Calorie restriction increases serum parathyroid hormone and decreases serum calcitonin levels in patients with maturity onset diabetes mellitus

Calorie restriction is important in managing patients with maturity onset diabetes mellitus (NIDDM). The effect of such restriction on calcium metabolism is not known. The objective of this study was to determine whether patients on calorie restricted diets would show any modification of parathyroid hormone (PTH) and calcitonin (CTN). The serum levels of PTH and CTN were measured by radioimmunoassays in 269 patients with NIDDM. The patients were divided into two groups depending on the intake of calorie, and PTH and CTN were monitored for 2 years. Plasma levels of vitamin D were measured by competitive protein binding assays before and after each program. The level of PTH (520.8±266.0 pg/ml) (mean±S.D.) was significantly (P<0.01) higher in 109 diabetic patients whose calorie intake was restricted for 2 years (diet (D) group) as compared with that (256.6±103.8 pg/ml) of 160 diabetic patients whose calorie intake was not restricted (non-diet (ND) group). The daily oral calcium intake of the two groups did not differ significantly. We found no significant difference in the serum PTH level in the ND groupVS. normal control subjects (248.8±98.4, N=78). The serum calcium concentration and the amount of calcium excreted in urine were slightly but significantly (P<0.01) lower in the D than in the ND group. The rate of tubular reabsorption of phosphate (% TRP) was significantly lower in the D group than that in the ND group (P<0.01). The serum CTN level was significantly (P<0.01) lower in the D group (33.9±11.3 pg/ml) than in the ND group (64.9±21.2 pg/ml) 2 years after each treatment. The plasma 1,25-(OH)₂-vitamin D level was significantly (P<0.01) lower in the D group (22.2±6.6 pg/ml) than in the ND group (50.6±4.2 pg/ml). When the restriction of calorie intake in the D group was canceled, their PTH levels decreased, which was accompanied by increase in the 1,25-(OH)₂-vitamin D levels, whereas their CTN levels were unchanged. These observations suggested that a restricted calorie intake is a risk factor for secondary hyperparathyroidism as well as for a low serum level of CTN in patients with NIDDM.     

‘Ischemic tolerance’ phenomenon detected in various brain regions

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the ‘ischemic tolerance’ phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of ‘ischemic tolerance’.     

Reduction of osteoclasts in a critical embryonic period is essential for inhibition of mouse tooth eruption.

Alveolar bone resorption by osteoclasts is essential for tooth eruption. Osteoclast-deficient Csfm(op) homozygous (op/op) mice, which lack functional macrophage colony-stimulating factor (M-CSF), suffer from osteopetrosis and completely lack tooth eruption. Although osteoclasts appear, and osteopetrosis is cured with age in op/op mice, tooth eruption is never seen. This fact suggests that there is a critical period when osteoclasts are required for tooth eruption. In this study, to detect the critical period, we administered an antagonistic antibody directed against c-Fms, a receptor for M-CSF, to inbred C57BL/6 mice for various periods. Administration of this antibody decreased tartrate-resistant acid phosphatase-positive (TRAP) osteoclasts, and incisor eruption was completely inhibited by continual administration of this antibody from embryonic day 15.5 (E15.5) until postnatal day 12.5 (D12.5). A 1-day delay of this administration abolished the inhibition of incisor eruption. The number of TRAP-positive osteoclasts was significantly reduced between E16.5 and E18.5 in the mice treated with antibody from E15.5 compared with those treated from E16.5. These results indicate that this period, during which the number of osteoclasts decreases significantly, is critical for inhibiting incisor eruption in C57BL/6 mice.     

