Muscle mass index in haemodialysis patients: a comparison of indices obtained by routine clinical examinations.

BACKGROUND: Measurement of muscle mass is useful for evaluating protein nutritional status. Various methods for estimating muscle mass in haemodialysis patients have recently been developed. METHODS: The validity of the estimate of creatinine production calculated with the creatinine kinetic model (CKM) was examined in 46 haemodialysis patients by comparing it with the actual creatinine production, this being determined from the sum of creatinine appearing in the dialysate and the estimated metabolic degradation. The correlation of various other muscle mass indices with creatinine production was also investigated in these patients. RESULTS: The estimate of creatinine production using CKM was significantly correlated with creatinine production calculated from the spent dialysate plus an estimate for the extra-renal creatinine degradation (r=0.90, P<0.001). A Bland-Altman analysis revealed that the mean prediction error for the estimate of creatinine production by CKM was +0.10 g/day and the limits of agreement were +0.34 to -0.14 g/day. The cross-sectional area of the thigh muscle measured by computed tomography (CT) was also significantly correlated with creatinine production (r=-0.86, P<0.01). In contrast, the correlations of 3-methylhistidine production measured in the spent dialysate, the mid-upper arm muscle circumference and the skeletal muscle mass estimated by an anthropometric prediction model with creatinine production were lower (r<0.82). CONCLUSION: Creatinine production calculated using CKM and CT measurement of thigh muscle area are valid methods for estimating muscle mass during routine clinical examinations of haemodialysis patients.     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

Comparison of [I]metaiodobenzylguanidine kinetics with heart rate variability and plasma norepinephrine level

Background. [¹²³I]Metaiodobenzylguanidine (MIBG) imaging has been used to assess cardiac sympathetic nerve abnormalities. We evaluated the clinical significance of myocardial MIBG imaging as a measure of cardiac sympathetic nervous system function by comparing it to heart rate variability and plasma norepinephrine level.Methods and Results. In 211 subjects, we analyzed heart rate variability with 24-hour electrocardiography, performed scintigraphy with MIBG, and measured plasma norepinephrine levels. Time and frequency domain measures of heart rate variability were calculated with the Marquette heart rate variability program (Marquette Electronics, Milwaukee, Wis.). Early and late myocardial MIBG uptakes were measured at 15 and 150 minutes after injection, respectively. MIBG clearance rate from the heart and heart-to-lung and heart-to-mediastinum ratios of MIBG activities were calculated. On the whole, heart rate variability, including low-frequency power, correlated positively, but modestly so, with late MIBG uptake and negatively with MIBG clearance rate. The plasma norepinephrine level correlated negatively with late MIBG uptake and with heart rate variability, including low-frequency power, and positively with MIBG clearance rate. Similar correlations were also observed in patient subgroups with coronary artery disease, diabetes mellitus, and renal failure, but these correlations were weak (R² < 0.5).Conclusions. Increased cardiac sympathetic nervous system activity may be associated with increased myocardial MIBG clearance and decreased heart rate variability, including low-frequency power. Because these associations were not strong, however, the combination of heart rate variability with MIBG may allow an interactive assessment of the cardiac autonomic nervous system.     

Structural alterations of the N-linked sugar chains of glycoproteins produced by tumor cells and their clinical application]

Enrichment of complex type N-linked sugar chains containing the Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----4GlcNAc beta 1----2)Man group was found to be the structural background of Warren-Glick phenomenon. This alteration is induced by enhanced expression of N-acetylglucosaminyltransferase V in malignant cells. The phenomenon is positively correlated with the tumorigenicity and the potency of blood-borne metastasis of tumor cells. Further investigation of the surface sugar chains of lectin mutants of mouse B16 melanoma revealed that the occurrence of sialylated tetraantennary sugar chains is essential for the metastasis of tumor cells.     

Traf6 is essential for murine tooth cusp morphogenesis.

Ectodermal appendages such as skin, hair, teeth, and sweat glands are affected in patients with hypohidrotic (anhydrotic) ectodermal dysplasia (HED). It has been established that mutations in the tumor necrosis factor (TNF) superfamily of molecules, i.e., ectodysplasin (EDA), EDA receptor (EDAR), and EDAR-associated death domain (EDARADD; the intracellular adaptor for EDAR), are responsible for several forms of HED in humans and mice. We show here by in situ hybridisation that another TNF family (orphan) receptor, TROY (also known TAJ, TAJ-alpha, TRADE, and TNFRSF19), is strongly coexpressed with Edar in the epithelial enamel knot signalling centres that are believe to regulate cuspal morphogenesis during murine tooth development. Traf6 is known to function as an intracellular adaptor protein for Troy and examination of Traf6 mutant mice revealed abnormalities in molar teeth that are similar but more severe than those produced by mutations in Eda signalling molecules. This finding suggests that, in additional to ectodysplasin, another TNF pathway involving Troy/Traf6 is involved in molar tooth cusp formation and identifies an essential role for a Traf in tooth development. Developmental Dynamics 229:131-135, 2004.     

