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Biomedical subjects

A Tang

Publications and source records attributed to A Tang.

At least 37 records · Page 2Linked to original sources

Unequal VH gene rearrangement frequency within the large VH7183 gene family is not due to recombination signal sequence variation, and mapping of the genes shows a bias of rearrangement based on chromosomal location.

Much of the nonrandom usage of V, D, and J genes in the Ab repertoire is due to different frequencies with which gene segments undergo V(D)J rearrangement. The recombination signal sequences flanking each segment are seldom identical with consensus sequences, and this natural variation in recombination signal sequence (RSS) accounts for some differences in rearrangement frequencies in vivo. Here, we have sequenced the RSS of 19 individual V(H)7183 genes, revealing that the majority have one of two closely related RSS. One group has a consensus heptamer, and the other has a nonconsensus heptamer. In vitro recombination substrate studies show that the RSS with the nonconsensus heptamer, which include the frequently rearranging 81X, rearrange less well than the RSS with the consensus heptamer. Although 81X differs from the other 7183-I genes at three positions in the spacer, this does not significantly increase its recombination potency in vitro. The rearrangement frequency of all members of the family was determined in microMT mice, and there was no correlation between the in vitro recombination potential and V(H) gene rearrangement frequency in vivo. Furthermore, genes with identical RSS rearrange at different frequencies in vivo. This demonstrates that other factors can override differences in RSS potency in vivo. We have also determined the gene order of all V(H)7183 genes in a bacterial artificial chromosome contig and show that most of the frequently rearranging genes are in the 3' half of the region. This suggests that chromosomal location plays an important role in nonrandom rearrangement of the V(H)7183 genes.

Animals↗

Local vs systemic corticosteroids in the treatment of carpal tunnel syndrome.

The authors compared the effectiveness of low-dose, short-term oral prednisolone vs local methylprednisolone injection in a prospective, double-blinded, parallel treatment study of carpal tunnel syndrome (CTS). A single injection of 15 mg methylprednisolone resulted in significant improvement in global symptom scores over a 12-week period. This study demonstrated the superiority of local steroid injection to oral steroid in the treatment of CTS.

Administration, Oral↗

Nystrom plus correction method for solving bound-state equations in momentum space.

A method is presented for solving the momentum-space Schrödinger equation with a linear potential. The Lande-subtracted momentum-space integral equation can be transformed into a matrix equation by the Nystrom method. The method produces only approximate eigenvalues in the cases of singular potentials such as the linear potential. The eigenvalues generated by the Nystrom method can be improved by calculating the numerical errors and adding the appropriate corrections. The end results are more accurate eigenvalues than those generated by the basis function method. The method is also shown to work for a relativistic equation such as the Thompson equation.

Journal Article↗

The coiled coils in the design of protein-based constructs: hybrid hydrogels and epitope displays.

Recombinant DNA technology provides a powerful tool for producing protein-based biomaterials. Genetically engineered coiled coils have been used as a structural module for the construction of a variety of bio-based systems useful in drug delivery studies. Two of such approaches developed in the authors' laboratory were described here. One approach was to assemble hybrid hydrogels from coiled coil protein domains and synthetic polymers. Preliminary results showed that temperature-sensitive volume transition of the hybrid hydrogels could be triggered by the thermal unfolding of the engineered coiled coil protein domains. The other approach, discussed in detail, was to construct an epitope display model system based on a coiled coil stem loop peptide self-assembled on a solid substrate. This model construct displayed a constrained nonapeptide sequence, which was found to mediate specific binding with immunocompetent cells bearing complementary surface receptors. These novel approaches will likely find important applications in the rational design of more effective drug delivery systems.

Amino Acid Sequence↗

Identification of zeta-crystallin/NADPH:quinone reductase as a renal glutaminase mRNA pH response element-binding protein.

