Anetoderma of Jadassohn-Pellizzari

Anetoderma (derived from the Greek anetos, meaning slack) is a term used to describe localized increased laxity of the skin with herniation or outpouching, resulting from abnormal dermal elastic tissue. Primary anetoderma is distinctly rare. We describe a case where we suspect an auto-immune aetiology.     

Activation and cell cycle antigens in CD4+ and CD8+ T cells correlate with plasma human immunodeficiency virus (HIV-1) RNA level in HIV-1 infection

gamma-Sarcoglycan is a transmembrane, dystrophin-associated protein expressed in skeletal and cardiac muscle. The murine gamma-sarcoglycan gene was disrupted using homologous recombination. Mice lacking gamma-sarcoglycan showed pronounced dystrophic muscle changes in early life. By 20 wk of age, these mice developed cardiomyopathy and died prematurely. The loss of gamma-sarcoglycan produced secondary reduction of beta- and delta-sarcoglycan with partial retention of alpha- and epsilon-sarcoglycan, suggesting that beta-, gamma-, and delta-sarcoglycan function as a unit. Importantly, mice lacking gamma-sarco- glycan showed normal dystrophin content and local- ization, demonstrating that myofiber degeneration occurred independently of dystrophin alteration. Furthermore, beta-dystroglycan and laminin were left intact, implying that the dystrophin-dystroglycan-laminin mechanical link was unaffected by sarcoglycan deficiency. Apoptotic myonuclei were abundant in skeletal muscle lacking gamma-sarcoglycan, suggesting that programmed cell death contributes to myofiber degeneration. Vital staining with Evans blue dye revealed that muscle lacking gamma-sarcoglycan developed membrane disruptions like those seen in dystrophin-deficient muscle. Our data demonstrate that sarcoglycan loss was sufficient, and that dystrophin loss was not necessary to cause membrane defects and apoptosis. As a common molecular feature in a variety of muscular dystrophies, sarcoglycan loss is a likely mediator of pathology.     

A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-fluorouracil and twice daily radiation followed by selective bladder preservation in operable patients with muscle invading bladder cancer

PURPOSE: We describe a protocol designed to evaluate the use of twice daily radiation used together with cisplatin and 5 fluorouracil (5-FU) in the treatment of operable transitional cell carcinoma of the bladder with potential bladder preservation. MATERIALS AND METHODS: A total of 18 consecutive patients with T2-T4a bladder tumors underwent as complete a transurethral resection as possible, which was visibly complete in 14 cases. They then received twice daily radiation and infusion cisplatin and 5-FU during an induction phase. No therapy was given for 3 weeks, following which patients were reevaluated cystoscopically. Cases of clinical complete response by biopsy and cytology were consolidated with further chemotherapy/radiation using the same chemotherapeutic agents and radiation schedule. Patients who had incomplete responses were advised to undergo an immediate radical cystectomy. Of the 18 patients 15 subsequently received 3 cycles of adjuvant chemotherapy, consisting of methotrexate, cisplatin and vinblastine. Median followup for the entire group is 32 months. RESULTS: Of the 18 patients 14 had no detectable tumor after induction therapy. Of the 4 patients with persistent tumor 2 underwent radical cystectomy and 2 refused cystectomy, 1 of whom was treated with partial cystectomy and the other with consolidation chemotherapy/radiation. The actuarial overall survival at 3 years was 83%. The chance of a patient being alive at 3 years with a native bladder was 78%. No patient required cystectomy for hematuria or bladder shrinkage. Three patients in whom superficial tumors developed were treated successfully with bacillus Calmette-Guerin. Small bowel obstruction in 1 case was corrected surgically. CONCLUSIONS: This pilot study demonstrates a high rate of response to this combined chemotherapy/radiation regimen in conjunction with a visibly complete transurethral resection. Reevaluation after a short induction phase allows for the early selection of patients with persistent disease for radical cystectomy.     

