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Michael Lishner

Publications and source records attributed to Michael Lishner.

At least 19 recordsLinked to original sources
PubMed2007

Overexpression of tetraspanins affects multiple myeloma cell survival and invasive potential.

Cellular interactions with microenvironmental components are critical in multiple myeloma (MM) and impede effective disease treatment. Membranal-embedded tetraspanins, associated with metastasis suppression, are underexpressed in MM. We aimed to investigate the consequences of CD81/CD82 tetraspanins over-expression in MM cell lines. CAG and RPMI 8226 were transfected with pEGFP-N1/C1 fusion vectors of CD81/CD82. Employing flow cytometry, immunocytochemistry, and activity assays we assessed transfected cells for: morphology, survival, death, caspases, cell cycle, proliferation, oxidative stress, adhesion, motility and invasion. Overexpressed CD81/CD82 pEGFP-N1 vectors reduced survival without elevation of pre-G1 or AnnexinV+/7AAD- and independently of caspases. Decreased Ki67 and elevated intracellular glutathione were detected. No perturbations in cell cycle distribution were observed. The pEGFP-C1 vectors of CD81/CD82 caused reduction of MM cell adherence with/without fibronectin, insulin-like growth factor (IGF)-I, and matrigel. They also reduced cell motility and attenuated invasion potential, expressed by reduced secreted MMP-9 activity. These novel findings delineate the significance of CD81/CD82 expression to MM cell survival and their negative effects on cell adhesion, motility, and invasion thus, supporting their role as tumor metastasis suppressors.

Animals↗
PubMed2006

Microsatellite instability in multiple nonfamilial malignancies.

Development of multiple tumors of different histopathologic types may suggest a profound generalized genetic defect, such as malfunction of DNA mismatch repair (MMR) mechanism. Defects in this mechanism are best reflected in microsatellite instability (MSI). We aimed to determine the role of MSI in a group of patients with dual malignancies and compared the data with that of patients with a single malignancy. Fifty patients were enrolled in the study, of whom 16 patients developed both solid and hematologic nonfamilial malignancies, 18 patients developed a single matched hematologic malignancy, and 16 a single matched solid malignancy. Five microsatellite markers were replicated by polymerase chain reaction (PCR) after DNA extraction from paraffin-embedded tissue blocks and analyzed by the GeneScan Analysis Software. The MSI-high phenotype was defined as instability in at least 40% of the examined loci. A higher prevalence of MSI-high phenotype was found in patients with dual malignancies (31.3%) compared with patients with single hematologic (5.6%) or solid malignancy (6.3%) (P = 0.0498 and 0.07, respectively). In conclusion, defects in DNA MMR mechanism may have an important role in the development of multiple sporadic nonfamilial malignancies.

Base Pair Mismatch↗
PubMed2006

Factors influencing selection of internal medicine residency--a prospective study.

Recently, the popularity of internal medicine residency has been decreasing. We studied the effect of an improved working environment and a decrease in residents' workload on the selection of internal medicine residency. An organizational diagnosis team joined our department and identified several causes for residents' heavy workload. These findings were subsequently discussed in a workshop and led to a modification of the daily routine and a parallel decrease in workload and rise in residents' satisfaction. Following these changes, the demand for residency in our department rose. We conclude that an improvement in the working environment and workload during residency increases the residents' satisfaction and the demand for residency in internal medicine.

Journal Article↗
PubMed2006

Fertility status among women treated for aggressive non-Hodgkin's lymphoma.

In young women treated for intermediate-high-grade non-Hodgkin's lymphoma with CHOP (cyclophosphamide, adriamycin, oncovine and prednisone), there is insufficient data concerning gonadotoxicity or the need for fertility-preserving measures. The aim of the present study was to evaluate the fertility status in the first complete remission of women who were treated for aggressive non-Hodgkin's lymphoma. A cohort of 36 women with aggressive non-Hodgkin's lymphoma in first remission, who were treated in five university-affiliated hospitals in Israel, was evaluated. All women were aged younger than 40 years at diagnosis and received frontline protocols, including cyclophosphamide and adriamycin, mostly CHOP. Menstrual cycle characteristics, as well as pregnancies before the diagnosis, during treatment and in first complete remission, were evaluated. The patients' mean age at the diagnosis was 28 +/- 7 years (range 17 - 40 years). All patients were treated with chemotherapy, although 10 patients received additional radiotherapy. Follow-up time at first complete remission was 84 +/- 48 months. Before diagnosis, all patients had menstrual cycles, which were regular in 31 (86%). Three patients received gonadtropin-releasing hormone analogs, whereas nine received contraceptive pills together with cytotoxic treatment. During treatment, 18 patients (50%) had amenorrhea, six (17%) had irregular menstrual cycles, and 12 (33%) continued their regular cycles. All but two women resumed menses in the first complete remission, and these were regular in 22 (61%) patients. In 63% of patients, the menstrual cycle recovered within 3 months of the discontinuation of chemotherapy. Eighteen patients (50%) became pregnant during the first complete remission. There was no significant difference between those patients who received fertility-preserving measures versus the remainder concerning regular menstrual cycles recovery or pregnancies. The two patients who developed amenorrhea were 40 years old at the time of diagnosis. In conclusion, the rate of gonadal dysfunction is very low among young, CHOP treated, non-Hodgkin's lymphoma female patients. Fertility-preserving techniques are not needed for women aged younger than 40 years and should probably be reserved for those who are at high risk for gonadal toxicity.