Increased renal ammoniagenesis and bicarbonate synthesis from glutamine during chronic metabolic acidosis facilitate the excretion of acids and partially restore normal acid-base balance. This adaptation is sustained, in part, by a cell-specific stabilization of the glutaminase mRNA that leads to an increased synthesis of the mitochondrial glutaminase. A direct repeat of an 8-base AU sequence within the 3'-nontranslated region of the glutaminase mRNA binds a unique protein with high affinity and specificity. Expression of various chimeric mRNAs in LLC-PK(1)-FBPase(+) cells demonstrated that a single 8-base AU sequence is both necessary and sufficient to function as a pH response element (pH RE). A biotinylated oligoribonucleotide containing the direct repeat was used as an affinity ligand to purify the pH RE-binding protein from a cytosolic extract of rat renal cortex. The purified binding activity retained the same specific binding properties as observed with crude extracts and correlated with the elution of a 36-kDa protein. Microsequencing by mass spectroscopy and Western blot analysis were used to identify this protein as zeta-crystallin/NADPH:quinone reductase. The purified protein contained eight tryptic peptides that were identical to sequences found in mouse zeta-crystallin and three peptides that differed by only a single amino acid. The observed differences may represent substitutions found in the rat homolog. A second protein purified by this protocol was identified as T-cell-restricted intracellular antigen-related protein (TIAR). However, the purified TIAR neither bound nor affected the binding of zeta-crystallin/NADPH:quinone reductase to the pH RE. Furthermore, specific antibodies to zeta-crystallin, but not TIAR, blocked the formation of the complex between the pH RE and either the crude cytosolic extract or the purified protein. Thus, zeta-crystallin/NADPH:quinone reductase is a pH response element-binding protein.

Animals↗

pH regulation of renal gene expression.

The increase in intracellular pH (pHi) associated with various tumour cells triggers changes in gene expression. Similar adaptations also occur as part of the physiological response to changes in acid base balance. For example, during metabolic acidosis, increased renal ammoniagenesis and bicarbonate synthesis are sustained by the increased expression of various transport proteins and key enzymes of glutamine metabolism. In rat kidney, increased expression of the mitochondrial glutaminase (GA) and glutamate dehydrogenase (GDH) results from stabilization of their respective mRNAs. The 3'-untranslated region (UTR) of the GA mRNA contains a direct repeat of an 8-base AU sequence that functions as a pH-response element. This sequence exhibits a high affinity and specificity for z-crystallin. The same protein binds to two separate, but homologous, 8-base AU sequences within the 3'-UTR of the GDH mRNA. The apparent binding activity of z-crystallin is increased significantly during onset of metabolic acidosis. Thus, increased binding of z-crystallin may initiate the pH-responsive stabilization of the two mRNAs. In contrast, induction of the phosphoenolpyruvate carboxykinase (PEPCK) gene occurs at the transcriptional level. In LLC-PK1-FBPase+ kidney cells, a decrease in pHi leads to activation of the p38 stress-activated protein kinase and subsequent phosphorylation of ATF-2. This transcription factor binds to the CRE-1 element within the promoter of the PEPCK gene to enhance transcription. Similar mechanisms may contribute to altered gene expression in tumour cells.

Animals↗

Recurrence after a first untreated seizure in the Hong Kong Chinese population.

PURPOSE: There is wide variation in the reported prognosis after a first unprovoked generalized tonic-clonic convulsion and in the risk factors that are associated with recurrence. Estimates for the risk of recurrence range from 26 to 71%. We investigated the likelihood of a second attack in Hong Kong Chinese patients. METHODS: One hundred thirty-two patients with a first convulsion that was unexplained by acute neurological or medical causes were retrospectively ascertained. Patients' demographic details, potential risk factors for recurrence, and current seizure status were recorded. Survival analysis was performed using the Kaplan-Meier procedure. RESULTS: The cumulative probability of a second attack at 1, 2, 3, and 4 years was 30, 37, 42, and 47%, respectively. Seizures in patients with abnormal computer tomography scans of the brain were associated with an increased risk of recurrence on multivariate analysis. CONCLUSIONS: Thirty percent of the sample population experienced a second seizure after 1 year. An additional 17% continue to be at risk of a second convulsion during the next 3 years.

Adolescent↗

Plasma cell balanitis of Zoon: response to Trimovate cream.

Our objective was to evaluate the response to Trimovate cream in patients with Zoon's balanitis. Patients attending the penile dermatosis clinic between October 1996 and October 1999 with the clinical and histological features diagnostic of Zoon's balanitis were included in this study. They were treated with Trimovate cream for a varying length of time according to clinical response, having declined circumcision as first-line treatment. All cases had photographs taken before and after treatment. Ten cases of histologically-confirmed Zoon's balanitis were treated. Clinical resolution was observed in all cases, all of whom remain on long-term follow-up. In conclusion, topical Trimovate cream is an effective treatment for Zoon's balanitis.

