Late-onset obesity in mice transgenic for the human renin gene

We previously generated a strain of transgenic mice carrying the human renin gene, hRN8-12, in the background of C57BL/6j. In this study, we discovered that hRN8-12 male mice, but not females, developed obesity starting at 15 weeks of age. The body weight of 60-week-old male transgenic mice was 2 times higher than that of age-matched wild-type mice. Interestingly, male mice heterozygous for the human renin gene showed moderate weight gain compared with transgenic and wild-type mice. Obese hRN8-12 mice exhibited hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia, and increase in weight in the adipose tissue, liver, heart, and kidneys. Histological analysis demonstrated that fatty hRN8-12 mice developed hypertrophy of pancreatic islets and fatty liver. These results suggested that hRN8-12 mice are associated with obesity dependent on the transgene dosage and should be a genetic model for late-onset obesity.     

Mixed connective tissue disease with fatal pulmonary hypertension and a review of literature

Summary The paper presents an autopsy case of mixed connective tissue disease (MCTD) with pulmonary hypertension (PH) and a review of literature. A 33-year-old woman with Raynaud's phenomenon and dyspnea of one year duration was diagnosed as having MCTD on the basis of a higher titer (1:163,840) of serum antibodies to the ribonucleoprotein (RNP). Cardiac catheterization showed complicating PH, confirmed an autopsy by the findings of concentric intimal cellular proliferation and typical plexiform lesions in the small arteries and arterioles of the lung, suggesting primary PH. Fatal PH with MCTD has been reported only 6 cases in literature including our case. All were young females, with histopathological findings consistent with plexogenic pulmonary arteriopathy in 5 cases and with recurrent pulmonary thromboembolism in the other. The aetiology of PH is still unknown, but it may be due to vasoconstriction evoked by the hyper-reactivity of the vessels.     

Histochemical demonstration of endogenous estrogen in breast carcinomas: Biochemical and clinical correlation

Summary In a study of 277 patients with breast carcinomas, the PAP immunoperoxidase method for demonstrating endogenous estrogen was correlated with the sucrose density gradient (SDG) assay and with histologic and clinical features. The results from the PAP method and SDG assay agreed in 59 of 84 patients (82.1%) on whom both methods were performed. Histologically, the PAP method was positive in 7 of 7 patients with non-invasive carcinomas, in 164 of 233 patients (70.4%) with common invasive ductal carcinoma, and in 21 of 22 of those with special histological types of invasive carcinomas not including Paget's disease, medullary or apocrine carcinoma, where only 5 of 14 were positive. Clinically, 15 of 18 patients with positive endogenous estrogen showed a response to endocrine therapy as opposed to 1 of 9 patients with a negative endogenous estrogen. The mean survival was 31.2 and 15.6 months, respectively for patients with positive and negative endogenous estrogen. Remission for longer than 2 years was seen more often in patients with positive endogenous estrogen. These results suggest a clinical utility of the present PAP method which, therefore, deserves a further trial as an alternative to histochemical methods aiming at the estrogen receptors.This work was supported by Grants-in Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (No. 56480119).This paper was presented at the 72nd Annual Meeding of International Academy of Pathology (United States-Canadian Division), Atlanta, Georgia, March 1, 1983.     

Evidence of the monoclonal composition of human endometrial epithelial glands and mosaic pattern of clonal distribution in luminal epithelium

The endometrium is a highly regenerative tissue that plays a crucial role in implantation. We examined the clonal constitution of glandular cells as well as the luminal epithelium of this unique tissue. Using collagenase-based digestion techniques with microscopic manipulation, we isolated individual human endometrial glands and examined their clonality using a polymerase chain reaction-based assay for nonrandom X chromosome inactivation with an X-linked androgen receptor gene. Most of the glands analyzed were composed of monoclonal populations of epithelial cells and one of the glands exhibited a loss of heterogeneity in the androgen receptor gene. In addition, adjacent glands within a 1-mm(2) area shared clonality, suggesting that clonality of the luminal epithelium is regionally defined. The clonality of endometrium was further confirmed in a study of female mice that harbor the green fluorescent protein gene on either the maternal or paternal X chromosome. Fluorescent microscopy of uterine sections revealed that individual endometrial glands consisted completely of either fluorescent or nonfluorescent cells and that the surface epithelium exhibited a clear boundary between these cell types. These findings suggest that single or multiple stem cells with uniform clonality exist on the bottom of each endometrial gland and genetic alterations occurring in such cells may play a critical role in endometrial carcinogenesis. The possible association between area-specific X inactivation of the endometrial surface and the endometrial receptivity of embryo implantation remains to be clarified.     

