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Biomedical subjects

T Han

Publications and source records attributed to T Han.

At least 55 records · Page 3Linked to original sources

[Free fatty acids in gallbladder bile].

Using gas chromatography and high performance liquid chromatography (HILC), we examined free fatty acid and lecithin molecular species in gallbladder biles from patients with cholesterol gallstones. Effect of free fatty acids on cholesterol nucleation in model bile was studied by a sensitive cholesterol crystal growth assay. Compared to bile of controls, biles from patients with gallstones had higher total free fatty acid level, more palmitic acid, more stearic acid, more linoleic acid and arachidonic acid. The lecithin pattern was similar in all. After free fatty acids were added to model bile, palmitic acid, oleic, acid, linoleic acid and arachidonic acid had significant effect of pro-nucleating, free fatty acids on non-protein pro-nucleating factor. These data suggest that variations in quantitation and composition of free fatty acids are importanct in the pathogenesis of cholesterol gallstone formation.

Bile↗

Interferon-alpha alters spectrin organization in normal and leukemic human B lymphocytes.

Interferon-alpha (IFN-alpha) regulates the growth, differentiation, and recirculation of normal and malignant B lymphocytes. In this report we examine the effects of IFN-alpha on the distribution of the cytoskeletal protein spectrin in peripheral blood B lymphocytes from normal donors and patients diagnosed with chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). Exposure of normal and leukemic B cells to IFN-alpha in vitro was shown by immunofluorescence microscopy to cause a dose-dependent increase in the percentage of cells containing discrete focal accumulations of spectrin, ie, a single large aggregate or cap-like structure near the plasma membrane. Although the magnitude of this effect was variable among individual patient samples, in some experiments IFN-alpha induced a fourfold increase in the percentage of leukemic B cells exhibiting focal accumulations of spectrin. Spectrin reorganization induced by IFN-alpha was abrogated by the protein synthesis inhibitor cycloheximide. In addition, IFN-alpha increased the total cellular content of spectrin in B-CLL cells by approximately twofold to fourfold. Finally, a role for protein kinase C in mediating the effects of IFN-alpha on spectrin's organization is implicated by studies in which calphostin C inhibited the IFN-induced focal accumulation of spectrin. Taken together, these studies suggest that the immunomodulatory activities of IFN-alpha in normal and malignant B cells involve a change in the organization of the spectrin-based cytoskeleton.

Antigens, CD↗

Three new monoclonal antibodies that define a unique antigen associated with prolymphocytic leukemia/non-Hodgkin's lymphoma and are effectively internalized after binding to the cell surface antigen.

Prolymphocytic leukemia (PLL) is closely related to chronic lymphocytic leukemia (CLL), but present with distinctive clinical/laboratory features and associated with much worse prognosis. In this study, we generated three new IgG1-kappa monoclonal antibodies (MoAbs), termed SN8, SN8a and SN8b, by use of an unconventional approach, ie, by using an isolated B PLL antigen preparation to immunize mice. These MoAbs, particularly SN8, showed a highly selective reactivity to B PLL and B non-Hodgkin's lymphoma (NHL) among various human leukemia-lymphoma specimens tested; eg, SN8 was capable of effectively distinguishing B PLL from B CLL as well as from hairy cell leukemia (HCL) cell specimens. The cell surface antigen defined by the three MoAbs was determined to be a covalently linked heterodimeric glycoprotein complex (gp49/40) consisting of a 49,000 dalton (alpha-chain) and a 40,000-dalton component (beta-chain). Epitope comparison showed that the epitope defined by SN8 (SN8 epitope) is in close proximity to SN8a epitope but in a distant position from SN8b epitope. Western blot analysis showed that both SN8 and SN8a epitopes are on the beta-chain, but SN8b epitope was not detected on either the alpha- or the beta-chain of the reduced antigen in the same analysis. Binding of either SN8 or SN8b to the cell surface gp49/40 did not cause significant downregulation of the antigen expression whereas binding of SN8a to the antigen caused small (approximately 20%) decrease in the antigen expression. Among the various normal peripheral blood cells, only a subpopulation (6.0% to 24.2% among different specimens derived from different donors) of B cells reacted with the SN8 series MoAbs; these MoAbs showed no significant reactivity against T cells, granulocytes, monocytes, erythrocytes, and platelets. Minimal or no significant reactivity (0 to 2.6% among different specimens) was detected against normal bone marrow cells. Ricin A-chain conjugates of the three MoAbs are all strongly effective for specific killing of SN8 antigen-expressing leukemia cells in the absence of any potentiators; furthermore, the addition of 10 mmol/L NH4Cl, a potentiator, enhanced strongly the cytotoxic activities of the SN8, SN8a, and SN8b conjugates. Thus, each of the three MoAbs was effectively internalized after binding to the cell surface antigen.

