Interferon-alpha 2 produced by normal human leukocytes is predominantly interferon-alpha 2b

Peripheral blood leukocytes, isolated from the buffy coats of greater than 10,700 normal healthy donors, were induced with Sendai virus to produce biologically active interferon alpha (IFN-alpha). The IFN-alpha was purified to near homogeneity by immunoaffinity chromatography, followed by size-exclusion chromatography. The resultant product, IFN-alpha n3, is reproducibly > or = 98% pure (to be reported elsewhere). The different IFN-alpha proteins in IFN-alpha n3 were separated by reverse-phase high performance liquid chromatography (RP-HPLC) and the identity of the IFN-alpha 2 isolated by HPLC was determined by amino-terminal sequencing. IFN-alpha 2 was found to migrate as two closely eluting peaks on RP-HPLC, and they have been designated as peaks 1.1 and 1.2. Distinction among the three possible variants of IFN-alpha 2, i.e., IFN-alpha 2a, IFN-alpha 2b, and IFN-alpha 2c, was determined by amino-terminal sequencing of the first 35 amino acids in peaks 1.1 and 1.2. Protein sequence data showed that the discriminating amino acids found at positions 23 and 34 are Arg and His, respectively. The presence of Arg and not Lys at amino acid position 23 and His at amino acid position 34 argues that IFN-alpha 2b is the major component in the Sendai virus-induced leukocyte IFN-alpha 2 and that IFN-alpha 2a is not present. These findings were verified by subjecting RP-HPLC peaks 1.1 and 1.2 to CNBr cleavage, followed by separation of the fragments by RP-HPLC and sequencing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surgical treatment of Peyronie's disease: a new approach

We treated 12 patients with intractable Peyronie's disease with a new approach based on simple incision of the fibrotic plaque(s) and stenting of the corpora with penile implants. Infection in 1 case necessitated removal of the prostheses, while the remaining 11 patients had satisfactory functional and anatomical results. The procedure is indicated for patients with 1) Peyronie's disease and impotency, 2) normal potency and extensive disease and 3) normal potency and localized disease in selective cases. In this series insertion of the penile prostheses did not change sexual prowess in previously potent patients.     

A surgical algorithm for the treatment of Peyronie's disease

PURPOSE: When conservative treatment of Peyronie's disease fails, the optimal surgical approach is not well defined. Multiple factors, including penile rigidity, degree of curvature, shaft narrowing with hinge effect and erectile response to vasoactive penile injections, indicate that no single approach is likely to solve the problem in all patients. MATERIALS AND METHODS: A surgical algorithm was developed for the treatment of Peyronie's Disease based on our previous surgical experience, which was used prospectively in 103 consecutive men. Penile straightening without prosthesis was offered to patients with adequate rigidity for coitus. Specifically, for mild to moderate curvature less than 60 degrees without hourglass or hinge effect deformity the less complicated tunica albuginea plication procedure was performed. For those men with more severe, complex curvature greater than 60 degrees and/or significant hourglass or hinge effect deformity plaque incision or partial excision with dermal grafting was offered to limit shaft shortening and to reconstruct a shaft with normal caliber to provide optimal axial support during intromission. For men with poor sexually induced erections and/or inadequate response to intracavernosal pharmacotherapy penile prosthesis placement was recommended to provide adequate straightening and rigidity. RESULTS: Of 22 patients who underwent plication procedures 91% remained potent and the penis remained straight postoperatively. Of 52 patients who underwent an incision or partial excision and grafting procedure, 48 had dermal grafts with the penis remaining straight in 94% and 75% remaining potent postoperatively. A total of 29 patients received a prosthesis with the penis remaining straight in 93% who were sexually active postoperatively. During the follow up period (mean 22.3 months) there have been no mechanical device failures. CONCLUSIONS: Surgical outcome was optimized with this algorithm, which correlates surgical complexity to the underlying severity of the penile deformity and erectile capacity.     

Is there an immunogenetic basis for Peyronie's disease?

