Correlation of cytoplasmic beta-catenin and cyclin D1 overexpression during thyroid carcinogenesis around Semipalatinsk nuclear test site.

The Semipalatinsk nuclear test site (SNTS), the Republic of Kazakhstan, has been contaminated by radioactive fallout. The alteration of oncogenic molecules in thyroid cancer around the SNTS was considered worthy of analysis because it presented the potential to elucidate the relationship between radiation exposure and thyroid cancer. This study aimed to analyze both beta-catenin and cyclin D1 expressions in thyroid carcinomas around the SNTS. We examined nine cases of chronic thyroiditis, eight cases of follicular adenomas, and 23 cases of papillary carcinomas. Immunohistochemically, all carcinomas displayed a strong cytosolic beta-catenin expression, while both chronic thyroiditis and follicular adenomas showed a significantly lower cytoplasmic beta-catenin (22.2% and 37.5%, respectively). No cyclin D1 immunoreactivity was evident in chronic thyroiditis. In contrast, 62.5% of follicular adenomas and 87.0% of papillary carcinoma showed cyclin D1 overexpression. Additionally, a strong correlation between cytoplasmic beta-catenin and cyclin D1 expression was suggested in thyroid tumors. This study revealed a higher prevalence of both aberrant beta-catenin expression and cyclin D1 overexpression in papillary thyroid cancers around the SNTS than sporadic cases. The analysis of the alteration of the Wnt signaling-related molecules in thyroid cancer around the SNTS may be important to gain an insight into radiation-induced thyroid tumorigenesis.     

Reperfusion injury in dog hearts with permanent occlusion of a coronary artery, probably due to reperfusion via collateral vessels

To clarify whether or not reperfusion injury occurs in the permanent occlusion of a coronary artery, we analyzed quantitatively contraction band necrosis as an indicator of early recanalization, coagulation necrosis, infarct size and measured regional blood flow in dog hearts with collateral circulation. Fifty mongrel dogs were divided into four groups: 15 dogs with a 24-hour occlusion of the left anterior descending coronary artery just distal to the first diagonal branch (permanent occlusion group): 15 dogs a with 3-hour occlusion followed by 24-hour recanalization (recanalization group); 10 dogs with a 2-hour occlusion without recanalization (transient occlusion group); 10 dogs with a 4-hour occlusion without recanalization (transient occlusion group).

The regional blood flow in the subepicardium and subendocardium determined by the generated hydrogen gas clearance method was greatly decreased 30 minutes after occlusion (14 + 8%/12 ± 9%) and was relatively restored from 180 minutes (31 ± 21%/21 ± 14%) to 24 hours later (41 + 19%/26 + 16%) in spite of complete occlusion of the coronary artery. The percentage infarct area in the risk area was significantly greater in the permanent occlusion group (60 ± 26%) than in the recanalization group (35 ± 31%). Although most of the infarct was occupied by contraction band necrosis in the recanalization group (86 ± 12%), contraction band necrosis was diffusely seen even in the permanent occlusion group (54 ± 27%). In both the permanent and recanalization groups, contraction band necrosis was the main histological feature of small infarcts occupying less than 30% of the risk area, while coagulation necrosis was the main feature in very large infarcts occupying more than 80% of the risk area. In the occlusion groups without recanalization, the percentage area of contraction band necrosis in the risk area was 6 ± 8% after the 2-hour occlusion, 23 ± 17% after the 4-hour occlusion and 31 ± 21% after permanent occlusion; the difference between the 4-hour and permanent occlusion groups was not significant. In the permanent occlusion group, the percentage infarct area in the risk area was inversely correlated with regional blood flow during occlusion, an indicator of collateral flow. It was concluded that reperfusion injury occurs even in hearts without recanalization. The pathogenesis may involve reperfusion in the risk area via collateral circulation. Protection against reperfusion injury is important to minimize the infarct size even in hearts with permanent occlusion, although the presence of collateral flow is an important factor in limiting infarct size.     

