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Biomedical subjects

T Aoki

Publications and source records attributed to T Aoki.

At least 1,405 records · Page 78Linked to original sources

Effects of antithyroid drug therapy on blood glucose, serum insulin, and insulin binding to red blood cells in hyperthyroid patients of different ages.

The mechanism of glucose intolerance in thyrotoxicosis was investigated in 119 patients with Graves's disease with careful consideration of the age-related deterioration of glucose tolerance. Before and after treatment of thyrotoxicosis with antithyroid drug, changes of blood glucose (BG) and serum immunoreactive insulin (IRI) in response to 50 g oral glucose tolerance test (OGTT) and insulin binding to red blood cell (RBC) were evaluated. In control subjects, the sigma IRI/sigma BG ratio after 50-g OGTT decreased progressively with age without significant change in absolute sigma IRI value, suggesting the occurrence of age-related insulin resistance. Glucose intolerance was much more apparent in hyperthyroid patients because of age-related relative decrease of insulin secretion. Such a decrease of insulin secretion was not found in age-matched postgastrectomy patients with a similar degree of hyperglycemia, however. Maximal binding of labeled insulin and number of insulin receptors of RBC were decreased in old patients but binding affinity was unchanged. Elevation of BG was partially suppressed when serum thyroxine (T4) and triiodothyronine (T3) were reduced to moderately supernormal levels, whereas sigma BG, sigma IRI, sigma IRI/sigma BG ratio, and insulin binding to RBC were all returned to normal when normal serum thyroid hormone concentration was maintained. Our data indicate that insufficient insulin secretion and reduced insulin action at the target cell are responsible, at least in large part, for age-related glucose intolerance in hyperthyroid patients.

Adolescent↗

Type I wheat ingestion allergy: a model of masked allergy.

Type I wheat ingestion allergy is a special type of food allergy because the patient usually is not aware of his allergy. The unawareness comes from two reasons; one is that the clinical symptom appears not immediately after ingestion of wheat products but occurs sometime (30-60 min) later, and the other is that it may not appear if the patient does not exercise at this particular time. Therefore, the reaction does not always follow wheat ingestion. The study of enzymatically digested gluten antigens in the patients disclosed that the allergenicity to wheat was reinforced by peptic digestion but abolished by further tryptic digestion, indicating that allergen activity was most potent in the stomach. Anaphylaxis may occur in some patients after wheat ingestion and exercise. Therefore, in exercise-induced anaphylaxis without apparent allergy, one should consider wheat allergy.

Adolescent↗

Effect of artificial and human external qigong on electroencephalograms in rabbit and spontaneous electrical activity of the rat pineal gland.

External gigong emitted by a quartz crystal upon application of electric current was evaluated by its biological effects, such as changes in frequency-analyzed electroencephalograms (EEG) in rabbits and spontaneous electrical activity of the rat pineal gland. Physical properties of this external gigong cannot be evaluated by currently available physical means. Three types of EEG changes were produced depending on the intensity of current applied to the crystal. These changes corresponded fairly well to the dose-dependent EEG changes after intravenous administration of 5-hydroxytryptophan. A gigong-containing medal also produced similar EEG changes depending on threshold to gigong. Human gigong similarly influenced EEG. All EEG changes disappeared after pinealectomy or after application of methysergide (10 mg/kg), a serotonin antagonist. The rate of spontaneous electrical activity of the pineal gland was depressed by reorientation of the rat to the north or to the south, by gigong emitted by a quartz crystal, or by application of a gigong-containing medal. Human gigong also depressed this electrical activity. The EEG changes produced by external gigong might be caused by increased serotonin concentration in the pineal gland, since the pineal gland is responsive to gigong as well as the earth's magnetic field, which is known to inhibit N-acetyltransferase by increasing serotonin concentration in the pineal gland. Hence, the finding that current-intensity-dependent EEG changes induced by quartz crystal-emitted gigong were analogous to dose-dependent EEG changes produced by 5-hydroxytryptophan might be attributed to increased serotonin levels by current-intensity-dependent inhibition of N-acetyltransferase by external gigong.