A case of aseptic meningitis caused by relapsing polychondritis]

We report a patient of relapsing polychondritis (RP) with antecedent aseptic meningitis. A 65-year-old man has developed headache and fever. Neurological examination showed meningeal signs, and cerebrospinal fluid (CSF) examination revealed meningeal inflammation which contained 450 polymorphonuclear cells/microl, 302 mononuclear cells/microl, and 0 red cells/microl, with 79 mg protein/dl. Serologic testing for autoimmune disease as well as the culture and cytology of CSF were negative. He admitted our hospital as having aseptic meningitis and experienced antibiotic therapy. However, his pyrexia continued and he developed repeating visual and hearing impairment reacting to steroid. Three months later, he became behaviorally deaf, and bilateral auricular chondritis occurred with nonerosive seronegative inflammatory polyarthritis. The result of condral biopsy was consistent with the diagnosis of RP showing cartilage surrounded by an intense inflammatory cell response with a decreased number of chondrocytes. A clinical diagnosis was made and prednisolone 60 mg/day was begun with the result of resolution of the auricular chondritis, and slight improvement of his deafness. Aseptic meningitis is a rare complication of RP. Only one report detailed RP patient who had preceding meningitis. RP is a potentially lethal disease resulting from suffocation by airway collapse, the complications of a cardiac large vessel, and so on. For improvement of a life prognosis, an early diagnosis and treatment are indispensable. Although RP is a rare discovery, it is necessary that RP should be taken into consideration and be differentiated as a cause of relapsing aseptic meningitis.     

JC病毒样颗粒可直接转运进入细胞核

目的探讨JC病毒(JCV)病毒样颗粒(VLP)是否可以直接转运进入细胞核。方法心用JCV主要外壳蛋白VP1体外表达、重组VIP，在其表面标记异硫氰基荧光素(FTTC)，同时在其内部包裹荧光染料Cy3，感染培养的HeLa细胞和SVG细胞，荧光显微镜观察VLP入核转运。结果HeLa和SVG细胞感染包裹Cy3的FTTC-VLP时，FTTC与Cy3同时出现于细胞核内相同部位；而感染FTTC—VP1与Cy3混合物时，FTTC虽可在细胞核内检测到，但Cy3信号几乎消失。包裹Cy3的VIP用SDSPAGE展开，荧光显像后行考马斯亮蓝(CBB)染色，发现Cy3和VLP移行至不同部位，证明Cy3不能与VP1结合，提示VLP以完整的颗粒形式转运进入细胞核。应用包裹外源性DNA的VLP感染培养的HeLa和SVG细胞，发现包裹的DNA在细胞浆和细胞核内均可检测到，提示JCV入核过程与VIP相同。结论VLP可以不经裂解直接转运进入细胞核，JCV入核转运可能与VLP相同。     

Recent research on the JC virus]

JC virus (JCV) is a causative agent of progressive multifocal leukoencephalopathy and belongs to Polyomavirus. In this article we describe our recent research relating to this virus. First, JCV's major capsid protein VP1 possesses a nuclear localization signal (NLS) and has the ability to construct a virus-like particle (VLP). We have investigated the mechanism of nuclear entry of JCV using VLP, and clarified the role of NLS. In vitro transport assay revealed that wild type VLP (wtVLP), but not deltaNLSVLP, entered the nuclei of cells. The nuclear transport of wtVLP was dependent on the addition of importins alpha and beta and was prevented by antibodies to nuclear pore complex (NPC). These results suggested that JCV VLP binds to cellular importins via the NLS of VP1 and is transported into the nucleus through the NPC. Second, a yeast two-hybrid screen of a human brain cDNA library demonstrated that the fasciculation and elongation protein zeta 1 (FEZ1) and the heterochromatin protein lalpha (HPla) are proteins that interacted with JCV agnoprotein (Agno). In vitro binding assay showed that Agno interacts directly with FEZ1 and HPlalpha. We have also shown that Agno induces the dissociation of FEZ1 from microtubules and dissociates the interaction between HPlalpha and lamin B receptor. We have demonstrated that interaction between Agno and these host proteins inhibited nuclear egress of JCV. Third, in order to inhibit JCV infection in infected cells, we synthesized siRNA which is specific for JCV Agno. Immunoblotting and immunocytochemical analysis demonstrated that expression levels of agnoprotein and VP1 were significantly inhibited by specific siRNA. In addition, levels of viral mRNAs and viral production were decreased in the cells transfected with Agno siRNA. Furthermore, viral production of cell treated with Agno siRNA was significantly inhibited. These results indicate that post-infection treatment with siRNAs, that targets JCV Agno suppresses virus production in JCV infected cells. Thus, siRNA directed against JCV encoding genes may provide a useful tool for suppression of JCV infection.     

Rare associations of dens invaginatus and mesiodens.

