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Biomedical subjects

O Kucuk

Publications and source records attributed to O Kucuk.

At least 55 records · Page 3Linked to original sources

Sterols stabilize the ripple phase structure in dihexadecylphosphatidylcholine.

The presence of various sterols in mixtures with dihexadecylphosphatidylcholine (DHPC) was studied using static X-ray diffraction of temperature equilibrated samples, and real-time X-ray diffraction of samples undergoing temperature scans. It was found that these sterols eliminate the interdigitation of the alkyl chains in the DHPC sub-gel and gel-state bilayers while stabilizing the ripple gel-state at the expense of the gel-state bilayer phase. The ripple-ripple phase transition previously observed for dipalmitoylphosphatidylcholine in the presence of low molar concentrations of sterols (Wolfe et al. (1992) Phys. Rev. Lett. 68, 1085-1088) was also observed for similar DHPC-sterol mixtures. In addition, we show the first evidence that the presence of 5 alpha-cholestane-3 beta,5,6 beta-triol will cause the lipid mixtures to continue to adopt a ripple mesophase structure even after the DHPC alkyl chain becomes disordered.

Cholestanols↗

Flow cytometric measurement of proliferation-associated nuclear antigen P105 and DNA content in immuno-proliferative small intestinal disease (IPSID).

Immunoproliferative small intestinal disease (IPSID), most common in Mediterranean countries, is characterized by lymphomatous infiltration of the small intestine and is usually associated with the synthesis of anomalous immunoglobulin alpha heavy chains. Flow cytometric analysis of DNA content, S phase fraction, and quantitative analysis of the proliferation-associated nuclear antigen, P105, were performed in 23 patients with IPSID to determine if they could be used as prognostic indicators in this disease. Eighteen patients had low-grade, two had intermediate-grade, and three had high-grade lymphoma. Eight patients had clinical stage IE disease, 12 had stage IIE, and three had stage IIIE disease. Eleven patients survived > 5 yr (good prognosis), four survived between 2-5 yr (intermediate prognosis), and eight survived 2 yr or less (poor prognosis). The S phase fraction of patients with poor prognosis was significantly higher than those with intermediate or good prognosis (P < 0.004). Flow cytometric evaluation of S phase fraction may offer important prognostic information in patients with IPSID and could be useful in the clinical management of patients with this highly variable clinical syndrome. Further studies evaluating the value of DNA flow cytometry in larger groups of patients with IPSID are warranted.

Adult↗

DNA ploidy, proliferative activity, and concanavalin A reactivity in breast cancer.

Paraffin-embedded primary tumor specimens from 48 patients with breast cancer were examined for DNA ploidy, S-phase fraction (SPF), and concanavalin A (Con A) reactivity. The results were correlated with clinicopathological prognostic factors, including patients' age and menopausal status, stage of disease, nuclear grade, and size of the primary tumor. There were no associations among ploidy, SPF, Con A reactivity, and menopausal status, stage of disease, or size of the primary tumor. However, among patients who were 50 years or older, 81% had diploid tumors and 73% had good reactivity (3+ or better staining score) with Con A. In contrast, among patients who were younger than 50 years, 45% had diploid tumors (P < 0.05) and 21% had good Con A reactivity (P < 0.05). Seven of 19 (37%) poorly differentiated tumors and 7 of 9 (78%) moderately differentiated tumors had good reactivity with Con A (P < 0.05). Reactivity of tumor cells with Con A in primary breast cancer tissues deserves further evaluation as a potential biomarker of prognosis.

Adult↗

Antiphospholipid antibodies in sickle cell disease.

Antiphospholipid antibody formation can be induced in mice by phospholipid in a hexagonal II phase but not by phospholipid in a bilayer phase. Since sickle red cell membranes have increased hexagonal II phase content, we have measured serum antiphospholipid antibody levels in 25 patients with sickle cell disease to determine whether anti-phospholipid antibody may similarly be induced in these patients. Seventeen of the 25 patients (68%) had increased levels of antiphospholipid antibodies. Eleven patients (65%) had IgG and six each (35%) had IgM and IgA isotypes. Antiphosphatidylethanolamine, antiphosphatidylserine, antiphosphatidylinositol, and antiphosphatidic acid were the most frequently increased antibodies. The finding of increased antiphospholipid antibodies in these patients is compatible with the concept that antiphospholipid antibody formation is associated with structural changes in the red cell membrane and that such structural changes occur in the red cells of patients with sickle cell disease.