PURPOSE: Despite numerous studies, there has been no definitive HLA association with Peyronie's disease. Results of available studies have been reviewed and compared to determine if the cumulative evidence supports any immunogenetic, HLA association with Peyronie's disease. MATERIALS AND METHODS: Data from reports of HLA associations with Peyronie's disease were reanalyzed by categories of reported HLA class I or class II antigens in comparison with recently available large population analysis of the frequencies of these antigens in the normal population. Data were also considered by whether they were derived from population or family analyses. RESULTS: The results of 4 series of patients testing an association of Peyronie's disease with the HLA class I antigens, in particular the B7 related antigens, were contradictory. A B7 association was not confirmed in 2 larger series and, in fact, the B7 related antigens were observed in frequencies expected in a normal population, suggesting that the associations observed in the smaller series were due to chance. An association with the HLA class II antigen, DQ2, was found in 1 of the larger series. Reported family studies suggest a genetic basis for Peyronie's disease but do not indicate a gene closely linked to the HLA complex. CONCLUSIONS: Considering all available data, Peyronie's disease appears to be multifactorial in pathogenesis. Because Peyronie's disease is likely heterogeneous and because available studies have analyzed serologically defined HLA antigens, future studies to define HLA alleles molecularly and to characterize patient subgroups may clarify an immunogenetic basis.     

Late effects of treatment for early-stage Hodgkin's disease

A comprehensive survey of late effects (physical, social and reproductive) following treatment at a single institution for early stage Hodgkin's disease (HD) was performed. A total of 611 patients with stage I and II HD treated between 1973 and 1984 were reviewed; 460 were alive and were mailed a self-reported questionnaire. A total of 363 (79%) replies were received. Twenty patients died of second malignancy, 14 of heart disease and nine from respiratory disease. There were 37 cases of second malignancy [relative risk (RR) 2.2, absolute excess risk (AR) 35.8]. The 15-year incidence of heart disease was 11% and there were nine myocardial infarction deaths (RR 1.55, AR 5.4). Twenty-eight (8%) respondents stated that their career had been greatly interfered with, 53 (14.5%) perceived financial loss. Sexual activity was disrupted in 25.8%. In total, 56 men had fathered 112 pregnancies. Of 171 women, 40.3% became pregnant, resulting in 92 live births. A total of 43 men and 16 women had sought medical advice with regard to infertility.     

Local treatment with IL-12 is an effective inhibitor of airway hyperresponsiveness and lung eosinophilia after airway challenge in sensitized mice

The relationships between personality disorder clusters and defense mechanism factors were evaluated in 31 female and 24 male psychiatric inpatients from an urban hospital, who ranged in age from 19 to 57 years. The degree to which defense factors predicted personality disorder psychopathology was assessed, with gender entered as a covariate. The degree of borderline psychopathology had the strongest relationship with the Immature defense style (F(1,54) = 9.83, R2 = .54, p < .05). The results support previous research demonstrating a stronger link between Borderline personality disorder and defense styles relative to other personality disorders.     

Fibrin deposition in Peyronie's disease plaque

PURPOSE: Peyronie's disease is a pathological fibrosis characterized by excessive deposition of collagen in the plaque. Although the etiology of Peyronie's disease is unknown, trauma has been hypothesized as the inciting event. In an effort to obtain more insight into the pathogenesis of Peyronie's disease plaque tissue was examined for collagen, elastic fiber, and fibrin content and distribution. MATERIALS AND METHODS: Plaque tissue specimens from 33 patients with Peyronie's disease, control penile tissue and nodular tissue from 8 patients with Dupuytren's contracture were analyzed histochemically for collagen staining and elastic fiber structure and distribution. Plaque tissue from 19 Peyronie's disease patients, control tissue and nodular tissue from Dupuytren's disease were also analyzed for the presence of fibrin by histochemical staining and immunoblotting. RESULTS: Aberrantly stained collagen was detected in 32 of 33 plaque specimens (97%) and disrupted elastic fibers in 31 of the same specimens (94%). Fibrin deposition was detected histochemically in plaque tissue from 18 of 19 patients (95%) but it was not detectable in normal or scarred tunica from control patients. The presence of authentic fibrin accumulation in plaque tissue was confirmed by immunoblot analysis but fibrin was not detected in dermal tissue extracts from the same patient. Aberrant collagen staining and fibrin deposition were detected in nodular tissue from 7 of 8 Dupuytren's contracture patients (88%) and altered elastic fibers in 5 of the same patients (63%). CONCLUSIONS: Deposition of fibrin in plaque tissue is consistent with the hypothesis that repetitive microvascular injury results in fibrin deposition in the tissue space and has served to provide insights into the pathophysiology of Peyronie's disease. We propose a model that accounts for the clinical and biological features of Peyronie's disease.     

