[Congenital Left Internal Mammary Artery to Pulmonary Artery Fistula with Aneurysmal Change Diagnosed Incidentally:Report of a Case].

An internal mammary artery to pulmonary artery (IMA-PA) fistula is a very rare vascular abnormality. Patients with this disease are often asymptomatic, but they may develop symptoms such as heart failure and hemoptysis. A 60-year-old woman was incidentally diagnosed with left IMA-PA fistula by chest computed tomography (CT) during an examination for colon cancer. She was asymptomatic, but we determined that surgery was indicated because of the presence of an aneurysmal change. We performed complete surgical resection of the IMA-PA fistula and aneurysm under cardiopulmonary bypass. Her postoperative course was uneventful. Although a specific management strategy for IMA-PA fistula has not yet been established, surgical treatment should be performed to prevent rupture in cases with aneurysmal change.

[Successful Pulmonary Embolectomy using a Bronchoscope:Report of a Case].

Surgical pulmonary embolectomy is indicated for acute massive pulmonary thromboembolism complicated by floating thrombi in the right heart system. Postoperative residual thrombi are associated with persistent pulmonary hypertension and subsequent right heart failure, resulting in poor surgical outcome. A 67-year-old man was admitted to our institution owing to dyspnea on exertion. Transthoracic echocardiography revealed a floating right atrial mass and right ventricular overload. In addition, enhanced computed tomography (CT) showed a right atrial mass as well as bilateral massive pulmonary embolism. We performed an urgent pulmonary embolectomy using a bronchoscope as an adjunctive angioscope to completely remove the peripheral thrombi and to prevent serious complications, such as endobronchial hemorrhage due to pulmonary arterial injury. A clear, bloodless view of peripheral pulmonary arteries was obtained using short intermittent circulatory arrest technique. Postoperative course was uneventful, and he was discharged ambulatory 20 days after the surgery without any symptoms.

Oxidative stress associated with rapid weight reduction decreases circulating adiponectin concentrations.

The effect of stress associated with acute weight reduction on adipocytokine production is incompletely understood. In the present study, we have investigated the changes in circulating adipocytokine concentrations and urinary concentrations of stress markers in male collegiate wrestlers during acute weight reduction for a competition. Twenty healthy Japanese male wrestlers (18-22 years of age) who participated in the national collegiate wrestling tournament were studied. Body weight, body fat amount, serum testosterone, serum leptin, serum adiponectin, urinary 8-hydroxy-2'- deoxyguanosine (8-OHdG) and urinary biopyrrins were analyzed during acute weight reduction for the competition. Body weight, body fat amount and the serum concentrations of testosterone, leptin and adiponectin significantly decreased on the day of weigh-in compared with the levels 12 days before weigh-in. In contrast, urinary concentrations of 8-OHdG and biopyrrins significantly increased on the day of weigh-in compared with the concentrations 12 days before weigh-in. A positive correlation was observed between the serum concentrations of adiponectin and testosterone, and a negative correlation was observed between the concentrations of serum adiponectin and urinary biopyrrins. The present results suggest that rapid weight reduction increases the urinary concentrations of stress markers, which is associated with a decrease in serum concentrations of adiponectin.

Thyroglobulin gene mutations producing defective intracellular transport of thyroglobulin are associated with increased thyroidal type 2 iodothyronine deiodinase activity.

CONTEXT: Most patients with defective synthesis and/or secretion of thyroglobulin (Tg) present relatively high serum free T3 (FT3) concentrations with disproportionately low free T4 (FT4) resulting in a high FT3/FT4 ratio. The mechanism of this change in FT3/FT4 ratio remains unknown. OBJECTIVE: We hypothesize that increased type 2 iodothyronine deiodinase (D2) activity in the thyroid gland may explain the higher FT3/FT4 ratio that is frequently observed in patients with abnormal Tg synthesis. DESIGN: We recently identified a compound heterozygous patient (patient A) with a Tg G2356R mutation and one previously described (C1245R) that is known to cause a defect in intracellular transport of Tg. In the current study, after determining the abnormality caused by G2356R, we measured D2 activity as well as its mRNA level in the thyroid gland. We also measured the thyroidal D2 activity in three patients with Tg transport defect and in normal thyroid tissue. RESULTS: Morphological and biochemical analysis of the thyroid gland from patient A, complemented by a pulse-chase experiment, revealed that G2356R produces a defect in intracellular Tg transport. D2 activity but not type 1 deiodinase in thyroid glands of patients with abnormal Tg transport was significantly higher than in normal thyroid glands, whereas D2 mRNA level in patient A was comparable with that in normal thyroid glands. Furthermore, there was a positive correlation between D2 activity and FT3/FT4 ratios. CONCLUSION: Increased thyroidal D2 activity in the thyroid gland is responsible for the higher FT3/FT4 ratios in patients with defective intracellular Tg transport.