Adult↗

Improvement in diabetes control with a monitoring system based on a hand-held, touch-screen electronic diary.

We conducted a six-month prospective interventional crossover study examining a computerized diabetes monitoring system (DMS) that conveyed dietary information. The objectives were to compare glycaemic control between intervention and control periods, and to assess patients' acceptance of the DMS. Nineteen patients were randomized into two groups, each using the DMS for three months and serving as the control group for another three months. The patients recorded information about their meal portions and blood glucose readings in a hand-held electronic diary. After transmitting the data to the DMS through a telephone modem, the patients received immediate feedback about the carbohydrate, protein and fat content of the meal, as well as the calorie content. A significant improvement in glycaemic control was achieved during intervention compared with control periods (mean HbA1C reduction of 0.825%). The DMS was also highly acceptable: 95% patients found it easy to operate while 63% found it useful. The DMS was thus a feasible model of telemedicine in diabetes care and a larger study is warranted to examine its cost-effectiveness.

Adult↗

[Confirmation of patulous eustachian tube syndrome by Tubo-tymanoaerodynamic graphy].

OBJECTIVE: To compare the advantage of tympanogram, Morimitsu's method and Tubotymanoaerodynamic graphy (TTAG) in the confirmation of patulous eustachian tube syndrome. METHOD: Twenty ears with patulous eustachian tube syndrome diagnosed clinically were selected. The tympanogram, Morimitsu's method and TTAG were examined in these ears and the positive rate was estimated. RESULT: The confirmation of patulous eustachian tube syndrome by tympanogram, Morimitsu's method and TTAG was 5, 12 and 20 ears in 20 ears with patulous eustachian tube syndrome. The positive rate was 25%, 60% and 100% respectively. TTAG also was useful in following-up. CONCLUSION: TTAG is an important method for diagnosis and following-up in patulous eustachian tube syndrome.

Acoustic Impedance Tests↗

[Detection of radiation-induced apoptosis in nasopharyngeal carcinoma].

OBJECTIVE: To investigate the pathological changes after radiotherapy and its clinical significance of nasopharyngeal carcinoma (NPC). METHOD: Paraffin-embedded tissue blocks obtained from 30 cases of NPC before and during radiotherapy were used in this study. Using terminal oxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) and HE staining, the spontaneous and radiation-induced apoptotic rate (AR) were examined, and the pathological changes of NPC tissues before and after radiotherapy were compared. RESULT: The AR of radiation-induced apoptosis was significant higher than that of spontaneous apoptosis, but the AR was decreasing and the differentiation of proliferatic tumor clonogehic cell getting better during radiotherapy of NPC. CONCLUSION: The process of apoptosis was accelerated and the differentiation of proliferative tumor clonogehic cell getting better during radiotherapy of NPC.

Adolescent↗

Gonadal hormone levels in injection drug users.

Levels of serum sex hormones, particularly testosterone, luteinizing hormone, and follicle-stimulating hormone, have been shown to change in various disease states. Hypogonadism has been well-documented in patients with HIV infection. As HIV infection and injection drug use are closely linked, we examined whether injection drug users (IDU's) exhibit hormone abnormalities. We evaluated men participating in the ALIVE study (AIDS Linked to Intravenous Experiences), a large cohort study conducted in Baltimore, MD. We found that 20% of 40 IDU subjects (20 HIV+, 20 HIV-) with a mean age 41.5+/-0.9, had low serum total testosterone concentration. We were unable to detect a direct correlation between drug use and hormone levels. Further study is needed on the hormonal milieu of the IDU patient.

Adult↗

Nutritional assessment in intravenous drug users with HIV/AIDS.