5-Hydroxytryptophan↗

Microglial and astrocytic change in brains of Creutzfeldt-Jakob disease: an immunocytochemical and quantitative study.

AIM: The relationship between microglial cells and astrocytes in brains from patients with Creutzfeldt-Jakob disease (CJD) was immunohistochemically and quantitatively studied. MATERIALS AND METHODS: CJD cases, including three with subacute spongiform encephalopathy (SSE), three with panencephalopathic type of CJD (PECJD) and six normal controls were examined. Microglial cells were preferentially labeled by monoclonal anti-KP1 (CD68) antibody and astrocytes by polyclonal anti-glial fibrillary acidic protein (GFAP) antibody. Two cytokines were labeled by polyclonal anti-tumor necrosis factor-alpha (TNF-alpha) and polyclonal interleukin-1alpha (IL1alpha). RESULTS: In the CJD brains, microglial cell density was significantly higher in the white matter than in the cerebral cortex. In contrast, astrocyte density was significantly higher in the cortex than in the white matter. In the PECJD cases, many hypertrophic microglial cells were clustered along the margin of the demyelinated white matter whereas severely demyelinated white matter contained few microglial cells. The microglial cells were also located in vacuoles in myelinated fibers of the internal capsule in the PECJD cases, which resembled myelinopathic alteration in vacuolar myelopathy. The GFAP-positive astrocytes proliferated much more numerously in the severely demyelinated white matter. The densities of astrocytes and microglial cells showed a significantly negative correlation in the cerebral cortex. The density of the white matter microglia did not differ between the PECJD and SSE cases. TNF-alpha and IL1alpha were expressed by microglial cells, but the TNF-alpha-positive microglial cells were very few in both SSE and PECJD cases. A subset of IL1alpha-positive microglia was found in the SSE case white matter, although the number of KP 1-positive microglial cells greatly surpassed the number of IL1alpha-positive ones. CONCLUSION: These results imply that microglia are increased in number before demyelination and become hypertrophic while phagocytosing myelin in PECJD, and that the negative correlation between the density of microglia and astrocytes is not regulated by either cytokine.

Adult↗

KP1 expression of ghost Pick bodies, amyloid P-positive astrocytes and selective nigral degeneration in early onset Picks disease.

We present a patient with early-onset Pick's disease in which selective nigral degeneration, KP1 expression of ghost Pick bodies and amyloid P-positive astrocytes were found. We also review the literature on early-onset Pick's disease. A 34-year-old man showed personality change including stereotypical behavior. Muscle rigidity and spasticity developed later, and he died twelve years after the onset of his illness. The brain showed lobar cerebral atrophy prominent in the temporal lobe, and to a lesser degree in the prefrontal and orbitofrontal cortex. The substantia nigra displayed profound degeneration whereas the head of the caudate nucleus and the putamen were not so seriously affected because the neurons were preserved and only slight astrocytic proliferation was seen. Many Pick bodies were found in the hippocampal formation, and ballooned neurons (Pick cells) were dispersed throughout the cerebral cortex, subcortical grey matter and hippocampal formation. The affected white matter exhibited severe fibrillary gliosis, and numerous astrocytes positive for glial fibrillary acidic protein and microglial cells positive for CR3/43 were found in the atrophied cortical lesions. The intraneuronal Pick bodies expressed ubiquitin, neurofilament and tau, and KP1 distinctly stained ghost Pick bodies. Tau-positive astrocytes were found in the striatum, hippocampal formation, pontine tegmentum, substantia nigra and affected frontotemporal cortices. These astrocytes were also positive for amyloid P. Extensive search of the literature on early-onset Pick's disease disclosed only a few cases with selective nigral degeneration, and we failed to find any differences in duration, progression of the illness and the extent of subcortical gray matter involvement between cases of early-onset and presenile onset of Pick' s disease. We conclude that the striatopallidal and nigral system can be affected independently in Pick's disease and report new immunohistochemical findings.

Adult↗

Serum stimulation and cell density regulate the proliferation of AsPC-1 cells through control of cyclin E and p27KIP1 expression.