Regulation of iodothyronine deiodinase and roles of thyroid hormones in human coronary artery smooth muscle cells.

Thyroid hormones have been reported to have significant effects on the peripheral vascular system, including relaxation of vascular smooth muscle cells and prevention of atherosclerosis. To exert its biological activity, thyroxine (T4) needs to be converted to 3,5,3'-triiodothyronine (T3) by type 1 and type 2 iodothyronine deiodinases. We have previously identified type 2 iodothyronine deiodinase (D2) expression in cultured human coronary artery smooth muscle cells (hCASMCs). In the present study, we have characterized the regulation of D2 expression in hCASMCs by stable prostacyclin analogue beraprost sodium (BPS) and platelet derived growth factor (PDGF), and the roles of thyroid hormones in the functions of hCASMCs. BPS increased D2 expression, whereas PDGF suppressed BPS stimulated D2 expression without affecting cAMP production in hCASMCs. PDGF increased DNA synthesis, while BPS, T3 or T4 suppressed PDGF stimulated DNA synthesis in hCASMCs. Inhibition of D2 activity by 3,3',5'-triiodothyronine (rT3) partially restored T4 suppression of PDGF stimulated DNA synthesis in hCASMCs. PDGF increased migration activity, whereas BPS, T3 or T4 suppressed PDGF stimulated migration activity of hCASMCs. These results suggest that D2 expression is increased by BPS and suppressed by PDGF in hCASMCs, and that intracellular thyroid hormone activation may be involved in the suppression of DNA synthesis and migration activity of hCASMCs.

A new model of focal cerebral ischemia in the miniature pig.

OBJECT: The purpose of this set of studies is to design a minimally invasive, reproducible stroke model in the gyrencephalic brain. This paper provides information on both surgical technique and methods of quantification of ischemic damage to both gray and white matter in the miniature pig. METHODS: Sixteen male miniature pigs were randomly divided into three groups and underwent transcranial surgery involving a frontotemporal approach with orbital rim osteotomy for permanent middle cerebral artery occlusion (MCAO; five animals), permanent internal carotid artery occlusion (ICAO; six animals), and a sham operation (five animals). Histological mapping and magnetic resonance (MR) imaging were used to delineate the areas of ischemic damage. The volumes of infarction measured directly from MR images were 16.2 +/- 1.1, 1.5 +/- 0.5, and 0.0 +/- 0.0 cm3 (mean +/- standard deviation [SD], p < 0.001) in the MCAO, ICAO, and sham-operated groups, respectively. The areas of ischemia identified through histological analysis and MR imaging showed a good correlation (r2 = 0.86, p < 0.0001). Immunohistochemical staining with an amyloid precursor protein (APP) antibody was used to evaluate axonal damage and calculate a total APP score for axonal damage of 44.8 +/- 2.9 in the MCAO, 13.2 +/- 6.6 in the ICAO, and 0.0 +/- 0.0 (mean +/- SD, p < 0.002) in the sham-operated animals. CONCLUSIONS: This new model of focal cerebral ischemia induces a reproducible amount of ischemic damage in both gray and white matter, and has significant utility for studies of the pathophysiology of ischemia in the gyrencephalic brain and for assessment of the therapeutic efficacy of drugs prior to the initiation of human clinical trials.

Relationships between blood rheology and age, body mass index, blood cell count, fibrinogen, and lipids in healthy subjects.

