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Biomedical subjects

Z Han

Publications and source records attributed to Z Han.

At least 73 records · Page 4Linked to original sources

Modulation of 9-nitrocamptothecin-induced apoptosis by hyperthermia in human leukemia HL-60 cells.

We have investigated whether hyperthermia (HT) treatment at 43 degrees C for 15-60 min can affect the extent of apoptosis induced in human leukemia HL-60 cells by the anticancer drug 9-nitrocamptothecin (9NC). Quantitative changes in the apoptotic (Ap) fraction in the cell cultures were monitored by flow cytometry. The results showed that (i) heating for 15 min prior to or concurrently with 9NC exposure had no effect on the Ap fraction generated by the drug alone, whereas 60 min heating resulted in an increase in the Ap fraction; and (ii) heating of the cells at 6-24 h after exposure to the drug enhanced the Ap fraction. These results indicate that appropriate scheduling of HT and 9NC treatments may lead to thermochemotherapy protocols that will result in increased 9NC-induced death of human leukemia cells.

Antineoplastic Agents↗

Fast relaxation of a hexagonal Poiseuille shear-induced near-surface phase in a threadlike micellar solution.

The dynamics of near-surface conformations in complex fluids under flow should dramatically affect their rheological properties. We have made the first measurements resolving the decay kinetics of a hexagonal phase induced in a threadlike polyionic micellar system under Poiseuille shear near a quartz surface. Upon cessation of shearing flow, this minimum interference crystalline phase formed within approximately 20 microm of the surface "melts" to a metastable two-dimensional liquid of aligned micelles in approximately 0.7 s. This is some three orders of magnitude shorter than the time required for bulk (Couette) shear-aligned micelles in this system to reach a fully entangled state.

Journal Article↗

Propionate and butyrate esters of camptothecin and 9-nitrocamptothecin as antileukemia prodrugs in vitro.

Six camptothecin (CPT) alkyl esters and four 9-nitrocamptothecin (9NC) alkyl esters were assayed for ability to inhibit proliferation and induce programmed cell death (apoptosis) in human leukemia HL-60 and U-937 cells, which exhibit differential sensitivity to CPT and 9NC. In general, CPT-propionate and CPT-butyrate demonstrated activities, while the other esters were practically inactive. Similarly, 9NC-propionate and 9NC-butyrate were active, while the other 9NC esters exhibited little or no activity. The biologically active esters required metabolic conversion (i.e., de-esterification) to their parental compounds as demonstrated by the conversion of CPT-propionate to CPT in mouse liver homogenate, and the topoisomerase I-inhibition assay. In conclusion, the propionate and butyrate esters of CPT and 9NC are CPT and 9NC prodrugs, that can develop to important chemotherapeutic agents for the effective treatment of human leukemias and other malignancies.

Animals↗

Cif (Cytochrome c efflux-inducing factor) activity is regulated by Bcl-2 and caspases and correlates with the activation of Bid.

The cytosolic factor Cif (cytochrome c-efflux inducing factor) was activated by the apoptosis inducers staurosporine and anti-Fas antibodies and rapidly induced the efflux of cytochrome c from purified human mitochondria. HL-60 cells that stably overexpressed a bcl-2 cDNA transgene (Bcl-2:HL-60 cells) contained mitochondria and a cytosol that were resistant to exogenous Cif and that lacked detectable endogenous Cif activity, respectively. Therefore, Bcl-2 overexpression negated Cif activity and suggested that the requirement for Cif resides upstream of Bcl-2 on the apoptotic signal transduction pathway. The addition of purified caspase 3, caspase 7, or caspase 8 to the cytosolic extract from Bcl-2:HL-60 cells, however, restored Cif activity, demonstrating that the inhibition of Cif by Bcl-2 overexpression could be overcome by activated caspases. Moreover, the addition of purified caspases to cytosolic extracts prepared from parental HL-60 cells was also sufficient to cause Cif activation, suggesting that caspases might be required for Cif activation. Consistent with these observations, Fas-induced apoptosis in Jurkat cells resulted in caspase 8 activation and subsequently in activation of Cif. Finally, we demonstrate that the activation of Cif correlated with the activation of the Bcl-2 family member Bid by caspases and that Cif activity was selectively neutralized by anti-Bid antibodies. Taken together, these results indicate that Cif is identical to Bid and that it can be inhibited by Bcl-2 and activated by caspases. Thus, Cif (Bid) is an important biological regulator for the transduction of apoptotic signals.