Natural killer cell-mediated eradication of neuroblastoma metastases to bone marrow by targeted interleukin-2 therapy

Targeted interleukin-2 (IL-2) therapy with a genetically engineered antidisialoganglioside GD2 antibody-IL-2 fusion protein induced a cell-mediated antitumor response that effectively eradicated established bone marrow and liver metastases in a syngeneic model of neuroblastoma. The mechanism involved is exclusively natural killer (NK) cell-dependent, because NK-cell deficiency abrogated the antitumor effect. In contrast, the fusion protein remained completely effective in the T-cell-deficient mice or immunocompetent mice depleted of CD8+ T cells in vivo. A strong stimulation of NK-cell activity was also shown in vitro. Immunohistology of the leukocytic infiltrate of livers from treated mice revealed a strong staining for NK cells but not for CD8+ T cells. The therapeutic effect of the fusion protein was increased when combined with NK-cell-stimulating agents, such as poly I:C or recombinant mouse interferon-gamma. In conclusion, these data show that targeted delivery of cytokines to the tumor microenvironment offers a new strategy to elicit an effective cellular immune response mediated by NK cells against metastatic neuroblastoma. This therapeutic effect may have general clinical implications for the treatment of patients with minimal residual disease who suffer from T-cell suppression after high-dose chemotherapy but are not deficient in NK cells.     

The role of splenectomy in treating severe aplastic anemia

A hypotensive effect of clonidine in non-narcotized intact and aorta baro-denervated rats is studied under conditions of minimization of stress actions (radiotelemetry) and under standard conditions of direct recording arterial pressure (AP). Direct AP recording is shown to determine an increase in background AP in baro-denervated rats, but not in control rats. An increase in background AP level under conditions of direct recording is not accompanied with decreasing hypotensive effect of clonidine in baro-denervated rats.     

Screening sigmoidoscopy. Factors associated with utilization

Although screening sigmoidoscopy (SS) reduces colorectal cancer mortality, surveys indicate that fewer than half of primary care physicians routinely recommend SS and less than 10% of eligible patients receive this test. The purpose of this study was to explore barriers to compliance with SS through a cross-sectional survey of general medicine patients. Clinician advice, perceived benefit of the test, and having a family member who has had the test are associated with SS, while perceived pain is a barrier to compliance and can negate the positive effects of clinician advice. These factors can be targeted as part of efforts to improve compliance with SS.     

Capillary zone electrophoretic determination of the four vitamin C esters L-ascorbyl-2-phosphate, L-ascorbyl-2-sulfate, L-ascorbyl-2-diphosphate and L-ascorbyl-2-triphosphate in fish feed, plasma and tissue

Pig conceptuses undergo morphological development from spherical to filamentous forms during days 10 to 12 of pregnancy, coincident with a high content of mRNAs encoding insulin-like growth factor (IGF)-I in the uterine endometrium and secretion of IGF-I into the uterine lumen. The potential regulation by developing conceptuses of the bioavailability of IGF-binding proteins (IGFBPs) within the uterine microenvironment was investigated. Uterine luminal flushings (ULFs) were obtained between days 10 and 18 of pregnancy and the presence of specific IGFBPs was detected by ligand blot analysis. ULFs collected at days 10 and 11 of pregnancy contained 46 and 43 kDa IGFBP-3, several IGFBPs of about 30 kDa including IGFBP-2, and an unidentified 26 kDa IGFBP; IGFBP-3 was the most abundant. By day 12, however, IGFBPs were substantially diminished or undetectable. Examination of the morphology of flushed conceptuses revealed that the loss of IGFBPs in ULF was associated with the transition from spherical to filamentous morphology. The abundance of IGFBP-3 mRNA in uterine endometrium, as monitored by blot-hybridization, was not altered in a similar way, suggesting that lack of IGFBP-3 in 'filamentous' ULF resulted from proteolysis rather than from decreased expression of the IGFBP-3 gene. Consistent with this, incubation of 'spherical' ULF with or without added 'filamentous' ULF at 37 degrees C resulted in the disappearance of endogenous IGFBP-3 only in 'spherical + filamentous' ULF. The protease activity in 'filamentous' ULF was inhibited by EDTA, but unlike matrix metalloproteinases, was not zinc ion-dependent or inhibited by 1,10-phenanthroline. Moreover, this activity was partially inhibited by the serine protease inhibitor aprotinin, but not by 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), a known inhibitor of plasmin. The IGFBP protease activity of ULF may therefore comprise a group of enzymes including an unidentified serine protease. The results suggest that elongating pig conceptuses induce IGFBP protease activity which may increase the intrauterine bioavailability of IGF.     

Detection of lead in environmental objects and biologic materials during monitoring]

The authors specified methods to detect lead in biologic materials. The quality control covered use of Russian and foreign standard samples, the results proved to agree. Lead was detected by AAS technique (direct and flow-type variants with preliminary concentration of lead) and ELRA method. The authors determined measurement limits sufficient for analysis of complex biologic materials. The measurement range for lead varied from 0.002 mg/kg (plants) to 3,000 mg/kg (soil); the range of serum lead levels was < 0.5-39 mg/dl.