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Biomedical subjects

N Dang

Publications and source records attributed to N Dang.

At least 19 recordsLinked to original sources

Hodgkin's disease in patients infected with human immunodeficiency virus: frequency, presentation and clinical outcome.

We report the frequency, presenting characteristics, progression-free survival, event-free survival, overall survival and AIDS-free survival of patients with previously untreated Hodgkin's disease (HD) in the setting of infection by human immunodeficiency virus (HIV). To accomplish this we retrospectively reviewed all untreated patients presenting to the University of Texas M.D. Anderson Cancer Center between July 1985 and August 1999 with HD and HIV infection. All available records were reviewed to determine presentation, clinical characteristics, treatment outcome, progression-free survival and overall survival. We identified 887 patients with HD and 3,500 with Non-Hodgkin's Lymphoma (NHL). The ratio of NHL to HD in HIV-negative versus HIV-positive patients was 3.9 versus 6.9, respectively. There were 14 HIV-positive patients with HD and 97 with NHL. The median age of the HIV-positive HD patients was 33 years, and 13 were male. Three patients had Acquired Immune Deficiency syndrome (AIDS) at the time of HD diagnosis, and seven had B-symptoms. Ann Arbor stage was I in one, II in three, III in four and IV in six patients. Mixed cellularity histology was seen in eight, bone marrow involvement in five and extranodal disease in seven patients. Four patients had elevated serum lactate dehydrogenase, three low serum albumin, and nine elevated serum beta2-microglobulin, The median CD4 count was 160/microl. Eleven patients received ABVD or equivalent regimens, followed by radiotherapy in five. One patient was treated with COPP and radiotherapy, one with NOVP and radiotherapy and one only with radiotherapy. All patients received some antiretroviral therapy, but it was variable over the years. With a median follow-up of 64 months for survivors, the projected 5-year progression-free survival was 64%, event-free survival 45%, overall survival 54% and AIDS-free survival 45%. Six patients died of complications arising from HIV infection, including one patient who had preexisting AIDS at HD presentation. Two patients died of HD, without developing other conditions diagnostic of AIDS. We conclude that in our referral patient population HIV infection is associated with preferential development of NHL rather than HD, which appears curable with standard treatment regimens. Since HIV-related deaths exceed those caused by HD, future investigation should focus on integration of chemotherapy and highly active antiretroviral therapy.

Actuarial Analysis↗

Recognition of shared melanoma antigens in association with major HLA-A alleles by tumor infiltrating T lymphocytes from 123 patients with melanoma.

A total of 123 tumor-infiltrating T lymphocyte (TIL) cultures established from patients with HLA-A1, -A2, -A3, -A24, or -A31 metastatic melanoma in the Surgery Branch, National Cancer Institute, were screened for recognition of shared melanoma antigens including five melanosomal proteins (tyrosinase, MART-1/melan-A, gp100, TRP1, TRP2) as well as peptides derived from MAGE-1 and MAGE-3. Examination of the specificity of these T cells indicated that 16% of HLA-A1 TIL, 57% of HLA-A2 TIL, 7% of HLA-A3 TIL, 13% of HLA-A24 TIL, and 27% of HLA-A31 TIL recognized shared melanoma antigens restricted by major histocompatibility complex class I. Melanosomal proteins were frequently recognized by these TIL, and MART-1(27-35), gp100(154-162), gp100(209-217), and gp100(280-288) represent highly immunogenic epitopes that were recognized by a high percentage of HLA-A2 restricted melanoma reactive TIL. Recognition of gp100 by HLA-A2 restricted TIL significantly correlated with clinical response to adoptive immunotherapy with TIL in 21 HLA-A2 melanoma patients (p = 0.024). Four HLA-A1, two HLA-A2, two HLA-A3, one HLA-A24, and two HLA-A31 restricted shared antigen-specific TIL did not recognize the previously identified antigens tested in this study, and may be useful for the identification of new melanoma antigens. The observation that TILs isolated from patients with metastatic melanoma recognized melanosomal proteins in the context of predominant HLA-A alleles implies that it may be possible to develop immunotherapies for patients with melanoma expressing diverse HLA types.

