Reversible hepatic dysfunction associated with rhabdomyolysis

Hepatic dysfunction was observed in 34 patients with nontraumatic rhabdomyolysis. The serum levels of lactic dehydrogenase were markedly elevated in all patients. The peak values occurred within 72 h of hospitalization. There was no significant difference among patients with (9,044 +/- 1,154 U/l) and without acute renal failure (ARF; 9,125 +/- 3,067 U/l). Similarly, marked elevation in both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed within 72 h after admission to the hospital. They were significantly higher in patients with ARF (ALT: 4,718 +/- 785 vs. 2,496 +/- 927 U/l, p less than 0.01; AST: 3,635 +/- 820 vs. 1,352 +/- 624 U/l, p less than 0.01). Hyperbilirubinemia was noted in 13 of 22 (60%) patients with ARF and in 5 of the 12 (41%) of those without ARF. Serum levels of bilirubin ranged from 2.6 to 14.3 mg/dl. Prothrombin time was prolonged in 4 of 12 (33%) without ARF and in 14 of 22 (63%) of patients with ARF. This abnormality lasted from 1 to 13 days. The magnitude and duration of hyperbilirubinemia and abnormal prothrombin time were similar in patients with and without ARF. Hepatic dysfunction appears to occur in about 25% of patients with rhabdomyolysis. The pathogenesis of these abnormalities is not well defined and may be multifactorial. Hyperpyrexia, hypotension and proteases released from injured muscle may each or all be contributory. These hepatic derangements are reversible.     

Tumor necrosis factor-alpha-induced changes in insulin-producing beta-cells

The migration of macrophages and lymphocytes that produce cytokines such as tumor necrosis factor-alpha (TNF-alpha) causes beta-cell death, leading to type 1 diabetes. Similarly, in type 2 diabetes, the adipocyte-derived cytokines including TNF-alpha are elevated in the circulation, causing inflammation and insulin resistance. Thus, the studies described in this article using TNF-alpha are relevant to furthering our understanding of the pathogenesis of diabetes mellitus. We used RINr1046-38 (RIN) insulin-producing beta-cells, which constitutively express calbindin-D(28k), to characterize the effect of TNF-alpha on apoptosis, replication, insulin release, and gene and protein expression. Western blots of TNF-alpha-treated RIN cells revealed a decrease in calbindin-D(28k). By ELISA, TNF-alpha-treated beta-cells had 47% less calbindin-D(28k) than controls. In association with the decline in calbindin-D(28k), TNF-alpha treatment of RIN cells led to a 73% greater increase in changes in intracellular calcium concentration (Delta[Ca(2+)](i)) in TNF-alpha-treated cells as compared to that in control RIN cells upon treatment with 50 mM KCl; caused a greater increase in the [Ca(2+)](i) following the addition of 5.5 microM ionomycin; increased by more than threefold the apoptotic rate, expressed as the percentage of TUNEL-positive nuclei to total nuclei; decreased the rate of cell replication by 36%; and increased and decreased selectively the expression of specific genes as determined by microarray analysis. The subcellular localizations of Bcl-2, an antiapoptotic protein, and Bax, a proapoptotic protein, within RIN cells were altered with TNF-alpha treatment such that the two were colocalized with mitochondria in the perinuclear region. We conclude that the proapoptotic action of TNF-alpha on beta-cells is manifested via decreased expression of calbindin-D(28k) and is mediated at least in part by [Ca(2+)](i).     

A novel autosomal recessive non-syndromic deafness locus (DFNB35) maps to 14q24.1-14q24.3 in large consanguineous kindred from Pakistan

Autosomal recessive nonsyndromic deafness is one of the most frequent forms of inherited hearing impairment. Over 30 autosomal recessive nonsyndromic hearing loss loci have been mapped, and 15 genes have been isolated. Of the over 30 reported autosomal recessive nonsyndromic hearing loss (NSHL) loci, the typical phenotype is prelingual non-progressive severe to profound hearing loss with the exception of DFNB8, which displays postlingual onset and DFNB13, which is progressive. In this report we describe a large inbred kindred from a remote area of Pakistan, comprising six generations and segregating autosomal recessive nonsyndromic prelingual deafness. DNA samples from 24 individuals were used for genome wide screen and fine mapping. Linkage analysis indicates that in this family the NSHL locus, (DFNB35) maps to a 17.54 cM region on chromosome 14 flanked by markers D14S57 and D14S59. Examination of haplotypes reveals a region that is homozygous for 11.75 cM spanning between markers D14S588 and D14S59. A maximum two-point LOD score of 5.3 and multipoint LOD score of 7.6 was obtained at marker D14S53. The interval for DFNB35 does not overlap with the regions for DFNA9, DFNA23 or DFNB5.     

