A case of painless thyroiditis possibly triggered by tamoxifen citrate, a synthetic antiestrogen.
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Biomedical subjects
Publications and source records attributed to H Kawabe.
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At the age of 18, our patient was diagnosed as complete androgen insensitivity syndrome(AIS) based on androgen receptor studies in cultured genital skin fibroblasts. Compatible with this diagnosis, both testosterone and LH levels in her plasma were elevated as compared to levels in normal females. Later, the patient had been uneventful until she sought medical attention for headache at the age of 38. Magnetic resonance imaging (MRI) of the brain pointed to pituitary apoplexy. Since her symptoms were not alleviated by conservative therapy, neurosurgical decompression via a transsphenoidal approach was performed. A histopathological examination of a surgical specimen revealed that the pituitary hemorrhage occurred in an LH-producing adenoma. It is likely that the adenoma developed from gonadotroph hyperplasia which could exist in the AIS pituitary. It may be worth noting that this patient has never had a chance of receiving hormonal replacement therapy with estrogen and progesterone. Considering the fact that the majority of AIS patients are treated with gonadal steroids and such a treatment reestablishes an appropriate negative feedback on enhanced LH secretion, it is possible that the lack of hormonal therapy in our patient may have served as a precipitating factor for the apoplectic episode. Although we are not aware of any documented case report of pituitary apoplexy developed in AIS, such a pituitary emergency should be born in mind in the long-term follow-up of patients with AIS. In addition, it is also suggested that the hormonal replacement therapy with gonadal steroids may be recommended for AIS patients not only to endow them with physical characteristics as a woman but also to prevent the development of gonadotroph hyperplasia and possibly also of LH-producing adenoma in the pituitary.
We experienced an unusual combination of painless thyroiditis and Sheehan's syndrome in a single patient. A 29-year-old postpartum woman was referred to us for suspected Sheehan's syndrome. Endocrine tests confirmed the diagnosis, but, unexpectedly, her thyroid hormone levels in the plasma were elevated. Based on the data from various examinations on her thyroid including an extremely low uptake of radioactive iodine and spontaneous alterations of the thyroid function without any therapy for the thyroid, we diagnosed the patient as suffering from Sheehan's syndrome and painless thyroiditis simultaneously. Underlying mechanism(s) whereby painless thyroiditis occurred in our patient may be an immunological rebound after parturition, an immunological alteration induced by secondary hypoadrenocorticism, or a combination of these. The simultaneous occurrence of Sheehan's syndrome and painless thyroiditis is rare, as evidenced by the existence of only one similar case report in the literature. However, since neither Sheehan's syndrome nor painless thyroiditis is a rare endocrine disorder, the thyroid function of patients with postpartum hypopituitarism and previously diagnosed chronic thyroiditis should be carefully evaluated.
Smg GDS is a regulator having two activities on a group of small G proteins including the Rho and Rap1 family members and Ki-Ras; one is to stimulate their GDP/GTP exchange reactions, and the other is to inhibit their interactions with membranes. Structurally, it has 11 Arm repeats, a protein interaction motif, found in the Drosophila Armadillo protein, a homolog of mammalian beta-catenin. We have isolated here an Smg GDS-interacting protein from a human brain cDNA library by use of the yeast two-hybrid method and named it SMAP (Smg GDS-associated protein). SMAP was a protein with a Mr of 91,189 and 792 amino acids. SMAP had 9 Arm repeats. Recombinant SMAP interacted with recombinant Smg GDS but did not affect the two activities of Smg GDS on RhoA. SMAP was tyrosine phosphorylated by v-Src, and this phosphorylation reduced the affinity of SMAP for Smg GDS. Tissue and subcellular distribution analyses indicated that SMAP was ubiquitously expressed and highly concentrated at the endoplasmic reticulum area. Searches for sequence homology to SMAP revealed that SMAP was significantly homologous to sea urchin SpKAP115, suggesting that SMAP is a mammalian counterpart of SpKAP115 or its related protein. SpKAP115 is an accessory subunit of sea urchin kinesin II, an ATPase motor that transports vesicles along microtubules. These results suggest that SMAP serves as an adaptor for both Smg GDS and kinesin II or its related protein and links them with both the Smg GDS-regulated small G protein and Src tyrosine kinase signalings.