We investigated the relationships between blood rheology assessed by microchannel method and the various hemorheologic factors in healthy subjects. One hundred seventy-six healthy volunteers (90 men and 86 women, mean age; 32.9+/-11.3 years) were participated in this study. Body weight, body mass index, red blood cell count, hematocrit, hemoglobin, white blood cell count, and platelet count, plasma fibrinogen, and fasting serum lipid and lipoprotein concentrations were measured. In order to assess blood rheology, blood passage time was determined by a microchannel method (Micro Channel Array Flow Analyzer). Age, body mass index, red blood cell count, hematocrit, hemoglobin, white blood cell count, total cholesterol, low-density lipoprotein cholesterol, and triglyceride were positively correlated with blood passage time in all subjects, respectively (p<0.01) and high-density lipoprotein cholesterol was inversely correlated with blood passage time (p<0.01). However, platelet count, and fibrinogen were not correlated with blood passage time. The present study showed that increased age, body mass index, red blood cell count, white blood cell count, total cholesterol, low-density lipoprotein cholesterol, and triglyceride and decreased high-density lipoprotein cholesterol were associated with impaired blood rheology measured by microchannel method in healthy subjects, suggesting that aging, obesity, erythrocytosis, leukocytosis, and dyslipidemia may be related to hemorheological disorders. This microchannel method may be useful to study blood rheology which may be associated with various risk factors of cardiovascular disorders.

Expression of type 2 iodothyronine deiodinase in human osteoblast is stimulated by thyrotropin.

Thyroid hormones play important roles in bone growth, development, and turnover. To exert its biological activity, T(4) needs to be converted to T(3) by iodothyronine deiodinase. In human thyroid gland as well as rat brown adipose tissue, type 2 iodothyronine deiodinase (D2) expression is regulated by a TSH receptor-cAMP-mediated mechanism. TSH receptor knockout mice demonstrated the direct effects of TSH on bone via TSH receptors found on osteoblast and osteoclast precursors. In the present study we investigated the possible expression and function of iodothyronine deiodinase and TSH receptors in human osteoblast-like osteosarcoma (SaOS-2) cells and normal human osteoblast (NHOst) cells. Iodothyronine deiodinase activity was detected in SaOS-2 cells and NHOst cells, and all of the characteristics of deiodinating activity were compatible with those of D2. Northern analysis demonstrated D2 mRNA expression in SaOS-2 cells and NHOst cells. D2 mRNA levels as well as D2 activities were rapidly increased by dibutyryl cAMP or forskolin in SaOS-2 cells and NHOst cells. TSH receptor mRNA was demonstrated in SaOS-2 cells and NHOst cells, and D2 mRNA and D2 activity were stimulated by TSH in both cells. In addition, all T(3) receptor isoforms were detected by RT-PCR in SaOS-2 cells and NHOst cells. The present results indicate the expression of functional TSH receptors and D2 in human osteoblasts and suggest previously unrecognized roles of TSH receptors and local T(3) production by D2 in the pathophysiology of human osteoblasts.

Cyclophilin C-associated protein and cyclophilin C mRNA are upregulated in penumbral neurons and microglia after focal cerebral ischemia.

Immunophilin ligands, such as cyclosporin A and FK506, have neuroprotective effects in experimental stroke models, although the precise mechanism is unclear. Cyclophilin C-associated protein (CyCAP) is a natural cellular ligand for the immunophilin, cyclophilin C, and has a protective effect against endotoxins by downmodulating the proinflammatory response. Expressions of CyCAP and cyclophilin C mRNA in a rat middle cerebral artery (MCA) occlusion ischemia model were investigated by Northern blotting and in situ hybridization. Both CyCAP and cyclophilin C mRNAs were ubiquitously distributed in the neurons of the normal brain. Expression increased in neurons of the periinfarct zone up to 7 days after MCA occlusion. The neuronal distribution was confirmed by counterimmunostaining of NeuN. Both mRNAs were predominantly expressed in microglia of the ischemic core at 7 days, confirmed by immunostaining with the microglial marker, ED1. The quantification of CyCAP and cyclophilin C mRNAs at 7 days by Northern blot analysis showed the 8.5-fold increase (P<0.005, n=6) and 6.8-fold increase (P<0.005, n=6), respectively, in ischemic core compared with control. The coincidence of CyCAP and cyclophilin C expression in neurons and microglia suggests distinct roles in each cellular population. In particular, the early increase in penumbral neurons might be related to protection in periinfarct neurons.

