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Biomedical subjects

L Liu

Publications and source records attributed to L Liu.

1,367 records · Page 76Linked to original sources
PubMedDate not supplied

Expression of p73 in colorectal carcinoma: clinicopathological relevance.

p73 gene expression and its correlation with clinicopathological variables were examined in 92 patients (53 male, 39 female; age range 38 - 89 years) with colorectal carcinoma. Gene expression was determined by immunohistochemical analysis of resected formalin-fixed and paraffin-embedded carcinoma specimens. When p73 staining of each specimen was divided into two modes (small expression, 0-50% and large expression, > 50%), small expression of p73 was obtained in most cases. Tumour, grade, stage, site and size did not correlate with the mode of expression, but tumour recurrence differed according to mode. Expression of p73 was also related to prognosis: large expression indicated a shorter survival period. Our findings suggest that p73 expression plays a role in inducing tumour recurrence, and that analysis of the expression is useful in evaluating the clinical course of colorectal carcinoma post-surgery.

Adult↗
PubMedDate not supplied

Characterization of Bovidae sex-determining gene SRY.

In mammals, testis determination is under the control of the sex-determining gene SRY. This Y-linked gene encodes a protein with a DNA binding domain similar to those found in high-mobility-group proteins. Here we report the cloning and sequences of the SRY genes of yak and Chinese native cattle. Our data show that SRY genes in Bovidae are less divergent, especially in the coding and 3' regions.

3' Untranslated Regions↗
PubMedDate not supplied

Preparation and characterization of liposome-encapsulated haemoglobin by a freeze-thaw method.

Haemoglobin (Hb) was encapsulated into liposomes as a blood substitute by a freeze-thaw method. The encapsulation efficiency was affected by the Hb/lipid ratio, starting Hb concentration, pH and salt concentration. Liposome-encapsulated haemoglobin (LEH) prepared by this method contains 5-10 mM Hb with 4-10 per cent methaemoglobin (Met-Hb), depending on the starting Hb/lipid ratio and Met-Hb content. The encapsulated Hb has the same absorption spectrum as free Hb and shows oxygen-dissociation characteristics similar to normal red blood cells when 2,3-diphosphoglycerate is co-entrapped in the liposomes. LEH exhibited some leakage, which was greatly reduced by sequential extrusions of LEH through polycarbonate membranes (1.0 and 0.45 microns). Stability of LEH was studied using different Hb preparations, and antioxidants of lipids or/and Hb either at 4 or 37 degrees C. alpha-tocopherol or butylated hydroxytoluene, antioxidants of lipids, inhibited not only the peroxidation of liposomes but also Hb oxidation. Among antioxidants of Hb, NADH was most effective in preventing the oxidation of Hb. Glutathione had a moderate preventive effect. However, catalase had no effect and ascorbate accelerated the oxidation of Hb. Glucose and glutathione decreased the oxidation of Hb only in the Hb preparation obtained by hypotonic lysing, not in that by toluene lysing. These results indicate that the Met-Hb reductase system in the latter is lost or inactivated during isolation.

Antioxidants↗
PubMedDate not supplied

Implications of the Systolic Hypertension in China trial.

In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group started to investigate whether active treatment could reduce the incidence of stroke and other cardiovascular complications of isolated systolic hypertension. After stratification for center, sex and previous cardiovascular complications, alternate patients (n = 1253) were assigned nitrendipine 10-40 mg daily, with the possible addition of captopril 12.5-50.0 mg daily, or hydrochlorothiazide 12.5-50.0 mg daily, or both drugs. In 1141 control patients, matching placebos were employed similarly. At entry, sitting blood pressure averaged 170 mm Hg systolic and 86 mm Hg diastolic, age averaged 66 years, and total serum cholesterol was 5.1 mmol/L. At 2 years, the between-group differences were 9.1 mm Hg systolic (95% confidence interval: 7.6-10.7 mm Hg) and 3.2 mm Hg diastolic (2.4-4.0). Active treatment reduced total stroke by 38% (p=0.01), all-cause mortality by 39% (p=0.003), cardiovascular mortality by 39% (p=0.03), stroke mortality by 58% (p=0.02) and all fatal and nonfatal cardiovascular endpoints by 37% (p=0.004). In conclusion, antihypertensive treatment prevents stroke and other cardiovascular complications in older Chinese patients with isolated systolic hypertension. Treatment of 1000 Chinese patients for 5 years could prevent 55 deaths, 39 strokes, or 59 major cardiovascular endpoints.