Alleles↗

Infectious complications of pentostatin therapy.

Managing the infectious complications associated with pentostatin (Nipent), used alone or in combination with other agents in patients with low-grade lymphomas, poses a significant problem for clinicians. Since there is limited experience with these therapies, definitive treatment recommendations concerning prophylaxis cannot be made. The panel members discussed the use of valacyclovir (Valtrex) to provide prophylaxis for herpes zoster, trimethoprim/sulfamethoxazole for Pneumocystis, and acyclovir (Zovirax) for varicella zoster. They also considered combinations of pentostatin with agents such as interferon, rituximab (Rituxan), and chlorambucil (Leukeran) and their effect on the immune system. The biology of B and T cells was discussed, with an emphasis on clinical application.

Acyclovir↗

A PET study of human auditory spatial processing.

To learn more about human auditory spatial processing, we used positron emission tomography (PET) to measure regional cerebral blood flow in human volunteers engaged in sound localization tasks. Spectral and binaural cues of localized sound were reproduced by a sound system and delivered via headphones. During localization tasks, subjects activated inferior parietal lobules (IPL) bilaterally. In a second experiment, matched in design to the first, subjects made non-spatial auditory discriminations based on frequency, activating the IPL bilaterally with left hemispheric predominance. A between-study comparison revealed that the right IPL was significantly more activated during the sound localization task compared with the feature discrimination task, suggesting a preferential role for the right IPL in auditory spatial processing.

Adult↗

Pulmonary metastasectomy for head and neck cancers.

BACKGROUND: Distant metastases from carcinomas that arise from the head and neck region are infrequent. The most common site is the lung. To evaluate the results of resection of pulmonary metastases for head and neck cancers, we reviewed our own cases of these metastases. METHODS: Between November 1966 and March 1995, 83 patients with pulmonary metastases from head and neck cancers underwent 94 thoracic operations. All patients had obtained or had obtainable locoregional control of their primary head and neck cancers. Kaplan-Meier and Cox regression models were used to analyze the prognostic factors for survival after metastasectomy. RESULTS: Median age was 53 years (range, 17-77). Fifty-nine were male and 24 were female. Forty-one patients had squamous cell cancers, and 36 had glandular tumors that consisted mostly of thyroid and adenoid cystic carcinomas. The median disease-free interval from the time of treatment of the head and neck primary cancers to the development of pulmonary metastases was 27 months. Sixty-eight (82%) patients had complete resection. Overall operative mortality rate was 2%. Overall actuarial survival rate after metastasectomy was 50% at 5 years. Patients with glandular tumors had a 5-year survival rate of 64% compared with 34% for patients with squamous cell cancers. When the patients with glandular tumors were analyzed according to their histology, patients with adenoid cystic carcinomas had an 84% 5-year survival, but none remained disease-free. Patients with thyroid cancers fared similarly whether they were treated medically or surgically. On multivariate analysis, the adverse prognostic factors for patients with squamous cell cancers were incomplete resection, age greater than 50 years, and disease-free interval less than or equal to 2 years. CONCLUSIONS: Approximately 30% of patients with pulmonary metastases from squamous cell cancers of the head and neck who underwent complete resection of all their metastases can expect to achieve long-term survival. The role of pulmonary resection for patients with glandular tumors is unclear.

Adenocarcinoma↗

Apical bridging in association with regular root formation following single-visit apexification: a case report.

A case report is presented in which continuing root formation occurred in a carious nonvital and immature mandibular second premolar after single-visit calcium hydroxide apexification treatment. An apical hard tissue barrier was formed, accompanied by a separate, mesioapically growing root, 7 months posttreatment. Treatment was concluded with gutta-percha root canal restoration. The success of this single-visit apexification treatment supports the contention that frequent changing of the calcium hydroxide dressing is not always required to induce apical closure.

Calcium Hydroxide↗

Transgenic mice over-expressing the C-99 fragment of betaPP with an alpha-secretase site mutation develop a myopathy similar to human inclusion body myositis.

