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Biomedical subjects

J Mai

Publications and source records attributed to J Mai.

At least 19 recordsLinked to original sources
PubMed2002

Bag1 is a regulator and marker of neuronal differentiation.

Bag 1 acts as a co-chaperone for Hsp70/Hsc70. We report here that stable over-expression of Bag1 in immortalized neuronal CSM14.1 cells prevents death following serum deprivation. Bag1 over-expression slowed the proliferative rate of CSM14.1 cells, resulted in increased levels of phospo-MAP kinases and accelerated neuronal differentiation. Immunocytochemistry revealed mostly nuclear localization of Bag1 protein in these cells. However, during differentiation in vitro, Bag1 protein shifted from predominantly nuclear to mostly cytosolic in CSM14.1 cells. To explore in vivo parallels of these findings, we investigated Bag1 expression in the developing mouse nervous system using immunohistochemical methods. Early in brain development, Bag1 was found in nuclei of neuronal precursor cells, whereas cytosolic Bag1 staining was observed mainly after completion of neuronal precursor migration and differentiation. Taken together, these findings raise the possibility that the Bag1 protein is expressed early in neurogenesis in vivo and is capable of modulating neuronal cell survival and differentiation at least in part from a nuclear location.

Animals↗
PubMed2001

Comparision of four different dose specification methods for high-dose-rate intracavitary radiation for treatment of cervical cancer.

PURPOSE: To compare the dose delivered to target tissues and dose-limiting structures as defined by specific dose points with high-dose-rate intracavitary brachytherapy using tandem and ring or tandem and ovoids applicators, and to provide a reasonable approach to dose optimization. METHODS AND MATERIALS: Dosimetry was obtained using four different dose specifications: (1) 100% of the dose prescribed in a tapered fashion along the tandem and 140% at the ovoid/ring surface, (2) 100% of the dose prescribed along the tandem and 100% at the ovoid/ring surface, (3) 100% of the dose prescribed to point A without any additional applicator specification points, and (4) nonoptimized plan using relative dwell weighting to simulate classic Fletcher low-dose-rate (LDR) loading with the dose specified at point A. Point doses were recorded at A, B, and T (cervical tumor point), ICRU rectum, and ovoid/ring surface. RESULTS: For the tandem and ovoids applicators, significant differences were found among the four different dose specification methods for point T and vaginal mucosal doses. When the dose was optimized to point A alone, the ovoid dwell weights were reduced, resulting in higher point T doses and underdosing of the vaginal mucosa. Fixed weighting based on Fletcher LDR loading specifications resulted in higher vaginal mucosa doses. For the tandem and ring applicators, significant differences were observed for vaginal mucosal doses and the ICRU rectal dose. Optimization to point A alone resulted in widely varying dosimetric distributions and vaginal mucosa doses up to 632% of the prescription dose. With nonoptimized fixed weighting, the vaginal wall dose and ICRU rectal dose were increased. CONCLUSION: Prescribing to dose optimization points in a tapered fashion along the tandem and at the ovoid/ring surface results in a pear-shaped dose distribution resembling classic LDR systems. The other dose specification methods may result in underdosing of important target tissues or overdosing of adjacent dose-limiting structures.

Brachytherapy↗
PubMed2001

Directed particle diffusion under "burnt bridges" conditions.

We study random walks on a one-dimensional lattice that contains weak connections, so-called "bridges." Each time the walker crosses the bridge from the left or attempts to cross it from the right, the bridge may be destroyed with probability p; this restricts the particle's motion and directs it. Our model, which incorporates asymmetric aspects in an otherwise symmetric hopping mechanism, is very akin to "Brownian ratchets" and to front propagation in autocatalytic A+B-->2A reactions. The analysis of the model and Monte Carlo simulations show that for large p the velocity of the directed motion is extremely sensitive to the distribution of bridges, whereas for small p the velocity can be understood based on a mean-field analysis. The single-particle model advanced by us here allows an almost quantitative understanding of the front's position in the A+B-->2A many-particle reaction.

Biophysics↗
PubMed2001

[Dietary intake of antioxidant vitamins and personal demographic characteristics of Guangdong residents].

