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Biomedical subjects

T Obara

Publications and source records attributed to T Obara.

At least 127 records · Page 7Linked to original sources

Four new nucleotide sequence polymorphisms in the LDL receptor gene detected by SSCP analysis.

Seven nucleotide sequence polymorphisms were detected within exons of the low-density lipoprotein (LDL) receptor gene using single-strand conformation polymorphism (SSCP) analysis followed by direct sequence analysis on amplified DNA. Four nucleotide changes at nucleotide positions 1617, 1725, 2232, and 2635 were new nucleotide sequence polymorphisms not previously described. The remaining three nucleotide changes were identical with restriction fragment length polymorphisms and a previously reported nucleotide sequence polymorphism. These nucleotide sequence polymorphisms, detectable by SSCP analysis, are useful genetic markers for linkage analysis of the LDL receptor gene and familial hypercholesterolemia.

DNA, Single-Stranded↗

Soluble CD4, CD8 in patients with polymyositis/dermatomyositis.

The concentrations of soluble CD4 (sCD4) and soluble CD8 (sCD8) were determined in 64 patients with polymyositis/dermatomyositis (PM/MD). The patients with PM/DM had significantly higher concentrations of sCD8, though the concentrations of sCD4 did not significantly increase. Patients with high concentrations of sCD8 tended to have too high concentrations of soluble interleukin-2 receptor (sIL-2R). The patients with high levels of myogenic enzymes tended to have high concentrations of sCD8. The results of a serial study indicated that the concentrations of sCD8 decreased simultaneously with the decrease of the myogenic enzymes. These results may suggest that the activation of CD8+ cells are related to muscular involvement.

Adult↗

Soluble CD4 and CD8 molecules in patients with systemic sclerosis.

The concentrations of sCD4 and sCD8 in 69 patients with systemic sclerosis (SSc) were examined by using a sandwich enzyme-linked immunosorbent assay. The patients with SSc had significantly higher concentrations of sCD8 (mean 249.2 U/ml (SD 155.1), median 224 U/ml) than the normal subjects (mean 149.3 U/ml (SD 42.1), median 148 U/ml). The concentration of sCD4 in patients with SSc were significantly lower (mean 6.2 U/ml (SD 3.8), median 5.0 U/ml) than in the normal subjects (mean 10.9 U/ml (SD 4.1), median 10.3 U/ml). The concentration of sCD8 in patients with diffuse sclerosis tended to be higher than in those with sclerodactyly.

Adult↗

Intraductal papillary neoplasms of the pancreas: diagnosis by endoscopic pancreatic biopsy.

Intraductal papillary neoplasms of the pancreas (IPN) are rare tumors, distinct from other pancreatic duct cell carcinomas both in terms of papillary polyp formation in the main pancreatic duct and their favorable prognosis. In the present study, endoscopic pancreatic biopsy (EPB) under fluoroscopic control was employed in three cases of IPN to obtain a tissue diagnosis prior to surgery. There were no complications and all biopsy specimens were adequate for histopathological evaluation. In our experience, EPB is a simple, safe and effective method, yielding sufficient material for preoperative tissue diagnosis of pancreatic tumors, especially in the case of IPN.

Adenocarcinoma, Papillary↗

Pathogenesis of autoimmune hypothyroidism induced by lymphokine-activated killer (LAK) cell therapy: in vitro inhibition of human thyroid function by interleukin-2 in the presence of autologous intrathyroidal lymphocytes.

Lymphokine-activated killer (LAK) cell therapy frequently results in primary hypothyroidism. To elucidate the responsible mechanism, we investigated the effects of interleukin-2 (IL-2) on thyroid function of cultured human thyroid follicles in the presence or absence of autologous thyroid-derived lymphoid cells (TDLC). Human thyroid follicles, obtained by subtotal thyroidectomy from patients with Graves' disease, were cultured in serum-free medium containing bTSH and various concentrations of human IL-2, with or without TDLC. After 5 days of culture, 125I was added, and after an additional 3 days of culture, 125I incorporated into thyroid follicles and organic 125I (125I-T4 + 125I-T3) released into the culture medium were estimated. In the absence of TDLC, IL-2 did not affect bTSH-induced thyroid function. In the presence of TDLC, however, IL-2 inhibited the bTSH-stimulated thyroid function in a concentration-dependent manner. The minimum IL-2 concentration required to inhibit thyroid function was 1 U/ml. At 100 U/ml, IL-2 inhibited thyroid function completely. IL-2 increased the concentration of IFN-gamma in the culture medium conditioned by TDLC but not by thyroid follicles. When both were cocultured, IL-2 more significantly increased the concentration of IFN-gamma to an extent sufficient for inhibiting thyroid function per se. Furthermore, the addition of anti-IFN-gamma antibody to the medium partially restored the IL-2-inhibited thyroid function. In summary, by coculturing human thyroid follicles and autologous intrathyroidal lymphocytes with IL-2, it was possible to reproduce the thyroid dysfunction associated with LAK cell therapy. Our data indicate that IL-2 inhibits thyroid function, at least partly, by stimulating production of IFN-gamma, a potent inhibitory cytokine for thyroid cells.