BACKGROUND: Cellular proliferation in normal cells is tightly regulated by environmental conditions. Growth factors stimulate proliferation while cell confluence inhibits it. Human pancreatic cancer AsPC-1 cells were believed to escape from these restrictions because they possessed several mutations which promote cell proliferation. In this study, we focused on the relationships between growth conditions and the proliferation of AsPC-1 cells. MATERIALS AND METHODS: AsPC-1 cells were cultured under several growth conditions and the proliferation of cells was studied by incorporation of 3H-thymidine. The alterations of cell-cycle-related genes were studied by immunoblotting. RESULTS: By four consecutive days in culture, the nucleotide incorporation of AsPC-1 cells was markedly suppressed and the suppression was overcome by medium change or reduction of cell density. The induction of cyclin D1 by serum stimulation was observed, concomitant with the transient activation of extracellular signal-regulated kinases (ERKs). The most prominent changes of cell-cycle-regulating genes following consecutive culture or serum reduction were the down-regulation of cyclin E and the induction of p27KIP1. The down-regulation of cyclin E was more sensitive to cell density, while the induction of p27KIP1 was regulated by both increased cell density and reduction of serum. The down-regulation of p27KIP1 was caused by protein degradation. CONCLUSIONS: The proliferation of AsPC-1 cells was still controlled by cell density and serum stimulation; nevertheless, the cells possessed several oncogenic mutations. These results may provide a rationale for modifying the growth environment for treatment of pancreatic cancers.

Adenocarcinoma↗

Diagnostic application of CD44 variant expression in pancreatic juice for detection of pancreatic neoplasm.

Recently, increased and disorganized expression of CD44 variant exons (CD44v) has been demonstrated in several types of human malignancy. We tried to investigate CD44v expression in pancreatic juice from patients who underwent endoscopic retrograde pancreatography. We analyzed 24 patients with pancreatic neoplasms diagnosed histologically (adenocarcinoma, 17; adenoma, 7) and 15 patients with non-neoplastic lesions. The expression of CD44v mRNA in pancreatic juice was detected by using the reverse-transcription polymerase chain reaction technique followed by Southern hybridization with exon-specific probes. Of 17 patients with adenocarcinoma, 14 (82%) showed expression of CD44v6 mRNA and 11 (65%) showed expression of CD44v2 mRNA. Of 7 patients with adenoma, 6 (86%) were positive CD44v6 mRNA expression and 2 (29%) for CD44v2 mRNA expression; while, out of 15 patients with non-neoplastic lesion, 5 (33%) showed positive findings for CD44V6 mRNA and 3 (20%) for CD44v2 mRNA. Comparing of diagnostic accuracy among CD44v6, CD44v2 and cytological examination, the sensitivities for adenocarcinoma were 82%, 65% and 41% respectively. However, the specificity was lower in CD44v6 (50%), CD44v2 (77%) than in cytology (100%), because CD44v was positive in adenoma cases and normal cases. A combination of RT-PCR analysis for the expression of CD44v with cytological examination in the pancreatic juice may increase the accuracy of diagnosis for pancreatic cancer.

Adenocarcinoma↗

Intraosseous cholesterol granuloma of radius showing a lamellar structure on MR images: a case report.

We report a case of an intraosseous cholesterol granuloma in the radius showing a lamellar structure on MRI. T1-weighted imaging revealed a central area of mildly increased signal intensity with a surrounding low-intensity layer. On T2-weighted images, the central lesion demonstrated low-intensity signals, and the surrounding area exhibited a lamellar structure with three layers of high, low, and high intensity from the inside. On histological examination, the central area was found to consist of cholesterine crystals embedded in erythrocytes, and in the surrounding lamellar structure collagenous tissue may have provided the low signals, with vessel- and giant cell-enriched structures present at both the inner and outer margins, presumably evoking the high-intensity signals. The present lesion may have been formed by chronic hemorrhage into a preexisting simple bone cyst.

Adult↗

Induction of immunopotentiation activity by a protein-bound polysaccharide, PSK (review).

