Leptomeninges as a site of relapse in locally controlled,diffuse pontine glioma with review of literature

Case report Leptomeningeal involvement in diffuse intrinsic brain stem gliomas is rarely diagnosed clinically and in majority of the instances diagnosed only on postmortem examination. We report two cases of diffuse pontine glioma diagnosed clinicoradiologically and treated with conventional radiotherapy.Observations On follow-up, both patients showed clinical features suggestive of meningeal spread although imaging for pontine tumor showed stable disease. Leptomeningeal disease in the spine was confirmed on imaging and in one case by cerebrospinal fluid examination also. During the follow-up of patients with pontine glioma, the possibility of leptomeningeal involvement must be borne in mind.     

Practicing Behavioral Sex Therapy in India: Selection, Modifications, Outcome, and Dropout

A file review of 178 male patients with sexual dysfunction revealed that high income, married status, presence of partner at evaluation, and liberal attitude towards sexuality increased the chances of selection for behavioral sex therapy. The outcome of therapy was associated with treatment adherence. Participation of the conjoint unit resulted in lower dropout rates.     

Psoriasis: To Cut or Not to Cut, What Say You?

BACKGROUND: A common problem facing patients suffering from psoriasis is the need for surgery that requires incision through active psoriatic skin. Many patients have been denied surgery because of the fear of an increased risk of infection, decreased wound healing ability, and worsening of the psoriatic lesions. OBJECTIVE: To assess the practices and beliefs of dermatologists and surgeons (orthopedic and plastic surgeons) faced with the decision of whether to operate through active psoriatic skin. METHODS: Dermatologists, orthopedic surgeons, and plastic surgeons selected from various professional membership lists from five representative cities were sent a survey to ascertain their opinions on operating on active psoriatic skin. Psoriatic patients were also given forms asking about the severity of their psoriasis and whether they had ever been denied surgery. RESULTS: Dermatologists are more likely to condone surgery in active psoriatic skin and to believe that there is not a risk of increased infection or decreased wound healing than are orthopedic surgeons and plastic surgeons. These findings are statistically significant (P<0.05). CONCLUSION: With proper preoperative measures and dermatologic treatment, surgery can be performed on active psoriatic skin in most cases with minimal reservations, although a controlled, prospective study is necessary to arrive at a definitive conclusion.     

Disease associations and altered immune function in CD45 138G variant carriers

The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance.     

Intracellular calcium changes in rat aortic smooth muscle cells in response to fluid flow

Vascular smooth muscle cells (VSM) are normally exposed to transmural fluid flow shear stresses, and after vascular injury, blood flow shear stresses are imposed upon them. Since Ca²⁺ is a ubiquitous intracellular signaling molecule, we examined the effects of fluid flow on intracellular Ca²⁺ concentration in rat aortic smooth muscle cells to assess VSM responsiveness to shear stress. Cells loaded with fura 2 were exposed to steady flow shear stress levels of 0.5–10.0 dyn/cm² in a parallel-plate flow chamber. The percentage of cells displaying a rise in cytosolic Ca²⁺ ion concentration ([Ca²⁺]_i) increased in response to increasing flow, but there was no effect of flow on the ([Ca²⁺]_i) amplitude of responding cells. Addition of Gd³⁺ (10 M) or thapsigargin (50 nM) significantly reduced the percentage of cells responding and the response amplitude, suggesting that influx of Ca²⁺ through ion channels and release from intracellular stores contribute to the rise in ([Ca²⁺]_i) in response to flow. The addition of nifedipine (1 or 10 M) or ryanodine (10 M) also significantly reduced the response amplitude, further defining the role of ion channels and intracellular stores in the Ca²⁺ response. © 2002 Biomedical Engineering Society. PAC2002: 8716Uv, 8719Uv, 8716Dg, 8719Ff     

Vaccinia virus K1L protein mediates host-range function in RK-13 cells via ankyrin repeat and may interact with a cellular GTPase-activating protein