The study aim at revealing the associations between the intake of dietary antioxidant vitamins and personal characteristics on age, sex, education, working status and household gross income etc. The intake of antioxidant vitamins in a population of Guangdong Province was studied. A total of 418 males and 503 females, aged 25-84 year were interviewed, and questionnaires on socio-demography and on a 12-month food intake frequency (FFQ) were completed in 1995. The daily average intake of antioxidant vitamins and energy was higher in male than in female. Older subjects consumed lesser antioxidant vitamins. The vitamin E intake of higher education persons as well as high family income females (> 15001RMB) was higher. Individual business owners and farmers consumed lesser antioxidant vitamins than the other counterparts. The highest vitamin E intake was found in the currently unemployed men and retired women. BMI was positively associated with the intake of antioxidant vitamins excepted for the obesity group. The result suggests that the consumption of antioxidant vitamins varies with characteristics of socio-demographic status. Health promotion programs, such as suggestions on eating more fruits and vegetables should be targeted at the elderly, the less educated, lower income families and rural community.

Adult↗
PubMed2001

[Evaluation of sensorineural hearing loss in childhood].

OBJECTIVE: To explore the clinical and audiological characteristics of sensorineural hearing loss (SHL) with pathological changes both in cochlea and retrocochlear in children and evaluate the relationship between SHL and the lesions in the central nervous system (CNS). METHODS: Three hundred and ten cases (500 ears) of SHL accepted between 1998 and 2000 were studied. The age of patients was ranged from 1 month to 6 years old. According to the evaluation of function of CNS by pediatric neurologist, all cases were divided into two groups: SHL with CNS disease and SHL without CNS disease. Some same age children without hearing loss were subjected as control group. All children were tested using both auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE). RESULTS: 1. The rate of SHL accompanied with CNS diseases was very high in these children. 2. Patients with kernicterus-cerebral palsy usually had serious hearing loss caused by acoustic nerve lesion at retrocochlear, but their cochlea function was injured slightly. Patients with external hydrocephalus had only slight acoustic nerve lesion at retrocochlear, and patients with other CNS diseases usually had no change for their cochlea function. 3. In the group of SHL caused by cochlea lesion, amplitudes of DPOAE decreased obviously when the threshold of wave V of ABR was up to 60 dB nHL, and amplitudes of DPOAE seriously decreased or disappeared when the threshold of wave V was up to above 70 dB nHL. CONCLUSION: The patients with SHL are usually accompanied with CNS diseases in childhood, and their hearing loss appears very difference from audiological characteristics. We suggest that it is necessary to test both ABR and DPOAE in these patients, and it is important that pediatric neurologist join in audiologist team for our clinical study.

Brain Edema↗
PubMed2000

Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells.

To study potential roles of plasma membrane-associated extracellular cathepsin B in tumor cell invasion and metastasis, we used the yeast two-hybrid system to screen for proteins that interact with human procathepsin B. The annexin II light chain (p11), one of the two subunits of the annexin II tetramer, was one of the proteins identified. We have confirmed that recombinant human procathepsin B interacts with p11 as well as with the annexin II tetramer in vitro. Furthermore, procathepsin B could interact with the annexin II tetramer in vivo as demonstrated by coimmunoprecipitation. Cathepsin B and the annexin II tetramer were shown by immunofluorescent staining to colocalize on the surface of human breast carcinoma and glioma cells. Taken together, our results indicate that the annexin II tetramer can serve as a binding protein for procathepsin B on the surface of tumor cells, an interaction that may facilitate tumor invasion and metastasis.

Annexin A2↗
PubMed2000

Cell surface complex of cathepsin B/annexin II tetramer in malignant progression.

The cysteine protease cathepsin B is upregulated in a variety of tumors, particularly at the invasive edges. Cathepsin B can degrade extracellular matrix proteins, such as collagen IV and laminin, and can activate the precursor form of urokinase plasminogen activator (uPA), perhaps thereby initiating an extracellular proteolytic cascade. Recently, we demonstrated that procathepsin B interacts with the annexin II heterotetramer (AIIt) on the surface of tumor cells. AIIt had previously been shown to interact with the serine proteases: plasminogen/plasmin and tissue-type plasminogen activator (tPA). The AIIt binding site for cathepsin B differs from that for either plasminogen/plasmin or tPA. AIIt also interacts with extracellular matrix proteins, e.g., collagen I and tenascin-C, forming a structural link between the tumor cell surface and the extracellular matrix. Interestingly, cathepsin B, plasminogen/plasmin, t-PA and tenascin-C have all been linked to tumor development. We speculate that colocalization through AIIt of proteases and their substrates on the tumor cell surface may facilitate: (1) activation of precursor forms of proteases and initiation of proteolytic cascades; and (2) selective degradation of extracellular matrix proteins. The recruitment of proteases to specific regions on the cell surface, regions where potential substrates are also bound, could well function as a 'proteolytic center' to enhance tumor cell detachment, invasion and motility.