A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, has been recognized for its host-mediated induction of antitumor and antimicrobial activities in mice. Intravenous administration of PSK, in association with OK-432 (Picibanil), transiently induced endogenous production of a cytotoxic factor (CF) (possibly tumor necrosis factor, TNF) in normal mice. The ability to produce CF depended greatly on both dose and interval between administration of the PSK and OK-432. Although PSK has been reported to contain several active ingredients, unfractionated PSK has been used in almost all experiments performed so far. We recently reported that, of the four subfractions separated by successive filtration through membrane filters, only the highest molecular weight fraction F4 (MW greater than 200 kD) induced significant antimicrobial activity in mice. PSK stimulated the NBT-reducing activity of mouse peritoneal macrophages and the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN). Among the subfractions of PSK, the highest molecular weight fraction F4, and the fraction precipitated at pH 4.0-4.5 (Fr. 4), stimulated macrophage NBT-reducing activity and PMN iodination most. In contrast, natural and chemically modified glucans had little or no stimulating activity. PSK, F4 or Fr. 4 additively or synergistically stimulated TNF-induced cytotoxicity against L-929 cells, differentiation of human myelogenous leukemia cell lines toward monocytes/macrophages, and iodination of human peripheral blood PMN. The active PSK subfractions significantly reduced the down regulation of specific 125I-TNF or 125I-IFN-gamma binding to cellular receptors. These data suggest that (i) immunopotentiation activity of PSK might be ascribed, at least in part, to stimulation of cytokine action and production, and (ii) PSK might have some unique structural features.

Adjuvants, Immunologic↗

Mixed glioblastoma and sarcoma with osteoid-chondral tissue.

A 56-year-old man had a right temporal lobe tumor with calcification, which was removed surgically and treated with irradiation. The histology of the tumor was mixed tumor of glioblastoma and fibrosarcoma, and in the sarcoma portion osteoid-chondral tissue was found. With stains for proteoglycan and enzyme digestion tests, hyaluronic acid and chondroitin sulfate were demonstrated in the cartilage matrix. The positive reactivity of the proteoglycans to high iron diamine staining in the first surgical specimens changed to negative in the second and autopsy specimens. It is likely that the osteoid-chondral tissue derived from metaplastic change in sarcoma cells and in the later stage pleomorphism appeared.

Astrocytoma↗

Effects of the angiotensin II receptor antagonist, TCV-116, on blood pressure and the renin-angiotensin system in healthy subjects.

TCV-116 is a new, nonpeptide, angiotensin II type-1 receptor antagonist that acts as a specific inhibitor of the renin-angiotensin system. In this study, 36 healthy male volunteers were administered single and repeated oral doses of TCV-116 to investigate its effects on blood pressure and heart rate, and to evaluate the safety and pharmacokinetics of the drug. At single doses of 2.5 mg and greater, TCV-116 significantly lowered blood pressure even in normotensive subjects. This hypotensive effect was maintained during repeated administration on a once-daily regimen over an 8-day period. Serum concentration of M-1, an active metabolite of TCV-116, increased in a dose-dependent manner, reaching a peak 3 to 4 hours after administration. An amount of M-1 equivalent to approximately 10% of the administered dose of TCV-116 was excreted in the urine during the first 24 hours following administration. No accumulation of M-1 was observed in subjects receiving repeated administration of TCV-116. No adverse effects were observed except for mild headache in three subjects. These results suggest that the renin-angiotensin system plays a role in the regulation of blood pressure, even in normotensive subjects, and that TCV-116 may prove to be useful in the treatment of hypertension.

Adult↗

Hepatoid adenocarcinoma of the stomach: a case report.

A patient with primary gastric carcinoma showing a high level of serum a-fetoprotein (AFP) (368 ng/ml) is described. Subtotal gastrectomy was performed, and a month after surgery the level of serum AFP fell rapidly to within normal limits. Histologically, two types of cells coexisted in the tumor: medullary-type cells resembling trabecular-type hepatocellular carcinoma, and moderately differentiated adenocarcinoma cells. The cells of the former type were arranged mostly in a trabecular pattern with bile granules, but also showed a scirrhous pattern in a restricted area. Immunohistochemistry demonstrated that both types of tumor cells stained positively for AFP. This tumor, which should be classified as a hepatoid adenocarcinoma of the stomach, is of interest because of its rarity, bile secretion (indicating marked differentiation toward a hepatocyte form), and two cellular arrangements-trabecular and scirrhous.