The K1L protein of vaccinia virus is required for its growth in certain cell lines (RK-13 and human). The cowpox host-range protein CP77 has been shown to complement K1L function in RK-13 cells, despite a lack of homology between the two proteins except for ankyrin repeats. We investigated the role of ankyrin repeats of K1L protein in RK-13 cells. The growth of a recombinant vaccinia virus, with K1L gene mutated in the most conserved ankyrin repeat, was severely impaired. Infection with the mutant virus caused shutdown of cellular and viral protein synthesis early in infection. We also investigated the interaction of K1L protein with cellular proteins and found that K1L interacts with the rabbit homologue of human ACAP2, a GTPase-activating protein with ankyrin repeats. Our result suggests the importance of ankyrin repeat for host-range function of K1L in RK-13 cells and identifies ACAP2 as a cellular protein, which may be interacting with K1L.     

Optimedin: a novel olfactomedin-related protein that interacts with myocilin

Mutations in the MYOC gene may lead to juvenile open-angle glaucoma with high intraocular pressure, and are detected in about 4% of people with adult onset glaucoma. Most of these mutations are found in the third exon of the gene encoding the olfactomedin-like domain located at the C terminus of the protein. Another olfactomedin-related protein, known as noelin or pancortin, is involved in the generation of neural crest cells. Here we describe the identification of a novel olfactomedin-related gene, named optimedin, located on chromosome 1p21 in humans. Optimedin and noelin are both expressed in brain and retina. However, unlike noelin, rat optimedin is also highly expressed in the epithelial cells of the iris and the ciliary body in close proximity to the sites of Myoc expression. In the human eye, optimedin is expressed in the retina and the trabecular meshwork. Both optimedin and myocilin are localized in Golgi and are secreted proteins. The presence of mutant myocilin interferes with secretion of optimedin in transfected cells. Optimedin and myocilin interact with each other in vitro as judged by the GST pulldown, co-immunoprecipitation and far-western binding assays. The C-terminal olfactomedin domains are essential for interaction between optimedin and myocilin, while the N-terminal domains of both proteins are involved in the formation of protein homodimers. We suggest that optimedin may be a candidate gene for disorders involving the anterior segment of the eye and the retina.     

Effect of gossypol in association with chromium protoporphyrin on heme metabolic enzymes

Gossypol prevents the liberation of oxygen from oxyhemoglobin and exerts a hemolytic effect on erythrocytes. In excessive dosages of gossypol, an extreme burden is placed upon the respiratory and circulatory organs owing to the reduced oxygen carrying capacity of blood. Chromium protoporphyrin (CrPP) has been shown to either competitively suppress or to significantly ameliorate a variety of naturally occurring or experimentally induced forms of jaundice in animals and man. In this communication, a novel tissue dependent response to gossypol (50 micromol/kg bw) and gossypol in association with CrPP (50 micromol/kg bw) is described. Our results revealed that gossypol stimulated the hepatic, splenic, and renal delta-aminolevulinic acid synthase (ALA-S) activity, the heme biosynthetic enzyme, and simultaneous administration of CrPP and gossypol synergized the gossypol-mediated increase of ALA-S activity. Gossypol was found to be a potent stimulator of heme oxygenase (HMOX) activity in rat liver and kidney to varying degrees. This tissue response contrasted with that of the spleen, where gossypol decreased the activity of the enzyme. In consonance with the increased hepatic and renal HMOX activity, a marked increase was observed in total serum bilirubin concentration in gossypol treated rats. When rats were given CrPP simultaneously with gossypol, the gossypol mediated increase in hepatic and renal HMOX activity was effectively blocked. Furthermore, the increase in enzymatic activity was accomplished by a decline in the total microsomal protein content on gossypol administration. These findings emphasize the toxic effect of gossypol in eliciting increased heme degradation by stimulating HMOX activity in the liver and the kidney and the potential usefulness of CrPP in experimental and perhaps clinical conditions in which hyperbilirubinemia occurs.