Antibodies, Antiphospholipid↗

Intratumor heterogeneity of DNA ploidy and correlations with clinical stage and histologic grade in prostate cancer.

Paraffin blocks from 60 patients with prostate cancer were used to study the DNA ploidy patterns by flow cytometry. Nineteen patients had stage A disease, 11 had stage B, 9 had stage C, 20 had stage D, and 1 was of unknown stage. Histologically, 32 of the cancers were well differentiated, 21 were moderately differentiated, and 7 were poorly differentiated. Eighteen patients had an aneuploid or tetraploid (A/T) pattern and 42 had a diploid pattern. Seventy-one percent (5/7) of patients with poorly differentiated, 48% (10/21) with moderately differentiated, and 9% (3/32) with well-differentiated histology had A/T patterns (P < 0.01). Forty-five percent (9/20) of patients with stage D, 44% (4/9) with stage C, 27% (3/11) with stage B, and 5% (1/19) with stage A had A/T patterns (P < 0.05). Nine patients with an A/T pattern also had DNA ploidy studies done on the "benign" part of the specimen. These specimens showed diploid patterns although three of these patients had well-differentiated tumor in the "benign" designated part of the specimen. One patient with mixed histology had an aneuploid pattern on the poorly differentiated section and a diploid pattern on the well-differentiated section of the "malignant" designated part of the same specimen. We conclude that prostate cancer patients with non-diploid tumors have more advanced disease and less differentiated tumors than patients with diploid tumors and that considerable histological and ploidy heterogeneity may be present in different parts of the same paraffin-embedded specimen.

DNA, Neoplasm↗

The effects of cholesterol oxidation products in sickle and normal red blood cell membranes.

The oxysterol content in normal and sickle red blood cell (RBC) membranes was assessed using thin-layer chromatography and capillary gas chromatography/mass spectrometry. Several more oxysterols were present in sickle RBCs compared to normal RBCs. Sickle RBC membranes had a higher concentration of 5 alpha,6 alpha-epoxycholesterol, 5 alpha-cholestane-3 beta,5,6 beta-triol, 7-ketocholesterol and 19-hydroxycholesterol than normal RBC membranes. The increased oxysterols in sickle RBC may be an effect of the increased oxidative stress which occurs in sickle RBC membranes. Physical characteristics of normal and sickle RBC membrane ghosts with and without inserted oxysterols were examined by Fourier transform infrared spectroscopy. The data are consistent with a greater sterol content in sickle cells compared to normal RBC membranes, and a possible oxysterol-cholesterol synergism.

Cholesterol↗

Simultaneously occurring alopecia areata and Hodgkin's lymphoma: complete remission of both diseases with MOPP/ABV chemotherapy.

A 43-year-old man presented with simultaneously occurring alopecia areata and stage IIIB nodular sclerosing Hodgkin's disease. Systemic symptoms of Hodgkin's disease were present for 6 months, and rapidly developing patchy hair loss of the scalp was present for 2 weeks prior to presentation. The patient was treated with eight cycles of MOPP-ABV chemotherapy that resulted in complete remission of Hodgkin's-disease. Four months after the completion of chemotherapy, the patient had normal hair regrowth with no evidence of alopecia areata. Alopecia areata may be an autoimmune disease and may respond to chemotherapy.

Adult↗

Inhibition of NK cell-mediated cytotoxicity by oxysterols.

Some of the oxidation products of cholesterol (oxysterols) have profound effects on plasma membrane structure and function. The present studies were undertaken to determine the effects of oxysterols on NK cell-mediated cytotoxicity. When mouse spleen cells were preincubated with certain oxysterols, NK cell cytotoxicity was inhibited without loss of effector cell viability. The strongest inhibition was observed with oxysterols that are oxidized at the C-5, C-6, or C-7 positions of the sterol nucleus. Among these, 7 beta-hydroxycholesterol caused more inhibition than 7 alpha-hydroxycholesterol suggesting that the spatial orientation of the hydroxyl group in the beta-position results in a greater perturbation in plasma membrane structure than that oriented in the alpha-position. In contrast, oxysterols that are oxidized at the C-20 and C-25 positions that are located on the C-17 acyl chain had little or no inhibitory effect, suggesting that oxidation in the cholesterol nucleus which is situated closer to the phospholipid headgroups at the lipid bilayer-aqueous interface results in a more profound effect on the plasma membrane physical structure. These results suggest that the lytic function of NK cell is sensitive to alterations in the physical state of its plasma membrane induced by oxysterols.