Pulmonary metastases from a low-grade endometrial stromal sarcoma confirmed by chromosome aberration and fluorescence in-situ hybridization approaches: a case of recurrence 13 years after hysterectomy

Pulmonary metastasis from low-grade endometrial stromal sarcomas (ESSs) occasionally are found after long, disease-free periods, mostly as incidental histological or radiological discoveries. We describe a case of low-grade ESS presenting as nodular pulmonary metastases finally diagnosed by estrogen-receptor staining, cytogenetic and fluorescence in situ hybridization (FISH) analyses, and perusal of the histology of hysterectomy material. An abnormal nodule in the lung field was discovered by means of chest X-ray of a 47-year-old woman. She had been disease free for 13 years after hysterectomy for an alleged leiomyoma. A computed tomographic scan revealed nodules, with fluctuation in size over the 2-year period, in both lungs. Finally the lesion in the left lung was resected, and pulmonary endometriosis was suspected because of the lack of stromal cell nuclear atypia and positive immunohistochemical reactions for estrogen and progesterone receptors. However, a characteristic karyotype was identified cytogenetically: 46, XX, t(7;17)(p15;q11), the translocation of which, specific to ESS, was confirmed by FISH analysis. A final diagnosis of pulmonary metastases from an ESS could be made by reviewing the histology of the previous uterine tumor. In this case, metastatic lesions from an ESS showed a decrease as well as an increase in size, despite the malignant potential. Immunostaining for estrogen and progesterone receptors and cytogenetic and FISH analyses, together with clinical information on the past gynecological history, are valuable diagnostic keys.     

Expression of tumor necrosis factor ligand superfamily costimulatory molecules CD27L, CD30L, OX40L and 4-1BBL in the heart of patients with acute myocarditis and dilated cardiomyopathy.

BACKGROUND: T-cell-mediated myocardial damage is known to be involved in acute myocarditis and dilated cardiomyopathy. Recently, we found that tumor necrosis factor (TNF) ligand superfamily costimulatory molecules, especially 4-1BBL, played an important role in the myocardial damage of murine acute viral myocarditis. METHODS AND RESULTS: To investigate the roles for CD27L, CD30L, OX40L and 4-1BBL, which belong to TNF ligand superfamily, in the development of acute myocarditis and dilated cardiomyopathy, we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and dilated cardiomyopathy. We also examined expression of the receptors for these molecules, CD27, CD30, OX40 and 4-1BB, which belong to TNF receptor superfamily, on the infiltrating cells. Strong expression of CD27L, CD30L and 4-1BBL and weak to moderate expression of OX40L was found in the cardiac myocytes of patients with acute myocarditis. Moderate expression of CD27L, CD30L and 4-1BBL and weak expression of OX40L was found on the cardiac myocytes of patients with dilated cardiomyopathy. Most of the infiltrating cells expressed CD27, CD30 and 4-1BB and a part of the infiltrating cells expressed OX40. CONCLUSIONS: Our findings suggest that expression of TNF ligand superfamily costimulatory molecules on cardiac myocytes may play a role in the cell-mediated myocardial damage in patients with acute myocarditis and dilated cardiomyopathy as in murine viral myocarditis.     

Development of a rapid PCR method using the insertion sequence IS1203 for genotyping Shiga toxin-producing Escherichia coli O157

We developed a rapid PCR method utilizing the diversity of the insertion site IS1203 for genotyping Shiga toxin-producing Escherichia coli (STEC) O157 (IS1203 PCR typing). DNA fragments digested by PvuII, which cut IS1203 at one site, were ligated with themselves and detected by PCR with outward-facing primer pairs for IS1203. To minimize nonspecific bands, nested PCR was also performed. Two fingerprinting patterns produced from the upstream or downstream regions of IS1203 were obtained within 1 or 2 days. By combining the two patterns, 79 STEC O157 isolates were classified into 39 types, which were then classified into 36 subtypes by pulsed-field gel electrophoresis (PFGE). The discriminatory power of IS1203 PCR typing (D = 0.974) is similar to that of PFGE (D = 0.981). This method can be used for rapid and simplified genotyping.     

Apoptosis with FasL+ cell infiltration in the periphery and thymus of corrected autoimmune mice.

Fas (CD95) ligand (L) is a death factor that binds to its receptor, Fas, and induces apoptotic cell death, a crucial process in immunological tolerance. gld (generalized lymphoproliferative disorder) mice, which have a point mutation in the FasL gene, develop spontaneous systemic autoimmune syndromes characterized by hypergammaglobulinaemia and lymphoid hyperplasia owing to accumulation of abnormal B220+ CD3+ cells. Transplantation of wild-type (wt) bone marrow cells into old gld mice on the same strain background results in normalization of autoimmune syndromes. We characterized the cellular mechanisms (functionally and histologically) of the above phenomena in gld mice after bone marrow transplantation (BMT) to determine the role of apoptosis via Fas/FasL interactions in inducing and maintaining self-tolerance in vivo. Activated splenocytes from wt and BMT (wt to gld) mice showed significant cytotoxic activity against Fas transfectant cells while those from BMT (gld to gld) mice did not. Cells in the thymus, spleen and lymph nodes of gld mice uniformly upregulated Fas expression and were sensitive to Fas-mediated apoptosis compared with those in wt mice. Cells sensitive to Fas-mediated apoptosis in gld mice resided not only among abnormal B220+ CD3+ cells but also among conventional lymphocytes. More importantly, histological analysis revealed that cells in the spleen, lymph nodes and thymus frequently underwent apoptosis with infiltration of FasL+ cells in BMT (wt to gld) mice compared with BMT (gld to gld) mice. Our results indicated that apoptosis via Fas/FasL interactions can directly eliminate pathogenic cells responsible for autoimmunity in the periphery and possibly in the thymus in vivo.