Studying metabolic, endocrine, and gastrointestinal (MEG) disorders in drug abuse and HIV infection is important. Equally important, however, are the tools we use to assess these disorders. Assessment of nutritional status may include any combination of biochemical and body composition measurements, dietary intake assessment, and metabolic studies. Each method has its strengths and weaknesses and there is no perfect tool. When assessing nutritional status in injection drug users (IDU) and in HIV-infected people, the decision on which method or methods to use becomes even more complex. A review of studies reported during the XII World Conference on AIDS reveals that of 64 abstracts on the topic of nutrition in HIV-infected adults, only 11 assessed diet, 41 assessed anthropometry, and 24 assessed some form of biochemical measure. The most commonly reported methods for dietary intake included 24-hour recalls, food records, and food frequencies. The commonest methods used for measuring body composition included height, weight, bioimpedance, and dual-energy x-ray absorptiometry (DEXA). Biochemical measurements included various blood nutrients, lipids, and albumin. Methods varied greatly between studies, and caution should be taken when trying to compare results across studies, especially among those using different methods. Currently, few studies deal with the development of methods that can be used for research in HIV-infected and IDU populations. We need to work toward better tools in dietary intake assessment, body composition, and biochemical measurements, especially methods that will allow us to track changes in nutritional status over time.

Body Composition↗

Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators.

BACKGROUND: The mortality rate among patients with coronary artery disease, abnormal ventricular function, and unsustained ventricular tachycardia is high. The usefulness of electrophysiologic testing for risk stratification in these patients is unclear. METHODS: We performed electrophysiologic testing in patients who had coronary artery disease, a left ventricular ejection fraction of 40 percent or less, and asymptomatic, unsustained ventricular tachycardia. Patients in whom sustained ventricular tachyarrhythmias could be induced were randomly assigned to receive either antiarrhythmic therapy guided by electrophysiologic testing or no antiarrhythmic therapy. The primary end point was cardiac arrest or death from arrhythmia. Patients without inducible tachyarrhythmias were followed in a registry. We compared the outcomes of 1397 patients in the registry with those of 353 patients with inducible tachyarrhythmias who were randomly assigned to receive no antiarrhythmic therapy in order to assess the prognostic value of electrophysiologic testing. RESULTS: Patients were followed for a median of 39 months. In a Kaplan-Meier analysis, two-year and five-year rates of cardiac arrest or death due to arrhythmia were 12 and 24 percent, respectively, among the patients in the registry, as compared with 18 and 32 percent among the patients with inducible tachyarrhythmias who were assigned to no antiarrhythmic therapy (adjusted P<0.001). Overall mortality after five years was 48 percent among the patients with inducible tachyarrhythmias, as compared with 44 percent among the patients in the registry (adjusted P=0.005). Deaths among patients without inducible tachyarrhythmias were less likely to be classified as due to arrhythmia than those among patients with inducible tachyarrhythmias (45 and 54 percent, respectively; P=0.06). CONCLUSIONS: Patients with coronary artery disease, left ventricular dysfunction, and asymptomatic, unsustained ventricular tachycardia in whom sustained ventricular tachyarrhythmias cannot be induced have a significantly lower risk of sudden death or cardiac arrest and lower overall mortality than similar patients with inducible sustained tachyarrhythmias.

Aged↗

Aspirin-associated intracerebral hemorrhage: clinical and radiologic features.

OBJECTIVE: To identify the clinical and radiologic features of intracerebral hemorrhage (ICH) in aspirin users. BACKGROUND: Although the benefits of aspirin outweigh its hemorrhagic risks for patients at high risk of vascular diseases, prolonged use of aspirin is associated with an increased risk of ICH. METHODS: The authors enrolled consecutive patients with acute stroke who were admitted to a regional hospital from 1993 to 1998 into a stroke registry. From this registry, they identified all stroke patients who had ICH confirmed by CT scan and then selected those taking regular aspirin before ICH as the study group. For each study patient, they selected the immediate next two patients with ICH but not taking aspirin as controls. RESULTS: The authors identified 58 aspirin users and 1193 nonusers among all patients hospitalized for ICH. From the group of nonusers, they selected 116 patients as controls. The locations of the hematoma were different (p = 0.002), with more lobar hematoma in the aspirin group (32.8%) than in the control group (10.3%). Prior cerebrovascular disease was the reason for taking aspirin in 37 (64%) patients but five patients had prior ICH. CONCLUSIONS: The propensity for lobar hematoma in aspirin-associated ICH suggests its pathology may be somewhat different from spontaneous ICH among nonaspirin users. Further research to examine the risks and benefits of aspirin use in certain subgroups at risk of both thrombotic and hemorrhagic events is needed.

Adult↗