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Biomedical subjects

T Obara

Publications and source records attributed to T Obara.

At least 91 records · Page 5Linked to original sources
PubMed1996

Pheochromocytomas: tendency to degenerate and cause paroxysmal hypertension.

Eighty-four patients with pheochromocytoma underwent surgery during the 13-year period from 1981 to 1994. These patients were divided into three groups according to the degree of parenchymal degeneration, which was estimated by preoperative dynamic computed tomography (CT) scans and resected specimens: solid group, cystic group, and highly cystic group. The relation between the degree of parenchymal degeneration and the clinical variety, size of the tumor, predominant plasma catecholamine, and type of blood pressure disturbance was analyzed. There were 39 cases of solid pheochromocytoma, 37 cases of cystic tumor, and 8 cases of highly cystic pheochromocytoma. The maximal mean diameters for each group were as follows: 5.1 +/- 2.3, 6.8 +/- 3.0, and 7.9 +/- 3.2 cm, respectively. Of the tumors < 3 cm in diameter, 84% were solid; when the tumors were >/= 6 cm in diameter, approximately 50% were cystic and 20% highly cystic. Of the adrenal pheochromocytomas, 60% were degenerated; 79% of the extraadrenal tumors were solid. Of the epinephrine-secreting tumors, 70% were degenerated, and 55% of the norepinephrine-secreting tumors were solid. The clinical pattern of hypertension was related to the degree of degeneration: In the paroxysmal hypertension group 87% of the tumors were degenerated, and in the sustained hypertension group 69% were solid. We therefore believe that parenchymal degeneration of pheochromocytoma is highly correlated with the tumor diameter, location of the tumor, secreted catecholamine, and clinical pattern of hypertension.

Adolescent↗
PubMed1996

Efficacy of high-frequency ultrasound probes for the preoperative staging of invasion depth in flat and depressed colorectal tumors.

BACKGROUND: Flat and depressed nonpolypoid types of colorectal tumors have drawn much attention. Since endoscopic mucosal resection technique is available, it is of great importance to distinguish intramucosal carcinoma from invasive carcinoma because determination of the invasion depth is essential for choosing this therapy. The usefulness of high-frequency (20 MHz) ultrasound probes for preoperative staging of invasion depth in this type of colorectal tumor was evaluated. METHODS: Forty-nine cases of flat and depressed tumors were examined with the ultrasound probe and diagnostic accuracy was confirmed by comparing ultrasonic images with the pathologic findings of the specimens resected either by endoscopic mucosal resection or surgical operation. RESULTS: The normal colonic wall was visualized as a nine-layered structure and the muscularis mucosae was depicted in 37 (76%) of 49 cases. Flat and depressed tumors were visualized as hypoechoic lesions and the invasion depth was accurately diagnosed in 43 (88%) of 49 lesions. CONCLUSIONS: High-frequency ultrasound probes proved to be useful in determining the invasion depth and therapeutic strategy in flat and depressed colorectal tumors.

Adenoma↗
PubMed1996

Trisomy 18 mosaicism associated with secondary amenorrhea: ratios of mosaicism in different samples and complications.

A 28-year-old woman who complained of irregular menstruation was diagnosed as suffering from trisomy 18 mosaicism. She was karyotyped because of her characteristic face, mild mental retardation and aberrant hyperpigmentation of the skin. Her motor function was within normal range. Physical and laboratory examinations, however, revealed obesity, short stature, minor anomalies of the fingers, many areas of hyperpigmentation on the trunk and the hips, hypergonadotropinemia, diabetes mellitus, liver dysfunction, and hyperlipidemia. The ratios of normal/trisomy 18 were 4:135 in blood lymphocytes, 3:11 in a hyperpigmented area of the skin, 20:0 in a normally pigmented area of the skin, and 14:6 in ascitic cells. Laparoscopy revealed that her ovaries contained neither follicles nor germ cells.

Abnormalities, Multiple↗
PubMed1996

Interleukin-6 (IL-6) inhibits thyroid function in the presence of soluble IL-6 receptor in cultured human thyroid follicles.