Analysis of Variance↗

Reversible inhibition by interferons alpha and beta of 125I incorporation and thyroid hormone release by human thyroid follicles in vitro.

When interferons (IFN-alpha-2a, IFN-alpha-2b, natural IFN-alpha and IFN-beta) were cultured with human thyroid follicles, each IFN inhibited TSH-induced thyroid function (125I incorporation and release of 125I-T4) in a concentration-dependent manner. The minimal inhibitory effect was exerted at 1-10 U/ml. However, the inhibitory effect was reversible, and no inhibitory effect was detected when IFNs were removed from the medium within 12 h. These in vitro findings suggest that each IFN directly inhibits human thyroid function at clinically attainable levels. However, since the inhibitory effect was reversible, IFN therapy would provoke only subtle thyroid dysfunction in a majority of patients without preexisting thyroid autoimmunity.

Culture Techniques↗

A patient with primary hyperparathyroidism associated with osteomalacia: markedly increased serum levels of intact PTH and 1,25-dihydroxyvitamin D with normo- and hypercalcemia.

A 65-year-old female patient was admitted with complaining chiefly of lower back pains and arthralgia in the bilateral knee joints of 10-years duration. The serum calcium concentration was normal or only slightly increased, whereas the serum intact PTH and 1,25-dihydroxyvitamin D concentrations were substantially increased. Serum phosphate and 25-hydroxyvitamin D concentrations were decreased. Renal function was normal. Serum alkaline phosphatase activity, the osteocalcin concentration and urinary hydroxyproline excretion were markedly increased. Bone X-ray examination showed severe osteopenia and bone biopsy revealed hyperosteoidosis without tetracycline deposition, consistent with osteomalacia. A parathyroid adenoma was demonstrated by echography and CT-scan. Surgical exploration of the neck revealed a chief cell adenoma behind the right upper pole of the thyroid gland. After parathyroidectomy, all the abnormal biochemical data gradually normalized and the patient has been doing well without any symptoms for the last 13 months. These clinical data suggest that osteomalacia of the patient was probably induced by hypophosphatemia of prolonged duration. When hypercalcemia is not evident in a patient with primary hyperparathyroidism, in whom serum alkaline phosphatase and intact PTH levels are inappropriately increased, osteomalacia should be taken into consideration.

Adenoma↗

Effects of environmental temperature on atrial natriuretic peptide (ANP)-granules of auricular cardiocytes and plasma ANP level in pregnant rats.

The atrial natriuretic peptide (ANP) levels of auricular cardiocytes and plasma were examined by immunohistochemistry, ultrastructural morphometry, and radioimmunoassay (RIA) in pregnant rats (4th, 12th, 20th day of gestation) under 22 degrees C and 33 degrees C environmental conditions. Immunohistochemically, ANP immunoreactivity was stronger on the 20th day of gestation in the 22 degrees C environmental groups, but weaker on the 12th and 20th days of gestation in the 33 degrees C environmental groups. According to the results of ultrastructural morphometry, the number of ANP-granules had increased significantly by the 20th day of gestation in the 22 degrees C environmental groups, but was decreased on the 12th and 20th days of gestation in the 33 degrees C environmental groups. RIA demonstrated that the maternal plasma ANP concentration decreased gradually during pregnancy in the 22 degrees C environment. The plasma ANP concentration in the 33 degrees C environmental groups tended to be lower than that at the same stage of pregnancy in the 22 degrees C environmental groups.

Animals↗

[HCV subtypes and their clinical significance].

