Circulation of subtype A and gagA/envB recombinant HIV type 1 strains among injecting drug users in St. Petersburg, Russia, correlates with geographical origin of infections

Countries of the former Soviet Union are experiencing an emerging HIV-1 epidemic due to a rapid expansion of HIV-1 among injecting drug users (IDUs). To study the molecular epidemiology of HIV-1 among IDUs in St. Petersburg, Russia, virus sequences were obtained from 22 individuals. Phylogenetic analysis of the env and gag regions revealed circulation of two major HIV-1 populations, one belonging to HIV-1 subtype A, and another being a recombinant of subtype A and B viruses (gagA/envB). Both virus populations were highly homogeneous, with a mean pairwise genetic distance of <2%, and similar to viruses obtained earlier from IDUs in other regions of the former Soviet Union. Distribution of the two major HIV-1 genotypes in St. Petersburg correlated with geographical origin of infections. In one individual, a virus type previously unseen among IDUs was found, which demonstrates the possibility that new viruses are entering this risk group.     

Capping of leukemic cells with monoclonal anti-HLA-A,B,C related to prognosis in childhood acute lymphoblastic leukemia

Capping of leukemic cells with a monoclonal antibody against HLA A,B,C determinants was studied in 53 cases of childhood acute lymphoblastic leukemia (ALL). Determination of the percentages of capped cells after different times of incubation with anti-HLA A,B,C show that T ALL and common ALL do have quite different kinetics of HLA capping. In T ALL all cases reach levels of percentage of capped cells above 30%, in common ALL only 11 of 31 cases cap well. Dilution of the antiserum in 6 common ALL cases results in an increase of capped cells, but the original kinetics of the common ALL capping remain. ALL cases with capping curves above 30% have a worse prognosis (shorter continuous complete remission) than cases with capping curves below 30% in the total group as well as in the non-high-risk group.     

Differences in capping behavior between immunological phenotypes in childhood acute lymphoblastic leukemia. A study with ConA and an anti-HLA-ABC backbone

Capping with concanavalin A (ConA) and monoclonal anti-HLA-ABC backbone was studied in childhood acute lymphoblastic leukemia (ALL). Capping with ConA and HLA gave quite different results, both in common ALL and T-ALL. With ConA most cases capped poorly, comparable to results described in chronic lymphatic leukemia and lymphoma, but in several cases capping was comparable to that of normal lymphocytes. In HLA capping T-ALL cells capped better than common ALL cells. HLA capping of T-ALL cells is comparable to that of normal lymphocytes. HLA capping results in handmirror cell formation giving support to the hypothesis that capping and motility are associated events.     

Membrane association of African horsesickness virus nonstructural protein NS3 determines its cytotoxicity

The smallest RNA genome segment of African horsesickness virus (AHSV) encodes the nonstructural protein NS3 (24K). NS3 localizes in areas of plasma membrane disruption and is associated with events of viral release. Conserved features in all AHSV NS3 proteins include the synthesis of a truncated NS3A protein from the same open reading frame as that of NS3, a proline-rich region, a region of strict sequence conservation and two hydrophobic domains. To investigate whether these features are associated with the cytotoxicity of NS3 or altered membrane permeability, a series of mutants were constructed and expressed in the BAC-TO-BAC baculovirus-expression system. Our results indicate that mutations in either of the two hydrophobic domains do not prevent membrane targeting of the mutant proteins but abolish their membrane anchoring. This prevents their localization to the cell surface and obviates their cytotoxic effect. The cytotoxicity of NS3 is therefore dependent on its membrane topography and thus involves both hydrophobic domains. NS3 has many of the characteristics of lytic viral proteins that play a central role in viral pathogenesis through modifying membrane permeability.     

Is Melphalan Dose Adjustment According to Ideal Body Weight Useful in Isolated Limb Infusion for Melanoma?

Background

Isolated limb infusion (ILI), introduced in 1992, is a technique used to deliver regional chemotherapy to treat advanced melanoma confined to a limb. Adjusting melphalan dose according to ideal body weight (IBW) has been proposed as a method of decreasing limb toxicity without compromising outcome. The current study analyzed this proposed dose adjustment.

Methods

We reviewed 99 consecutive patients with lower extremity melanomas treated by ILI at our institution between May 1998 and February 2009. Toxicity and outcomes were tested for correlation with differences between administered dose and calculated adjusted dose, both in mg and mg/L, and with differences between actual limb volume and calculated adjusted limb volume.

Results

The median actual body weight was 71?kg, whereas the calculated median IBW was 57?kg (p?p?Conclusions Adjusting the melphalan dose for IBW does not appear to reduce toxicity following ILI for melanoma. The effect on outcome remains uncertain. More research is needed to optimize melphalan concentrations in individual patients during ILI to limit toxicity without compromising the response.     

Primary Melanoma Location on the Scalp is an Important Risk Factor for Brain Metastasis: A Study of 1,687 Patients with Cutaneous Head and Neck Melanomas

Background

Primary cutaneous head and neck melanomas (HNM) are reported to be associated with a higher incidence of brain metastasis than trunk and limb melanomas (TLM). In this study, the incidence of brain metastases in patients with HNM and risk factors for the development of brain metastases were analyzed.

Methods

From a large, prospectively-collected database, 1,687 HNM patients and 8,793 TLM patients who presented with American Joint Committee on Cancer (AJCC) stage I and II disease were identified. Survival was assessed using the Kaplan–Meier method and multivariate Cox regression analysis. Independent risk factors were determined by binary logistic regression analysis.

Results

The incidence of brain metastases 5 years after diagnosis of HNM was 6.7 % compared with 4.7 % for brain metastases from TLM (p = 0.003). Patients with scalp melanomas were most likely to develop brain metastases (12.7 %). Independent risk factors for brain metastasis in patients with HNM were Breslow thickness, ulceration, and scalp location.

Conclusion

Patients with primary scalp melanomas had a much higher incidence of brain metastasis than patients with melanomas on other head and neck sites, who in turn had a higher incidence than patients with melanomas on sites elsewhere on the body. More intensive monitoring of patients with scalp melanomas, who are at particularly high risk of brain metastasis, might lead to earlier discovery of metastatic disease in the brain, offering the prospect of earlier intervention and better outcomes.     

Recurrent iritis as the initial symptom in plasmacytoma (IgG type)

The author presents a case report on a 47-year-old man with recurrent serofibrinous iritis. As a result of intensive investigations an IgG-type myeloma was finally diagnosed with the aid of serum electrophoresis, immunoelectrophoresis, and sternal puncture. Apart from ocular symptoms of acute iritis all findings were normal. General clinical findings were also normal and the patient was subjective free of complaints.