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Biomedical subjects

R Zhang

Publications and source records attributed to R Zhang.

At least 145 records · Page 8Linked to original sources
PubMed2000

Formulation optimization technique based on artificial neural network in salbutamol sulfate osmotic pump tablets.

The aim of this study was to develop a formulation optimization technique in which an artificial neural network (ANN) was incorporated; 30 kinds of salbutamol sulfate osmotic pump tablets were prepared, and their dissolution tests were performed. The amounts of hydroxypropyl methylcellulose (HPMC), polyethylene glycol 1500 (PEG1500) in the coating solution, and the coat weight were selected as the causal factors. Both the average drug release rate v for the first 8 hr and the correlation coefficient r of the accumulative amount of drug released and time were obtained as release parameters to characterize the release profiles. A set of release parameters and causal factors was used as training data for the ANN, and another set of data was used as test data. Both sets of data were fed into a computer to train the ANN. The training process of the ANN was completed until a satisfactory value of error function E for the test data was obtained. The optimal formulation produced by the technique gave the satisfactory release profile since the observed results coincided well with the predicted results. These findings demonstrate that an ANN is quite useful in the optimization of pharmaceutical formulations.

Albuterol↗
PubMed2000

Preparation and evaluation of a sustained-release formulation of nifedipine HPMC tablets.

A nifedipine (NF) polyethylene glycol (PEG) solid dispersion was prepared. Using this solid dispersion, NF hydroxypropylmethylcellulose (HPMC) matrix tablets were prepared. Both the high-viscosity grade HPMC (Methocel K15M) and low-viscosity grade HPMC (Methocel K100) were applied in the tablets to form the matrix. The dissolution and absorption of NF from the tablet were evaluated as a formulation that had a sustained release over 24 hr. The Hixson-Crowell equation and Higuchi equation were used to investigate the dissolution mechanism, and the erosion and diffusion codependent mechanism was established. Adalat GITS 30 was used as a reference dosage form. Each beagle dog was also administered an intravenous injection to obtain the pharmacokinetics parameters. The Loo-Riegelman method was applied to study the in vitro/in vivo correlation of the tested tablets and Adalat GITS 30, and significant correlation was proved. Absolute bioavailability and comparative bioavailability of the tested tablet were studied. The results indicated that the NF HPMC tablet could be an ideal 24-hr sustained-release formulation.

Absorption↗
PubMed2000

Gene therapy of established medullary thyroid carcinoma with herpes simplex viral thymidine kinase in a rat tumor model: relationship of bystander effect and antitumor efficacy.

Bystander effect (BSE) refers to killing of cells adjacent to a cell engineered to express a killing gene segment. BSE is considered an important aspect of suicide gene therapy with thymidine kinase. We evaluated the BSE of adenovirus expressing herpes simplex thymidine kinase (AdCMVtk) in rat medullary thyroid carcinomas (rMTC) and three rat thyroid epithelial cancer cell lines using an in vitro BSE assay. In the assay, different proportions of infected and uninfected cells are mixed. Only the proportion of directly infected cells was inhibited in the proliferation assay using rMTC cells. This indicates that there is little BSE in this cell line. One rat thyroid epithelial cancer cell line (RTC-R2) has a high BSE, with BSE index (BSEi) of 7. In the proliferation assay a greater proportion of cells was inhibited than those directly infected. BSE was also evaluated during in vivo tumor growth by subcutaneous injection of mixtures of AdCMVtk infected and uninfected cells. Ganciclovir (GCV) treatment of tumors developing from a 1:1 mixture of infected to uninfected rMTC cells failed to inhibit their growth. In contrast, GCV treatment of a 2:8 mixture of infected to uninfected RTC-R2 cells completely inhibit tumor development, indicating a high BSE. BSE is related to in vivo antitumor efficacy when replication-defective adenovirus AdCMVtk is directly injected into rMTC tumors. After treatment with 100 mg/kg per day of GCV, a growth-retardation effect was observed in small tumors (<100 mm3), but there was little antitumor activity in large tumors (>100 mm3). Our results indicate that there is a good correlation between this in vitro BSE assay and in vivo treatment efficacy. Not all kinds of tumors are suitable for thymidine kinase (TK)/GCV gene therapy because some lack BSE. Methods to improve BSE and/or transduction efficiency are needed in order to obtain an effective therapeutic result. It will be appropriate to test the BSE in human tumor cells before performing clinical trials with current adenoviral vectors expressing TK.

