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Biomedical subjects

S Bolis

Publications and source records attributed to S Bolis.

At least 19 recordsLinked to original sources
PubMed2001

Short term wear of high Dk soft contact lenses does not alter corneal epithelial cell size or viability.

BACKGROUND/AIMS: Current contact lenses (CLs) when worn on an extended wear basis cause corneal epithelial alterations. The aim of this study was to evaluate changes in corneal epithelial cell morphology and physiology following short term (3 months) wear of highly oxygen permeable CLs and to compare this with disposable CLs. METHODS: Subjects were wearers of highly oxygen permeable CLs (n=11, wearing CLs on a 30 night schedule), disposable CL users (n=6, wearing CLs on a 6 night schedule), and non-CL wearers (n=20). Mean CL wear experience was 3 months. Epithelial cells were harvested using corneal cytology and were stained using acridine orange and ethidium bromide. Epithelial cell size and viability were determined. RESULTS: The majority of epithelial cells recovered were non-viable (71%), and the mean longest cell diameter was 38 (SD 8) microm. Disposable CLs caused an increase in cell size (42 (7) microm) compared with both non-wear (39 (7) microm, p=0.01) and wear of highly oxygen permeable CLs (37 (10) microm, p=0.0049). There was no difference in cell viability between groups. CONCLUSIONS: Extended wear of disposable CLs caused an 8% increase in cell diameter in harvested corneal epithelial cells following 3 months of CL wear. Cells harvested following 3 months' wear of highly oxygen permeable CLs were indistinguishable from those recovered from non-CL wearers.

Adult↗
PubMed1997

Establishment of the human reflex tear two-dimensional polyacrylamide gel electrophoresis reference map: new proteins of potential diagnostic value.

To understand the changes in protein expression associated with various physiological states as well as the development of pathological eye disease, we have begun to map the protein components of normal human reflex tears. An analytical reference map of normal human reflex tears was created using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) with pH 3.5-10 immobilized pH gradients (IPGs). Micropreparatively loaded gels were transferred to polyvinylidene difluoride (PVDF) and analysed by a combination of N-terminal sequence tagging and amino acid compositional analysis. Thirty spots were sequence tagged, resulting in identification of six different proteins (lipocalin, lysozyme, lactotransferrin, zinc-alpha-2 glycoprotein, cystatin S, cystatin SN) that matched to entries in the SWISS-PROT database. A group of N-terminally blocked proteins was clearly identified from SWISS-PROT by amino acid analysis, isoelectric point (pI) and molecular weight (Mr). A number of highly expressed protein components remain unidentified despite being subjected to amino acid analysis and Edman sequencing. A majority of the abundant proteins showed varying degrees of charge heterogeneity attributed to post-translational processing such as glycosylation and N-terminal truncation. We have identified a previously undescribed protein that we have named lacryglobin. This protein displays strong homology with mammaglobin, a protein overexpressed in breast cancer. The discovery of this homologue in tears offers the potential for disease diagnosis by screening tear fluid proteins.

Databases, Factual↗
PubMed1995

Effect of exogenous hyaluronan and hyaluronan oligosaccharides on hyaluronan and aggrecan synthesis and catabolism in adult articular cartilage explants.

The addition of hyaluronan to the culture medium of explant cultures of articular cartilage was shown to suppress the synthesis of hyaluronan and aggrecan, the major proteoglycan present in cartilage, and resulted in a greater proportion of the newly synthesized aggrecan and hyaluronan appearing in the culture medium. This effect of exogenous hyaluronan on aggrecan and hyaluronan synthesis was concentration-dependent and reversible on removal of the glycosaminoglycan from the culture medium. The addition of tetra- and hexasaccharides derived from Streptomyces sp. hyaluronidase digestion of hyaluronan to explant cultures of articular cartilage did not change the rate of synthesis of aggrecan or hyaluronan or their ultimate distribution between tissue and medium. However, the addition of tetra- and hexasaccharides of hyaluronan resulted in a decrease in the rate of loss of hyaluronan from the tissue but not that of aggrecan, which remained the same as in control cultures. This suppression of the rate of loss of hyaluronan was eliminated on removal of the hyaluronan oligosaccharides from the culture medium. Analysis of the hydrodynamic size of the newly synthesized hyaluronan indicated that the presence of hyaluronan tetra- and hexasaccharides brought about an accumulation of hyaluronan of intermediate molecular mass. Since no radiolabeled hyaluronan was detected in the culture medium, it was concluded that the tetra- and hexasaccharides inhibited the internalization and intracellular catabolism of hyaluronan by the cartilage explant cultures. Regardless of whether hyaluronan or tetra- and hexasaccharides of hyaluronan were added to the culture medium, newly synthesized hyaluronan underwent depolymerization at a rate consistent with a mechanism involving oxygen-derived radicals.