Interleukin-6 (IL-6), a pleiotropic cytokine, is postulated to be involved in the pathogenesis of sick euthyroid syndrome, although the direct in vitro effects of IL-6 on human thyroid function are controversial. Because IL-6 signal can be transduced when the complex of IL-6 and soluble IL-6 receptor (sIL-6R) binds to gp 130, an IL-6 signal transducer, we studied the effects of IL-6 and sIL-6R on thyroid function, using human thyroid follicles obtained from patients with Graves' disease. IL-6 alone had no inhibitory effect on TSH-induced thyroid function (125I incorporation and organic 125I release), even at supraphysiological concentrations. However, in the presence of physiological concentrations of sIL-6R (100 ng/ml), IL-6 inhibited thyroid function dose dependently and completely, accompanied with the decreased ratio of 125I-T3/125I-T4 not only in the thyroid follicles but also in the culture medium. Thyroid follicles did not secrete sIL-6R but produced IL-6 constitutively. Consistent with these findings, sIL-6R inhibited thyroid function slightly at high concentrations. Furthermore, RT-PCR analyses revealed that human thyroid follicles expressed the messenger RNAs for IL-6 and gp130 but scarcely messenger RNA for IL-6R. These in vitro findings suggest that IL-6 alone hardly affects thyroid function in thyroid follicles in which IL-6R gene is scarcely expressed. However, because sIL-6R is present abundantly in serum, IL-6 in vivo would be capable of inhibiting the synthesis and release of T4 and, to a greater extent, T3 from the thyroid gland. These in vitro findings are at least partly related to the development of sick euthyroid syndrome.

Analysis of Variance↗
PubMed1996

Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia.

Bone and vitamin D metabolism are examined in patients with primary hyperparathyroidism (1 degree HPT), humoral hypercalcemia of malignancy (HHM), and local osteolytic hypercalcemia (LOH) with normal renal function. Among the bone resorption markers, T scores of total deoxypyridinoline (Dpyd) were highest in HHM and were significantly higher than those in 1 degree HPT. Among the formation markers, T scores of osteocalcin (OC) were highest in 1 degree HPT but were negative in HHM. The elevation in total Dpyd was associated with an increase in OC in 1 degree HPT, and the ratios of total Dpyd/OC were similar to those in controls. In contrast, many patients with HHM and LOH exhibited elevated total Dpyd and suppressed OC with increased total Dpyd/OC ratios, but the ratios varied widely. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was elevated in 1 degrees HPT but was suppressed in HHM and LOH at any serum Ca levels. These results demonstrate that increased bone resorption is associated with enhanced bone formation in 1 degrees HPT but are uncoupled in many of the HHM and LOH patients, and that total Dpyd/OC ratio can be a useful index to estimate the coupling state of bone. It is suggested that the reduction in serum 1,25(OH)2D cannot be explained by an elevation in serum Ca in HHM and LOH, and that the differences in bone and vitamin D metabolism in HHM and LOH from those in 1 degree HPT may be caused by a common mechanism such as the secretion of some cytokines from tumors.

Adult↗
PubMed1996

Bilateral adrenalectomy with autotransplantation of adrenocortical tissue or unilateral adrenalectomy: treatment options for pheochromocytomas in multiple endocrine neoplasia type 2A.

Surgical strategies for pheochromocytomas in patients with multiple endocrine neoplasia (MEN) type 2 syndrome have been controversial. The purpose of this study is to review the current status of patients with MEN 2 who underwent adrenalectomy with or without adrenal autotransplantation. We studied 15 patients with MEN 2A who underwent adrenal surgery between 1981 and 1992. The follow-up survey included physical examination and biochemical determinations. The median period from initial surgery to follow-up was 54 months (range, 0-145 months). Initial bilateral total adrenalectomy was performed on seven patients, and subtotal adrenalectomy was carried out on two. Among six patients who initially underwent unilateral adrenalectomy, four had remained normotensive (median follow-up, 61 months), whereas the other two patients had to undergo reoperation on the contralateral side because of recurrent symptoms. Two patients were suspected of having had a relapse of the disease after total adrenalectomy. Seven patients underwent adrenal autotransplantation; however, none of them were able to discontinue glucocorticoid replacement therapy. In MEN 2A patients having large pheochromocytomas on only one side, unilateral adrenalectomy can be a suitable alternative to bilateral adrenalectomy in terms of blood pressure control and preservation of adrenocortical function. The attempt to preserve adrenocortical function by autotransplantation is discouraged.

Adolescent↗
PubMed1995

Decision Making Using Postoperative CEA and CA 15-3 for Detection of Breast Cancer Recurrence.