Aged↗
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Working memory and older adults: implications for occupational therapy.

Atkinson and Shiffrin's (1968) modal model of memory is still commonly used by rehabilitation professionals to evaluate memory impairment in older adults. However, research to date has been unable to indicate that short-term memory declines with age. These findings have led some rehabilitation professionals to mistakenly conclude that short-term memory is not affected by the aging process. This article reviews both the traditional concept of short-term memory, as outlined by Atkinson and Shiffrin, and the more recent conceptualization of short-term memory in terms of Baddeley and Hitch's (1974) model of working memory. The implications of the concept of working memory has implications for occupational therapy interventions for older adults. For example, clients with dementia may experience difficulties in performing tasks that require drawing inferences. Similarly, language that contains vague references may present problems for these clients. In addition, changes in working memory in older adults suggest that they may experience difficulties with medication management and what Rule, Milke, and Dobbs (1992) called wayfinding. Therefore, evaluations of working memory would provide a better indication of older adults' memory performance than the modal model.

Aged↗
PubMedDate not supplied

Drosophila mushroom bodies are dispensable for visual, tactile, and motor learning.

A total of 18 associative learning/memory tests have been applied to Drosophila melanogaster flies lacking mushroom bodies. Only in paradigms involving chemosensory cues as conditioned stimuli have flies been found to be compromised by a block in the mushroom body pathway. Among the learning tasks not requiring these structures are a case of motor learning (yaw torque/heat), a test of the fly's spatial orientation in total darkness, conditioned courtship suppression by mated females, and nine different examples of visual learning. The latter used the reinforcers of heat, visual oscillations, mechanical shaking, or sucrose, and as conditioned stimuli, color, intensity contrast, as well as stationary and moving visual patterns. No forms of consolidated memory have been tested in mushroom body-less flies. With respect to short-term memory the mushroom bodies of Drosophila are specially required for chemosensory learning tasks, but not for associative learning and memory in general.

Animals↗
PubMedDate not supplied

New cytotoxic agents for the treatment of metastatic malignant melanoma: temozolomide and related alkylating agents in combination with guanine analogues to abrogate drug resistance.

The chloroethylating nitrosoureas (lomustine, fotemustine, cystemustine (BCNU) and methylating agents temozolomide (TMZ), dacarbazine (DTIC), procarbazine) have documented activity in metastatic malignant melanoma with single agent response rates of 15-25%. Chloroethylating agents form chloroethyl adducts at the O6 position of guanine, resulting in N1-guanine, N3-cytosine interstrand crosslinks which are cytotoxic. Methylating agents attack DNA at multiple sites, although most of their cytotoxic activity is due to the formation of methyl adducts at the O6 position of guanine. The presence of these adducts results in a futile recycling of the mismatch repair pathway resulting in DNA strand breaks and apoptotic cell death. An intact mismatch repair system is required to achieve their cytotoxic effect. Repair of adducts by the DNA repair protein O6-alkylguanine DNA alkyltransferase (AGT) impairs the cytotoxic action of both methylating and chloroethylating agents, and mediates a major resistance pathway to these drugs. During DNA repair, irreversible inactivation of AGT occurs. To regenerate AGT activity, synthesis of new molecules is required. Increased but variable AGT activity is found in malignant melanoma, is higher in metastatic lesions than in primary tumours, and is higher in tumours than normal skin. Expression of AGT activity, is higher in melanoma metastases after DTIC chemotherapy compared to expression prior to therapy. TMZ alone depletes human AGT in tumour tissue and peripheral blood progenitor cells. As the t1/2 of TMZ via the oral route is short (approximately 1.8 hours), and the anti-tumour activity of the drug is known to be schedule-dependent, twice daily or prolonged administration schedules of TMZ prevent regeneration of AGT, and render tumour cells more sensitive to the drug. O6-benzylguanine (BG) is a potent AGT inactivating agent. BG and its analogues reduce AGT activity, and increase the in vitro and in vivo efficacy of both methylating and chloroethylating agents. In clinical trials, non-toxic doses of BG deplete AGT to undetectable levels. AGT depleting agents in combination with methylating and chloroethylating agents are now in clinical testing, and may result in greater clinical efficacy in metastatic malignant melanoma.