Animals↗
PubMed2000

Characterization of a class of cationic peptides able to facilitate efficient protein transduction in vitro and in vivo.

Protein transduction domains (PTDs), such as the third helix of the Drosophila Antennapedia homeobox gene (Antp) and the HIV TAT PTD, possess a characteristic positive charge on the basis of their enrichment for arginine and lysine residues. To determine whether cationic peptides are able to function as protein transduction domains, 12-mer peptide sequences from an M13 phage library were selected for synthesis on the basis of their varying cationic charge content. In addition, polylysine and polyarginine peptides were synthesized in order to assess the effect of charge contribution in protein transduction. Coupling of the biotinylated peptides to avidin-beta-galactosidase facilitated transduction in a wide variety of cell lines and primary cells, including islet beta-cells, synovial cells, polarized airway epithelial cells, dendritic cells, myoblasts, and tumor cells. Two of the peptides, PTD-4 and PTD-5, mediated transduction nearly 600-fold more efficiently than a random control peptide, but with an efficiency similar to the TAT PTD and the 12 mers of polylysine and polyarginine. Furthermore, confocal analysis of biotinylated peptide-streptavidin-Cy3 conjugates demonstrated that the internalized PTDs are found in both the nuclei and the cytoplasm of treated cells. When tested in vivo, the PTDs were able to facilitate efficient and rapid protein delivery into rabbit synovium and mouse solid tumors following intraarticular and intratumoral administration, respectively. These novel PTDs can be used to transfer therapeutic proteins and DNA for the treatment of a wide variety of diseases, including arthritis and cancer.

Amino Acid Sequence↗
PubMed2000

Observing proteases in living cells.

The lysosomal cysteine protease cathepsin B has been implicated in tumor progression and metastasis in part due to its altered trafficking. In order to analyze the trafficking of cathepsin B in living cells, we utilized enhanced green fluorescent protein (EGFP) fused to various cathepsin B constructs for transfecting two cell lines: an invasive human breast adenocarcinoma cell line (BT20) and a cathepsin B deficient mouse embryonic fibroblast cell line (MEF T -/-). The cells were transiently transfected with four cathepsin B-EGFP fusion constructs: full-length preprocathepsin B-EGFP, cathepsin B preregion-EGFP, cathepsin B prepro region-EGFP, and cathepsin B prepro region-EGFP with a mutation of the glycosylation site in the pro region. The full length construct showed vesicular distribution throughout the cells in both cell lines. In both BT20 and MEF T -/- cells, preregion-EGFP was localized in a ring tightly associated with the cell nucleus, suggesting distribution to the endoplasmic reticulum. The distribution of the prepro region-EGFP construct was similar except that it also included some patchy areas adjacent to the nucleus. This suggested that the cathepsin B prepro region-EGFP might have entered the Golgi. Distribution of the mutated cathepsin B prepro region-EGFP was similar to that of wild-type prepro region-EGFP in the MEF T -/-. In the invasive BT20 cells, however, the mutated prepro region-EGFP showed a vesicular distribution throughout the cytoplasm and in cell processes. This distribution is similar to that of endogenous cathepsin B in these cells. Our results suggest that: 1) tumor cells have an alternative mechanism for trafficking of cathepsin B which is independent of the mannose-6-phosphate receptor pathway, and 2) the pro region of cathepsin B may contain the sorting sequence necessary for its trafficking via this pathway.

Adenocarcinoma↗
PubMed2000

Front propagation in one-dimensional autocatalytic reactions: the breakdown of the classical picture at small particle concentrations

The autocatalytic scheme A+B-->2A in a discrete particle system is studied in one dimension via Monte Carlo simulations. We find considerable differences in the results for the front velocities and front forms compared to the classical, continuous picture, which is only valid in the limit of very small reaction probabilities p. Interestingly, we also obtain front propagation velocities fairly below the classical minimal velocity.

