Prognosis in malignant melanoma

A uniform and practical classification and staging system for melanoma must exist and be widely adopted if useful comparisons between different treatment centers and databases are to be made. This article reviews the 1992 American Joint Committee on Cancer pTNM staging system. In this classification, localized disease without regional nodal involvement is defined as stage I or II, depending on the tumor thickness of the primary melanoma. Regional lymph node involvement and/or in-transit metastasis is defined as stage III, and systemic metastatic disease is defined as stage IV.     

Absence of PTEN/MMAC1 germ-line mutations in sporadic Bannayan-Riley-Ruvalcaba syndrome

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare hamartomatous polyposis condition with features of macrocephaly, intestinal juvenile polyposis, developmental delay, lipomas, and pigmentation spots of the male genitalia. An autosomal dominant pattern of inheritance exists in some families, but others appear as sporadic cases. Germ-line mutations in PTEN, a tyrosine phosphatase and putative tumor suppressor gene, have been demonstrated in two families with BRRS, and chromatin loss at the PTEN gene locus on chromosome 10q23 has been demonstrated in two BRRS patients. Germ-line mutations in PTEN have also been described in Cowden disease and in a small number of patients with juvenile polyposis syndrome. In an attempt to assess the nature of PTEN mutations in BRRS, we analyzed three sporadic BRRS patients for chromosome 10q23 deletion or PTEN germ-line mutations. All 3 patients demonstrated no loss of parental alleles at 15 chromosome 10q23 markers that encompassed the region of PTEN. In addition, analysis of mRNA and genomic DNA revealed no nonsense, missense, or insertion/deletion mutations of PTEN. Thus, other mechanisms besides mutation of PTEN must have occurred to cause BRRS in these patients. We speculate that BRRS and juvenile polyposis syndrome may have a heterogeneous etiology to cause their syndromes.     

A simulation study comparing tests for the equality of coefficients of variation

The coefficient of variation is commonly used in medical and biological sciences. In this paper, several parametric and non-parametric tests for the equality of coefficients of variation in kappa populations are reviewed. Simulation studies are conducted to compare the sizes and power of these tests. It is found that the parametric tests perform well if the data are normally distributed, but perform poorly if otherwise. The non-parametric test, however, is rather robust against the underlying distribution. An example using data of the Quality Assurance Program from the Hong Kong Medical Technology Association in Haematology and Serology is provided. The insensitivity of the non-parametric test to outliers is demonstrated.     

Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis

OBJECTIVES: Herein we describe an additional case of myelolipoma of the adrenal gland, an uncommon tumor of the adrenal cortex, that had been incidentally discovered during abdominal US evaluation of the biliary tree. The clinical features, diagnosis and treatment of the condition are discussed. METHODS: Surgical treatment of the biliary tree and myelolipoma was performed through a Chevron transversal incision during the same surgical session. RESULTS: Surgery achieved good results and the postoperative course was unremarkable. CONCLUSIONS: Myelolipoma is a benign nonfunctioning tumor of the adrenal cortex comprised of adipose and hematopoietic tissue. It is usually asymptomatic and incidentally discovered during diagnostic evaluation for other pathologies. The diagnosis is made by US, CT and MRI. There is no agreement on whether surgical treatment is warranted.     

A novel isoform of the mitochondrial outer membrane protein VDAC3 via alternative splicing of a 3-base exon. Functional characteristics and subcellular localization

Voltage-dependent anion channels (VDACs) are pore-forming proteins found in the outer mitochondrial membrane of all eucaryotes. VDACs are the major pathway for metabolites through the outer mitochondrial membrane and, in mammals, bind several cytosolic carbohydrate kinases. Whereas yeast contain a single VDAC (YVDAC), to date three isoforms have been described in the mouse that constitute a gene family. We have observed an additional isoform of VDAC3 that appears to be generated via the tissue-specific alternative splicing of a 3-base exon (ATG). The exon is predicted to introduce a methionine 39 amino acids downstream of the amino terminus of the polypeptide. Between exons 3 and 4 is an intronic sequence that potentially encodes the exon, with flanking splice enhancer elements. Expression of this alternative form in the mouse is limited to brain, heart, and skeletal muscle. Complementation of YVDAC-deficient yeast by the two isoforms and with other sequence variants of VDAC3 suggests this residue is an important modulator of VDAC3 function. In transfected mammalian cells both isoforms localize to mitochondria. A similar variant is present in humans.     