Animals↗

Variables contributing to anticipatory nausea and vomiting in cancer chemotherapy.

Forty cancer patients receiving parenteral chemotherapy were assessed for characteristics associated with the development of anticipatory nausea and vomiting (ANV). The patients who developed ANV were more likely to have increased pretreatment anxiety (p less than 0.05), greater posttreatment dizziness/lightheadedness (p less than 0.01), more severe postchemotherapy vomiting (p less than 0.01), and a delayed onset of postchemotherapy nausea and vomiting (PCNV) compared to the patients who developed neither ANV nor PCNV. However, when patients who did not develop PCNV were excluded from the analysis, the difference between the ANV and non-ANV patients remained significant only for postchemotherapy dizziness/lightheadedness (p less than 0.05). In an attempt to identify a group of variables that better predict the development of ANV, we analyzed the data for combinations of variables. Two indices were found to correctly classify ANV and non-ANV patients 71% of the time (p less than 0.05). Index A refers to the presence of at least two of the following variables, pretreatment anxiety, posttreatment dizziness/lightheadedness, and latency of PCNV. Index B refers to the presence of at least two of the following variables: pretreatment anxiety, severity of nausea, and severity of vomiting. The identification of characteristics associated with the development of ANV could lead to new intervention strategies.

Affect↗

Approaches to and effectiveness of current cancer interventions in the elderly.

The effectiveness of early detection depends to a great extent on the particular category of the malignancy. Cancers fall into three categories: 1) Those for which there is evidence that early detection reduces mortality; 2) those for which available evidence indicates that early detection produces no demonstrable mortality reduction; 3) those for which there is insufficient evidence as to the effect of early detection. The use of early detection modalities for these patients is problematic, since such testing can result in unnecessary medical costs and personal burdens. This paper makes some suggestions for practical office screening approaches for cancers of the breast, colon and rectum, cervix, prostate, lung, skin, oral cavity, and endometrium. The evidence relating to screening tests for cancer are reviewed in order to provide a practical approach for the practitioner.

Aged↗

Effect of inserted oxysterols on phospholipid packing in normal and sickle red blood cell membranes.

Fourier transform infrared (FTIR) spectroscopy was used to examine the effect of oxysterol insertion into normal and sickle RBC membranes and the total lipid extracts of the membranes. Examination of the FTIR C-H stretch and fingerprint regions reveal that the insertion of 7 alpha- and 7 beta-hydroxycholesterol has the greatest effect on the fluidity of RBC membranes and lipid extracts. The results confirm the observation that sterol molecules are oriented in the membrane so that the 7 position is located in the phospholipid head group region at the lipid/water interface. The substitution of a keto for a hydroxy group at the number seven position decreases the effect of the sterol on membrane packing.

Anemia, Sickle Cell↗

Diet and stomach cancer incidence. A case-control study in Turkey.

A case-control study of diet and stomach cancer was conducted in Ankara, Turkey, between December 1987 and March 1988. One hundred patients with adenocarcinoma of the stomach were matched with 100 control subjects according to age, sex, and residential area. A dietary questionnaire was administered to all subjects by one of the authors. Gastric cancer patients consumed less fresh fruit and yellow-green vegetables (P less than 0.0001) and meats (P less than 0.001), and more salted food (P less than 0.001), condiments (P less than 0.0001), and salt (P less than 0.001) compared with the control group. Twenty-four percent of the gastric cancer patients and 4% of the groups with regard to the consumption of starches, fried foods, cereals, milk, dairy products, tea, alcohol, and tobacco. Stomach cancer patients brushed their teeth less frequently (P less than 0.0001) and had more deficient teeth (P less than 0.0001) compared with the control group.

Adenocarcinoma↗

Lower extremity vasospasm associated with ischemic neuropathy, dermal fibrosis, and digital gangrene in a patient with carcinoid syndrome.

Bilateral lower extremity vasospasm associated with severe pain and hyperesthesias in the legs, and digital gangrene in both feet developed in a 50-year-old man with carcinoid syndrome. Nifedipine and chemical lumbar sympathectomy were partially effective in relieving the vasospasm. Electromyographic findings were consistent with ischemic neuropathy. A skin biopsy specimen showed striking dermal fibrosis. Serotonin and other vasoconstrictor substances released from the tumor may be responsible for the vasospasm, the dermal sclerosis, and the ischemic neuropathy. The early use of lumbar sympathectomy in patients with lower extremity vasospasm may prevent these irreversible ischemic complications.