Adenoviridae↗
PubMed2000

Hydraulic permeability of (un)bounded fibrous media using the lattice boltzmann method

Several articles have been written regarding the hydraulic permeability of ordered and disordered fibrous media. Here, we explore wall effects on hydraulic permeabilities for ordered and disordered media using the lattice Boltzmann (LB) simulation method. Simulation results are found to be in excellent agreement with the semi analytic result of Sangani and Acrivos, and simulation results for disordered media are in good agreement with the results of Jackson and James and Higdon and Ford's fcc lattice. The macroscopic behavior, the hydraulic permeability, shows a distinct connection with the geometry of the system. This connection is explored and elucidated for ordered and disordered media. Finally, hydraulic permeabilities for bounded media at various wall separations are presented for both ordered and disordered media and results are compared with hydraulic permeabilities calculated for the unbounded media, and a phenomenological correlation is presented to facilitate rapid prediction of hydraulic permeabilities for both unbounded and bounded fibrous media.

Journal Article↗
PubMed2000

Molecular characterization of the melanin-concentrating hormone/receptor complex: identification of critical residues involved in binding and activation.

A molecular model of the human melanin-concentrating hormone (MCH) peptide was constructed and docked into a helical, bacteriorhodopsin-based model of the recently identified human MCH receptor. From this hormone-receptor complex, potential sites of agonist-receptor interaction were identified, and site-directed mutagenesis was used to substitute residues predicted to reside within the receptor binding pocket. Substitution of Asp(123)(3.32) in the third transmembrane domain of the receptor resulted in a loss of detectable (125)I-MCH binding and of MCH-stimulated Ca(2+) flux; cell surface expression of the mutant receptor was not affected. Arg(11) and Arg(14) of the MCH ligand were identified as potential sites of interaction with Asp(123)(3.32). [Ala(14)]-MCH was equipotent to native MCH in its ability to bind to and activate the wild-type MCH receptor, whereas [Ala(11)]-MCH displayed a 3000-fold reduction in binding affinity and a complete loss of measurable functional activity. Furthermore, [Lys(11)]-MCH and [D-Arg(11)]-MCH displayed reduced affinity for the receptor. [Lys(11)]-MCH was observed to be a partial agonist, eliciting approximately 67% of the native peptide's activity in a Ca(2+) flux assay, and [D-Arg(11)]-MCH was determined to be a functional antagonist with a K(b) valve of 15.8 microM. These data provide evidence that a basic moiety with specific stereochemical requirements at this site is needed for receptor activation. We conclude that both Asp(123)(3.32) in the MCH receptor and Arg(11) in the MCH peptide are required for the formation of the MCH peptide/receptor complex and propose that they form a direct interaction that is critical for receptor function.

Amino Acid Sequence↗
PubMed2000

Virus-specific cofactor requirement and chimeric hepatitis C virus/GB virus B nonstructural protein 3.