Penile trauma: an etiologic factor in Peyronie's disease and erectile dysfunction

PURPOSE: It has been postulated that trauma to either the partially or fully erect penis is a potential cause of Peyronie's disease. In addition, it has been proposed that engaging in sexual relations with a partial erection due to mild impotence is a risk factor for the development of Peyronie's disease. This study was performed to determine whether patients with either Peyronie's disease or non-Peyronie's disease impotence had an increased rate of penile trauma compared with potent controls. MATERIALS AND METHODS: We mailed surveys to 207 men who had been seen for management of Peyronie's disease, 250 impotent men without Peyronie's disease, and 275 age-matched urologic patients without a history of either impotence or Peyronie's disease. The survey inquired whether the individual had a history of penile trauma to the flaccid or erect phallus or injury during sexual intercourse. In addition, patients were questioned whether they had been engaging in sexual relations with a partial erection. RESULTS: The mean age of the impotent patients was slightly less than both the Peyronie's disease patients and controls. A similar response rate to the survey was found among the 3 groups. The mean duration of illness was 6 years for Peyronie's disease and 10 years for impotence. The frequency of penile trauma of any kind was significantly greater in both the Peyronie's disease (40%) and impotence (37%) patients than in the controls (11%). There was no significant difference between the Peyronie's disease and impotence groups. However, the Peyronie's disease patients had a lower frequency of attempting sexual relations with a partial erection than the 2 other groups. CONCLUSIONS: The results of this survey demonstrate a significantly higher incidence of penile trauma in both impotent patients and patients with Peyronie's disease compared with controls. This study demonstrates an association between penile trauma and both Peyronie's disease and impotence. The reduced incidence of engaging in sexual relations with a partial erection among the Peyronie's disease patients implies that partial impotence is not a predisposing factor for Peyronie's disease.     

Comparison of tunica albuginea substitutes for the treatment of Peyronie's disease

PURPOSE: Peyronie's disease is a connective tissue disorder resulting in fibrotic plaque formation on the tunica albuginea of the penis. One approach to repair consists of plaque excision and patching with one of many potential patch materials. Because the optimal patch material for covering the resultant defect has not been determined, this study compares histological and cavernosometric changes in the penis as a result of the placement of three different types of patch grafts used in surgery for Peyronie's disease. MATERIALS AND METHODS: Eleven mongrel dogs were divided into three groups, each receiving a different patch material (superficial dorsal penile vein, silicone fabric, and dermabraded preputial flap). Each dog had dynamic infusion cavernosometry (DIC) performed prior to placement of the patch over a 6 x 3 mm. defect surgically created in the tunica albuginea. Three months later, DIC was repeated prior to sacrifice. Histology of the penis was examined using Masson's trichrome, and hematoxylin and eosin stains. RESULTS: The only difference among the cavernosometric parameters (preop versus postop) was a higher initial pressure in the dermabraded preputial flap group postoperatively. The dogs undergoing vein patch had moderate fibrosis with apparent reformation of the tunica albuginea over the patch site. The normal venous architecture of the graft was no longer recognizable. Those dogs receiving a silicone patch had moderate fibrosis with a fibrous sheath of compressed histiocytes and fibroblasts enveloping the graft site. Finally, the dermabraded preputial flap patch group had mild-moderate fibrosis with focal loss of the cavernosal space underlying the flap. CONCLUSIONS: We feel that continued use of the vein patch for repair of Peyronie's disease is warranted.     

Local treatment of breast carcinoma: when is breast-saving therapy not indicated?