Apoptosis↗

Metabolic and genetic determinants of HDL metabolism and hepatic lipase activity in normolipidemic females.

The metabolic and genetic determinants of HDL cholesterol (HDL-C) levels and HDL turnover were studied in 36 normolipidemic female subjects on a whole-food low-fat metabolic diet. Lipid, lipoprotein, and apolipoprotein levels, lipoprotein size, and apolipoprotein turnover parameters were determined, as were genetic variation at one site in the hepatic lipase promoter and six sites in the apolipoprotein AI/CIII/AIV gene cluster. Menopause had no significant effect on HDL-C or turnover. Stepwise multiple regression analysis revealed that HDL-C was most strongly correlated with HDL size, apolipoprotein A-II (apoA-II), and apolipoprotein A-I (apoA-I) levels, which together could account for 90% of the variation in HDL-C. HDL size was inversely correlated with triglycerides, body mass index, and hepatic lipase activity, which together accounted for 82% of the variation in HDL size. The hepatic lipase promoter genotype had a strong effect on hepatic lipase activity and could account for 38% of the variation in hepatic lipase activity. The apoA-I transport rate (AI-TR) was the major determinant of apoA-I levels, but AI-TR was not associated with six common genetic polymorphism in the apoAI/CIII/AIV gene cluster.A simplified model of HDL metabolism is proposed, in which A-I and apoA-II levels combined with triglycerides, and hepatic lipase activity could account for 80% of the variation in HDL-C.

Adult↗

Jun N-terminal kinase in rheumatoid arthritis.

Potential mechanisms of joint destruction in rheumatoid arthritis (RA) were examined by studying the regulation of mitogen-activated protein kinases and collagenase gene expression in fibroblast-like synoviocytes (FLS). The three main mitogen-activated protein kinase families [p38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases (ERKs)] were constitutively expressed in RA and osteoarthritis (OA) FLS. p38 and ERK1/2 were readily phosphorylated in both RA and OA FLS after interleukin-1 (IL-1) stimulation. JNK was phosphorylated in RA FLS but not OA FLS after IL-1 stimulation. Reverse transcription-polymerase chain reaction studies suggested that JNK2 is the major isoform of the JNK family expressed by FLS. Northern blot analysis of collagenase gene expression demonstrated that RA FLS contained significantly more collagenase mRNA than OA FLS after IL-1 stimulation. The roles of JNK and p38 kinase were evaluated with the p38/JNK inhibitor SB 203580. Low concentrations of SB 203580 (1 microM, a concentration that only inhibits p38) had no significant effect on IL-1-induced collagenase expression in RA FLS whereas 25 microM (which inhibits p38, JNK2, and c-raf) blocked collagenase mRNA accumulation. IL-1-stimulated AP-1 binding was also inhibited by 25 microM SB 203580 in RA FLS. These studies suggest that OA and RA FLS have a different pattern of JNK phosphorylation, which might lead to enhanced collagenase gene expression in RA.

Arthritis, Rheumatoid↗

[Genetic complementation group analysis of xeroderma pigmentosum patients in China].

OBJECTIVE: To establish skin fibroblast cell strains derived from Chinese xeroderma pigmentosum(XP) patients and to analyze the genetic complementation group and distribution. METHODS: From four XP patients, skin fibroblast cell strains were derived and used for the complementation group analysis by autoradiography and cell-fusion technique. RESULTS: Of the four XP patients from apparently independent families, three were assigned to group C, and one belonged to group E. This is the first report on XP-E patient in China. CONCLUSION: Based on the data from the previous 7 cases and the present 4 cases, the distribution of complementation group in Chinese XP patients known at present is: nine XP-C, one XP-F and one XP-E. Although the number of cases is still limited, XP-C appears to be more frequent in China. This forms a marked contrast to Japanese XP patients, who are dominated by XP-A with infrequent presence of XP-C.

Adolescent↗

Study on pottical type, palmar and plantar digital formulae, hand clasping, arm folding, handedness, leg folding and stride type in the Daur population, China.