GB virus B (GBV-B) is closely related to hepatitis C virus (HCV) and causes acute hepatitis in tamarins (Saguinus species), making it an attractive surrogate virus for in vivo testing of anti-HCV inhibitors in a small monkey model. It has been reported that the nonstructural protein 3 (NS3) serine protease of GBV-B shares similar substrate specificity with its counterpart in HCV. Authentic proteolytic processing of the HCV polyprotein junctions (NS4A/4B, NS4B/5A, and NS5A/5B) can be accomplished by the GBV-B NS3 protease in an HCV NS4A cofactor-independent fashion. We further characterized the protease activity of a full-length GBV-B NS3 protein and its cofactor requirement using in vitro-translated GBV-B substrates. Cleavages at the NS4A/4B and NS5A/5B junctions were readily detectable only in the presence of a cofactor peptide derived from the central region of GBV-B NS4A. Interestingly, the GBV-B substrates could also be cleaved by the HCV NS3 protease in an HCV NS4A cofactor-dependent manner, supporting the notion that HCV and GBV-B share similar NS3 protease specificity while retaining a virus-specific cofactor requirement. This finding of a strict virus-specific cofactor requirement is consistent with the lack of sequence homology in the NS4A cofactor regions of HCV and GBV-B. The minimum cofactor region that supported GBV-B protease activity was mapped to a central region of GBV-B NS4A (between amino acids Phe22 and Val36) which overlapped with the cofactor region of HCV. Alanine substitution analysis demonstrated that two amino acids, Val27 and Trp31, were essential for the cofactor activity, a finding reminiscent of the two critical residues in the HCV NS4A cofactor, Ile25 and Ile29. A model for the GBV-B NS3 protease domain and NS4A cofactor complex revealed that GBV-B might have developed a similar structural strategy in the activation and regulation of its NS3 protease activity. Finally, a chimeric HCV/GBV-B bifunctional NS3, consisting of an N-terminal HCV protease domain and a C-terminal GBV-B RNA helicase domain, was engineered. Both enzymatic activities were retained by the chimeric protein, which could lead to the development of a chimeric GBV-B virus that depends on HCV protease function.

Amino Acid Sequence↗
PubMed2000

Spontaneous fluctuations in cerebral blood flow: insights from extended-duration recordings in humans.

To determine the dependence of cerebral blood flow (CBF) on arterial pressure over prolonged time periods, we measured beat-to-beat changes in mean CBF velocity in the middle cerebral artery (transcranial Doppler) and mean arterial pressure (Finapres) continuously for 2 h in six healthy subjects (5 men and 1 woman, 18-40 yr old) during supine rest. Fluctuations in velocity and pressure were quantified by the range [(peak - trough)/mean] and coefficients of variation (SD/mean) in the time domain and by spectral analysis in the frequency domain. Mean velocity and pressure over the 2-h recordings were 60 +/- 7 cm/s and 83 +/- 8 mmHg, associated with ranges of 77 +/- 8 and 89 +/- 10% and coefficients of variation of 9.3 +/- 2.2 and 7.9 +/- 2.3%, respectively. Spectral power of the velocity and pressure was predominantly distributed in the frequency range of 0.00014-0.1 Hz and increased inversely with frequency, indicating characteristics of an inverse power law (1/f(alpha)). However, linear regression on a log-log scale revealed that the slope of spectral power of pressure and velocity was steeper in the high-frequency (0.02-0.5 Hz) than in the low-frequency range (0.002-0.02 Hz), suggesting different regulatory mechanisms in these two frequency ranges. Furthermore, the spectral slope of pressure was significantly steeper than that of velocity in the low-frequency range, consistent with the low transfer function gain and low coherence estimated at these frequencies. We conclude that 1) long-term fluctuations in CBF velocity are prominent and similar to those observed in arterial pressure, 2) spectral power of CBF velocity reveals characteristics of 1/f(alpha), and 3) cerebral attenuation of oscillations in CBF velocity in response to changes in pressure may be more effective at low than that at high frequencies, emphasizing the frequency dependence of cerebral autoregulation.

Adolescent↗
PubMed2000

Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans.

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.

Adult↗
PubMed2000

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure.

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

Adult↗
PubMed2000

VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain.