Adult↗
PubMed1994

Amikacin and ceftazidime as empirical antibiotic therapy in severely neutropenic patients: analysis of prognostic factors.

This study aimed to evaluate the efficacy of amikacine and ceftazidime as an empirical antibiotic therapy for neutropenic patients affected by haematological neoplasms and to investigate the presence of prognostic features suggesting a poor outcome with this antibiotic combination at the onset of infection. This could allow the identification of subgroups of patients with a low rate of response to amikacin/ceftazidime therapy; in these patients different initial empirical therapy may be indicated. The study population comprised 166 severely neutropenic (absolute neutrophil count below 500/microliters) oncohaematological patients with fever or clinical signs of infection. Multivariate analysis confirmed four negative prognostic factors: 3 or more days of hospitalization at the onset of an infectious episode, a diagnosis of acute myelmany factors are present, cases can be stratified into three groups, of significantly different prognosis: favourable (0 or 1 factor) 76% success; intermediate (2 factors) 52% success; unfavourable (3 or 4 factors) 19% success. At the onset of an infectious episode a subgroup of patients with a very low response rate to empirical amikacin/ceftazidime antibiotic therapy is identifiable, for whom a different therapy is indicated. Because of the high rate of proven or probable fungal infections in this group, the immediate administration of a systemic antifungal therapy, in addition to antibacterial agents, could be considered in these high-risk patients. Studies should be specifically addressed to evaluating a stratification of empirical antibiotic therapy according to risk factors present at the onset of infection.

Adult↗
PubMed1994

[Multiple myeloma. Role of prognostic factors and staging in a therapeutic program].

Patients affected with multiple myeloma constitute an heterogeneous population with very different clinical patterns, varying from asymptomatic to very compromised patients with severe and uncontrolled disease. Most common clinical and biological staging systems have been in use for many years. Recently new prognostic factors have been identified; among them, serum levels of beta-2 microglobulin, C-reactive protein and interleukin-6 employed with already known parameters have been useful in the new staging system, permitting a more focalized therapy. As today is not yet possible to define the best treatment schedule, as the most common treatments are incapable to eradicate myeloma neoplastic clone even in responsive patients. Nevertheless extensive use of biologic response modifiers in the last years, as alpha interferon, have added new powerful and hopeful therapeutic tools even if the results need to be confirmed in future trials. It is important to remind the primary role of bone marrow transplantation associated with high dose polychemotherapy even if just a minority of patients is eligible for this therapeutic chance.

Forecasting↗
PubMed1991

Oxidation of articular cartilage glyceraldehyde-3-phosphate dehydrogenase (G3PDH) occurs in vivo during carrageenin-induced arthritis.

Articular cartilage proteoglycan biosynthesis was substantially inhibited by the competitive glycolytic inhibitor 2-deoxyglucose (approximately 65% at 100 mM), but to a much lesser degree (approximately 10%) by the oxidative phosphorylation uncoupler, 2,4-dinitrophenol. These results confirm that articular cartilage proteoglycan synthesis mostly utilises ATP which is generated by glycolysis. In addition, we have utilised the loss of the relatively specific labelling of glyceraldehyde-3-phosphate dehydrogenase (G3PDH) by [3H]-iodoacetic acid to show that rabbit articular G3PDH is oxidised in vivo during the animal model of acute arthritis, carrageenin-induced arthritis, in the same way as we have previously shown that cartilage G3PDH is oxidised after in vitro exposure to sublethal doses of H2O2. The oxidation of rabbit G3PDH in vivo (18 hr post-injection) corresponds with the maximal influx of PMNL cells into the arthritic synovial fluid and with substantial inhibition of proteoglycan core protein synthesis. We propose that H2O2 released from "activated" PMNLs and macrophages is responsible for the "down-regulation" of biosynthetic processes found in cartilage during acute inflammation.

2,4-Dinitrophenol↗
PubMed1990

Surgery and chemotherapy in the treatment of gastric non-Hodgkin's lymphoma.

We have retrospectively examined 35 cases of non-Hodgkin's lymphoma (NHL) with gastric involvement at the onset. All patients have completed induction therapy at the time of this report. Histologic specimens have been classified according to the Working Formulation. Patients have undergone surgery and/or chemotherapy. Twenty out of 22 patients with stage I or II disease had surgery. Seventeen out of 20 gastrectomized patients achieved complete remission (11 with stage I and 6 with stage II): Fifteen of these are in their first complete remission with median follow-up of 24 months (range 8-68). Three patients with stage IV had surgery, two of which achieved CR. These data confirm that combined therapy is useful in gastric NHL presenting with stage I and II; no conclusions can be drawn regarding disseminated disease.