The pottical type, palmar and plantar digital formulae, hand clasping, arm folding, handedness, leg folding and stride type have been investigated on a sample of 143 male and 160 female students of the Daur population of Molidawa Banner, Inner Mongolia. The results of this study are the following: 1. the frequency of the hyperextensive pottical type is 49.17%, the relative length of index over annularis 12.21%, right hand clasping 45.87%, right arm folding 49.50%, right handedness 94.39%, right leg folding 72.28% and right stride type 44.88%, 2. pottical type, hand clasping, handedness, leg folding and stride type do not show significant sex differences, 3. there are some relations between hand clasping and arm folding as well as between arm folding and stride type, 4. compared with other population groups, the Daur population shows a low frequency of right hand clasping, a moderate frequency of right arm folding and a low frequency of left handedness.

Adolescent↗

[The hemoprotective effect of platelet factor 4 (PF4) and tetrapeptide AcSDKP].

OBJECTIVE: To study the effects of platelet factor 4(PF4) and tetrapeptide N-acetyl-Ser-Asp-Lys-Pro(AcSDKP) on hemopoietic progenitors in mice treated with 5-Fluorouracil (5-FU). METHODS: Mice were injected with PF4 (40 micrograms/kg) or AcSDKP (4 micrograms/kg) twice at 6 h intervals, and 20 h after the second injection they were given one injection of 5-FU (150 mg/kg), and the high proliferative potential-colony forming cell (HPP-CFC), burst-forming unit erythroid (BFU-E), colony forming unit megakaryocyte (CFU-MK), and megakaryocyte (MK) were examined 6, 8 and 13 days later. RESULTS: The administration of PF4 or AcSDKP resulted in a significant increase of the number of HPP-CFC on days 6-8 and BFU-E and CFU-GM on day 8 when compared to 5-FU alone. Furthermore, PF4 was found to increase significantly the number of CFU-MK and MK on day 8, which was not observed with AcSDKP. CONCLUSION: PF4 or AcSDKP accelerate the recovery in vivo of HPP-CFC, CFU-GM and BFU-E after 5-FU treatment but their effect may be different on megakaryocytic progenitors. Both molecules may have a hemoprotective effect against chemotherapeutic agents.

Animals↗

[Increased release of orphanin FQ (OFQ) in brain of chronic morphine tolerant rats].

The changes in OFQ-immunoreactivity (OFQ-ir) content and release of cerebroventricular perfusate, periaqueductal gray (PAG) and amygadala of chronic morphine tolerant rats were measured with radioimmunoassay (RIA). The results indicate: (1) chronic morphine tolerance was achieved in rats by injecting increasing doses of morphine (10, 20, 40, 50, 60 mg/kg, s.c., tid). The content of OFQ-ir in cerebroventricular perfusate in the rats of normal saline (NS) group remained at a steady level during the injections from d 1 to d 5, while in the morphine-treated group of rats the content of OFQ-ir showed 25% increase (P < 0.05 vs NS) and 52% increase (P < 0.01 vs NS) after 3 and 5 days' morphine injection respectively. (2) The content of OFQ-ir in PAG of rats receiving morphine injection for 1, 3 and 5 days showed respectively increases of 17% (P < 0.05), 48% (P < 0.05) and 80% (P < 0.01) against the NS group. (3) The content of OFQ-ir in rat amygdala receiving 1 day injection of morphine showed a 8% decrease, which was not significantly different from NS group. However, there was a 36% and 55% (P < 0.05) increase respectively after injection for 3 and 5 days. It is suggested that in the later stage of chronic morphine treatment, large amount of OFQ was released from rat brain to antagonize the effect of opioids, which may play an important role in the development of morphine tolerance.

Amygdala↗

[Heparin enhances the stimulating effect of thrombopoietin on megakaryocytopoiesis].