VEGF is a secreted mitogen associated with angiogenesis and is also a potent vascular permeability factor. The biological role of VEGF in the ischemic brain remains unknown. This study was undertaken to investigate whether VEGF enhances cerebral microvascular perfusion and increases blood-brain barrier (BBB) leakage in the ischemic brain. Using magnetic resonance imaging (MRI), three-dimensional laser-scanning confocal microscope, and functional neurological tests, we measured the effects of administrating recombinant human VEGF(165) (rhVEGF(165)) on angiogenesis, functional neurological outcome, and BBB leakage in a rat model of focal cerebral embolic ischemia. Late (48 hours) administration of rhVEGF(165) to the ischemic rats enhanced angiogenesis in the ischemic penumbra and significantly improved neurological recovery. However, early postischemic (1 hour) administration of rhVEGF(165) to ischemic rats significantly increased BBB leakage, hemorrhagic transformation, and ischemic lesions. Administration of rhVEGF(165) to ischemic rats did not change BBB leakage and cerebral plasma perfusion in the contralateral hemisphere. Our results indicate that VEGF can markedly enhance angiogenesis in the ischemic brain and reduce neurological deficits during stroke recovery and that inhibition of VEGF at the acute stage of stroke may reduce the BBB permeability and the risk of hemorrhagic transformation after focal cerebral ischemia.

Animals↗
PubMed2000

Cell-specific induction of sensitivity to ganciclovir in medullary thyroid carcinoma cells by adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase.

Herpes simplex virus thymidine kinase (HSVtk) gene transfer followed by ganciclovir administration is a common strategy for experimental cancer therapy. To evaluate the feasibility of using the human calcitonin promoter to target medullary thyroid carcinoma (MTC), we developed adenovirus vectors containing Escherichia coli beta-galactosidase gene under the control of the CALC-I promoter (AdCTlacZ), or the human cytomegalovirus promoter (AdCMVlacZ). Beta-galactosidase activity driven by the CALC-I promoter was higher than by the CMV promoter in rat MTC cells after infection with adenovirus vectors. AdCTlacZ induced an equal or lower expression level of beta-galactosidase in TT (human MTC), T98G, Cos1, HepG2, and HeLa cells compared with AdCMVlacZ. To inhibit the growth of MTC cells, we developed two adenovirus vectors, AdCMVtk carrying HSVtk driven by the cytomegalovirus promoter and AdDCTtk containing a human CALC-I minigene under the control of the CALC-I promoter. HSVtk is fused to a portion of calcitonin coded in exon 4 to direct cell-specific regulation of splicing. All cell lines infected with AdCMVtk were rendered sensitive to ganciclovir, whereas T98G and Cos1 cells infected with AdDCTtk were not affected. Cell killing was also observed in HeLa, HepG2, rat MTC and TT cells infected with AdDCTtk.

Adenoviridae↗
PubMed2000

The effects of verapamil SR and bisoprolol on reducing the sympathetic nervous system's activity.

To assess the response of the sympathetic nervous system (SNS) to the handgrip test in essential hypertensive patients and to evaluate the effects of verapamil SR and bisoprolol on the reduction of the SNS's activity. Seventy eight essential hypertensive patients (50 receiving verapamil SR treatment and 28 receiving bisoprolol treatment) took the handgrip test while the SBP, DBP, and HR were measured on three occasions during the test (before test, 3 min after the patients squeezed the handgrip, and 2 min after the handgrip was released). Before and after the patients received Verapamil SR or Bisoprolol treatment, the plasma concentrations of epinephrine(E), norepinephrine (NE), angiotensin-II (AII), aldosterone (ALD), endothelin-1 (ET-1) and renin activity (RA) were measured post-test. 1) In about 70% of the essential hypertensive patients, SNS activity was above normal. Their HR and BP exceeded 20% when responding to stress. 2) In these patients, the baseline plasma concentrations of E, NE, AII, ET-1, ALD, and RA were higher than those whose SNS's activity was normal. 3) After 6 weeks of treatment, all the patients' BPs decreased remarkably. Verapamil SR could reduce the plasma concentrations of NE, AII, and ET-1 and increase RA. Bisoprolol could reduce E and RA. These two antihypertension drugs can both decrease BP and reduce the activity of SNS through different mechanisms.

