) or 10(-6) M KM2210 for 4 days was not rescued by removal of the drug and the addition of estradiol. By treatment of MCF-7 with KM2210 for 4 days, estrogen receptor-binding sites were decreased at 10(-8) M and were not detected at 10(-6) M but were unaltered by 10(-8) M chlorambucil. Moreover, estrogen receptor immunoreactivity and the level of estrogen receptor mRNA were decreased through treatment with 10(-6) M KM2210 for 4 days. These suppressions occurred prior to the onset of inhibitory action on MCF-7 growth. Secretion of TGF-alpha from MCF-7 was decreased by 4 days of treatment with 10(-8) and 10(-6) M KM2210 but not with chlorambucil. The addition of exogenous TGF-alpha generally restored the growth of MCF-7 treated with 10(-8) M KM2210. We concluded that KM2210 has irreversible or at least long-standing inhibitory effect on estrogen-dependent growth of MCF-7. It is conceivable that the decrease of estrogen receptor renders the cell unable to respond to estrogen with increased TGF-alpha secretion and succeeding cell growth.
Antineoplastic Agents↗
Comparative studies by cell culture and in vivo implantation test on the toxicity of natural rubber latex materials.
Colony assay using V79 cells, the agar diffusion assay with L929 cells, and the 7-day rabbit muscle implantation test were employed to evaluate the cytotoxicity and tissue toxicity of natural rubber latex (NRL) materials. The in vivo implantation test showed that, among 13 histological parameters, thickness of inflammatory layer was the most useful index to evaluate tissue responses quantitatively. A comparison of the in vivo and in vitro parameters revealed the following correlations between the thickness of the inflammatory layer and cytotoxicity indices: Colony assay of the extracts, IC50: r = 0.80; Agar diffusion assay, Zone index: r = 0.73; Lysis index: r = 0.61. From these results, it appears that the colony assay provides a more reliable prediction of the tissue response than the agar diffusion assay.
Animals↗
Postprandial hypotension in patients with non-insulin-dependent diabetes mellitus.
This study attempted to determine whether postprandial hypotension (PPH) is associated with diabetes mellitus by 24-h ambulatory blood pressure monitoring (24-h ABPM) and by monitoring blood pressure during 75-g oral glucose tolerance test (75-g OGTT) in 15 normal subjects and 35 patients with non-insulin-dependent diabetes mellitus. When we defined PPH as a postprandial decrease in systolic blood pressure of greater than 20 mmHg, the incidence of PPH in diabetics was 37% by 24-h ABPM and 20% by 75-g OGTT. The incidence of proliferative retinopathy and proteinuria was greater in diabetics with PPH than in those without PPH. All of the patients with PPH had somatic and autonomic neuropathy. The C-peptide response was lower in diabetics with PPH than in those without PPH. We revealed the presence of PPH in diabetics, and found that PPH was closely related to disease severity, especially diabetic autonomic neuropathy.
Adult↗
Peroxidase and coupling activities of thyroid peroxidase in benign and malignant thyroid tumor tissues.
The coupling activity of thyroid peroxidase (TPO) in thyroid glands from patients with benign adenoma, papillary carcinoma, and diffuse goiter (Graves' disease) was measured for the first time, in addition to the peroxidase activity of these tissues. The peroxidase activity of TPO in the mitochondria-microsomes fraction was measured with guaiacol or iodide as the second substrate. In the case of papillary carcinoma, the mean protein-based specific activity obtained by the guaiacol assay was about 1/7 of that of diffuse goiter. The iodide oxidation activity of carcinoma was very low, about 1/25 [corrected] of that in diffuse goiter and 1/70 of that in adenoma. The peroxidase activity in adenoma was almost similar in the guaiacol oxidation assay and approximately one half in the iodide oxidation assay as compared with that in diffuse goiter. There was a close correlation between the guaiacol and iodide oxidation assays in individual patients with adenoma and diffuse goiter, but not in patients with papillary carcinoma. The coupling activity of TPO was measured with thyroglobulin purified from pooled toxic diffuse goiters and chemically iodinated to contain little additional T3 and T4. The specific coupling activity of TPO in mitochondria-microsomes from carcinoma was significantly lower (about 1/5) than that of diffuse goiter, and the activity in adenoma was not significantly different (about 1/2) from that of diffuse goiter. The data of coupling activities has a close correlation with that of peroxidase activities in individual patients with adenoma but not in patients with carcinoma. Based on these findings, the qualitative abnormality of TPO and its relation to the cold 123I scintigram in thyroid tumors are discussed.
Adenoma↗
Thyroid-stimulating antibodies and thyroid stimulation-blocking antibodies during the pregnancy and postpartum period: a case report.