Conservative treatment of breast cancer is now an accepted oncological procedure. It further allows a good functional and cosmetic result. This treatment needs more skills and time than mastectomy, as it does not only include a surgical excision but also a postoperative local radiotherapy and a sometimes difficult follow-up during many years. The contraindications for conservative breast cancer therapy are numerous and depend on factors as tumor, patient and radiotherapy. As more than 1100 patients have been treated since 1977 in our area at a single radiooncological center by a breast conserving procedure. We have confirmed or defined criteria which lead to a good local tumor control as well as to good functional and cosmetic results.     

Salicylic acid is a reducing substrate and not an effective inhibitor of ascorbate peroxidase

This communication describes the interactions of salicylic acid (SA) with plant ascorbate peroxidase (APX). Contrary to a recent report (Durner, J., and Klessig, D. F. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 11312-11316) we show conclusively that ascorbate oxidation by APX is not inhibited by SA (10 mM), but that SA is a slow reducing substrate of this enzyme. The suggestion that SA-dependent inhibition of APX in planta may result in the elevation of H2O2 levels, which in turn acts as a second messenger in systemic acquired resistance signaling, is therefore not tenable. We conclude that APX remains a key antioxidant during systemic acquired resistance following pathogenic infection of plants. The transient products of SA oxidation by APX appear to be SA free radicals that undergo subsequent chemistry. APX-dependent oxidation of SA could be essential for diminishing the detrimental effects of this phenolic acid on plant cells.     

CD44 is an independent prognostic factor in early-stage cervical cancer

Leptin and neuropeptide Y (NPY) are involved in the regulation of food intake and body weight. Both hormones act through specific receptors in the central nervous system. The objective of this study was to investigate the relation of leptin and NPY in human plasma and cerebrospinal fluid (CSF). Leptin and NPY in CSF and in serum/plasma were measured by radioimmunoassays in 35 patients. Leptin concentrations in serum were 100-200 fold higher than in CSF. There was a significant correlation between leptin levels in CSF and in serum (r=0.88, P<0.0001). Female patients had significantly higher leptin serum concentrations than males (16.6+/-10.9 microg/l vs. 6.5+/-7.3 microg/l, P=0.002). In contrast, NPY levels were only twofold higher in CSF than in plasma. There was no relation between leptin and NPY in CSF and serum/plasma, respectively. The ratio of CSF and peripheral leptin levels did not correlate with the respective albumin ratio, indicating that leptin did not merely leak into the CSF via a defective blood-CSF barrier. It is concluded that leptin uptake from the circulation into CSF is a regulated process. The NPY concentration in CSF is not directly related to leptin CSF levels.     

Human chagasic disease is not associated with an antiheart humoral response

An inflammatory cardiomyopathy occurs in humans with chronic Trypanosoma cruzi infection (Chagas' disease). This study finds that T. cruzi infection is not associated with the production of cardiac-specific autoantibodies in humans with cardiac manifestations.     

Legionnaires' disease is not uncommon in Croatia

Legionella pneumophila has been relatively frequent pathogen of pneumonias worldwide. It causes 2-15% of pneumonias requiring hospitalization. It appears sporadically and in outbreaks, and frequently as hospital-acquired infection. The main aim of this study is to show the permanent presence of Legionnaires' disease in our country. In the 9-year period (1986-94), 42 patients were treated in the University Hospital of Infectious Diseases "Dr. Fran Mihaljevic" in Zagreb. The disease was diagnosed every year, and only one patient came from an outbreak, while all other cases of pneumonia were sporadic ones of pneumonia from the community. There were 40 males and only two women. Most of the patients (14) were in aged 30-39 yrs. There were six times more patients during summer and fall than in winter and spring time (36:6), and the highest number was in July (10). In 17 (40.5%) patients exposure to some potential sources of infection was recorded. Provocative factors i.e. underlying chronic diseases have been reported in 13 patients. There were 33 (78.6%) smokers, and 15 patients consumed greater quantities of alcoholic drinks. Legionnaires' disease affects also previously healthy persons as well as those without recognized provocative factors.     