Animals↗

Establishment and characterization of the tumors of chronic lymphocytic leukemia cell line in nude and SCID mice.

A new cell line, designated MO1043, was established from the peripheral blood (PB) of a patient with B-cell chronic lymphocytic leukemia (CLL). Both the PB leukemia cells and MO1043 were found to have an abnormal cytogenetic marker of trisomy 12, the most common cytogenetic abnormality in CLL. In addition, both the PB cells and MO1043 expressed a cell surface phenotype of typical B-CLLs. The MO1043 was efficiently transplanted into X-irradiated athymic nude mice by i.p. inoculation after it was subjected to serial passages in new born (1 week old) and irradiated adult nude mice. The tumor of a CLL cell line (termed CLL tumor) was also generated in the nude mice by s.c. inoculation of the cells. The MO1043 was inoculated i.p. into mice with severe combined immunodeficiency (SCID) which had not been subject to any preconditionings. The CLL tumor in the non-conditioned SCID mice was disseminated to various tissues in a manner more analogous to CLL tumors in patients as compared with nude mice, where the CLL tumors were not as widely disseminated. At each of four different tumor doses, i.e. 2 x 10(6), 6 x 10(6), 1.8 x 10(7) and 5.4 +/- 10(7) cells of MO1043, the transplantability was 100%. Titration experiments revealed a reciprocal relationship between survival and the number of tumor cells inoculated. FACS analysis showed that several cell surface markers of the parental MO1043 were maintained in CLL tumors from nude and SCID mice. Fluorescence in situ hybridization with novel DNA probes demonstrated that CLL tumors of both nude and SCID mice maintained trisomy 12. The CLL tumor models developed here, particularly the SCID mouse model, may be very useful for therapeutic studies of CLL.

Aged↗

Antigenic expression of B-cell chronic lymphocytic leukemic cell lines.

A flow cytometric analysis of five B cell chronic lymphocytic leukemic (B-CLL) cell lines was undertaken using 129 unknown reagents from the blind panel (BP) and 72 reagents from the known CD panel obtained from the Fourth International Leucocyte Differentiation Conference and Workshop, B cell section (Vienna, 1989). The five cell lines examined were: SeD (PNAS 75, 5706, 1978), B-CLL-LCL (BLOOD 71, 9, 1988), JVM-HH and JVM-2(INT J CAN 38, 531, 1986), and WR#1 (TH and BD). The reagents were #1-129 (blinded panel) and reagents 1-44 and 53-84 (CD panel with CD23 reagents missing). Positivity was defined as greater than 30% of the cells having a three fold increase or more in mean channel fluorescence. Fourty-three reagents of the blinded panel were negative by these criteria while all remaining reagents were positive on all five lines. SeD showed the lowest reactivity; B-CLL-LCL and JVM-2 showed the most reactivity; JVM-HH and WR#1 were intermediate. The known CD panel confirmed the reactivity of the blinded panel. An average immunophenotype was constructed and compared to published normal EBV lymphoblastoid cell lines and several differences were noted. There was an absence or significant decrease in the expression of CD19, CD21, CD22 and CD37 while there was an increased expression of CD38, CD54, CD74 and CD76. The heterogeneity observed between the B-CLL lines may in part be due to polymorphisms but is more likely to represent the underlying heterogeneity seen in common and familial B-CLL.2+öff

Antigens, CD↗

Clinical significance of monoclonal proteins in chronic lymphocytic leukemia.

Serum monoclonal proteins were found in 36 of 111 (32%) chronic lymphocytic leukemia (CLL) patients studied using high-resolution agarose gel electrophoresis combined with immunofixation. In contrast, using immunoelectrophoresis (IEP) and serum protein electrophoresis (SPEP), monoclonal proteins were found in 20 and 4% of CLL patients, respectively. The presence of a monoclonal protein was associated with a median survival of 63 months compared to 103 months for individuals without a monoclonal spike (p < 0.012). This was independent of clinical stage. The data also suggests that the presence of a monoclonal protein may define a group of patients at greater risk for disease progression in the low and intermediate risk groups. (Rai stages, 0, I, II). Further follow-up will be required to determine if this is statistically significant.

Blood Proteins↗

[The use of 6-flavor Rehmannia decoction with additives in the prevention of ototoxic deafness induced by gentamicin in guinea pigs].

The purpose of this study is to discuss the effects of the Chinese medicine six-flavor Rehmannia Decoction with additives on preventing deafness induced by gentamicin (GM) in guinea pig by means of testing the thresholds of Preyer's reflex (PR) cochlear microphonic potential (CM), action potential of the auditory nerve (N1) and scanning electron microscope of inner ear (SEM). The results showed that the medicine is effective in reducing the ototoxic effect of GM on inner ear.

Action Potentials↗