Adolescent↗
PubMed2006

Age-related leukocyte and cytokine patterns in community-acquired bronchopneumonia.

BACKGROUND: Community-acquired bronchopneumonia in children is frequently accompanied by extreme leukocytosis, whereas in adults with the same diagnosis a high leukocyte count is uncommon. Data regarding differences in the serum levels of inflammatory cytokines between children and adults are limited. OBJECTIVES: To compare leukocyte counts and blood levels of various inflammatory cytokines in children and adults diagnosed with community-acquired bronchopneumonia. METHODS: We prospectively evaluated all pediatric and adult patients admitted for bronchopneumonia based on clinical and chest X-ray findings. Blood was drawn for complete blood count and serum concentration of the following cytokines: granulocyte colony-stimulating factor, interleukins-6, 8 and 10, interferon-gamma, tumor necrosis factor, as well as matrix metalloproteinase-9 and intercellular adhesion molecule-1. RESULTS: There were 31 children and 32 adults. The patients in both groups had similar parameters of infection severity. None of them required admission to the Intensive Care Unit. Mean (+/- SD) leukocyte counts in the pediatric and adult groups were 21,018/mm3 (+/- 10,420) and 12,628/mm3 (+/- 6735) respectively (P = 0.02). Age was inversely correlated with leukocytes in the pediatric group (P = 0.0001). A significant inverse correlation was also found between age and platelet counts. Although cytokine levels in both groups were not significantly different, age was directly correlated with MMP-9 (P= 0.03), IL-8 (P= 0.03) and G-CSF (P= 0.014). CONCLUSIONS: The immune response in community-acquired bronchopneumonia is, at least partly, age-dependent.

Adolescent↗
PubMed2006

Should bone marrow examination be routinely performed for the diagnosis of monoclonal gammopathy of undetermined significance?

BACKGROUND: Monoclonal gammopathy of undetermined significance is defined by the presence of: low serum and/or urine monoclonal protein level; less than 10% plasma cells in bone marrow; normal serum calcium, creatinine and hemoglobinlevels; and no bone lesions on full skeletal X-ray survey. OBJECTIVES: To study the necessity of bone marrow examination for the diagnosis and clinical course of MGUS. METHODS: We retrospectively screened the medical records of all patients in whom monoclonal protein was found in the serum during 2001-2002 in the medical laboratories of Meir Medical Center. Asymptomatic patients who had serum monoclonal immunoglobulin G < 3.0 g/dl or IgA < 2.0 g/dl or IgM < 1.0 g/dl without anemia, renal failure, hypercalcemia or any bone lesions on skeletal survey were eligible. Full records of patients who were evaluated in the hematology clinic were available (group 1). The remaining patients were followed by their family physicians; thus we had access only to their electronic files including laboratory results and new diagnoses (group 2). Demographic and clinical parameters as well as clinical course werewere evaluated. RESULTS: Both groups (57 and 255 patients, respectively) had similar demographic, laboratory and clinical characteristics. Bone marrow examination was performed in 30 of 57 patients (group 1): 16 were normal, 8 had an excess of normal plasma cells, and 6 had excess of pathologic plasma cells. However, only in two of the latter six could a diagnosis of multiple myeloma be established. All group 1 patients were followed for 22 +/- 11 months and onlytwo developed overt multiple myeloma. During the same period, 6 of 255 patients (group 2) were diagnosed as multiple myeloma and 3 as MGUS in other hospitals. The rest had a stable course with no change in their laboratory values. CONCLUSIONS: Our findings suggest that bone marrow examination should not be performed routinely in patients who fulfill strict clinical and laboratory criteria of MGUS.