Inferior vena cava thrombosis associated with a distended ileal neobladder.

Venous stasis is generally accepted to be a predisposing factor for venous thrombosis. However, benign causes of inferior vena cava (IVC) obstruction with associated thrombus formation have not been well described. We herein present a case of IVC compression caused by a distended ileal neobladder measuring 2,000 mL in capacity that led to IVC thrombosis. Following transurethral drainage for six weeks and anticoagulation therapy with warfarin for six months, the thrombus completely disappeared. The patient was considered to have a hypercoagulable state resulting from an acute urinary tract infection, a condition that may be associated with an increased risk of thrombosis.

[Study on blood rheology measured by MC-FAN].

We investigated the effects of various factors on blood rheology, which was evaluated by the passage time of heparinized whole blood using MC-FAN (Micro Channel array Flow ANalyzer). The time for 100 microliters of whole blood to pass through a microchannel array (Bloody 6-7) was determined. Each passage time was corrected by the saline passage time determined just before the measurement of sample blood. Our results suggest that blood rheology measured by MC-FAN is related to aging, body weight, body mass index and serum lipid parameters (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride). These results suggest that MC-FAN is useful to analyze blood rheology in pathophysiological conditions.

Experimental investigation of encephalomyosynangiosis using gyrencephalic brain of the miniature pig: histopathological evaluation of dynamic reconstruction of vessels for functional anastomosis. Laboratory investigation.

OBJECT: Encephalomyosynangiosis (EMS) is a surgical treatment for moyamoya disease that is widely used to provide increased intracranial blood flow via revascularization by arterial anastomosis from the external carotid artery. However, the angiogenic mechanism responsible for the revascularization induced by EMS has not been systematically evaluated. In this study the authors investigated the chronological angiogenic changes associated with EMS to clarify the favorable factors and identify revascularization mechanisms by using an experimental internal carotid artery occlusion (ICAO) model in the miniature pig. METHODS: Fourteen miniature pigs were used, 11 of which underwent ICAO before transcranial surgery for EMS was performed. Animals were allowed to recover for 1 week (4 pigs) or 4 weeks (7 pigs) after EMS. Control group animals were treated in the same way, but without occlusion (3 pigs). Magnetic resonance imaging, angiography, and histological investigation were performed. RESULTS: One week after EMS, on histological examination of both the ICAO and control groups it was found that the transplanted temporal muscle had adhered to the arachnoid via a granulation zone, which was enriched with immune cells such as macrophages associated with the angiogenic process. Four weeks after EMS, angiography and histological examination of the ICAO group showed patent anastomoses between the external carotid artery and the cortical arteries without any detectable boundary between the temporal muscle and the cerebral cortex. In contrast, histological examination of the control group found scar tissue between the cerebral cortex and temporal muscle. CONCLUSIONS: The initial step for formation of anastomoses resembles the process of wound healing associated with repair processes such as active proliferation of macrophages and angiogenesis within the new connective tissue. Functional revascularization requires a suitable environment (such as tissue containing vascular beds) and stimulus (such as ischemia) to induce vascular expansion.

Effect of a high-fat diet on diabetic mother rats and their offspring through three generations.

Pregnant diabetic Wistar rats were fed a high-fat diet starting at the first gestational day. The effect of the high-fat diet on the growth of the female, her offspring, and the offspring's offspring was studied. Pregnant rats (first generation) were divided into the Diabetic streptozotocin-induced group and the control group. Diabetic streptozotocin-induced rats and control rats were fed either a control diet (5% fat in diet) or high-fat diet (32% fat in diet), and observed up to the third generation. In each generation, after weaning, the pups were fed the respective diet. The fat content was mainly animal lard. Diabetic rats fed the high-fat diet were infertile, and the pregnant first-generation and diabetic rats fed the control diet had a stillbirth rate of 27.5 +/- 22.0% (mean +/- SE). In the first generation, the diabetic rats fed the control diet had a significantly lower body weight increase during the pregnancy than the control rats fed the control diet. The second-generation diabetic rats fed the control diet had a high blood glucose level at birth, and their triglyceride level was higher than that in the other two groups. The third-generation diabetic rats fed the control diet had a triglyceride level higher than that of control rats. Delivery was most difficult in diabetic rats fed the high-fat diet. Pups of diabetic rats fed the control diet had growth retardation and increased blood glucose levels. We conclude that when the mother rat had diabetes, the next generation was also affected.

