Primary malignant melanoma of the bladder

Primary malignant melanomma of bladder is extremely rare: 18 cases are reported to date. An 82 year-old man underwent trans-urethral resection of bladder for a bleeding tumor of the posterior wall. Histological diagnosis was melanoma of the bladder. There was no history of previous or regressed cutaneous malignant melanoma. Margins of the bladder lesion contained atypical melanocytes similar to those commonly seen in the periphery of primary mucous membrane lesions. Clinical studies and radiological examinations were negative for other primary site of melanoma. The patient had a bladder recurrence that was consistent with primary tumor and died of widespread disease 9 months after diagnosis.     

Chemical and enzymatic treatment of endothelin

Endothelin-1 (ET), the most potent vasoconstrictor yet discovered, is a peptide containirig 21 amino acids with two intrachain disulfide bridges. With the aim of obtaining two-chain derivatives, Et was submitted to chemical and enzymatic treatments. Reaction of ET with CNBr in 70% HCOOH gave, in addition to the expected [Hse⁷ lactone]-7,8-seco-ET and unreacted material, a by-product whose molecular weight was 25 m.u. greater than that of ET. When the reaction mixture, after lyophilisation, was immediately quenched with NH3-saturated dry MeOH, two products could be recovered in a 5:1 ratio, both obtained by nucleophilic attack of the homoserine lactone: the expected [Hse⁷-NH₂]-7,8-seco-ET and [Hse⁷]ET, resulting from competitive intramolecular reaction of the deprotonated α-amino group of the Asp⁸ residue. The Lys⁹-Glu¹⁰ bond turned out to be very resistant to enzymatic attack both by Lys-C-endopeptidase and trypsin. The 9,10-seco-ET derivative could be obtained by treatment with Lys-C-endopeptidase only by using a high enzyme/ET ratio and after a prolonged incubation time. Cleavage of the Lys⁹-Glu¹⁰ bond could not be achieved by treatment with trypsin, even with a high enzyme/substrate ratio. The main product was 13, 14-seco-ET, deriving from the action of chymotripsin (present as an impurity in the trypsin preparation) on Tyr¹³. The structure of these peptides was confirmed by amino-acid sequence analysis and fast atom bombardment mass spectrometry (FAB-MS). Nicking of the ET structure at different positions had different impact on the biological properties of the resulting derivatives. © Munksgaard 1995.     

Inhibition of Leukocyte Adherence by Potassium Chloride Extract of Allogeneic Squamous Cell Carcinoma of the Human Uterine Cervix

ABSTRACT: Leukocyte adherence inhibition (LAI) assay was used to evaluate cell-mediated immunity in patients with invasive squamous cell carcinoma of the cervix. The reactivity of the peripheral blood leukocytes of these patients was evaluated after incubation with pooled extracts of allogeneic squamous cell carcinoma of the cervix. One hundred sixty-seven sets of LAI assays were performed on 54 individuals, including 23 patients with Stage I squamous cell carcinoma of the cervix, 9 patients with other stages of this tumor, 9 patients with unrelated tumors and 13 normal healthy volunteers. A protein concentration of one milligram per milliliter in the tumor extract and 10% fetal bovine serum in the feeding media gave the best results. Eighty-seven percent (28/32) of patients with squamous cell carcinoma of the cervix showed marked specific reactivity. No difference was found in the LAI indices of different stages of the disease.     

Lack of Influence of Atrioventricular Delay on Stroke Volume at Rest in Patients with Complete Atrioventricular Block and Dual Chamber Pacing

Dual chamber pacing (DDD) maintains atrioventricular (AV) sequence; AV delay programmability modifies the relationship between atrial and ventricular contraction. To evaluate the hemodynamic effects of such a modification, ten patients with a DDD unit for complete AV block were studied by time-motion (M-mode) and Doppler echocardiography during inhibited ventricular pacing (VVI), atrial-triggered ventricular pacing (VDD) and atrioventricular sequential pacing (DVI) at different AV delay (90, 140, 190, 240 msec). A significant improvement in stroke volume (SV) (15%-20%, P less than 0.05) was seen during DDD versus VVI pacing; no changes, however, were observed in the same patient with different AV delay or during DVI versus VDD pacing. These data suggest that programming of AV delay does not affect systolic performance at rest; longer diastolic filling times recorded during DDD pacing with "short" AV delay (90-140 msec) do not seem to be a hemodynamically relevant epi-phenomenon of PM programming.     

Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission

We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study.   All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation ( n  =25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59–3.24), 0.69 (CI 0.27–1.77) and 0.35 (CI 0.06–1{\raise 5mu ..91), with an overall non-significant difference between the two groups ( P  = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR).   The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.     

p53 OVEREXPRESSION AND HUMAN PAPILLOMAVIRUS INFECTION IN TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER: CORRELATION WITH HISTOLOGICAL PARAMETERS

Seventy-nine transitional cell carcinomas (TCCs) of the urinary bladder (25 grade 1, 22 grade 2, and 32 grade 3 tumours) were examined for p53 overexpression by immunohistochemistry with a monoclonal antibody and for human papillomavirus (HPV) infection by the polymerase chain reaction (PCR). Positive immunostaining for p53 was detected in 40·5 per cent of the cases; the percentage of positive cases was significantly lower in low-grade (G1 and G2) TCCs than in high-grade (G3) tumours (10·6 per cent vs. 84·4 per cent; P <0·0001). The overall rate of HPV infection was 32·9 per cent; 20·3 per cent of the cases were positive for HPV 16, 3·8 per cent for HPV 18, and 8·9 per cent for both. Consensus primers as well as type-specific primers for HPV types 6, 11, and 33 failed to detect any additional case with HPV infection. The prevalence of HPV 16 and/or HPV 18 infection was significantly higher in low-grade than in high-grade tumours (44·7 per cent vs. 15·6 per cent; P =0·0061). p53-positive cases were more common among papillary, deeply infiltrating tumours, and HPV-positive cases among papillary, non-infiltrating lesions. According to these data, p53 overexpression and HPV 16/18 infection are common findings in bladder TCC and there appears to be an inverse correlation of p53 overexpression and of HPV infection with tumour aggressiveness. The possibility of different molecular pathways in superficial low-grade and in invasive high-grade tumours is suggested.     

Left Axillary Implantation of Loop Recorder

Background: We compared the clinical course of 10 patients who received an implantable loop recorder (ILR) at a traditional site with 11 patients whose ILRs were implanted via a subpectoral site via a left axillary approach without complications. Methods and Results: R‐wave amplitude was determined at implantation and during follow‐up. Each patient was followed after 7 days to optimize device setting and then at 1 and 3 months. The R‐wave amplitude obtained with the new technique was significantly higher and more stable than that obtained with the standard procedure. Our preliminary experience suggests that axillary access for ILR implantation is feasible, safe, well tolerated, and reliable in terms of sensing function and device performance. Moreover, it is superior aesthetically to the standard approach and carries the potential of minimizing permanent scarring after ILR extraction. (PACE 2010; 999–1002)     

Affinity enhancement of complementary peptide recognition

A peptide hydropathically complementary to Big Endothelin [Big ET] residues 16-29 has been synthesized in a multimeric form starting from an octadentate poiylysine core, essentially in a way similar to the procedure used for the production of multiple antigenic peptides [MAP's], Interaction between the multimeric complementary peptide [8δET] and the Big ET fragment 16-32 containing the target complementary region, also synthesized in a multimeric form [8ET], was evaluated by analytical high performance affinity chromatography and solid phase binding assays. While the binding interaction between the monomerics peptide pair was in the micromolar range, the recognition between the corresponding multimeric form was characterized by enhanced binding affinity of at least two orders of magnitude. In solution, complex formation between multimeric complementary peptide and target Big ET sequence in the monomeric and multimeric form was accompanied by precipitation at concentrations higher than 0.5 mg/mL and 0.1 mg/mL, respectively. Polyclonal antibodies raised against the multimeric target sequence recognized multimeric and monomeric ET target sequences with binding affinities similar to binding affinities exhibited by the multimeric complementary peptide. Multimerization of hydropathically complementary peptides could provide an improved opportunity to measure and thus probe quantitative binding properties of complementary peptides.     

In vitro interactions of opioid peptides with phospholipids

The interaction of leu-enkephalin with phosphatidylserine has been studied with ultraviolet and circular dichroism spectroscopy methods as well as with fluorescence anisotropy techniques. The data reported hereunder confirm the existence of binding between the two species, and also support the hypothesis that not only the tyrosine, but also the phenylalanine residue in the leu-enkephalin molecule is involved in peptide-lipid interaction. In addition, ultraviolet and CD evidence, taken together, tend to suggest that both aromatic residues are bound, with a different degree of involvement, to the same region of the lipid molecule. The data reported are discussed in terms of the interaction model previously proposed by us.