Animals↗
PubMedDate not supplied

The constitutive production of colony stimulating factor 1 by invasive human breast cancer cells.

Colony Stimulating Factor 1 (CSF-1) and its receptor, the c-fms proto-oncogene product, are expressed in normal and malignant tissues. The many actions of CSF-1 include induction of urokinase-type plasminogen activator (uPA), a serine protease involved in extracellular matrix degradation. To explore the role of CSF-1 in breast cancer progression, we evaluated the expression of CSF-1, c fms, and uPA in human breast cancer cell lines well-characterized for differing degrees of invasive, metastatic capability. The more invasive cell lines expressed elevated levels of CSF-1 by Northern analysis and ELISA. Increased uPA expression was noted in these same cell lines. CSF-1 receptor mRNA transcripts and protein were demonstrable in the different cell lines. These data suggest a role for CSF-1 in the autocrine and paracrine regulation of tumor progression in breast cancer.

Blotting, Northern↗
PubMedDate not supplied

Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis.

During the spermatid elongation stage of spermiogenesis approximately 85% of sperm nuclear histones are replaced by protamines. Protamines increase the packing ratio of sperm chromatin, presumably facilitating sperm motility and function. In this study we evaluated the incidence of abnormal protamine expression in 75 patients undergoing in vitro fertilization (IVF) and 50 donors of known fertility by isolation of sperm nuclear proteins, quantitative gel electrophoresis, and Western blot analysis. In addition, we evaluated the relationship between abnormal protamine expression and semen quality, sperm penetration ability, chromatin stability, and IVF outcome. Seventeen percent (13/75) of IVF patients had no measurable protamine 2 (P2) versus 0% (0/50) of donors of known fertility (P < .005). Sperm penetration rates were decreased in 12 of 13 patients without P2, and mean penetration rates (4.6 +/- 1.2 vs 32.8 +/- 2.9, P < .005), normal morphology (22.4 +/- 3.6 vs 48.7 +/- 4.2, P < .05), and progressive motility (22.3 +/- 2.5 vs 35.4 +/- 2.1, P < .05) were all significantly decreased compared with patients with measurable P2. The mean sperm concentration was not significantly different. The presence of protamine precursor bands was also associated with a diminished penetration capacity (18.4 +/- 2.8 vs 36.7 +/- 3.0, P < .05). Sperm chromatin decondensation following exposure to heparin sulfate was significantly increased in patients without a measurable P2 band. Twelve patients with no measurable P2 underwent intracytoplasmic sperm injection (ICSI), with 6 patients (6/12, 50%) becoming pregnant. ICSI fertilization and subsequent embryo cleavage were not different in patients without P2 compared with other patients undergoing ICSI. These data indicate that abnormal sperm protamine levels are a common defect in infertility patients, but not in donors of known fertility. It appears that abnormal protamine levels may reflect defects of late spermiogenesis, including sperm penetration capacity.

Anticoagulants↗
PubMedDate not supplied

Effects of danazol on thrombopoiesis in rats.

A synthetic analog of ethinyltestosterone, Danazol, has been used clinically for the treatment of immune thrombocytopenia. We investigated the effects of Danazol on thrombopoiesis in normal rats. Though 4-week treatment by Danazol slightly enhanced the DNA synthesizing enzyme activities and the number of S-phase cells in bone marrow and spleen, the number of megakaryocytes and thrombocytes were not increased in bone marrow and peripheral blood, respectively. These findings suggest that Danazol treatment will not induce thrombosis with thrombocytosis in normal human beings and animals.

Animals↗
PubMedDate not supplied

Risk factor awareness: a randomized telephone survey of public knowledge.