To determine the clinical implications of postoperative levels of serum carcinoembryonic antigen (CEA) and CA 15-3 as follow-up parameters for breast cancer, a retrospective study was conducted on 157 patients who underwent curative surgery for breast cancer. Twenty-three patients had recurrences and 134 patients were without recurrence for more than one year after measuring the tumor marker. The receiver operating characteristic (ROC) curves indicated that CA 15-3 performed more accurately than CEA in discriminating between patients with recurrence (n = 23) and those without (n = 134). Of 23 patients with recurrence, CEA was elevated above the normal range (<2.9 ng/ml) in 32% and CA 15-3 was elevated above the normal range (> 20U/ml) in 67%. The elevation of the markers preceded the clinical appearance of metastases in 2 patients for CEA and in 5 patients for CA 15-3. False positive rates for CEA and CA 15-3 in the 134 patients without recurrence were 4% and 10%, respectively. Nevertheless, these rated became 0% when the cut-off values were doubled. When the postoperative serum level of either CEA or CA 15-3 exceeds twice the upper limit of the normal range or when, in patients with unfavourable prognostic characteristics (node positive or large tumor), either of these values is between the upper limit of the normal range and double the value, recurrent breast cancer must be assumed. For such patients, further investigations with high-sensitivity radiographic modalities are warranted because early treatment may be able to provide survival benefit.

Journal Article↗
PubMed1995

Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC transgene.

We report the effect of the ornithine transcarbamylase (OTC) transgene composed of 1.3 kb of the 5' flanking region of the rat OTC gene fused to rat OTC cDNA on urinary orotic acid excretion in OTC-deficient spf-ash (sparse-fur with abnormal skin and hair) mice during overnight-starvation and nitrogen loading. During starvation, spf-ash mice with about 6% and 2% of control levels of OTC activity in the liver and small intestine excreted a large amount of orotic acid in the urine. Transgenic spf-ash mice with about 10% and 30% of the control OTC activities in the liver and small intestine did not excrete more than the normal level of orotic acid. Accidental parasitization of transgenic spf-ash mice with ticks (Myocoptes musculinus) resulted in decrease of the OTC activities in the liver and small intestine to the levels in spf-ash mice, and increased excretion of orotic acid. During extermination of the ticks, the mice showed varied levels of OTC activity and orotic acid excretion. On nitrogen loading, transgenic spf-ash mice as well as spf-ash mice excreted larger amounts of orotic acid, while control mice showed no increase in its excretion. The levels of urinary orotic acid were inversely correlated to the logarithms of the OTC activities in the liver and small intestine, the correlation being significantly higher with intestinal OTC than with hepatic OTC activity. These results suggest that the level of OTC activity in the small intestine is important for production of orotic acid.

Animals↗
PubMed1995

Surgical strategy for pheochromocytoma: emphasis on the pledge of flank extraperitoneal approach in selected patients.

BACKGROUND: Anterior transabdominal exploration has traditionally been advocated as the standard procedure for pheochromocytoma. However, some authors claim that a flank extraperitoneal approach with accurate unilateral localization is justifiable. METHODS: Retrospective analysis was performed on 87 patients with pheochromocytoma to determine the appropriateness of extraperitoneal exploration. RESULTS: There were 45 men and 42 women with a mean age of 44.7 years (range, 16 to 83 years). Fifteen patients (17.5%) had pheochromocytoma as a part of multiple endocrine neoplasia (MEN) type 2A, and four had familial pheochromocytoma, von Hippel-Lindau disease, or von Recklinghausen's disease. All tumors detected by preoperative localization studies were correctly identified and were resected through flank extraperitoneal (45 patients), transabdominal (28), thoracoabdominal (13), and posterior (1) approaches. Tumors were extraadrenal in 14, multiple in 22, bilateral in 12, and unequivocally malignant in 2 patients at the initial operation. Two patients died during the immediate postoperative period, giving an operative mortality of 2.3%. Two patients had persistent disease. During follow-up within a mean period of 5 years (range, 1 month to 13.7 years) 8 patients (9.1%) experienced recurrence or metastasis. Other than the patients with MEN 2, recurrence was not attributable to the operative approach. CONCLUSIONS: If a preoperative localization study is accurate, an extraperitoneal approach is justifiable for many patients with pheochromocytomas.

Adolescent↗
PubMed1995

Stimulation by thyroid-stimulating hormone and Grave's immunoglobulin G of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo.