Inclusion body myositis (IBM) is the most common muscle disease in the elderly. Amyloid-beta protein (A beta) has been shown to accumulate abnormally in the vacuolated fibers and to localize to amyloid-like fibrils in muscles from IBM patients. We studied the skeletal muscles from a line of transgenic mice over-expressing the carboxyl-terminal 99 amino acids (C99) of the beta-amyloid precursor protein (betaPP) with a substitution of lysine-612 to valine (K612V), intended to abolish alpha-secretase recognition and to preserve the A beta domain of C99. The majority (87%) of the 24-month-old transgenic mice showed myopathic changes, and approximately one-third of them had degenerating fibers with sarcoplasmic vacuoles and thioflavin-S-positive deposits. Ultrastructurally, the inclusions were aggregates of short thin amyloid-like fibrils, 6 to 8 nm in diameter. These features are similar to those of human IBM. Immunocytochemistry using an antibody against A beta showed membranous staining in most muscle fibers of transgenic mice, as well as granular or vacuolar cytoplasmic staining in the atrophic fibers. Western blots showed a high level of accumulation of carboxyl-terminal fragments of betaPP in the muscles of the transgenic mice with the most severe IBM-like lesions. The expression of IBM-like lesions was age dependent. These transgenic mice provide a model for the study of IBM and for the peripheral expression of a key element in the pathogenesis of Alzheimer disease.

Age Factors↗

Implicit and explicit learning in an auditory serial reaction time task.

OBJECTIVE: To explore the role of the motor cortex during implicit and explicit learning. MATERIALS AND METHODS: EEG signals were recorded from 30 channels by measuring task-related desynchronization (TRD) when 10 right-handed naive volunteers performed a variation of the serial reaction task. Stimuli, consisting of 4 pure tones of 500, 1000, 1500, and 2000 HZ, lasting 200 ms, were presented binaurally through a pair of tubephones at 60 dB with a 2-s constant interstimulus interval. A series of 10 repetitive tones represented the test sequence; the random sequence was the control. RESULTS: All subjects developed implicit and explicit knowledge reflected by decreased response time, increased accuracy, and the ability to generate the sequence. Six of 10 subjects demonstrated implicit learning without explicit learning during the first 3 blocks. When subjects acquired full explicit learning, 10 Hz TRD at C3 reached a peak amplitude, declining thereafter. CONCLUSIONS: Properties of the sensorimotor cortex change during learning and these changes are independent of stimulus modality.

Adult↗

Incoordination in pianists with overuse syndrome.

To investigate claims that painful musculoligamentous overuse in the arms and hands of pianists is accompanied by loss of motor control, we studied 18 pianists with overuse syndrome of one or both arms and hands and 22 skill-matched pianists with no history of overuse. All of the pianists performed continuous repetitions of a five-finger exercise on a piano keyboard at metronome-paced tempos. The main outcome measures were quantitative analysis of four measurements of performance (duration of key presses, interval between key presses, velocity of key presses [loudness], and time off the metronome beat [difference between actual and expected time of key press]); comparison of the errors in the two groups; and comparison of the performances by a listening panel. The two groups had significant differences in performance, and a classification tree had a sensitivity of 0.886 and a specificity of 0.862 in identifying the affected hands. The pianists with overuse syndrome made more skill-based errors. The listening panel could distinguish between the affected and unaffected hands. We conclude that pianists with overuse syndrome have a coordination disturbance.

Adult↗

Crouzon disease--a case report.

The present case of a ten year old boy with craniofacial dysostosis with the features of midfacial hypoplasia is a disease known as Crouzon disease. This disease is characterised by cranial deformities, facial malformation, eye changes and occasional other associated abnormalities. The aim of this case is to discuss the clinical, radiographic features and management of the problems.

Abnormalities, Multiple↗

Sport practice and osteoarthritis of the limbs.