We immunologically isolated a clone with a 177-bp DNA fragment, designated as #2-22, that had homology to the NS-5 region of a HCV genome. To classify this HCV isolate, we sequenced several clones (2028 bases in total) from a cDNA library constructed from a #2-22-positive patient's blood. They showed distinct similarity to the HC-J8 genome (type II b), among the known HCV subtypes. Using this #2-22 sequence for PCR, we screened the HCV-positive blood samples from Southern Kyushu, we could identify 27% of them as type II b. In another cDNA library, from a single blood donor, who did not have multiple infections of HCV, we found two clones that might have arisen from an ancestral (or previous or historical) intergenomic recombination. They had reversed orders of similarity to different HCV subtypes, that is, the first 149-bp clone had 94% identical bases with a segment of HC-J8 and 78% with the corresponding sequence of HC-J6, but the second 814-bp clone had 85% identical bases with a segment of HC-J8 and 94% to the corresponding sequence of HC-J6. The importance of subtype analysis is discussed in relation to its clinical application, such as diagnostics development.

Amino Acid Sequence↗

[Unfavorable characteristics in patients with early postoperative recurrence of Graves' disease after subtotal thyroidectomy].

Unfavorable characteristics of early postoperative recurrence of hyperthyroidism were studied in patients with Graves' disease after subtotal thyroidectomy. We examined 338 patients who underwent subtotal thyroidectomy during a 9-year period from 1981 to 1989. Thyroid functional status was determined biochemically and the following variables were collected and divided into two categories for each patient: sex, age at operation, indication for surgery, serum titer of antimicrosomal hemagglutination antibody, weight of resected thyroid tissue and size of remnant thyroid tissue relative to body surface area. Early postoperative recurrence was defined as relapse of the disease within one year after surgery, necessitating medication or radioiodine therapy. Logistic regression analysis disclosed that the most important characteristics were age < 20 yr, relatively large thyroid remnant and weight of resected thyroid tissue > or = 100g, the odds ratios for these variables being 20.6, 16.7 and 3.4, respectively (p < 0.05). Although candidates for surgical treatment of Graves' disease are likely to be younger and to have a large goiter, these characteristics are unfavorable, since they predict the early recurrence of hyperthyroidism. One alternative is to leave a smaller than usual thyroid remnant thyroid in these patients, even if the risk of postoperative hypothyroidism is high.

Adult↗

Surgical and medical management of patients with pulmonary metastasis from parathyroid carcinoma.

BACKGROUND: The aim of this study was to characterize patients with pulmonary metastasis of parathyroid carcinoma and to evaluate the long-term effect of surgical and medical therapy. METHODS: Seven patients with pulmonary metastasis of parathyroid carcinoma were treated between 1980 and 1992. Six patients underwent resection of pulmonary metastases, and one patient has had long-term bisphosphonate therapy alone. Bisphosphonate was also given before or after operation to three patients. RESULTS: Two patients underwent a unilateral thoracotomy for a single pulmonary lesion, and four other patients with multiple lesions underwent staged bilateral thoracotomies. The postoperative serum calcium level returned to normal after each thoracotomy in three patients who were alive and well 3, 8, and 12 years after the first thoracotomy. Hypercalcemia persisted in the other three patients. In two of the patients, bisphosphonate therapy was also unable to control hypercalcemia. In one patient the serum calcium level has been maintained in the 13 mg/dl range by bimonthly bisphosphonate therapy alone for 3 years. CONCLUSIONS: The aggressive surgical approach to pulmonary metastasis of parathyroid carcinoma was shown to be effective for palliation in selected patients. Bisphosphonate therapy is an alternative to resection but has only a temporary calcium-lowering effect.

Adolescent↗

[Effect of cigarette smoking on diffuse pulmonary uptake of 99mTc-HM PAO].

To investigate the clinical significance of pulmonary uptake of 99mTc-HM PAO, we studied the effect of cigarette smoking on pulmonary uptake of 99mTc-HM PAO. This study included 14 volunteers: 4 nonsmokers and 10 smokers (Brinkmann indexes 544 +/- 270.8). Following injection of 99mTc-HM PAO into the antecubital vein, time-activity curve was obtained with the regional activity of one frame/min. for 30 minutes and 64 x 64 matrices. Characteristics of pulmonary clearance curve, described as C(t) = A exp-kt, and lung/liver uptake ratio (Lu/Li index) at 30 min. after injection were determined, and groups of non-smokers and smokers were compared. In smokers, 99mTc-HM PAO clearance was delayed and k was smaller significantly. Lu/Li index was also higher in smokers. Brinkmann index correlated both with k (r = -0.815, p < 0.01) and Lu/Li index (r = 0.911, p < 0.01). In conclusion, the delayed clearance and retention of 99mTc-HM PAO in the lung may indicate metabolic disorders of the lung due to cigarette smoking.

Adult↗