To elucidate the pathogenesis of thyroid gland hypervascularity in patients with Graves' disease, we studied the expression of mRNAs for vascular endothelial growth factor (VEGF) and its receptor, Flt family, using human thyroid follicles in vitro and thiouracil-fed rats in vivo. Human thyroid follicles, cultured in the absence of endothelial cells, secreted de novo-synthesized thyroid hormone in response to thyroid-stimulating hormone (TSH) and Graves' IgG. The thyroid follicles produced VEGF mRNA but not flt-1 mRNA. The expression of VEGF mRNA was enhanced by insulin, tumor-promoting phorbol ester, calcium ionophore, dibutyryl cAMP, TSH, and Graves' IgG. When rats were fed thiouracil for 4 wk, their serum levels of TSH were increased at day 3. VEGF mRNA was also increased on day 3, accompanied by an increase in flt family (flt-1 and KDR/ flk-1) mRNA expression. These in vitro and in vivo findings suggest that VEGF is produced by thyroid follicles in response to stimulators of TSH receptors, via the protein kinase A and C pathways. VEGF, a secretable angiogenesis factor, subsequently stimulates Flt receptors on endothelial cells in a paracrine manner, leading to their proliferation and producing hypervascularity of the thyroid gland, as seen in patients with Graves' disease.

Animals↗
PubMed1995

Potent thyrotropic activity of human chorionic gonadotropin variants in terms of 125I incorporation and de novo synthesized thyroid hormone release in human thyroid follicles.

Using a highly sensitive bioassay for TSH, in which human thyroid follicles incorporate 125I and release de novo synthesized thyroid hormone into the culture medium, the thyrotropic activities of various hCG preparations were studied. Under the culture conditions employed, bovine TSH (bTSH) was approximately 6- to 9-fold more active than human TSH (hTSH). Highly purified hCG prepared from urine of normal pregnant women (CR 127) had only a trivial thyrotropic activity equipotent to 0.00022 microU bTSH/U hCG or 0.0013 microU hTSH/U hCG (19.7 microU hTSH/mg hCG). Hybrid hCG (AB1ER) also elicited low thyrotropic activity (14.0 microU hTSH/mg), whereas crude hCG had moderate thyrotropic activity (0.041 hTSH microU/U hCG or 127 microU/mg protein). Deglycosylated hCG, a very weak LH/hCG receptor agonist, was the most potent agonist in thyroid follicles (588 microU hTSH/mg protein). hCGs purified from urine of patients with trophoblastic tumors had greater TSH-like activity (37-84 microU hTSH/mg protein) than purified hCG. Asialo-hCG purified from a patient with choriocarcinoma had very potent TSH-like activity (468 microU hTSH/mg). Submaximal doses of bTSH and hCG variants produced additive stimulation of thyroid function. Furthermore, the thyrotropic effect of hCG was inhibited by anti-TSH receptor antibody obtained from patients with myxedema. These in vitro findings suggest that although hCG is reported to exert potent cAMP-stimulating activity on rat thyroid-like cells (FRTL-5) and Chinese hamster ovary cells transfected with hTSH receptor complementary DNA (0.092-0.72 microU hTSH/U hCG), the thyrotropic activity induced by authentic hCG in human thyroid follicles is too weak to cause hyperthyroidism in normal pregnancy. However, hCG produced by some trophoblastic tumors, particularly asialo-hCG, has potent thyrotropic activity sufficient to cause clinically overt hyperthyroidism when produced excessively.

Animals↗
PubMed1995

Rarity of oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in Japan.

Constitutively activating mutations have recently been identified in the thyrotropin receptor (TSHR) of hyperfunctioning thyroid adenomas and familial hyperthyroidism. In the present study, we evaluated the frequency of constitutively activating TSHR mutations in a large series of autonomously functioning thyroid nodules (AFTNs) in Japan. Forty-five AFTNs (38 solitary hyperfunctioning thyroid adenomas and 7 toxic multinodular goiters) were analyzed. Genomic DNA was extracted from paraffin-embedded tissue sections, from which DNA fragments encoding the mutational hot spots of the receptor (the third cytoplasmic loop and the sixth transmembrane segment) were amplified by polymerase chain reaction. In the single-stranded conformation polymorphism (SSCP) analysis, only one hyperfunctioning adenoma (no. 21) displayed a migration abnormality. In sequence analysis, an unusual mutation of alternate three-base deletions at nucleotides 1953-1957 (AAA GAT ACC to AAG TCC), resulting in one amino acid deletion (Asp at 619) and one conservative amino acid substitution (Thr to Ser at 620), was identified in tumor DNA but not in leukocyte DNA of no. 21. Further, the normal sequence in these regions was confirmed in 10 randomly selected samples with normal migrating patterns in SSCP analysis. The functional property of the mutant with delta 619 and T620S (designated TSHR delta 619) was then evaluated with in vitro mutagenesis and transfection studies. Unexpectedly, however, there were no significant differences in TSH binding affinity, and basal and TSH-stimulated levels of cAMP and inositol 1,4,5-triphosphate between the TSHR delta 619 and the wt-TSHR. In conclusion, the incidence of the constitutively activating TSHR mutations in AFTNs appears to be low in Japan. The oncogenic potential of a novel somatic mutant TSHR delta 619 identified in a hyperfunctioning adenoma in this study is at present uncertain because of its intact function.