Dens invaginatus is a developmental variation resulting from an alteration in the normal growth pattern of the dental papilla. Synonyms of this disturbance include dens in dente, invaginated odontome, tooth inclusion, and dentoid in dente. Radiographically, it is observed as infolding of a radiopaque ribbon-like structure, with equal density as enamel, extending from the cingulum into the root canal and sometimes reaching the root apex, assigning the appearance of a small tooth within the coronal pulp cavity. This article presents 2 case reports. The first describes an 8-year-old girl with dens invaginatus in a mesiodens; the second report describes a 16-year-old boy presenting with 2 mesiodens, both associated with dens invaginatus.     

Associations of brachial-ankle pulse wave velocity and carotid atherosclerotic lesions with silent cerebral lesions.

Silent cerebral lesions are increasingly found in mass screenings using MRI and magnetic resonance angiography (MRA). The purpose of this paper is to assess the usefulness of two non-invasive clinical tests-carotid ultrasound examination and brachial-ankle pulse wave velocity (baPWV) measurement-for predicting silent cerebral infarction (SCI) and silent intracranial arterial stenosis. Data were collected on 480 asymptomatic adult subjects who participated in a brain screening program at a single hospital between April 2003 and March 2006. All participants underwent baPWV measurement, B-mode ultrasonography of carotid arteries, MRI, and MRA. Data on 476 (99.1%) subjects were included in the analysis. Among these, 273 (57.4%) were male and the mean age was 51.5 years; 161 (33.8%) had carotid plaque; 33 (6.9%) had increased intima-media thickness (IMT); 99 (20.8%) had SCI; and 7 (1.5%) had intracranial arterial stenosis. The multivariate analysis showed that age (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.08-1.17), carotid plaque (OR: 2.69; 1.59-4.56), increased IMT (OR: 2.40; 1.02-5.65), and a history of hypertension treatment (OR 2.22; 1.11-4.43) were significantly associated with SCI. Also, increased IMT (OR 9.70: 1.48-63.71) was related to intracranial arterial stenosis. Brachial-ankle PWV was related to SCI (p<0.01) and intracranial stenosis (p=0.01) in univariate analysis but not in multivariate analysis. The presence of carotid plaque and that of increased IMT on ultrasound examination are useful for assessing the risk of SIC. Increased IMT is also predictive of intracranial arterial stenosis.     

Intraoperative packing of a pancreatic pseudocyst complicated with bleeding pseudoaneurysm

Hemosuccus pancreaticus (HP) is a rare cause of gastrointestinal bleeding, usually due to rupture of a visceral artery aneurysm in chronic pancreatitis. Other causes of HP are rare. We present a case of HP which occurred in a patient with chronic calcifying pancreatitis and a pancreatic pseudocyst documented by ultrasonography and computed tomography. With detectable fresh blood in the descending duodenum, an aneurysm in the pancreatic head was revealed by superior mesenteric angiography as the suspected origin of intermittent bleeding from the pancreatic duct. Because an artery feeding the pseudocyst could not be identified, angiographic embolization was not possible. Surgical resection or ligation was difficult by laparotomy; therefore, intraoperative packing of the pseudocyst with absorbable gelatin sponges was achieved via a cannula through a directly punctured site in the pseudocyst wall. The patient has been followed for 4.25 years with no further episodes of HP. It is possible that the packing of a pancreatic pseudocyst with gelatin sponges is a method that can be used in similar cases, where control of hemostasis is the primary concern. The packing of a pancreatic pseudocyst with gelatin sponges is a technique that can be performed not only via laparotomy but also via laparoscopy or concomitant angiography and ultrasonography.     

Solitary right ventricle metastasis by renal cell carcinoma.

A 57-year-old man with a history of renal cell carcinoma presented with presyncope. He underwent nephrectomy years earlier followed by HLA-matched allogeneic peripheral-blood stem-cell transplantation. Echocardiographic investigation revealed a solitary right ventricle mass without contiguous vena caval or right atrial involvement. The mass was pathologically confirmed to be metastatic carcinoma in the right ventricular cavity. This case highlights the need to consider an underlying neoplastic syndrome in patients presenting isolated right ventricle mass by echocardiography.