The role of prognostic factors in treatment selection for early-stage Hodgkin's disease

PURPOSE: To identify poor prognostic factors in early-stage Hodgkin's disease that predict a high rate of relapse after radiotherapy alone. MATERIALS AND METHODS: A total of 153 patients with stages I and II supradiaphragmatic Hodgkin's disease, treated between 1964 and 1986 with either radiotherapy alone (120 patients) or combined modality therapy (33 patients), were studied retrospectively to determine factors affecting freedom from relapse and absolute survival. Median follow-up was 13 years. Clinical factors were assessed by the stepwise use of a stratified log-rank test and included maximum tumor dimension in any site (< or = 6 cm or > 6 cm), age (< or = 40 or > 40), presence or absence of B symptoms, pathologic and clinical stages (I or II), number of sites involved (< or = 4 or > 4), gender, histologic subtype, and large mediastinal mass (none, small [< or = 6 cm], large [> 6 cm]). RESULTS: The only factors independently predicting a high rate of relapse were tumor dimension (> 6 cm) and number of sites (> 4 sites). At 10 years, in patients with and without the two poor prognostic factors treated with radiotherapy alone, the freedom from relapse rates were 53% and 84% (p < .0001) and the absolute survival rates were 72% and 85% (p = .004), respectively. Combined modality therapy significantly improved freedom from relapse, but not absolute survival, in patients with one or both poor prognostic factors. CONCLUSIONS: Two poor prognostic factors were identified that were highly significant in predicting a high risk of relapse after radiotherapy alone. The addition of three cycles of chemotherapy to standard radiotherapy significantly reduced the relapse rate in high-risk patients.     

Intrauterine insemination: is it an effective treatment for male factor infertility?

Results were collected from 11 studies comparing intrauterine insemination (IUI) with intracervical insemination (ICI) of frozen donor semen, 10 studies comparing IUI with timed natural intercourse (NI) or ICI in couples with semen defects and seven studies comparing ICI with NI or ICI in couples with unexplained infertility. IUI significantly increased the pregnancy rate relative to favourably timed ICI in donor insemination (DI) with frozen semen both with and without gonadotrophin stimulation of the female partner (odds ratios (95% confidence interval) 1.92 (1.02-3.61) and 2.63 (1.52-4.54) respectively). The benefit of IUI tended to be less when the pregnancy rate for ICI was high and IUI had no benefit with fresh donor semen. Overall IUI was of significant benefit in the male factor couples compared with NI-ICI (odds ratio 2.20 (1.43-3.39) and the advantage appeared to be maintained when comparison was confined to properly timed ICI although the odds ratios were not significantly greater than 1. IUI had no benefit relative to favourably timed NI-ICI for couples with unexplained infertility; an apparent advantage overall was produced by studies where NI was late. None of the studies on male factor used a sperm function test to define male subfertility and three only included couples with good mucus penetration by sperm. The range of semen defects defined was such that many couples would have had a good chance of conceiving naturally given a normal female partner but nevertheless the overall pregnancy rate (4.8%) was considerably less than in the unexplained group (11.6%), suggesting that some sperm dysfunction was present. We conclude that the available evidence suggests that IUI is valuable for DI with cryopreserved semen and for couples with mild to moderately impaired semen quality and postulate that it overcomes failure to fertilize due to impaired mucus penetration and poor survival in the female reproductive tract.     

Mammalian CD2 is an effective heterologous marker of the cell surface in Drosophila

Ectopic expression of neutral proteins, such as beta-galactosidase, in developing embryos has been an invaluable tool for studies of gene expression and embryonic development. However, expression of beta-galactosidase does not reveal the shape of the cells containing it. We have examined the suitability of rat CD2, a small transmembrane protein of the immunoglobulin superfamily, as a marker of cell morphology in Drosophila. We selected the regulatory sequences of the Drosophila mesoderm-specific gene twist to express CD2 and prepared a chimeric gene, twi-CD2. Embryos containing twi-CD2 faithfully express CD2 in the same pattern as Twist. Expression of CD2 on the surface of cells reveals the shape of cells when stained with existing monoclonal antibodies. We have also constructed a CD2 gene that can be used with the GAL4 system and show that CD2 can be expressed on the surface of epithelial cells and along the length of axons.