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The aim of this study was to demonstrate acute efficacy of photodynamic therapy on atheromas by using a pheophorbide derivative, PH-1126. Cholesterol-fed atherosclerotic rabbits were injected intravenously with 1 mg/kg of PH-1126. Twenty-four hours later, PH-1126 selectively accumulated in atherosclerotic plaques. Then, atherosclerotic lesions in the upper thoracic aorta were treated by irradiation with a krypton ion laser at a wave-length of 647 nm. At 6 h after photodynamic therapy, the treated aorta was examined by scanning electron microscopy. Numerous teardrop-shaped cells were observed on the endothelial surface of the plaque irradiated at a total energy of 100 J/cm2. These cells were larger than monocytes and macrophages, and resembled foam cells in size and shape. The body of the teardrop-shaped cell resembled pumice stone, mainly because of the presence of globular elements in the cytoplasm. A part of the cell appeared to remain in the subendothelial space. These findings suggest that the cells may be foam cells from the intimal layer of atherosclerotic plaque that were expelled into the aortic lumen. It may become possible to flatten atheroma in a long-term period after photodynamic therapy using PH-1126 as a potent photosensitizer.
This study was designed to investigate the possibility of sex and age differences in the insulin-blood pressure relationship in a general Japanese population with a wide age range. Fasting serum insulin, lipids, plasma glucose, blood pressure and anthropometric measurements were made on 1,537 men and 843 women aged 16 to 65 years. Of the 2,380 subjects in the present analysis, 290 (184 men, 106 women) were hypertensive. When divided into four age groups (16 to 17, 21 to 22, 30 to 49 and 50 to 65 years), the male hypertensive subjects were found to have significantly higher fasting insulin levels, triglycerides levels and body mass index and lower glucose/insulin ratios than normotensive male subjects in all age groups. In the women, there was no significant difference in serum insulin levels or glucose insulin ratios between the hypertensive and normotensive groups in any age group. Simple correlation analysis showed that blood pressure was statistically significantly correlated with serum insulin levels and body mass index in the men in all age groups. In women, the correlation between blood pressure and serum insulin was insignificant in the 21- to 22-year-old age group. In men but not women, multivariate analysis showed that blood pressure was significantly and independently correlated with fasting serum insulin levels. The results of this study suggests the existence of sex and age differences in the insulin-blood pressure relationship in a Japanese population.
The preoptic region of hypothalamus was disconnected from caudal structures with two different-size knife cuts in rats to investigate the pathway responsible for the effects of intracerebroventricular (ICV) and intravenous (IV) angiotensin II (ang II) on blood pressure and arginine vasopressin (AVP) release. Seven days after surgery ICV ang II (125 ng) in sham-operated (sham) rats increased mean arterial pressure (MAP) (+23 +/- 3 mmHg) and decreased heart rate (HR) (-58 +/- 5 beats/minute). However, ICV ang II had no effect on MAP or HR of rats with a large (preoptic-hypothalamic disconnection) cut. Both the pressor response (+12 +/- 2 mmHg) and the bradycardia (-39 +/- 6 beats/minute) were significantly reduced by a small (medial preoptic-hypothalamic disconnection) cut. The increased plasma AVP to ICV ang II in sham rats (9.8 +/- 3.6 pg/mL) was abolished in large-cut rats and attenuated in small-cut rats (3.2 +/- 0.7 pg/mL). IV bolus injection of ang II (125 ng) in sham rats increased MAP by 43 mmHg, whereas large-cut rats showed a blunted (25%) pressor response. The pressor response to IV infusion of ang II (8 ng/20 microL/minute for 15 minutes) was diminished in large-cut rats (+4 +/- 1 mmHg) as compared with that in sham rats (+19 +/- 2 mmHg). Both cuts transected the projection between the periventricular tissue surrounding the anteroventral third ventricle and supraoptic nucleus, but the supraoptic-neurohypophyseal pathway was severed only by the large cut.(ABSTRACT TRUNCATED AT 250 WORDS)
This paper describes a project to develop and test a new telemedicine system using image transmission. The system was implemented at Aomori prefecture, the northernmost prefecture of Japan, to provide medical consultation to remote hospitals from a medical center located in Aomori city, capital of the prefecture. The characteristics of the system are the combination of an HDTV still image transmission system and an ordinary tele-conference system using 65 kilobit telephone line i.e., an ordinary telephone line available in almost any part of Japan. We also developed a disk storage system that stores transmitted images automatically without human intervention. The system was assessed in real clinical settings and has proved to be effective in various areas of medical consultation, including radiology, pathology, dermatology, etc. We hope that this system becomes a standard telemedicine system in the future.
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The neutral proteinase II from Aspergillus oryzae (NpII) is a zinc proteinase with three intramolecular disulfide bonds. NpII is most unstable after 10 min at about 75 degrees C, but regains stability beyond this temperature and is relatively stable at 100 degrees C. We analyzed the thermal stability of wild-type NpII and apo NpII. The results suggested that NpII unfolds reversibly upon incubation up to 100 degrees C, and that the irreversible inactivation observed is mainly due to autoproteolysis. To further understand the stability, a mutant NpII (Cys78-->Ala) lacking one of the disulfide bonds, was produced in a heterologous yeast expression system. The mutant NpII showed a similar stability profile, but the most unstable temperature and the most catalytically active temperature decreased to the same extent (around 10 degrees C), confirming that autoproteolysis is the main cause of the irreversible inactivation. Several lines of evidence presented in this study demonstrated that the thermal stability of o++NpII is attributed to reversible thermal unfolding and autoproteolysis.