CCR5 coreceptor utilization involves a highly conserved arginine residue of HIV type 1 gp120

The seven-transmembrane CCR5 was recently found to double as a coreceptor for a genetically diverse family of human and nonhuman primate lentiviruses. Paradoxically, the main region of the envelope protein believed to be involved in CCR5 utilization was mapped to hypervariable region 3, or V3, of the envelope glycoprotein gp120. In this study, we addressed the question of whether functional convergence in CCR5 utilization is mediated by certain V3 residues that are highly conserved among HIV type 1 (HIV-1), HIV type 2, and simian immunodeficiency virus. Site-directed mutagenesis carried out on three such V3 residues revealed that the Arg-298 of HIV-1 gp120 has an important role in CCR5 utilization. In contrast, no effect was observed for the other residues we tested. The inability of Arg-298 mutants to use CCR5 was not attributed to global alteration of gp120 conformation. Neither the expression, processing, and incorporation of mutant envelope proteins into virions, nor CD4 binding were significantly affected by the mutations. This interpretation is further supported by the finding that alanine substitutions of five residues immediately adjacent to the arginine residue had no effect on CCR5 utilization. Taken together, our data strongly suggests that the highly conserved Arg-298 residue identified in the V3 of HIV-1 has a significant role in CCR5 utilization, and may represent an unusually conserved target for future anti-viral designs.     

Improvement of sini decoction on hemorheology following percutaneous transluminal coronary angioplasty

OBJECTIVE: To study the hemorheological effects of Sini decoction on patients following percutaneous transluminal coronary angioplasty (PTCA). METHODS: Forty-six patients were randomly divided into Sini decoction and control groups. The hemorheologic variables were determined before and after Sini decoction treatment. RESULTS: No hemorheologic changes were observed in the patients (n = 23) only with PTCA, but the patients (n = 23) with Sini decoction were found to be significantly decreased in whole blood viscosity and red cell aggregation and dredging the blood of microcirculation as post-PTCA compared to pre-PTCA. CONCLUSION: Sini decoction could improve the patient's hemorheology.     

Do descending influences alternate to produce episodic breathing?

This study examines the episodic breathing patterns of three disparate groups of vertebrates. In an in vitro bullfrog brainstem-spinal cord preparation, episodic breathing was replaced by uniformly spaced breaths following transection caudal to the optic chiasma. The same effect was produced in hibernating squirrels by inhalation of mild anesthesia. Preliminary data suggest that a similar conversion is also produced in hibernating squirrels by vagotomy, in conjunction with blockade of central NMDA-type glutamate receptors. In all cases, even though overall breathing frequency increased, due to elimination of periods of apnea, instantaneous breathing frequency slowed. Seals breathe episodically in sleep and when these animals awaken after the start of a breathing episode, breathing also immediately slows. The data presented here are consistent with the suggestion that in all vertebrates, higher centres can modulate the central rhythm generator for breathing, in both a positive and a negative fashion. During episodic breathing, in the species studied here, these modulating influences alternate in a fashion that produces periods of apnea alternating with periods of relatively high frequency ventilation.     

Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331-induced apoptosis

CDC 25 is a dual phosphatase responsible for dephosphorylation and, thus, activation of CDC 2 kinase in G2. Abnormal activation of cyclin B-associated CDC 2 kinase has been implicated in apoptosis induced by cancer chemotherapeutic agents such as paclitaxel (Taxol) and etoposide (VP-16). In this study, we found that the CDC 2 kinase could be transiently activated when nasopharyngeal carcinoma NPC-TW01 cells were treated for 3 h with a new anticancer agent, GL331. GL331 treatment also induced a concomitant increase in CDC 25A phosphatase activity and a reduced level of Tyr-15-phosphorylated CDC 2 in NPC-TW01 cells. Furthermore, subsequent apoptotic DNA fragmentation induced by GL331 could be interrupted by treatment of the cells with the cyclin B1-specific antisense oligonucleotides, suggesting that abnormal activation of cyclin B1-associated CDC 2 kinase and CDC 25A phosphatase was involved in GL331-induced apoptosis. Raf-1 has been shown to associate with CDC 25A and, thus, to stimulate its phosphatase activity. Our results revealed that GL331 could facilitate the association of CDC 25A with Raf-1, resulting in the cascade of CDC 25A phosphatase activation and CDC 2 kinase activation, as well as related signaling pathways, and ultimately causing apoptosis in cancer cells.