Adult↗
PubMed1989

Passive loss of proteoglycan from articular cartilage explants.

The addition of proteinase inhibitors (1 mM phenylmethylsulfonyl fluoride, 10 mM N-ethylmaleimide, 0.25 mM benzamidine hydrochloride, 6.25 mM EDTA, 12.5 mM 6-aminohexanoic acid and 2 mM iodoacetic acid) to explant cultures of adult bovine articular cartilage inhibits proteoglycan synthesis as well as the loss of the macromolecule from the tissue. Those proteoglycans lost to the medium of explant cultures treated with proteinase inhibitors were either aggregates or monomers with functional hyaluronic acid-binding regions, whereas proteoglycans lost from metabolically active tissue also included a population of monomers that were unable to aggregate with hyaluronate. Analysis of the core protein from proteoglycans lost into the medium of inhibitor-treated cultures showed the same size distribution as the core proteins of proteoglycans present in the extracellular matrix of metabolically active cultures. The core proteins of proteoglycans appearing in the medium of metabolically active cultures showed that proteolytic cleavage of these macromolecules occurred as a result of their loss from the tissue. Explant cultures of articular cartilage maintained in medium with proteinase inhibitors were used to investigate the passive loss of proteoglycan from the tissue. The rate of passive loss of proteoglycan from the tissue was dependent on surface area, but no difference in the proportion of proteoglycan aggregate to monomer appearing in the medium was observed. Furthermore, proteoglycans were lost at the same rate from the articular and cut surfaces of cartilage. Proteoglycan aggregates and monomer were lost from articular cartilage over a period of time, which indicates that proteoglycans are free to move through the extracellular matrix of cartilage. The movement of proteoglycans out of the tissue was shown to be temperature dependent, but was different from the change of the viscosity of water with temperature, which indicates that the loss of proteoglycan was not solely due to diffusion. The activation energy for the loss of proteoglycans from articular cartilage was found to be similar to the binding energies for electrostatic and hydrogen bonds.

Aminocaproic Acid↗
PubMed1989

[Non-Hodgkin's lymphomas: staging and therapy].

Some problems of non-Hodgkin's lymphomas are examined, with special consideration for those related to treatment. Some questions of staging are also considered, together with some particular presentations, such as bulky diseases, central nervous system localizations, lymphoblastic lymphoma. The unique features of this disease in immunocompromised patients and problems related to the growing numbers of older patients eligible for curative treatment are discussed.

Adolescent↗
PubMed1986

Stimulation of proteoglycan biosynthesis by serum and insulin-like growth factor-I in cultured bovine articular cartilage.

The addition of foetal calf serum to explant cultures of adult bovine articular cartilage is known to stimulate proteoglycan synthesis in a dose-dependent manner. We have now shown the activity in serum responsible for this effect to be heat- and acid-stable, to be associated with a high-Mr complex in normal serum but converted to a low-Mr form under acid conditions. The activity has an apparent Mr approximately 10,000 and isoelectric points similar to those reported for insulin-like growth factors (IGFs). Addition of a monoclonal antibody against insulin-like growth factor-I (IGF-I) prevented foetal calf serum from stimulating proteoglycan synthesis. Physiological concentrations of recombinant IGF-I or pharmacological levels of insulin when added to cartilage cultures mimicked the proteoglycan-stimulatory activity of serum. IGF-I appeared to act by increasing the rate of proteoglycan synthesis and did not change the nature of the proteoglycan synthesized nor the rate of proteoglycan catabolism by the tissue, suggesting that IGF-I may be important in the regulation of proteoglycan metabolism in adult articular cartilage. Furthermore, IGF-I can replace foetal calf serum in the culture medium, thereby allowing the use of a fully-defined medium which will maintain the synthesis and tissue levels of proteoglycan in adult articular cartilage explants for up to 5 days.

Animals↗
PubMedDate not supplied

Alpha interferon as initial treatment of essential thrombocythemia. Analysis after two years of follow-up.

AIMS AND BACKGROUND: Recombinant alpha-interferon has been shown to be effective in essential thrombocythemia and in thrombocytosis associated with other myeloproliferative disorders. PATIENTS AND METHODS: Twenty-five untreated patients were enrolled in our study from May 1989 to April 1992. Recombinant alpha interferon-2b was administered at an initial dose of 2 megaunits (MU)/m2 three times a week at escalating doses to 5 MU/m2 or the maximum tolerated dose. The mean follow-up for patients still in treatment at the time of this report was 35.9 months (range, 24-63). RESULTS: Fourteen patients (56%) had achieved a complete remission by a mean time of 152 days; 6 patients (24%) had achieved a good partial remission by a mean of 180 days. In addition to the favorable effect on platelet count, a marked improvement in clinical symptoms was observed. Treatment had to be discontinued in 9 patients (36%), 5 for toxicity (3 neurologic, 1 anemia and 1 severe hypertriglyceridemia) at a median of 155 days from the beginning of therapy (range, 30-400). Four patients refused to continue therapy because of low tolerance (flu-like syndrome) at mean of 160 days from the beginning of therapy (range, 34-301). CONCLUSIONS: In our study, lower doses were administered compared with previous short-time trials. The present data show that interferon is an effective alternative to cytostatic agents in long-term treatment of patients with essential thrombocythemia, even when used at lower dosages.