Unique regulation of thyroid hormone metabolism during fasting in the house musk shrew (Suncus murinus, Insectivora: Soricidae).

The active hormone, 3,3',5-triiodothyronine (T3) is derived from thyroxine (T4) by the action of iodothyronine 5'-deiodinases (5'-D). By now two types of 5'-D have been identified; Type 1 (D1) and type 2 (D2). A relative contribution of these isotypes to the circulating T3 levels in the human remains to be determined whereas a number of reports indicate that, under physiological conditions, D1 plays a major role in maintaining circulating T3 levels in rodents. In both human and rodents, sickness and starvation reduce serum T3 concentration mainly through decrease in D1 activity. Recently, we found that the house musk shrew (Suncus murinus, Insectivora: Soricidae) has a different tissue distribution of D1 activity. Because compared to rodents D1 activity in the shrew was found only in liver at a much reduced level, D2 rather than D1 may play a role in the maintenance of serum T3. Therefore, we questioned how D1 and D2 activities change in fasted shrews and how these changes affect circulating thyroid hormone levels. We thus starved shrews for 24, 48 or 72 h and measured changes in serum concentration of T3, T4, and 3,3',5'-triiodothyronine (reverse T3, rT3) and D1 activities as well as its mRNA expression in liver. D2 activities were also measured in brown adipose tissue (BAT) and cerebral cortex of shrews. Unlike in human and rodents, T3 levels in shrews remained constant during fasting while T4 levels tended to decrease, resulting in an increase in its T3/T4 ratio. On the other hand, changes in rT3 levels were similar to those in human and rodents, being elevated with fasting. D1 mRNA and its activity were significantly reduced in the liver whereas D2 activities in BAT and cerebral cortex were increased by fasting. These results indicated that fasting in shrews also reduced hepatic D1 activity but it did not affect circulating T3 levels. The increased T3/T4 ratio together with increased D2 activity in BAT and cerebral cortex with fasting suggest that D2 rather than D1 is responsible for the maintenance of T3 levels in the house musk shrew.

Association of antipituitary antibody and type 2 iodothyronine deiodinase antibody in patients with autoimmune thyroid disease.

Antipituitary antibody (APA) has been reported to be detected in patients with autoimmune thyroid disease. Type 2 iodothyronine deiodinase (D2) is expressed in both pituitary gland and thyroid gland. We studied the association of APA and D2 peptide antibody in patients with autoimmune thyroid disease. Rat pituitary gland homogenate and D2 peptide were used as antigens in the present study. APA and D2 peptide antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in sera obtained from 42 patients with Hashimoto's disease, 26 patients with Graves' disease and 70 healthy control subjects. Moreover, D2 activity precipitation assay was performed in some patients with Hashimoto's disease. APA and D2 peptide antibody were elevated in patients with Hashimoto's disease and patients with Graves' disease, compared with control subjects. APA was positive in 32.4% (22/68), D2 peptide antibody was positive in 26.5% (18/68) of patients with autoimmune thyroid disease. APA was positive in 31.0% (13/42) of patients with Hashimoto's disease and 34.6% (9/26) of patients with Graves' disease. D2 peptide antibody was positive in 26.2% (11/42) of patients with Hashimoto's disease and 26.9% (7/26) of patients with Graves' disease. D2 peptide antibody was correlated with APA in patients with autoimmune thyroid disease. Moreover, precipitation of D2 activity was increased in some patients with Hashimoto's disease including a patient who also had idiopathic diabetes insipidus, and was correlated with D2 peptide antibody. These results suggest that D2 antibody may be associated with APA in patients with autoimmune thyroid disease.