Base Sequence↗
PubMed1995

Fine structure of the parotid gland in tree shrew (Tupaia glis).

The parotid glands of Tupaia glis were examined by light and transmission electron microscopy. The acinar cells were seromucous in nature, and contained many acidophilic granules with strong affinity for periodic acid-Schiff (PAS) and weak affinity for alcian blue (AB). These granules consisted of a fine granular matrix of moderate density in which a denser corpuscles or semilunar materials were present. Intercalated duct cells had a few fine vesicles, vacuoles and very few dense granules in the apical region. In occasional epithelial cells, acidophilic, PAS-positive and AB-negative bodies with moderate density were observed in the supranuclear region. The striated ducts consisted of columnar light and dark cells containing round or small ovoid granules of moderate density and did not show the granular duct as seen in the parotid glands of kobe mole and tenrec which are placed in the order insectivora.

Alcian Blue↗
PubMed1995

Appropriate intravenous doses of L-thyroxine and magnesium in a thyroidectomized patient with thyroid and parathyroid carcinomas receiving total parenteral nutrition during acute necrotizing pancreatitis.

A totally thyroidectomized patient with thyroid and parathyroid carcinomas, which had developed after neck irradiation in childhood, became hypercalcemic due to pulmonary metastases. The hypercalcemia was ameliorated by intermittent iv administration of bisphosphonate for 3.5 years, but this gradually became refractory to the bisphosphonate treatment. After right thoracotomy for resection of pulmonary metastases, acute necrotizing pancreatitis developed. The patient was therefore placed on total parenteral nutrition supplemented with T4 and a restricted dose of magnesium. Thyroxine(T4) (30 micrograms/day, iv) was not sufficient to maintain euthyroidism, but a higher dose (60 micrograms/day) elicited mild hyperthyroidism to the same extent as that elicited by an oral dose of 100 micrograms/day. The present case showed that the appropriate iv dose of T4 in this thyroidectomized patient with acute pancreatitis was about 60% of the oral dose. Furthermore, bisphosphonates (pamidronate and alendronate) and magnesium depletion were very effective in controlling the hypercalcemia.

Acute Disease↗
PubMed1995

The antitumor effect of hyperthermia combined with fluorouracil and its analogues.

The effectiveness of 5-fluorouracil (5-FU), FT-207 and FT-207 + uracil in combination with two repetitions of 43 degrees C hyperthermia in the treatment of the Meth-A-Fibrosarcoma and Sarcoma-180 was examined in vivo in BALB/c mice. The antitumor effect was evaluated in terms of inhibition of tumor growth by measuring the tumor for 7 days. The 5-FU concentration in each tumor was also monitored. Hyperthermia combined with FT-207 or FT-207 + uracil showed a synergistic effect for the inhibition of growth of both tumors which was not observed with 5-FU. There were no significant differences in the intratumoral concentration of 5-FU in unheated or heated Sarcoma-180 for any drug treatment after the first hyperthermia treatment, except for significant decreases in the group given 5-FU with the first hyperthermia treatment. After the second hyperthermia treatment, significant decreases in the concentration of 5-FU and FT-207 + uracil were observed. In the Meth-A-Fibrosarcoma, the intratumoral concentration of 5-FU decreased significantly in the group given 5-FU and increased significantly in the group given FT-207 + uracil after the first hyperthermia treatment, while there were significant decreases in 5-FU, FT-207 and FT-207 + uracil administered with the second hyperthermia treatment. Hyperthermia combined with FT-207 or FT-207 + uracil is considered to be effective.

Animals↗
PubMed1995

[Primary hyperparathyroidism in elderly patients].

Retrospective analysis has been performed in 404 patients, undergoing initial operation for primary hyperparathyroidism for differences in clinical presentation, laboratory data, pathological findings and outcome of surgery. In elderly patients (> = 60 years of age, n = 116), neuromuscular and psychic symptoms, hypertension, cholelithiasis and pseudogout were significantly more common, while renal stones were less common than in younger patients. There were no significant difference in preoperative laboratory findings, parathyroid pathology and surgical cure rate. Parathyroidectomy could be safely performed under local anesthesia, particularly in elderly patients in whom general anesthesia was involved with an increased operative risk. An attack of pseudogout was the most common postoperative complication. Hence, immediate calcium supplementation after operation is recommended in patients with a radiologic finding of chondrocalcinosis.

Adolescent↗