Adult↗
PubMedDate not supplied

Blood concentrations of tumor necrosis factor-alpha in malignant lymphomas and their decrease as a predictor of disease control in response to low-dose subcutaneous immunotherapy with interleukin-2.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine provided by both immunomodulating and inflammatory activities, has been described to be abnormally increased in the blood of patients affected by malignant lymphomas, particularly NHL. However, the biological and clinical significance of TNF-alpha secretion in malignant lymphomas is still controversial. The present study was carried out to further define TNF-alpha secretion in untreated malignant lymphomas and during low-dose IL-2 immunotherapy. The study included 80 malignant lymphoma patients, 54 of whom were affected by HD and the other 26 by NHL. The mean TNF-alpha serum concentrations observed in untreated lymphoma patients were significantly higher than those seen in the healthy controls, without significant differences between HD and NHL. Moreover, both HD and NHL lymphoma patients at clinical stage III-IV showed significantly higher mean TNF-alpha levels than those at clinical stage I-II. Finally, patients with systemic symptoms had higher mean TNF-alpha concentrations than those without any systemic symptoms, even though statistical significance was observed only for NHL patients. In a second study we have evaluated changes in TNF-alpha levels in seven evaluable lymphoma patients (NHL: 6; HD: 1)--who did not respond to conventional therapies--during subcutaneous low-dose IL-2 (3 MIU/day, 6 days/week for 4 weeks). Long-term stable disease was achieved in four patients with NHL, whereas the other three progressed. In patients with stable disease the mean TNF-alpha concentrations significantly decreased during treatment, whereas they increased in progressing patients. This study, by showing an abnormally enhanced TNF-alpha secretion in both NHL and HD patients with advanced disease and systemic symptoms and a decrease in its levels in patients who achieved disease control on IL-2 immunotherapy, appears to confirm the unfavorable prognostic significance of enhanced TNF-alpha levels in malignant lymphomas.

Adolescent↗
PubMedDate not supplied

A phase II study of neuroimmunotherapy with subcutaneous low-dose IL-2 plus the pineal hormone melatonin in untreatable advanced hematologic malignancies.

Interleukin-2 (IL-2) has proven to be able to generate an effective anticancer immunity against both solid and hematologic malignancies. Moreover, recent advances in the knowledge of psychoneuroimmunology have demonstrated that anticancer immunity is under neuroendocrine control and that the pineal hormone melatonin (MLT) may stimulate the IL-2-dependent anticancer reaction. Finally, preliminary clinical studies have already shown that the concommitant administration of MLT may amplify the efficacy of IL-2 in the treatment of advanced solid neoplasms, whereas there are no data about MLT influence on IL-2 activity in hematologic malignancies. The aim of the present study was to evaluate the efficacy and tolerability of a neuroimmunotherapeutic combination of low-dose IL-2 plus MLT in advanced hematologic malignancies which did not respond to previous standard therapies. The study included 12 evaluable patients. Tumor histotypes were as follows: non-Hodgkin's lymphoma (NHL) 6; Hodgkin's disease (HD), 2; multiple myeloma, 2; acute myelogenous leukemia (ALM), 1 and chronic myelomonocytic leukemia (CMML), 1. IL-2 was injected subcutaneously at a dose of 3 million IU/day for 6 days per week for 4 weeks, corresponding to one cycle. MLT was given orally at 20 mg/day in the evening, without interruption. In non-progressing patients, a second IL-2 cycle was planned after a 3 week-rest period. A partial response was achieved in one patient with multiple myeloma. Stable disease occurred in 7 other patients (NHL, 3; HD, 1; AML, 1; CLLM, 1; multiple myeloma, 1), whereas the other 4 patients progressed. Therefore, lack of progression was obtained in 8 out of 12 (67%) patients, with a median duration of 21+ months (14-30+ months). The treatment was well tolerated in all patients. These preliminary results would suggest that the concomitant administration of low-dose IL-2 plus the pineal hormone MLT may prolong the survival time in untreatable advanced hematologic malignancies, with results comparable to those previously reported using a more toxic immunotherapy, consisting of high-dose IL-2 alone.

Adolescent↗