Aged↗
PubMed2005

Promoter hypermethylation of tetraspanin members contributes to their silencing in myeloma cell lines.

Multiple myeloma (MM) cell interactions with their microenvironment modulate acquired drug resistance and disease progression. Indeed, reported aberrant gene methylation underscores the possible role of epigenetic events in MM's molecular profile. Membranal tetraspanins are often inversely correlated with cancer prognosis and metastasis, however mutations were unidentified hitherto. Their promoter characteristics and frequent down-regulation conform to transcriptional silencing by chromatin remodeling. We delineated the baseline expression of select tetraspanins in MM cell lines (RPMI 8226, U266, ARP1, ARK, CAG and EBV transformed ARH77) and fresh bone marrow samples (n = 9) for the first time and determined reduced expression of CD9, CD81 and absence of CD82. Thus, we aimed to assess their promoter methylation status. Indeed, we established CD9, CD81 and CD82 promoter methylation in MM cell lines employing methyl-specific-PCR of bisulfite modified G-DNA and PCR of G-DNA digested with methylation-sensitive restriction enzyme (Hin6I). Re-transcription of assayed genes in the cell lines following de-methylation [5-aza-2'-deoxycytidine (5-aza-dC)] confirmed the mechanistic significance of methylation to their regulation. Combined de-methylation and de-acetylation [Trichostatin A (TsA)] induced synergistic elevation of CD82 mRNA. We conclude that chromatin remodeling contributes to tetraspanin silencing in MM.

Antigens, CD↗
PubMed2005

Iron deficiency anemia in patients without gastrointestinal symptoms--a prospective study.

BACKGROUND AND OBJECTIVES: Chronic gastrointestinal (GI) bleeding is the leading cause of iron deficiency anaemia (IDA) in men older than 50 years and post-menopausal women. There is a scarcity of data regarding IDA patients without GI symptoms or signs. We conducted a prospective study to determine the prevalence and the locations of the GI tract lesions in patients with asymptomatic IDA. METHODS: Forty-eight patients with asymptomatic IDA (25 men older than 50 years and 23 post-menopausal women) underwent colonoscopy, gastroscopy and abdominal computed tomography (CT) with contrast agent. RESULTS: An anaemia-causing lesion was found in 14 (29%) and 16 (33%) patients in the upper and the lower GI tract, respectively. The prevalence of dual lesions (in both the upper and lower GI tract) was low (6%). In 14 (29%) patients, a malignancy, predominantly right-sided colon carcinoma, was responsible for the IDA. Only one patient had a lesion in the small bowel. In 14 (29%) patients, the work-up was negative. CONCLUSION: Our prospective study demonstrates a high rate of malignancy, predominantly right-sided colon carcinoma, in men older than 50 years and post-menopausal women with asymptomatic IDA. This finding obligates a complete and rigorous GI tract examination in this group of patients, especially of the right colon.

Aged↗
PubMed2005

The effect of fermented yogurt on the prevention of diarrhea in a healthy adult population.

BACKGROUND: Probiotic dairy products are increasingly gaining popularity. Although the role of probiotic bacteria in the prevention and treatment of pediatric and antibiotic associated diarrhea is fairly well established, their role in the prevention of adult infectious diarrhea has not been well investigated. METHODS: Five hundred forty-one, young male military recruits were enrolled and randomly assigned to receive a yogurt containing Lactobacillus casei (n = 275) or a nonprobiotic yogurt (n = 266). The incidence and duration of diarrhea were documented and stool samples examined for bacteria and parasites. RESULTS: Five hundred and two participants were eligible for final analysis, 254 receiving probiotic yogurt and 248 in the control group. Seventy-one participants (14.14%) experienced diarrhea during the study period. The incidence of diarrhea in the probiotic group and the control group was 12.2% and 16.1%, respectively (P = .207). The mean duration of diarrhea was 3 +/- 1.95 days in the probiotic group and 2.6 +/- 1.08 days in the control group (P = .276). CONCLUSION: Our study demonstrated a nonsignificant trend for reduction of the incidence of diarrhea among healthy young adults consuming yogurt containing Lactobacillus casei . Further study is needed to evaluate the role of probiotics in adults.

Adolescent↗
PubMed2005

Pregnancy outcome following non-obstetric surgical intervention.

