Cell Cycle Abnormality in Metabolic Syndrome and Nuclear Receptors as an Emerging Therapeutic Target

In recent years, many researchers have emphasized the importance of metabolic syndrome based on its increasing prevalence and its adverse prognosis due to associated chronic vascular complications. Upstream of a cluster of metabolic and vascular disorders is the accumulation of visceral adipose tissue, which plays a central role in the pathophysiology. In the accumulation of adipose tissues, cell cycle regulation is tightly linked to cellular processes such as proliferation, hypertrophy and apoptosis. In addition, various cell cycle abnormalities have also been observed in other tissues, such as kidneys and the cardiovascular system, and they are critically involved in the progression of disease. Here, we discuss cell cycle abnormalities in metabolic syndrome in various tissues. Furthermore, we describe the role of nuclear receptors in cell growth and survival, and glucose and lipid metabolism in the whole body. Therapeutic strategies for modulating various cell cycles in metabolic disorders by targeting nuclear receptors may overcome obesity and its chronic vascular complications in the future

Reconstruction of Bone Defect Using the Bone Transport Technique for a Case of Osteosarcoma of the Femur

There are few reports on skeletal reconstruction using the bone transport technique to repair bone defects caused by resections of tumors associated with osteosarcoma. We attempted to reconstruct a 23 cm bone defect after resection of an osteosarcoma of the left femur, and succeeded in gaining 17 cm by bone transport. Five years after surgery, this patient remains alive without metastasis or local recurrence.</p

Mesenteric Bleeding due to a Ruptured Aneurysm of the Middle Colic Artery

An outpatient with repeated colic attacks of unknown cause was hospitalized and was subjected to CT scan, ultrasound inspection, cytodiagnosis via abdominocentesis, resulting in the diagnosis of epigastrial hematoma. Further angiographical investigation evidenced the presence of middle colic artery. Aneurysm was also detected in the right colic artery. Other celiac arteries, however, were normal. The aneurysms detected were surgically removed with a portion of the intestinal tract. The pathological investigation of the resected aneurysm in the present cast could not prove the association with several other diseases which have been mentioned as possible causes for aneurysm. While only 10 cases of aneurysm at the superior mesenteric arterial branch have been reported, the authors believe that angiographical inspection should indispensably be attempted for diagnosis in cases of abdominal pain or abdominal tumors of unknown causes

Immunohistochemical Analysis of Colorectal Cancer among Atomic Bomb Survivors in Hiroshima

In order to elucidate the biological characteristics of colorectal cancer among atomic bomb survivors in Hiroshima, a total of 159 cases of colorectal cancers comprising 73 cases in exposed atomic bomb survivors and 86 cases in non-exposed individuals were examined histologically and immunohistochemically for various functioning proteins. No statistical differences could be demonstrated in the incidence of various marker expressions of colorectal cancers between the exposed group and control group. However, comparison by the site of colorectal cancer showed that sigmoid colon cancers in the exposed group or high dose group showed a significantly higher frequency of glycoproteins such as α1-antichymotrypsin (ACT), secretory component (SC), α1-antitrypsin (AAT), and human chorionic gonadotropin (HCG) when compared with the control group. These results correlated well with the epidemiological data that the radiation effect on the incidence of colorectal cancer in atomic bomb survivors was most remarkable in the sigmoid colon.This study was supported in part by Grants in Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan

A Rare Case of Appendiceal Mucocele with Myxoglobulosis

A 63-year-old man was admitted with an abdominal mass in the right lower quadrant. The tumor was diagnosed as mucocele of the appendix after admission and surgically removed. The appendix containing gelatinous mucus with numerous round bodies was distended to the size of an egg. Therefore, a diagnosis of myxoglobulosis was postoperatively made. This is a rare disease and the diagnosis has been preoperatively made in none of patients in Japan. The present case could present an echographic pattern characteristic of this cyst. Studies on all available echograms from previous patients could provide information necessary for preoperative diagnosis of myxoglobulosis

Differencial Diagnosis of an Abdominal Tumors of Uncertain Origin Using Fine Needle Aspiration Biopsy (FNAB)

FNAB under ultrasonic guidance was performed on 14 cases with abdomical tumors of uncertain origin. All of them could not be clarified their relationship with the liver, the biliary tract, the pancreas or the alimentary tract by routine clinical exams including diagnostic imaging such as CT and Ultrasonography. Preoperating histological diagnosis has been obtained for 12 of these by FNAB, thus diagnostic rate being 85.7%. The details of tumors identified by autopsy and operations were: 3 cases of lymphoma; 3 cases of leiomyosarcoma; 4 cases of adenocarcinoma; 2 cases of hematoma; and 1 case of inflammatory mass. Non-epithelial tumor was most frequently observed. FNAB is a simple diagnostic method with high cost-effectiveness for determining the therapeutical plan for an abdominal tumor of uncertain origin which is encounted in the daily treatment