OBJECTIVE: To verify whether heparin could enhance the stimulating effect of Tpo on megakaryocytopoiesis. METHODS: Megakaryocytic leukemia cell line M07e, human cord blood CD34+ cells and BALB/c mice were used in this study. The effects of heparin and/or Tpo on megakaryocytopoiesis were studied by [3H]-TdR incorporation assay, CFU-MK plasmic semi-solid culture and in vivo experiment in BALB/c mice. RESULTS: Heparin could enhance the stimulating effect of Tpo on stimulating the proliferation of M-07e, the growth of CFU-MK from human cord blood CD34+ cells and in vivo megakaryocytopoiesis in mice. CONCLUSION: Heparin participates in positive regulation of megakaryocytopoiesis by enhancing the megakaryocytopoietic activities of Tpo.

Animals↗

[Type IV collagen and C-erbB-2 expression in oral candidal leukoplakia].

OBJECTIVE: To investigate type IV collagen and C-erbB-2 expression in oral candidal leukoplakia. METHODS: 27 cases of oral candidal leukoplakia were studied by immunohistochemistry. RESULTS: In normal and simple hyperplastic epithelia type IV collagen was noted as brown linear staining along the basement membrane. The most obvious change in the staining pattern was that the linear staining became very thin or discontinued in dysplastic epithelia. C-erbB-2 was demonstrated in 25 cases(78%). The positive staining, as a reticular pattern, was located at cell membrane, and not correlated with epithelial dysplasia. CONCLUSION: The results indicate that type IV collagen expression changed in candidal leukoplakia with epithelial dysplasia. This kind of change may be related to basement membrane destruction. The immunohistochemically expression of C-erbB-2 has no correlation with epithelial dysplasia.

Candidiasis, Oral↗

[Arthrocentesis and lavage of TMJ for the treatment of anterior disc displacement without reduction].

OBJECTIVE: To evaluate the clinical efficacy of the TMJ arthrocentesis and lavage as a treatment for anterior disc displacement without reduction of the TMJ. METHODS: 38 patients with limited mouth opening caused by anterior disc displacement without reduction were treated by using TMJ arthrocentesis and lavage. Clinical data including pain and mandibular motion were collected and then analyzed. Arthrography was used to evaluate disc position. RESULTS: The mandibular motion had increased significantly (P < 0.001) at different period of time, especially within 1 month. Jaw pain had also significantly improved (P < 0.01). Arthrography revealed that most of the TMJs studied had persistent anterior disc displacement with only 2 patients demonstrating a "reduced disc". CONCLUSION: Arthrocentesis and lavage is effective in reducing pain and increasing mandibular motion in patients with anterior disc displacement without reduction, especially in patients the duration of symptoms being less then 6 months. It is recommended as a simple alternative to more invasive TMJ procedures.

Adolescent↗

[Effect of immunologic treatment on lymphocyte subsets in patients with myasthenia gravis].

OBJECTIVE: To study the abnormalities of cellular immunity of myasthenia gravis (MG) and the effects of glucocorticoid (GC) therapy and thymectomy on lymphocyte subsets in patients with myasthenia gravis. METHODS: Phenotypic analysis of peripheral blood lymphocyte in 39 patients with MG and 18 healthy controls were completed using flow cytometry and immunofluorescence double-staining methods; changes of lymphocyte subsets were studied in 15 of the MG patients after GC therapy and 7 of the MG patients after thymectomy. RESULTS: (1) The percentage of pan-T (CD(+)(5)), pan-B (CD(+)(19)), traditional B cell, CD(+)(4)T cell in patients with MG did not significantly differ from that in healthy controls. An increase in CD(+)(8) cell was observed in MG patients as compared with normal controls. Among the CD(+)(4) T lymphocyte subsets, there was significant decrease of the percentage of CD(+)(4) CD(45)RA(+) (suppressor-inducer) and increase of the percentage of CD(+)(4) CD(45)RA(-) (helper-inducer) subsets in MG patients than controls; the percentage of CD(+)(5) B cell was significantly increased in MG patients as compared with that in healthy controls. (2) After GC therapy, the percentages of pan-T (CD(+)(5)), pan-B (CD(+)(19)), traditional B cell, CD(+)(4) T cell, CD(+)(8) T cell, CD(+)(4) CD(45)RA(-), CD(+)(5) B cell decreased. (3) After thymectomy, the proportions of T, B lymphocyte subsets did not change significantly. CONCLUSION: Not only changes of T cell subsets (CD(+)(4) and CD(+)(8) T lymphocyte subsets) were shown, but also there were abnormal changes of functional CD(+)(4) T lymphocyte subsets and CD(+)(5) B lymphocyte which may play an important role in the pathogenesis of MG. There is comprehensive inhibiting action of GC on cellular immunity in MG patients, while there is no such effect with thymectomy on the lymphocyte subsets in MG patients.