Health educators are often faced with the dilemma of developing materials or programs that begin at a level appropriate to the needs of individuals or the population as a whole. In 1992, a randomized telephone survey of the public's knowledge of risk factors relating to stroke was conducted in Saskatoon. The risk factors most frequently identified were poor diet (40%), hypertension (36%) and stress (36%). Respondents with a family history of stroke were significantly more likely to identify hypertension as a risk factor than those without such a history and significantly less likely to identify stress as a risk factor. In all, 24% reported a family history of acute myocardial infarction, and 28% reported a family history of stroke. Eighty percent were willing to learn more about the risk factors, and 88% were willing to make the appropriate lifestyle changes to reduce their risk of an event. Assessment of public knowledge can help in planning initiatives directed at prevention, early identification and appropriate referral.

Adolescent↗
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Effects of 5-fluorouracil derivatives on papillomas induced by application of 7,12-dimethylbenz(a)anthracene in mice.

We examined the effects of an application of 5-fluorouracil (5-FU) ointment and a chronic oral administration of 1-(2-tetrahydrofuryl)-5-FU plus uracil (UFT) on 7,12-dimethyl-benz(a)-anthracene-induced squamous cell papillomas in mice. Although application of 5-FU ointment reduced the growth of papillomas slightly, chronic oral administration of UFT could prevent tumorigenesis and suppress the growth of papillomas, resulting in the reduction of the tumorous viability and DNA synthesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Metabolic disposition of simvastatin in patients with T-tube drainage.

A study to investigate the disposition and biliary excretion of simvastatin (SV) was conducted in four cholecystectomy patients with T-tube drainage. Each patient received a single oral dose of 100 mg of [14C]SV (20 microCi). Of the 14C-labeled dose, approximately 35% was excreted in urine, 25% in bile, and 20% in feces. Thus, at least 60% of the oral dose was absorbed from the gastrointestinal tract. Of the AUC for radioactivity in plasma, 13% was contributed by the HMG-CoA reductase inhibitors. In addition, only 2% of the 14C-dose was eliminated in urine as HMG-CoA reductase inhibitors. Thus, most of the SV-related compounds in plasma and urine have little or no HMG-CoA reductase inhibitory activity. The same is probably true for these compounds in bile. Two major active metabolites were present in the bile. Based on HPLC and MS/MS data, they were identified as 6' beta-COOH-SVA and 6'-OH-SVA. In general, the majority of the radioactivity in the bile and urine was excreted within 24 hr postdose. Of the radioactivity excreted in the 0- to 24-hr bile, on average, approximately 30% was contributed by 6' beta-COOH-SVA and 6'-OH-SVA. These two metabolites accounted for the majority of HMG-CoA reductase inhibitory activity in the bile. Little or SV or no SVA was present in the bile.

Adult↗
PubMedDate not supplied

In vitro and in vivo evaluation of carboranyl uridines as boron delivery agents for neutron capture therapy.

The purpose of the present study was to evaluate 2' and 5'-O-(o-carboran-1-ylmethyl)uridine (CBU-2' and CBU-5') as delivery agents for Boron Neutron Capture Therapy (BNCT) of brain tumors. The in vitro cellular uptake, persistence, subcellular distribution and cytotoxicity, and in vivo biodistribution of CBU-2' have been studied as follows. Cellular uptake studies were carried out with the F98 rat glioma, U-87 MG human glioma, B16 melanoma, SP2/0 myeloma and MDCK fibroblasts. All tumor and non-tumor cell lines had high uptake of CBU-2' (46-75 ppm), indicating that uptake was not selective for neoplastic cells and was independent of cell proliferation. In vitro persistence studies showed high cellular retention of CBU-2' compared to sodium borocaptate (BSH), when cells were transferred from boron-containing to boron-free medium and cultured for an additional 24-48 hours. Subcellular fractionation revealed 75.6% of the recoverable boron was cell membrane associated, 15.6% was in the cytosol, and 8.8% was in the nuclear fraction, but no boron was detectable in the RNA and DNA fractions. F98 glioma cells were cultured in the presence of 3 metabolic inhibitors (rotenone, dipyridamole and NBMPR ¿6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine¿) and none of these blocked the cellular uptake of CBU-2' suggesting that uptake was neither energy nor nucleoside transport dependent. In vivo studies in F98 glioma bearing rats showed that CBU-2' in tumor attained concentrations of 8.0 +/- 2.1 micrograms B/g tissue, which was 13 x greater than that in normal brain of the ipsilateral and contralateral cerebral hemispheres (0.6 +/- 0.2 microgram B/g). The B levels, however, were still lower than the minimum 20-35 microgram B/g, which are required for in vivo BNCT. In summary, our in vitro and in vivo data indicate that CBU-2' was not sufficiently selective for in vivo targeting of brain tumors. However, CBU-2' and CBU-5' were highly toxic for F98 glioma cells in vitro (IC50 = 3 - 13 x 10(-5) M), as determined by measuring the uptake of 3H-thymidine, and the survival of F98 glioma cells using a clonogenic assay, which suggests that these compounds should be further evaluated as potential cytoreductive chemotherapeutic agents.