Non-functional adrenocortical adenoma with extensive degeneration

We report a case of non-functional adrenocortical adenoma of 5.5 x 5.5 x 3.2 cm in size that had an unusual histopathological appearance in two respects. First, the tumor contained small adipose foci with osteogenesis and was suspected of being a myelolipoma based on its appearance on computerized tomography (CT) and magnetic resonance imaging. However, pathologically, the fat element was seen focally and was not accompanied by hematopoietic cells, and the diagnosis of myelolipoma was abandoned. Second, the tumor was suspected of being an adrenal carcinoma based on its appearance on CT scans and showed extensive degeneration: fibrosis, hemorrhage, loss of parenchyma and moderate atypism of the tumor cells. However, as the architecture of the tumor cells was non-diffuse and there were no necrotic foci or mitoses, and vascular or capsular invasion were not present, the tumor was concluded to be an adrenocortical adenoma rather than a carcinoma. We diagnosed the tumor as a non-functional adrenocortical adenoma with extensive degeneration as the extensive areas of fibrosis were particularly remarkable. Furthermore, the extensive areas of degeneration might have been caused not only by an ischemic effect but also by low hormone levels.     

Dietary Olive Oil Intake Improves Running Endurance with Intramuscular Triacylglycerol Accumulation in Mice

Olive oil is a functional food shown to have a variety of bioactive effects. Therefore, we expect it to be a novel functional food with an exercise-mimetic effect on skeletal muscles. This study aimed to investigate the effect of olive oil on the endurance capacity and muscle metabolism in mice. Mice fed a 7% (w/w) olive oil diet for eight weeks showed improved treadmill running endurance and increased intramuscular triacylglycerol (IMTG) accumulation in the gastrocnemius muscle compared to soybean oil diet-fed controls. The increase in running endurance with olive oil intake was independent of the muscle fiber type. To elucidate underlying the mechanism of elevated IMTG levels, we examined the expression levels of the genes related to lipid metabolism. We found that the expression of diacylglycerol O-acyltransferase1 (DGAT1) was significantly upregulated in the muscle of olive oil diet-fed mice. In addition, the olive oil diet-fed mice showed no metabolic impairment or differences in growth profiles compared to the controls. These results suggest that dietary olive oil intake affects muscle metabolism and muscle endurance by increasing energy accumulation.     

Total hip arthroplasty using hydroxyapatite-coated cementless cup for rapidly destructive coxarthrosis: Minimum 10-year follow-up

BackgroundPerforming total hip arthroplasty (THA) as early as possible is recommended for rapidly destructive coxarthrosis (RDC) as it causes pain that becomes progressively more severe. However, acetabular bone loss remains an issue in THA. Special devices, such as a Kerboull-type plate, may be used for acetabular bone defects, but the procedure is highly invasive and often the patients are elderly, further complicating matters. We retrospectively investigated the clinical and radiographic results of THA using conventional hydroxyapatite-coated cementless cup in RDC.MethodsA total of 32 patients (35 hips) with RDC were enrolled in the study with a minimum 10-year follow-up. All THAs were performed using conventional hydroxyapatite-coated cementless cup. All patients were evaluated clinically according to the Harris hip score (HHS). Acetabular bone deficiency was classified according to the American Academy of Orthopaedic Surgeons (AAOS) classification.ResultsEleven hips (31%) were AAOS type III, and none were type IV. Total HHS significantly improved from 36.5 to 79.4 (p < 0.01). Two cups exhibited loosening. The overall implant-associated survival rate after 10 years was 91.4%.ConclusionsClinical results of THA using conventional cementless implants for patients with RDC were acceptable. Thus, THA using conventional cementless implant is an effective and safe surgery for patients with RDC, minimizing surgical stress.