Mesenteric hernia causing bowel obstruction in very low‐birthweight infants

Internal hernia through a mesenteric defect, called mesenteric hernia, is an uncommon cause of acute intestinal obstruction in newborns. Strangulated mesenteric hernia results in intestinal necrosis or perforation and progressive deterioration with fatal outcome, especially when it occurs in low‐birthweight infants. We report two very low‐birthweight (VLBW) infants, who presented with acute intestinal obstruction related to mesenteric defect. The initial diagnosis was meconium obstruction in those cases, which is a common cause of bowel obstruction occurring in VLBW infants. Correct diagnosis of mesenteric hernia was difficult in these cases because of rapid deterioration and non‐specific radiological findings. Awareness of the possibility of rare mesenteric hernia causing acute intestinal obstruction and surgical intervention in an appropriate timeframe are important for rescuing VLBW infants with such organic abnormalities.     

Clinical characteristics of supine hypertension in de novo Parkinson disease

Purpose

Supine hypertension is frequently associated with autonomic failure. However, its clinical characteristics in patients with Parkinson disease (PD) remain unclear. The present study aimed to clarify the characteristics of supine hypertension in patients with de novo PD.

Methods

The subjects were 72 patients with de novo PD. We studied blood pressure and plasma norepinephrine levels after the patients rested for 20 min in the supine position. Changes in blood pressure were also examined on head-up tilt-table testing.

Results

The disease duration was 1.7 ± 1.6 years (average ± SD). Thirty-three (45.8 %) patients had supine hypertension (defined as a blood pressure of ≥140/90 mmHg). Supine blood pressure positively correlated with the degree of orthostatic hypotension. Age and the proportion of patients with akinetic-rigid motor subtype or preexisting hypertension were higher among patients with supine hypertension than among those without supine hypertension. The Mini-Mental State Examination score was lower in patients with supine hypertension than in those without supine hypertension. Sex, disease duration, disease severity, and peripheral sympathetic nervous activity as evaluated by the cardiac uptake of ¹²³I-metaiodobenzylguanidine and the plasma norepinephrine level did not differ between patients with and those without supine hypertension.

Conclusion

Older age, akinetic-rigid motor subtype, and preexisting hypertension are independent risk factors for supine hypertension. Supine hypertension alone may be associated with milder peripheral sympathetic nervous denervation than orthostatic hypotension alone. As for global cognitive decline, supine hypertension is a far riskier comorbidity of early-stage PD than is orthostatic hypotension.

     

Preparation of glycoside polymer micelles with antioxidant polyphenolic cores using alkylated poly(arbutin)s

This paper describes the synthesis of long-chain-alkylated poly(arbutin)s (poly(Arb)-R_x, where R = alkyl-chain length and x = degree of substitution (DS)) and their aqueous micelle formation. DS was controlled by tailoring the alkyl reagent/main-chain phenol substituent feed ratio. The critical micelle concentrations (CMCs) of poly(Arb)-R_x were determined as 1.3–5.2 mg mL⁻¹ by the surface tension method. Introduction of longer alkyl substituents decreased CMC and also decreased aqueous solubility. In DLS measurement, the average micelle diameters were 225–616 nm, and micelle size decreased with increasing DS because of increased stabilization by hydrophobic alkyl substituents. Transmission electron microscopy indicated that mainly wormlike cylindrical micelles were formed, even with highly hydrophilic polymers. The alkylated polymer exhibited no cytotoxicity, and their antioxidant abilities were evaluated by the β-carotene bleaching method. Only 0.049 mol equivalents of poly(Arb)-C8₃₀ to linoleic acid was sufficient to preserve the β-carotene.

This paper describes the synthesis of long-chain-alkylated poly(arbutin)s (poly(Arb)-R_x, where R = alkyl-chain length and x = degree of substitution (DS)) and their aqueous micelle formation.     

Enhanced expression of the ubiquitin-proteasome system in the myocardium from patients with dilated cardiomyopathy referred for left ventriculoplasty: an immunohistochemical study with special reference to oxidative stress