Adenocarcinoma↗

Surgical treatments of chronic idiopathic thrombocytopenic purpura and prognostic factors for splenectomy.

To determine the prognostic factors for splenectomy in patients with chronic idiopathic thrombocytopenic purpura (ITP), 26 consecutive patients who had undergone splenectomy as a treatment for ITP in the last 20 years were investigated retrospectively. Predictive values of age, sex, the interval between diagnosis and surgery, presence of antiplatelet antibodies or accessory spleen, bleeding time, response to corticosteroids, response to high-dose immunoglobulin, weight of spleen, serum platelet-associated immunoglobulin G, preoperative maximal platelet count, and preoperative minimal platelet count were examined with multivariate analysis by multiple regression. Age less than 50 years at surgery, platelet count of 100 x 10(9)/l or more in response to high-dose immunoglobulin, and a maximal platelet count of 100 x 10(9)/l or more before splenectomy were favorable prognostic factors (p < 0.05). The correlation coefficient, sensitivity, specificity, and positive-predictive value of the analyzed multiple regression based on prognostic factors were 0.885, 68.8%, 85.7% and 91.7%, respectively. In conclusion, splenectomy is an effective treatment for younger patients, large maximal preoperative platelet counts and preoperative immunoglobulin dependence. Multivariate function analysis was useful for predicting outcome.

Adolescent↗

Suppressive effects of chronic hyperprolactinemia on penile erection and yawning following administration of apomorphine to pituitary-transplanted rats.

Recent studies showed in vivo and in vitro that acutely introduced prolactin (PRL) excess was capable of diminishing penile erectile function independently of the LH-testosterone (T) dynamics. In the present investigation, we examined if such independent suppressive effects can be demonstrated in the pituitary-transplant rat model with chronically elevated serum PRL. We also compared the effects of pituitary transplantation and castration on the level of erectile activity. Rats were made hyperprolactinemic by homologous transplantation of three anterior pituitaries underneath the kidney capsules, with the eutopic pituitaries left in situ. Before and 3, 5, and 8 weeks after transplant or sham surgeries, 80 micrograms/kg s.c. injection of apomorphine was given as an inducer of erection. This was followed by 30-minute observation periods during which the numbers of erections and yawning were recorded. Similar experiments were also performed with castrated rats without transplanted pituitaries. In the transplanted rats plasma PRL was markedly elevated (51.4 +/- 3.7 ng/ml) and was significantly (P < 0.001) higher than the values in the sham group (6.0 +/- 2.7 ng/ml). In contrast, plasma T was not different (P > 0.05) between the two groups. The castrated rats showed very low plasma T (0.17 +/- 0.01 ng/ml, P < 0.05 compared to the sham group) and normal PRL (P > 0.05). The numbers of both erection and yawning were significantly (P < 0.05-0.01) less in the transplant than in the sham group 8 weeks after surgeries. Castrated rats showed a significant reduction (P < 0.05) only in the numbers of erection. These results indicated that the pituitary transplantation with chronic excess of PRL and castration with T deficiency caused roughly comparable degrees of suppression of penile erectile activity through mechanisms presumably independent from one another in the rat.

Animals↗

Lung cancer associated with punctate calcification: CT and histological correlation.

The etiology of punctate calcifications in lung cancer was evaluated on the basis of CT and histological correlations. Seven cases of lung cancer with punctate calcifications were demonstrated on CT. The patients had undergone surgical resection (five men and two women, 60-70 years old; six adenocarcinomas and one squamous cell carcinoma), and each case was evaluated for its CT appearance and histological findings. The number of calcifications observed on CT varied from one to six. Most were eccentric, but some calcifications in four cases were within the more central portion of the nodules. Overall, in six of seven cases the calcifications were histologically estimated to be due to preexisting old granulomatous fibrotic changes or fragments of bronchial cartilage incorporated within the growing tumors. In only one case were the calcifications psammoma bodies within the tumor. We conclude that punctate calcifications in lung cancers correspond mostly to preexisting calcified granuloma or degenerated bronchial cartilage.

Adenocarcinoma↗