Journal Article↗
PubMed2000

Enhanced rate response algorithm for orthostatic compensation pacing.

Upon orthostatic stress after a period of rest, the heart rate increases rapidly to maintain cardiac output and minimize the fall in arterial pressure. Pacemaker patients are often prone to a deficient response to orthostatic stress. This may cause lightheadedness and, in rare patients with autonomic dysfunction, syncope. To alleviate these undesirable consequences, an enhanced rate response algorithm was developed using an accelerometer. The pacemaker generates two signals from its accelerometer: instantaneous activity level (Act) and long-term change in activity level (ActVar). Low values of both Act and ActVar indicate a resting state. An increase in Act while ActVar remains low indicates the onset of motion after prolonged rest. Upon detecting this transition, the algorithm increases the pacing rate to a programmable orthostatic compensation rate for a programmable duration. A taped-on pacemaker with this algorithm was evaluated in three healthy women and two healthy men, 36 +/- 8 years of age. Electrocardiogram and ventricular pacing pulses were recorded by a 24-hour ambulatory system. Each trigger of the orthostatic compensation rate was verified against a > 10 beats/min increase in heart rate, a response classified as appropriate. The overall specificity of the algorithm among the five subjects was 78%. The nocturnal specificity (10 PM to 7 AM) was 98%, considerably higher than during daytime (72%). In conclusion, a pacing algorithm to alleviate orthostatic stress was developed, which was highly specific during the night hours.

Acceleration↗
PubMed1998

Vigabatrin: placental transfer in vivo and excretion into breast milk of the enantiomers.

AIMS: Vigabatrin is a new antiepileptic medication consisting of a racemic mixture of 50% active S enantiomer and 50% inactive R enantiomer. Since patients suffering from epilepsy may become pregnant, it is important to understand the extent of placental transfer of such medication. METHODS: During steady-state, vigabatrin enantiomer concentrations were measured in maternal and umbilical blood and in breast milk of two patients. RESULTS: The concentration ratios from the umbilical vein to maternal plasma were R:0.068, S:0.16; 4h25 min after drug administration (case 1) and R: 1.39, S: 0.91; 9h after drug administration (case 2). The milk: plasma concentration ratio was lower than 1 at pre dose sampling in both cases, as well as 3 and 6 h post dose in one case. An estimate of the maximum amount of R and S enantiomers of vigabatrin that a suckling infant would ingest in a day is 3.6% and 1% of the weight-adjusted daily dose respectively. CONCLUSIONS: These results would suggest a slow placental transfer of the vigabatrin enantiomers and that the quantity ingested through milk is small.

Adult↗
PubMed1998

Relationship between lung function and blood pressure in Chinese men and women of Beijing and Guangzhou. PRC-USA Cardiovascular and Cardiopulmonary Epidemiology Research Group.

BACKGROUND: Previous studies of western populations have shown an inverse association between lung function and blood pressure. METHODS: As part of a People's Republic of China-United States cardiopulmonary epidemiology study, we investigated the cross-sectional relationship between lung function and blood pressure in 6757 Chinese men and women, aged 35-54, from Beijing and Guangzhou, China. We also evaluated the longitudinal association between lung function and incident hypertension among 4818 initially normotensive subjects followed up between 2 and 4 years later. RESULTS: In our cross-sectional analyses of baseline data, lung function varied inversely with baseline systolic (SBP) and diastolic blood pressure (DBP) in all women and in Beijing men. This association held for absolute and height-standardized forced vital capacity (FVC) and one-second forced expiratory volume (FEV1) (correlations: 0.10, -0.18, P < 0.0001), but was weaker after adjustment for age (correlations: -0.02, -0.11). The longitudinal follow-up showed that lower initial lung function levels were associated with a higher incidence of hypertension (SBP > or = 140 mmHg or DBP > or = 90 mmHg or currently using antihypertensive medications), but only among women in Guangzhou. Relative risks for hypertension incidence for those in the two lowest quintiles for FEV1 and FVC, compared to those in the two highest quintiles, ranged from 1.9 to 2.3 for Guangzhou women and from 0.9 to 1.4 for all other gender-city subgroups. Logistic regression analyses adjusting for age, baseline SBP, body mass index, smoking, education, and urban versus rural setting generally confirmed these patterns. CONCLUSIONS: These results suggest a statistically significant, though weak, inverse relationship between lung function and blood pressure in Chinese men and women. This association is largely attributable to age and is present prospectively only in women.