Telomeric fusion as a mechanism for the loss of 1p in meningioma

Characteristic cytogenetic aberrations are found in the various histopathological designations of meningioma. These aberrations range from the loss of 22q in histologically benign tumors to complex hypodiploid karyotypes in atypical and malignant tumors. This progression is characterized by increasing chromosome loss and instability, with a critical step being the loss of 1p. We report a detailed cytogenetic investigation of chromosome aberrations in a series of 88 meningiomas using Giemsa banding and multicolor spectral karyotyping (SKY). Clonal chromosome aberrations were identified in 46 (52%) tumors by G banding. Thirty-five tumors showing complex chromosome aberrations not fully characterized by G banding were subsequently reanalyzed by SKY. The SKY technique refined the G-band findings in 18 (51%) of the tumors on which it was applied. The most common features of cytogenetic progression in the complex karyotypes were chromosome arm-specific losses relating to the formation of deletions and dicentric chromosomes involving 1p. Part or all of 1p was lost in 19 tumors. Five tumors showed evidence for the loss of 1p in a progressive step-wise series of telomeric fusions involving the formation of unstable intermediates. Five recurring dicentric chromosomes were identified, including dic (1;11)(p11;p11), dic(1;12)(p12 approximately p13;p11), dic(1;22)(p11;q12 approximately q13), dic(7;19)(p11;p11), and dic(19;22)(p11 approximately p13;q11 approximately q13). These findings provide evidence that telomeric fusions play a role in the formation of clonal deletions, dicentrics, and unbalanced translocations of 1p. The loss of 1p has possible diagnostic and prognostic implications in the management of meningioma.     

Urachal malignant fibrous histiocytoma: a case report and review of the literature

Pathologic processes involving the urachus are usually related to inflammatory or sinofistular conditions. Neoplasms rarely arise within this structure, and when they do occur, they are typically epithelial, with mucinous adenocarcinoma being the most common. Mesenchymal lesions, both benign and malignant, have rarely been described in this location. We report the case of a 66-year-old white man who presented with a primary urachal malignant fibrous histiocytoma and died of metastatic disease 20 months after the initial diagnosis. This is an unusual case of malignant fibrous histiocytoma arising in a urachal remnant.     

Accumulation of allelic losses on chromosome 10 in human gliomas at recurrence

Aims—To elucidate the implications of allelic loss on chromosome 10 in the malignant progression of human gliomas.     

Mast cell activation markers for in vitro study

ABSTRACT

Mast cells (MCs) are well known for their role in allergic conditions. This cell can be activated by various types of secretagogues, ranging from a small chemical to a huge protein. Mast cell activation by secretagogues triggers the increase in intracellular calcium (iCa²⁺) concentration, granule trafficking, and exocytosis. Activated mast cells release their intra-granular pre-stored mediator or the newly synthesized mediator in the exocytosis process, in the form of degranulation or secretion. There are at least three types of exocytosis in mast cells, which are suggested to contribute to the release of different mediators, i.e.,, piecemeal, kiss-and-run, and compound exocytosis. The status of mast cells, i.e., activated or resting, is often determined by measuring the concentration of the released mediator such as histamine or β-hexosaminidase. This review summarizes several mast cell components that have been and are generally used as mast cell activation indicator, from the classical histamine and β-hexosaminidase measurement, to eicosanoid and granule trafficking observation. Basic principle of the component determination is also explained with their specified research application and purpose. The information will help to predict the experiment results with a certain study design.     

Bone formation using novel interconnected porous calcium hydroxyapatite ceramic hybridized with cultured marrow stromal stem cells derived from Green rat

The clinical use of cultured marrow stromal stem cells (MSCs) has recently attracted attention in the field of tissue engineering. For the clinical use of the MSCs, a prominent scaffold is needed. A scaffold hybridized with MSCs is transformed into a "bioactive bone substitute," and this provides good osteoconduction. In this study, a novel calcium hydroxyapatite ceramic with an interconnected porous structure (IP-CHA) was used as a scaffold. MSCs were harvested from Green rats containing Green Fluorescent Protein (GFP), and then these hybrids were implanted into the tibias of Sprague-Dawley rats. The purposes of this study were to examine the osteogenic ability of these hybrids without coculture, and to evaluate whether the resulting bone formation originated from the grafted MSCs or the recipient's cells. The hybridized group showed excellent bone formation compared with the IP-CHA-only implant group. Observation of the implanted MSCs revealed that they survived 8 weeks after surgery, and differentiated into osteoblast-like cells, thus providing bone formation. This implantation of the MSCs/IP-CHA composite provides excellent osteoconduction, and is expected to have extensive clinical applications.