Deformity of the proximal end of the femur following open reduction for developmental dislocation of the hip

We studied deformity of the proximal end of the femur following open reduction using the wide exposure method for developmental dislocation of the hip. We reviewed radiographs of 22 children with unilateral dislocation of the hip who had undergone open reduction between one and three years of age. Ages at final examination ranged from 14 to 21 years. None of the patients in this study had undergone any additional surgery. Avascular necrosis of the femoral head was not observed in any patients. Radiographic measurements were observed when the children were 3, 6, 9, and 12 years old, and at the final examination. Coxa magna and valga were the factors associated with poor results. Coxa valga had occurred at 6 to 12 years of age, but rapidly improved thereafter. Throughout the course of treatment the epiphysis-femoral neck angle was within the normal range. The fusion of the epiphyseal growth plates on both sides occurred simultaneously. The coxa valga was due to valgus of the femoral neck, and not to valgus head tilt. These results suggest that, provided the mechanics of the joint have been properly corrected as in our operation, the biomechanics of the hip will improve until growth ceases, but that it may take more than ten years to attain normality.</p

Nuclear Hormone Receptor Expression in Mouse Kidney and Renal Cell Lines

Nuclear hormone receptors (NHRs) are transcription factors that regulate carbohydrate and lipid metabolism, immune responses, and inflammation. Although several NHRs, including peroxisome proliferator-activated receptor-γ (PPARγ) and PPARα, demonstrate a renoprotective effect in the context of diabetic nephropathy (DN), the expression and role of other NHRs in the kidney are still unrecognized. To investigate potential roles of NHRs in the biology of the kidney, we used quantitative real-time polymerase chain reaction to profile the expression of all 49 members of the mouse NHR superfamily in mouse kidney tissue (C57BL/6 and db/m), and cell lines of mesangial (MES13), podocyte (MPC), proximal tubular epithelial (mProx24) and collecting duct (mIMCD3) origins in both normal and high-glucose conditions. In C57BL/6 mouse kidney cells, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and COUP-TFIII were highly expressed. During hyperglycemia, the expression of the NHR 4A subgroup including neuron-derived clone 77 (Nur77), nuclear receptor-related factor 1, and neuron-derived orphan receptor 1 significantly increased in diabetic C57BL/6 and db/db mice. In renal cell lines, PPARδ was highly expressed in mesangial and proximal tubular epithelial cells, while COUP-TFs were highly expressed in podocytes, proximal tubular epithelial cells, and collecting duct cells. High-glucose conditions increased the expression of Nur77 in mesangial and collecting duct cells, and liver x receptor α in podocytes. These data demonstrate NHR expression in mouse kidney cells and cultured renal cell lines and suggest potential therapeutic targets in the kidney for the treatment of DN

Pemt deficiency ameliorates endoplasmic reticulum stress in diabetic nephropathy

Phosphatidylethanolamine N-methyltransferase (Pemt) catalyzes the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) mainly in the liver. Under an obese state, the upregulation of Pemt induces endoplasmic reticulum (ER) stress by increasing the PC/PE ratio in the liver. We targeted the Pemt gene in mice to explore the therapeutic impact of Pemt on the progression of diabetic nephropathy and diabetes, which was induced by the injection of streptozotocin (STZ). Although the blood glucose levels were similar in STZ-induced diabetic Pemt+/+ and Pemt−/−mice, the glomerular hypertrophy and albuminuria in Pemt−/− mice were significantly reduced. Pemt deficiency reduced the intraglomerular F4/80-positive macrophages, hydroethidine fluorescence, tubulointerstitial fibrosis and tubular atrophy. The expression of glucose-regulated protein-78 (GRP78) was enriched in the renal tubular cells in STZ-induced diabetic mice, and this was ameliorated by Pemt deficiency. In mProx24 renal proximal tubular cells, the treatment with ER-stress inducers, tunicamycin and thapsigargin, increased the expression of GRP78, which was reduced by transfection of a shRNA lentivirus for Pemt (shRNA-Pemt). The number of apoptotic cells in the renal tubules was significantly reduced in Pemt−/− diabetic mice, and shRNA-Pemt upregulated the phosphorylation of Akt and decreased the cleavage of caspase 3 and 7 in mProx24 cells. Taken together, these findings indicate that the inhibition of Pemt activity ameliorates the ER stress associated with diabetic nephropathy in a model of type 1 diabetes and corrects the functions of the three major pathways downstream of ER stress, i.e. oxidative stress, inflammation and apoptosis