Adult↗
PubMed1998

Prevalence of carpal tunnel syndrome among individuals with Down syndrome.

We examined occurrence of carpal tunnel syndrome in 48 patients with Down syndrome clinically and electrophysiologically. In the median nerve the distal latency to the abductor pollicis brevis muscle and the distal sensory nerve conduction velocity to digit II and III were recorded. As a control, we examined the ulner nerve. In the median nerve, a distal latency above 4.3 msec and sensory nerve conduction velocity below 50 m/sec were considered indicative of Carpal tunnel syndrome. Twenty seven patients (56%) had normal findings, 13 (27%) had both prolonged distal motor latency and reduced distal sensory nerve conduction velocity, and 8 patients (17%) had one of these signs, a much higher frequency than expected. Results show that prevalence of electrophysiological carpal tunnel syndrome is high in individuals with Down syndrome.

Adolescent↗
PubMed1997

Renal cellular transport, metabolism, and cytotoxicity of S-(6-purinyl)glutathione, a prodrug of 6-mercaptopurine, and analogues.

The disposition of S-(6-purinyl)glutathione (6-PG) and its metabolites, including the antitumor agent 6-mercaptopurine (6-MP), was characterized in freshly isolated renal cortical cells from male F344 rats to assess the ability of the kidney to convert 6-PG to 6-MP. The intracellular transport and accumulation of 6-PG and 6-MP, the metabolism of 6-PG to 6-MP, and the potential cytotoxicity of 6-MP, 6-thioxanthine (6-ThXan), and 6-thioguanine (6-ThGua) were determined. 6-PG and 6-MP were accumulated by renal cortical cells by time- and concentration-dependent processes, reaching maximal levels of 14.2 and 1.52 nmol/10(6) cells, respectively, with 1 mM concentrations of each compound. Treatment with acivicin, an inhibitor of 6-PG metabolism by gamma-glutamyltransferase, increased accumulation of 6-PG, and treatment with alpha-keto-gamma-methiolbutyrate, a keto acid cosubstrate that stimulates activity of the cysteine conjugate beta-lyase (beta-lyase), which generates 6-MP, decreased accumulation of 6-PG. Incubation of renal cells with 10 mM 6-PG generated 6-MP at a rate of 2.4 nmol/min per 10(6) cells, demonstrating that the beta-lyase pathway forms the desired product from the prodrug within the intact renal cell. Preincubation of cells with acivicin or aminooxyacetic acid, an inhibitor of the beta-lyase, decreased the net formation of 6-MP, demonstrating further the function of the beta-lyase. 6-MP, 6-ThXan, and 6-ThGua exhibited approximately equivalent cytotoxicity (45-55% release of lactate dehydrogenase with 1 mM at 2 hr) in isolated renal cells. Based on the known antitumor potency of these agents, this suggests that cytotoxicity and antitumor activity occur by distinct mechanisms. The high amount of accumulation of 6-PG and its subsequent metabolism to 6-MP, as compared with the relatively low amount of accumulation of 6-MP, in renal cells suggest that 6-PG can function as a prodrug and is a more effective delivery vehicle for 6-MP to renal cells than 6-MP itself. Administration of 6-PG may be an effective means of treating renal tumors or suppressing renal transplant rejection.

Allopurinol↗
PubMed1997

Specific monoclonal antibody raised against the p33ING1 tumor suppressor.

An IgG1 mouse monoclonal antibody (CAb1) was produced against human recombinant p33ING1. The antibody is able to recognize native and denatured antigen in ELISA and Western blot protocols, respectively. CAb1 can be used to specifically detect the p33ING1 protein in dot blot and Western immunoblot protocols of both human and mouse cell lysates. In addition, this antibody is also useful for cellular localization of native and ectopically overexpressed p33ING1 protein by indirect immunofluorescence.

Animals↗