Bronchial Neoplasms↗

Autologous bone marrow transplantation in breast cancer: separation of clonogenic tumor cell colonies by gradient fractionation.

A major obstacle to successful autologous bone marrow transplantation in breast cancer is infiltration of the marrow by malignant cells. We layered bone marrow samples from seven breast cancer patients on a discontinuous bovine albumin gradient, then assessed hematopoietic potential (colony-forming units-culture [CFUc]) and clonogenic tumor cells (TCFUc) by standard techniques. We found that 78% of CFUc concentrated in fraction 3 of the gradient, which contained 10% of the total nucleated cell population. TCFUc were distributed across the gradient with 14% of colonies identified in this marrow fraction. We applied these techniques to two patients with metastatic breast cancer who were treated with high-dose mitomycin-C, doxorubicin, and cyclophosphamide before receiving 1.9 x 10(9) and 1.2 x 10(9) total cells, respectively, from CFUc-rich fraction 3. We observed tumor colony growth in three patients only in separated marrow fractions, suggesting that colony growth may be a function of the cell composition after fractionation or that growth factors may be separable. Ninety percent of clonogenic breast cancer cells can be separated from hematopoietic cells by discontinuous density gradient fractionation, a technique that is applicable to the large volumes necessary in bone marrow transplantation and that may be an important initial step in marrow purging for autologous transplantation.

Bone Marrow Transplantation↗

Fulminant leukemic polyradiculoneuropathy in a case of B-cell prolymphocytic leukemia. A clinicopathologic report.

A 52 year old man with a 10-month history of B-cell prolymphocytic leukemia (PLL) died of an apparent acute fulminant polyradiculoneuropathy, a condition generally attributed to paraneoplastic complication. The pathologic examination disclosed diffuse leukemic infiltrations of the peripheral nervous system. It is suggested that this particularly aggressive form of B-cell chronic prolymphocytic leukemia presented a constellation of features that promoted the invasion of the peripheral nervous system by way of the bloodstream and may explain the unusual clinical presentation.

B-Lymphocytes↗

The effect of intensive intermittent maintenance therapy in advanced low-grade non-Hodgkin's lymphoma.

One hundred and eleven patients with low-grade histology non-Hodgkin's lymphoma achieving a restaged complete response to one of three induction therapies on Eastern Cooperative Oncology Group (ECOG) protocol EST 2474 were randomized to receive either maintenance treatment with BCNU, cyclophosphamide, vincristine, and prednisone (BCVP) given every 6 weeks for an additional 18 months or no further therapy. Overall toxicity was moderate. The median progression-free survival (PFS) on maintenance therapy was 3.2 years versus 2.0 years for those observed without treatment (P = 0.02). Progression-free survival was significantly shorter for patients with nodular and diffuse pattern (ND), histiocytic or mixed histology compared with pure nodular lymphocytic, or poorly differentiated counterpart (P = 0.0007), thus confirming the prognostic significance of histologic subtypes. However, the overall survival of patients was not improved by maintenance treatment, suggesting that therapy upon relapse was an equally effective alternative clinical strategy.

Antineoplastic Combined Chemotherapy Protocols↗

Effect of the degree of nodularity on the survival of patients with nodular lymphomas.

The survival of patients with favorable lymphoma entered on various Eastern Cooperative Oncology Group (ECOG) studies was analyzed according to the degree of nodularity. A pure nodular pattern (NN), defined as nodularity involving 75% or more of the cross-sectional area, was found to be an important favorable prognostic indicator as compared with a nodular-diffuse pattern (ND). The median survival in 336 patients with NN of 68.2 months was significantly better than the 39.6 months in 87 patients with ND (P less than .003). The median survival in NN-lymphocytic poorly differentiated (LPD) was 77.2 months v 44.3 months for ND-LPD. NN-M median survival of 56.4 months contrasted with only 25.5 months for ND-mixed lymphocytic and histiocytic (M). The degree of nodularity as defined in this study appears to have significant prognostic implication and should be more widely used by pathologists.

Antineoplastic Combined Chemotherapy Protocols↗