This report describes a unique pattern of changes in thyroid function and thyroid antibodies in a woman during the course of two pregnancies and two postpartum periods. A 25-year-old woman developed hypothyroidism in the postpartum period after the delivery of her first child. She was found to have potent thyroid stimulation-blocking antibodies (TSBAb) in the serum. One year later, she became pregnant again, and during the pregnancy, TSBAb had decreased to an undetectable level. She gave birth to the second healthy child and developed postpartum thyrotoxicosis, probably due to destruction of the thyroid gland, which gradually resolved. In this postpartum period, serum TSBAb levels increased. Eight months postpartum, she developed what appeared to be Graves' disease with an elevated 123I-thyroid uptake. Serum thyroid-stimulating antibodies (TSAb) were found at that time, and the TSBAb had disappeared from her serum.
Adult↗
Epithelial hyperplasia and decreased colloid content of the thyroid gland in triiodothyronine-predominant Graves' disease.
Patients with T3-predominant Graves' disease have an increased serum T3 level despite a normal or even lower level of serum T4 caused by antithyroid drug treatment. This study investigated the morphological characteristics of the thyroid gland in this type of hyperthyroidism. Ultrasound showed a similar thyroid echogenicity in both T3-predominant and ordinary Graves' disease, but thyroid weight was significantly greater in T3-predominant Graves' disease than in the controls [91 +/- 37 g vs. 48 +/- 17 g (mean +/- SD); P < 0.01]. The height of thyroid follicular epithelial cells were significantly greater in T3-predominant Graves' disease than in the controls (9.6 +/- 1.0 vs. 6.4 +/- 1.1 microns), but the epithelial height did not correlate significantly with the serum TSH receptor antibody titers. Epithelial cells occupied 26.4 +/- 10.9% of the total thyroid tissue in T3-predominant Graves' disease, while they occupied only 14.5 +/- 6.8% in the controls. Intracolloidal vacuoles also occupied a significantly greater area in the T3-predominant group (6.6 +/- 3.9% vs. 1.9 +/- 1.0% for controls). These findings suggest that the thyroid gland is more active in T3-predominant Graves' disease and has a more rapid turnover of intrathyroidal iodine than in the ordinary type of Graves' disease.
Adolescent↗
Biochemical studies of the relationship between iodothyronine 5'-monodeiodinase and protein disulphide isomerase in rat liver.
The relationship between type I iodothyronine 5'-monodeiodinase (5'-MD) and protein disulphide isomerase (PDI) was investigated by using a synthetic 18-amino acid peptide (LAP475c), which corresponds to the sequence of amino acids at position 373-390 of PDI including its active site, and anti-LAP475c antibody. Western blot analysis revealed that our anti-LAP475c antibody was highly specific for 57K protein in solubilized rat liver microsomal protein (SRLMP) that corresponded to PDI. Anti-LAP475c IgG (1:100 dilution) precipitated 46% of 5'-MD. These data suggest that PDI may play a regulatory role in the 5'-monodeiodination reaction.
Amino Acid Sequence↗
Hepatic and renal expression of rat apolipoprotein E under control of the metallothionein promoter in transgenic mice.
We created three lines of transgenic mice with an integrated rat genomic apolipoprotein E gene fused with the mouse metallothionein I promoter. These lines transcribed rat apoE mRNA in the liver and/or in the kidney and expressed significant amounts of rat apoE in plasma. Enhancement of the plasma level by treatment with Zn ion or Bi ion was observed.
Animals↗
Insulin-dependent diabetes mellitus in which glycemic control was improved during pregnancy but deteriorated after delivery with the occurrence of postpartum thyrotoxicosis: a case report.
We report a patient, a twin, with diabetes mellitus whose hyperglycemic state fluctuated during the course of the pregnancy and the subsequent delivery. She was diagnosed as having slowly progressive IDDM because of her clinical course and the findings of serum positive ICA/CF, positive HLA-DR4 and disconcordance of diabetes mellitus with her identical twin. Insulin therapy was not initially needed in the first two years because the endogenous insulin secretion was not completely reduced. After two years of insulin therapy the patient became pregnant. Her glycemic control was remarkably improved without changes in dietary intake and insulin dosage. After delivery glycemic control deteriorated after delivery with the occurrence of postpartum thyroiditis. Urinary excretion of CPR was increased during pregnancy but decreased after delivery. ICA/CF in serum were persistently detected in the whole observation period. It seems that the improved glycemic control during pregnancy was caused by the reduction in the autoimmune reaction and the deterioration in glycemic control during the postpartum period was induced by the acceleration of the autoimmune reaction by the same mechanism of postpartum autoimmune thyroiditis.
Adult↗