Animals↗
PubMedDate not supplied

Critical evaluation of bispecific antibodies as targeting agents for boron neutron capture therapy of brain tumors.

Boron neutron capture therapy (BNCT) is based on the nuclear capture reaction that occurs when 10B, a stable isotope, is irradiated with low energy neutrons to produce high linear energy transfer (LET) alpha particles and recoiling 7Li nuclei. In order for BNCT to be successful in treating cancer, approximately 10(9) boron atoms must be delivered per tumor cell to sustain a lethal 10B, (n,a) 7Li capture reaction. In the present study, we have produced and characterized a bispecific antibody (BsAbB8), which was reactive with both human glioma and melanoma cell lines, as well as with a variety of polyhedral borane anions (PBA). The affinity constants (KA) of BsAb-B8 with D-54 MG and M21 cells were 3.49 and 2.57 x 10(8) M-1, respectively, which were almost identical to those of the parental mAb 9.2.27 with these cell lines. In vivo tumor localizing properties were studied in nude mice bearing subcutaneous xenografts of the D-54 MG glioma. Following intravenous injection of 131I-labeled BsAb-B8, 3.4 +/- 0.2% of the injected dose/g was detected in the tumor at 24 hours, and then slowly declined to 2.0 +/- 0.4% at 96 hours compared to 1.34 +/- 0.07% and 0.03 +/- 0.01%, respectively, for normal mouse IgG. Based on the assumption that all the tumor cell antigenic receptor sites could be saturated, the following calculations have been carried out. The maximum concentration of BsAb-B8 that could be delivered to 1 g of D-54 MG glioma cells would be 99.6 micrograms, which could bind 71.7 ng of a PBA. However, since at least 500 x more boron would be required per gram of tumor to sustain a lethal 10B (n,a) 7Li capture reaction, a macromolecule containing -10(3)-10(4) boron atoms rather than a low molecular weight PBA would be required to deliver this amount. Such boron containing macromolecules have been synthesized by us, and future studies should provide information on the feasibility of using them in combination with BsAb-B8 to deliver the requisite amount of 10B.

Animals↗
PubMedDate not supplied

The apurinic/apyrimidinic endonuclease (APE/ref-1) DNA repair enzyme is elevated in premalignant and malignant cervical cancer.

The multifunctional mammalian apurinic/apyrimidinic (AP) endonuclease (APE) is responsible for the repair of AP sites in DNA. In addition, this enzyme has been shown to function as a redox factor facilitating the DNA-binding capability of JUN and FOS, HeLa AP-1, and numerous other transcription factors, including Myb, members of the CREB family and nuclear factor-kappa B. Although previously presumed to be ubiquitously expressed at comparable levels in all tissues and cell types, recent evidence has shown APE to vary significantly in its expression between tissues and even within tissues. To further characterize APE expression at various stages of cervical neoplasia, we investigated the levels of APE protein expression using immunohistochemistry in normal cervix, pre-invasive and invasive squamous lesions of the cervix, as well as in cervical cancer cell lines. We report here that the APE protein is predominantly expressed in the nuclei of cells from both primary tumors and cervical cell lines, but the level of APE protein is significantly and dramatically elevated in cervical cancer tissue. These results implicate the use of anti-APE antibodies as an effective reagent in the early detection of premalignant and malignant cancer of the cervix. These findings are suggestive that the increase of a DNA repair enzyme in cancerous cells may allow these cells to be refractive to chemotherapy.

Antibody Specificity↗