Adult↗
PubMed2000

Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2).

BACKGROUND: Damaged articular cartilage has a limited ability to repair. Operative removal of damaged cartilage and penetration into the subchondral bone to allow population of the defect with progenitor cells can result in filling of the defect with repair tissue. However, this repair tissue often degenerates over time because of its inability to withstand the mechanical forces to which it is subjected. We previously reported that recombinant human bone morphogenetic protein-2 (rhBMP-2) improves the repair of full-thickness defects of cartilage as long as six months postoperatively. We have now extended that study to examine the quality of the repair tissue at one year. METHODS: Full-thickness defects of cartilage were created in the trochlear groove of twenty-five adult New Zealand White rabbits. Eight defects were left empty, eight were filled with a collagen sponge, and nine were filled with a collagen sponge impregnated with five micrograms of rhBMP-2. The animals were killed at fifty-two weeks postoperatively, and the gross appearance of the healed defect was assessed. The repair tissue was examined histologically and was evaluated, according to a grading scale, by four individuals who were blinded with respect to the treatment. The tissue sections were immunostained with antibodies against type-I collagen, type-II collagen, aggrecan, and link protein. The residence time of the rhBMP-2 in the cartilage defect was evaluated in vivo with use of scintigraphic imaging of radiolabeled protein. RESULTS: One year after a single implantation of a collagen sponge containing five micrograms of rhBMP-2, the defects had a significantly better histological appearance than the untreated defects (those left empty or filled with a collagen sponge). The histological features that showed improvement were integration at the margin, cellular morphology, architecture within the defect, and reformation of the tidemark. The total scores were also better for the defects treated with rhBMP-2 than for the untreated defects, but in no instance was the repair tissue identical to normal articular cartilage. The thickness of the cartilage in the defects treated with rhBMP-2 was 70 percent that of the normal cartilage, an observation that was identical to that at twenty-four weeks postoperatively. Immunostaining demonstrated significantly less type-I collagen in the defects treated with rhBMP-2 than in the untreated defects. Immunostaining for other matrix components showed no difference among the treatment groups. The mean residence time of rhBMP-2 in the cartilage defects was eight days with an elimination half-life of 5.6 days. Detectable amounts of rhBMP-2 were present as long as fourteen days after implantation. CONCLUSIONS: The problems associated with operative repair of cartilage include the formation of fibrocartilage rather than normal articular cartilage and the degeneration of that repair tissue over time. Our results demonstrate that the addition of rhBMP-2 to the operative site after creation of a full-thickness defect results in an improvement in the histological appearance and composition of the extracellular matrix at one year postoperatively. If these experimental results translate directly to the clinical situation, it is possible that the addition of rhBMP-2 to existing operative treatments for the repair of cartilage may improve the repair process and may help to maintain the integrity of the repair tissue.

Animals↗
PubMed2000

Differential regulation of apoptosis in normal versus transformed mammary epithelium by lutein and retinoic acid.

We examined the effects of all-trans retinoic acid (ATRA) and lutein (a nonprovitamin A carotenoid), on apoptosis and chemosensitivity in primary normal human mammary epithelial cells, SV40 transformed mammary cells, and MCF-7 human mammary carcinoma cells. ATRA and lutein selectively induced apoptosis in transformed but not normal human mammary cells. In addition, both compounds protected normal cells, but not transformed cells, from apoptosis induced by the chemotherapy agents etoposide and cisplatin. Furthermore, lutein and ATRA selectively increased the ratio of Bcl-xL:Bax protein expression in normal cells but not transformed mammary cells, suggesting a possible mechanism for selective modulation of apoptosis. The differential effects of lutein and ATRA on apoptotic pathways in normal versus transformed mammary epithelial cells may have important implications for chemoprevention and therapy.