OBJECTIVE: To evaluate the effects of non-obstetric surgical procedures on maternal and fetal outcome. METHODS: A systematic review of all English language literature. RESULTS: Fifty-four papers met the inclusion criteria. The overall number of patients reported was 12,452. Reported maternal death was rare at .006%. The miscarriage rate was 5.8%; however, this number is difficult to interpret since matched controls were not available. The rate of elective termination of pregnancy following non-obstetric surgery was 1.3%. The rate of premature labor induced by non-obstetric surgical intervention was 3.5% and this was noted specifically following appendectomy versus other types of interventions (P<.001). A total of 2.5% of pregnancies resulted in fetal loss. The prematurity rate was 8.2%. The rate of major birth defects among women who underwent non-obstetric surgical intervention in the first trimester was 3.9%. Sub-analysis of papers reporting on appendectomy during pregnancy revealed a high rate (4.6%) of surgery-induced labor. Fetal loss associated with appendectomy was 2.6%; however, this rate was increased when peritonitis was present (10.9%). CONCLUSIONS: Modern surgical and anesthesia techniques appear to diminish the rate of maternal death. Surgery in the first trimester does not appear to increase major birth defects and should not be delayed when indicated. Acute appendicitis with peritonitis is associated with higher risk to the mother and fetus.

Appendectomy↗
PubMed2005

Decreasing the use of anaerobic culture bottles in selected febrile patients--is it reasonable?

BACKGROUND: Two sets of blood cultures are routinely obtained from febrile patients in the medical wards. The purpose of the present study was to evaluate the distribution of the aerobic versus anaerobic isolates in such patients and to examine the rationale of reducing the number of anaerobic culture bottles in selected patients. METHODS: A retrospective analysis was performed of all febrile patients admitted to medical wards during 1998. Febrile patients from whom at least two sets of blood cultures were drawn and who had a bacterial isolation in at least one bottle were included. RESULTS: A total of 317 patients were included in the analysis. Some 98.5% of all isolates were aerobic pathogens. Only 1.5% of all isolates (5/317) included obligatory anaerobes. The rate of isolation in a single anaerobic bottle was 8.5%. Analysis of the available files of patients with a single anaerobic positive bottle demonstrated that an adequate antibacterial agent was administered empirically in most of the cases (93%). CONCLUSIONS: We conclude that in carefully selected medical patients suspected of having an infectious disease, it is reasonable to obtain one anaerobic and two aerobic bottles rather than two full sets. Such an approach is clinically safe and will cut expenses on culture bottles and laboratory staff work. This approach should be examined in a prospective, randomized study.

Journal Article↗
PubMed2005

Association between alopecia and response to chemotherapy in patients with Hodgkin lymphoma.

Alopecia and bone marrow suppression are prominent effects of doxorubicin-containing chemotherapy. The aim of the study was to validate our preliminary clinical observation that the lack of alopecia in Hodgkin lymphoma patients may predict poor response to chemotherapy and low rate of bone marrow suppression. Sixty-six patients with Hodgkin lymphoma were reviewed. They were treated between 1991 and 2001 with at least 4 courses of doxorubicin-containing chemotherapy (MOPP/ABV or ABVD) in 2 university-affiliated hematology departments. Thirty-four patients exhibited complete or near complete alopecia, and 32 retained their hair or had only minimal hair loss. The 2 groups were compared by response to treatment and episodes of bone marrow suppression. Alopecia was associated with a high rate of remission (OR 8.48, 95% CI 2.77-25.95), episodes of neutropenia (OR 3.55, 95% CI 1.28-9.84), leukopenia (OR 1.83, 95% CI 0.68-4.92), delays in scheduled treatments (OR 1.61, 95% CI 0.607-4.30), or number of courses with dose reduction (OR 1.63, 95% CI 0.56-4.74). Significantly more patients with alopecia had at least 1 of these parameters (88% versus 62%, P=0.015; OR 4.50, 95% CI 1.27-15.94). In conclusion, in patients with Hodgkin lymphoma treated with doxorubicin-containing chemotherapy, the absence of alopecia may predict poor response to treatment along with fewer episodes of bone marrow suppression. The absence of alopecia in such patients should alert clinicians to the possibility of treatment failure.

Adult↗
PubMed2004

Microsatellite instability in gastric MALT lymphoma.