The ubiquitin (Ub)-proteasome system (UPS) is an important proteolytic mechanism for selecting and digesting cytotoxic proteins. The aim of this study is to elucidate expression and in situ localization of the UPS in the myocardium from patients with dilated cardiomyopathy (DCM) with refractory heart failure. The expression profile of the oxidative stress-induced cytotoxic proteins was also examined. Myocardium was obtained from 26 patients with DCM at the left ventriculoplasty. Ten normal autopsied hearts served as controls. Myocardial expressions of Ub and proteasomes were studied immunohistochemically. Oxidative stresses were examined in point of localization of the oxidation-induced modifier molecules (OMM). The relationship between immunohistochemical results and clinical parameters was also evaluated. Both Ub and proteasomes were stained positive in granular structures accumulating between the myofibrils and adjacent to nuclei in cardiomyocytes. The OMMs were also positive in the same Ub-positive granular structures. The area fraction of Ub, proteasomes and OMM was significantly higher in DCM hearts than in normal controls. Significant positive correlation was observed between the area fractions of Ub and plasma levels of brain natriuretic peptide (p = 0.046) in DCM hearts. In conclusion, enhanced expression of the UPS colocalized with OMM in cardiomyocytes may be involved in the pathophysiology of DCM hearts.     

Analysis of HLA‐DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA‐DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC

Aims: Anti‐gp210 and anti‐centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown. Methods: We determined the HLA‐DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1–452‐month observation period. Results: Anti‐gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20–850.1) and anti‐centromere antibodies (OR, 2.36, 95% CI, 1.28–4.35) were significant risk factors for jaundice‐ and nonjaundice‐type progression, respectively. HLA‐DRB1*0405 and *0803 predisposed patients to anti‐gp210 (OR, 1.61, 95% CI, 1.08–2.39) and anti‐centromere (OR, 2.30, 95% CI, 1.41–3.73) antibody production, respectively. HLA‐DRB1*1502 and *0901 patients were predisposed to nonjaundice‐type progression (OR, 1.98, 95% CI, 1.13–3.40 and OR, 1.78, 95% CI, 1.02–3.03), while HLA‐DRB1*0803 and *0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48–3.41 and OR, 1.53, 95% CI, 1.11–2.11, respectively). Stratifying patients by HLA‐DRB1 alleles revealed that anti‐gp210 antibodies was a strong risk factor, regardless of the HLA‐DRB1 alleles for jaundice‐type progression, while anti‐centromere antibodies was a significant risk factor for nonjaundice‐type progression in patients with HLA‐DRB1*0405 (OR, 6.89, 95% CI, 2.18–26.56) and ‐DRB1*0803 (OR, 5.42, 95% CI, 1.47–24.62) but not other HLA‐DRB1 alleles. Conclusions: HLA‐DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.     

Synovial cyst of the hip in a patient with rheumatoid arthritis

A 67-year-old woman with rheumatoid arthritis (RA; Steinblocker stage IV, class 4) who had RA onset at 34 years of age had anterior thigh pain, femoral neuropathy and lower abdominal pain. Physical examination showed multidirectional limit of motion, and radiographic examination showed destruction of the hip joint. MRI and arthrography indicated a cystic lesion that communicated with the hip joint. The rheumatoid synovial cyst was removed during total hip arthroplasty. The symptoms were relieved, and the mass was reduced in size.     

Severe acute respiratory syndrome coronavirus infection in vaccinated ferrets

BACKGROUND: Development of vaccines to prevent severe acute respiratory syndrome (SARS) is limited by the lack of well-characterized animal models. Previous vaccine reports have noted robust neutralizing antibody and inflammatory responses in ferrets, resulting in enhanced hepatitis. METHODS: We evaluated the humoral immune response and pathological end points in ferrets challenged with the Urbani strain of SARS-associated coronavirus (SARS-CoV) after having received formalin-inactivated whole-virus vaccine or mock vaccine. RESULTS: Humoral responses were observed in ferrets that received an inactivated virus vaccine. Histopathological findings in lungs showed that infection of ferrets produced residual lung lesions not seen in both mock and vaccinated ferrets. SARS-CoV infection demonstrated bronchial and bronchiolar hyperplasia and perivascular cuffing in ferret lung tissue, as seen previously in infected mice. No evidence of enhanced disease was observed in any of the ferrets. All of the ferrets cleared the virus by day 14, 1 week earlier if vaccinated. CONCLUSIONS: The vaccine provided mild immune protection to the ferrets after challenge; however, there was no evidence of enhanced liver or lung disease induced by the inactivated whole-virus vaccine. The ferret may provide another useful model for evaluating SARS vaccine safety and efficacy.