Antineoplastic Agents↗
PubMed2000

[The association between A55V variant in UCP2 gene and body fat distribution, serum lipid profile in Chinese].

OBJECTIVE: Uncoupling protein 2(UCP2) could play an important role in energy metabolism and body weight regulation. The aim of this study was to investigate Ala55Val(A55V) variant in the UCP2 gene has effects on serum lipid profile, body fat and its distribution in Chinese. METHODS: The genotypes of A55V variant in the UCP2 gene were determined by a PCR-RFLP assay in 359 unrelated Chinese [including 193 normal glucose tolerance(NGT) and 166 type 2 diabetic subjects by ADA 97' criteria]. The parameters for regional adipose tissue distribution were measured by magnetic resonance imaging(MRI). RESULTS: In NGT group, an association between A55V variant in the UCP2 gene and body mass index(BMI) (P=0.0246), as well as femoral subcutaneous adipose tissue area (FA) (P=0.0017), was noted in females. A55V variant in the UCP2 gene was also associated with serum triglyceride (TG) level (P=0.0072) in males. However, in type 2 diabetes group, an association between A55V variant in the UCP2 gene and FA (P=0.0150) was replicated in females too. Those females who were homozygotes of AA in the UCP2 gene had decreased FA not only in NGT group but also in type 2 diabetes group. Furthermore, logistic regression analysis indicated that FA (P=0.0098 in NGT females, P=0.0071 in type 2 diabetic females) and BMI (P=0.0016 in NGT females), as well as TG level (P=0.0040 in NGT males) were associated with this variant in the UCP2 gene. CONCLUSION: A55V variant in the UCP2 gene is associated not only with FA (in NGT females and type 2 diabetic females) but also with BMI (in NGT females). Therefore A55V variant in the UCP2 gene appears to play a role in body fat and its distribution in Chinese females.

Adipose Tissue↗
PubMed2000

A genetic study of the depressive respiratory responses to hypoxia in chronic obstructive pulmonary disease patients with type II respiratory failure.

OBJECTIVE: The depression of the ventilatory and P(0.1 )responses to hypoxia and hypercapnia may play an important role in the development of CO(2) retention in the patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate if there is any linkage relationship between the depressed ventilatory and P(0.1) response phenotypes and the microsatellite markers on chromosome 6q21.1-21.2 among Chinese people. METHODS: P(0.1) and ventilatory responses to hypoxia were measured in six COPD patients with type II respiratory failure, as well as in their 21 normal adult offsprings. Polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis and silver staining techniques were used to study the amplified fragment length polymorphism. Linkage analysis was done with the LINKAGE program. RESULTS: Hypoxia response was low in 10 offsprings, and normal in the other 11 offsprings. Linkage analysis showed the maximum Lod score was 1.74(D6S276, theta = 0.10). CONCLUSION: The depressed hypoxia response might have been influenced by genetic factors. The model was in accord with autosomal dominant inheritance. The disease-related gene was linked to D6S276 locus.

Adult↗
PubMed2000

Expression of metallothionein in invasive ductal breast cancer in relation to prognosis.

The aim of this study was to assess the presence and clinical significance of metallothionein (MT) in primary invasive ductal carcinoma of the breast. We investigated 96 cases of routinely fixed and paraffin-embedded primary breast carcinomas with the immunohistochemical method. Positive staining for MT was observed in 52.1% of specimen. In most cases both nuclear and cytoplasmic staining was seen. A statistically significant association was found between MT-positive staining and nuclear grade (p < 0.01). MT-positive cases had a significantly poorer prognosis when compared with the MT-negative cases (p < 0.01). We concluded that the MT expression may be of a prognostic value for primary invasive ductal carcinoma of the breast and is possibly an indicator of more aggressive and less differentiated carcinoma cells.

Adult↗