The role of microsatellite instability and defects in DNA mismatch repair mechanism in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type is still controversial, as both negative and positive findings have been reported. This may be explained mainly by arbitrary selection of the tested loci, the use of various techniques of microsatellite instability analysis and by different definitions of replication error positive phenotype. The aim of our study was to evaluate the instability at selected microsatellite markers using the GeneScan Analysis Software. DNA from paraffin-embedded tissue blocks of 13 previously untreated patients with localized gastric MALT lymphoma was extracted. Five microsatellite markers, which are located in hMSH2, hMLH1, P16, APC and MLL loci, were selected from the genetic database. We found genetic instability in tumors of 9/13 patients with gastric MALT lymphoma (69%). Seven of them had replication-error-positive phenotype (54%). Microsatellite instability was found in 39% of the samples in the MLL locus, 39% in the APC, 46% in the P16, 23% in the hMLH1 and none in the hMSH2. This study demonstrates that microsatellite instability has more prominent role in pathogenesis of gastric MALT lymphoma than reported to date. We suggest that microsatellite instability should be analyzed with markers adjacent to chromosomal loci that are involved in lymphomas. Our findings support the 'Real Common Target genes' theory of high rate of microsatellite instability in specific genes, which are associated with related tumors.

Adult↗
PubMed2004

Is serum ferritin high in patients with diabetic retinopathy? A controlled study.

It is suggested that an excessive absorption and storage of dietary iron might contribute in the pathogenesis of type II diabetes mellitus and its complications. However, previous studies had methodological problems including design, lack of matched controls and unspecified inclusion criteria. The aim of the study was to evaluate the relationship between diabetic retinopathy and serum ferritin levels in well-defined diabetic patients and controls. The study population comprised of 3 groups: patients with type II diabetes mellitus and severe diabetic retinopathy, diabetic patients without retinopathy, and non-diabetic, non-retinopathy patients. The groups were well matched by age, gender and hemoglobin levels, whereas diabetes characteristics and treatment differed. Serum iron, transferrin and ferritin levels were compared between the patients' groups. Twenty-two patients had diabetes and retinopathy, 29 patients had diabetes without retinopathy and 40 were non-diabetic, non-retinopathy patients. Serum iron or ferritin levels did not differ significantly between the 3 groups. Also, there was no correlation between HbA1c level and serum iron or ferritin levels between the 2 diabetic patients' groups. Our findings suggest that iron does not have a major role in the development of diabetes mellitus or diabetic retinopathy.

Case-Control Studies↗
PubMed2004

Co-administration of simvastatin and cytotoxic drugs is advantageous in myeloma cell lines.

We have evaluated the potential application of simvastatin (Sim) combined with conventional cytotoxic drugs for the treatment of multiple myeloma. RPMI 8226 and U266 myeloma cells seeded in culture plates were treated with Sim (5 and 10 microM, respectively) combined with melphalan (Mel; 25 and 20 microM, respectively) or dexamethasone (Dex; 1 microM). We assessed cell cycle (propidium iodide staining and flow cytometric analysis), cell morphology, viability (WST1), total cell count and cell death (Trypan blue exclusion). Sim significantly enhanced the anti-myeloma activity of cytotoxic agents in vitro (p<0.05). Incubation of U266 and RPMI 8226 with Sim prior to Mel increased the cytotoxicity in an additive manner, whereas the exposure of U266 to combined Sim and Dex resulted in a synergistic amplification of the individual effects. Combined application of Dex and Sim to RPMI 8226 cells resulted in antagonistic activity. The possible roles of Ras and phosphoinositol 3-kinase are discussed.

Antineoplastic Agents↗
PubMed2004

Microenvironment factors do not afford myeloma cell lines protection from simvastatin.

BACKGROUND: The intensive interactions of myeloma cells (multiple myeloma, MM) with microenvironmental components of the bone marrow contribute significantly to their proliferation and survival. It has been shown that these signals confer drug resistance, delineating their circumvention as a primary objective in disease treatment. This study was designed to assess the effect of some major extracellular factors on the previously established anti-neoplastic response of myeloma cells to simvastatin (Sim). STUDY DESIGN: RPMI8226, U266, and ARH77 seeded in culture plates precoated with fibronectin (FN)/agarose/none were treated with Sim, insulin-like growth factor-I (IGF-I), interleukin-6 (IL-6) or combinations for 5 d. Then we assessed cell morphology, viability (WST1), cell cycle (propidium iodide, PI, staining and flow cytometric analysis), total cell count, and cell death (trypan blue exclusion), and DNA fragmentation. RESULTS AND CONCLUSIONS: Reduced viability was demonstrated with Sim in all treated cell lines with and without co-administration of IGF-I or IL-6 (P < 0.05). The extent of inhibition did not vary between Sim only and combinations (NS). FN did not influence cell response to Sim alone or combined with IL-6/IGF-I (NS). We conclude that IL-6, IGF-I, and FN do not afford myeloma cell lines protection from Sim modulation.

Bone Marrow↗