Adolescent↗

[Fatal side-effects of all-trans retinoic acid in the treatment of acute promyelocytic leukemia].

Of 82 patients with acute promyelocytic leukemia (APL) who were treated with all-trans retinoic acid (ATRA), 35 developed leukocytosis and 22 fatal side-effects(15 with retinoic acid syndrome and 7 intracranial bleeding). There was a high mortality in the patient with fatal side-effects. The relationship between leukocytosis and fatal side-effects was analyzed and the effect of therapeutic interventions on the development and prognosis of the fatal side-effects was investigated. The results showed that leukocytosis was a risk factor of the development of fatal side-effects in APL treated with ATRA. ATRA combined with small dose of harringtonin in treating APL can reduce the incidence of intracranial bleeding resulted from leukocytosis and corticosteroid can decrease the mortality of retinoic acid syndrome.

Adolescent↗

[PCR in combination with silver as a method for the determination of apolipoprotein E alleles].

OBJECTIVE: To present a rapid, sensitive and safe procedure for the determination of human apolipoprotein E alleles. METHODS: Genomic DNA was extracted from 0.5ml whole blood by a non-phenol protocol. After PCR and restriction enzyme digestion,short DNA fragments were detected by a simplified silver staining method. This technique was used to assay apolipoprotein E alleles in 19 patients with sporadic Alzheimer's disease and 41 normal aged persons. RESULTS: The short DNA fragments were visualized clearly on polyacrylamide gel processed by silver staining. It took 24 hours from DNA extraction to the final result. The A4 allele frequency in patients with sporadic Alzheimer's disease was 0.29, much higher than that in control group (0.02, P<0.001). CONCLUSION: PCR in combination with silver staining can satisfy the need for high-resolution and high-efficiency in the determination of apolipoprotein E alleles and can be used as a routine procedure in clinical and epidemiological investigations.

Alleles↗

The role of keratin filaments during nuclear envelope reassembly in Xenopus egg extracts.

We report here a new structure, named 'strings-of-pearls', which are seen to form in Xenopus egg extracts after incubation, as 200 nm membrane vesicles attach to 10 nm filaments. These membrane vesicles fuse together along the filaments to form annulate lamellae (AL) or attach to demembranated sperm chromatin to initiate assembly of a nuclear envelope. Immunoassay with anti-keratin antibodies AE3 showed that the filaments were mainly composed of a 56 kDa keratin-like protein. Addition of AE3 to the extracts resulted in inhibition of AL formation and defective assembly of NE. These results suggest a function of keratins in the assembly of nuclear envelopes during Xenopus development.

Animals↗

Regulation of aquaporin-4 water channels by phorbol ester-dependent protein phosphorylation.

The molecular mechanisms for regulating water balance in many tissues are unknown. Like the kidney, the eye contains multiple water channel proteins (aquaporins) that transport water through membranes, including two (AQP1 and AQP4) in the ciliary body, the site of aqueous humor production. However, because humans with defective AQP1 are phenotypically normal and because the ocular application of phorbol esters reduce intraocular pressure, we postulated that the water channel activity of AQP4 may be regulated by these agents. We now report that protein kinase C activators, phorbol 12,13-dibutyrate, and phorbol 12-myristate 13-acetate strongly stimulate the phosphorylation of AQP4 and inhibit its activity in a dose-dependent manner. Phorbol 12,13-dibutyrate (10 microM) and phorbol 12-myristate 13-acetate (10 nM) reduced the rate of AQP4-expressing oocyte swelling by 87 and 92%, respectively. Further, phorbol 12,13-dibutyrate significantly increased the amount of phosphorylated AQP4. These results demonstrate that protein kinase C can regulate the activity of AQP4 through a mechanism involving protein phosphorylation. Moreover, they suggest important potential roles for AQP4 in several clinical disorders involving rapid water transport such as glaucoma, brain edema, and swelling of premature infant lungs.

Animals↗