To determine whether any differences exist between young male subjects with elevated diastolic and systolic blood pressure (BP) and those with only an elevated systolic BP, the responses of BP and plasma catecholamines to a mental arithmetic test were studied in 11 young men (mean age of nineteen years) with BP of > or = 140/90 mm Hg at a routine health check-up (group I-hypertension [HT]), 26 age-matched men with only elevated systolic BP (> or = 140 mm Hg) (group II-HT), and 12 age-matched normotensive (NT) men (< 140/90 mm Hg). During an arithmetic test, group I-HT showed a significantly higher increment of systolic BP (+14.5-18.0%) than group II-HT (+9.3-10.2%) and NT controls (+6.4-8.2%). However, no significant difference in BP response was seen between group II-HT and NT controls. Plasma norepinephrine in group I-HT showed a significant increase after the test, (171 +/- 23-->202 +/- 27 pg/mL), whereas group II-HT and NT controls showed no change. No significant difference occurred in epinephrine response among the three groups. These results suggest that the young male subjects with screening BP above 140/90 mm Hg are hyperreactive to a mental stress as compared with subjects with only elevated systolic BP or NT controls.
The evidence that some older patients with essential hypertension have low urinary dopamine excretion has brought into question the levels of urinary dopamine and plasma dopa, the major source of urinary dopamine, in young patients with essential hypertension. Twenty-four-hour urine sodium, creatinine, dopamine and noradrenaline and plasma dopa were evaluated in 48 patients with essential hypertension aged 18 to 27 years and 25 normotensive subjects. In comparison with age-matched normotensive subjects, the hypertensive patients had higher urinary dopamine (1920 +/- 80 vs 1520 +/- 130 nmol/day, p < 0.01) and noradrenaline (216 +/- 11 vs 179 +/- 12 nmol/day, p < 0.05) excretion. There was a significant correlation between urinary dopamine and noradrenaline excretion. There was no difference in plasma dopa levels between normotensive and hypertensive subjects. These results suggest that the elevated conversion of dopa to dopamine in the kidney is leading to increased urinary dopamine excretion in young patients with essential hypertension.
We investigated the relation between home blood pressure (BP) and body weight in 38 young normotensive men (mean age, 16 years) whose parents were normotensive (PNT group) and 34 age- and sex-matched normotensive men, one or both of whose parents were hypertensive (PHT group). Although causal BP measurements were similar in both groups, home systolic BP was significantly higher in the PHT group (123 +/- 1 mm Hg) than in the PNT group (116 +/- 1 mm Hg). Body weight was significantly greater in the PHT group (66.0 +/- 1.4 v 61.8 +/- 1.3 kg, P < .05) and body mass index (BMI) was not significantly higher in the PHT group (22.4 +/- 0.5 v 21.3 +/- 0.5 kg/m2, P = .09). Body weight (r = 0.38) and BMI (r = 0.42) were significantly correlated with home systolic BP in the PHT group. There were no differences in serum lipid or uric acid concentrations between the two groups. Our results showed that young normotensive subjects with a genetic predisposition to hypertension weighed more and had higher home systolic BPs compared with subjects without a family history of hypertension. Our observations further indicated a close relationship between a family history of hypertension and increased body weight, even in young normotensive men.
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To further elucidate the role of the preoptic-hypothalamic region in fluid and electrolyte balance we studied the effect of surgical preoptic-hypothalamic disconnection using either a large (preoptic-hypothalamic disconnection) or a small (medial preoptic-hypothalamic disconnection) microknife. Both the large and small cuts seemed to transect the posterior projection originating in the periventricular tissue surrounding the anteroventral third ventricle (AV3V) and extending to supraoptic nucleus, but the supraoptic-neurohypophysial pathway was severed only by the large cut. Seven-day metabolic studies showed a disruption in hydromineral balance only in large cut rats; they had increased water intake and urine volume on day 1, a near-recovery of function on days 2 and 3, and polydipsia and polyuria on days 4 to 7. There was no difference between small cut rats and sham-operated rats in metabolic measurements. The large cut rats also had sustained hypernatremia and hyperosmolality, which was enhanced after water restriction for 48 h but was not accompanied by an increase in plasma arginine vasopressin. Our data therefore suggest that the efferent fibers running caudally from the AV3V are not involved in mediation of the hydromineral regulation of the AV3V.
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