Participation in sports has evolved as a cause of osteoarthritis (OA), especially in hip and knee joints. OA often occurs at a relatively early age in adult life, in certain sports (soccer, rugby, racket sports and other track and field sports) and under certain conditions (high level of practice). We review preclinical considerations and published epidemiological studies. Joint overuse even without notable trauma is likely the main mechanism of OA both in these sports and in certain occupational activities (relative risk ranges from 1.5 to more than 5 depending chiefly on the category of sport and on the level and duration of practice). Irregular or sudden impacts, heavy load application on the dominant weight-bearing lower limb and the pre-existing state of the joint including dysplasia, dystrophy or previous trauma are risk factors for OA. However, recreational sport activities at a reasonable level are not likely to be harmful for most individuals, in most sport activities.

Case-Control Studies↗

Suture splint: an alternative for luxation injuries of teeth in pediatric patients--a case report.

Stabilization of replanted tooth "splinting" is done to prevent further damage to the pulp and periodontal structure during the healing period. Suture and bonded resin splint is passive, semirigid and functional splint. It is easy to fabricate directly in mouth without lengthy laboratory procedures. A case is presented in which suture and bonded resin splint was performed on laterally luxated maxillary central incisor and avulsed lateral incisor. The splint was removed after one week and sufficient periodontal and gingival healing was observed.

Adolescent↗

Expression of apolipoprotein E inhibits aggregation of the C-terminal fragments of beta-amyloid precursor protein.

An important role of apolipoprotein E in the amyloidogenesis of Alzheimer's disease is suggested by an accumulation of apolipoprotein E in beta-amyloid plaques and a genetic association between Alzheimer's disease and one of the allelic variants (APOE4) of apolipoprotein E. Overexpression of a C-terminal region of beta-amyloid precursor protein brings about aggregation of the C-terminal fragments in COS cells. This COS cell culture system was used to study effects of apolipoprotein E on aggregation of the C-terminal fragments. When both apolipoprotein E and the C-terminal fragments were overexpressed in COS cells, Western blot analyses revealed significant inhibition of aggregation of the C-terminal fragments. No significant differences between apolipoprotein E3 and E4 in the inhibitory activities were found by this method. Apolipoprotein E may inhibit formation of amyloid fibrils.

Alzheimer Disease↗

Overexpressions of cDNAs for beta-amyloid precursor proteins 695, 751, and 770 enhance the secretion of beta-amyloid precursor protein derivatives and the survival of P19-derived neurons.

P19 is a C3H mouse-derived line of multipotent embryonic carcinoma cells that differentiate into neural cells. P19 cell clones overexpressing the three major forms of beta-amyloid precursor protein from their cDNA constructs were established. Unlike a previous study in which P19-derived neurons had a limited alpha-secretase activity, all of these clones produced significant amounts of secreted beta-amyloid precursor protein. When treated with retinoic acid, these transformed lines differentiated into neurons and survived better than did nontransformed parental P19 cells. Furthermore, P19-derived neurons survived better in medium conditioned by the transformed P19 line, and survival was reduced by immunoabsorption with an antibody to beta-amyloid precursor protein. These results suggest neurotrophic effects of secreted beta-amyloid precursor protein and contrast with a previous report in which overexpression of a full-length cDNA for beta-amyloid precursor protein led to degeneration of P19-derived neurons. Western blot analysis suggested that this difference might result from different levels of expression of putative neurotoxic C-terminal fragments of beta-amyloid precursor protein; moreover, P19-derived neurons differ from P19 stem cells in the processing of these C-terminal fragments.

Amyloid beta-Protein Precursor↗

Activity assays of nine heterogeneous promoters in neural and other cultured cells.

To express high levels of proteins encoded by transfected DNA constructs in a variety of cultured cells, including neuronal cells, the activities of nine different promoters were evaluated using Escherichia coli beta-galactosidase (beta-gal) (LacZ) as a reporter gene. These nine promoters were categorized into three distinct groups (high, intermediate, and low expresser), in terms of the levels of beta-gal expression. An expression vector containing the cytomegalovirus enhancer and the chick beta-actin promoter (high expresser) showed the highest levels of expression, followed by vectors containing the cytomegalovirus promoter/enhancer and the SV40 promoter/enhancer (intermediate expresser). The rest of the promoters (thymidine kinase, adenovirus, murine proliferative sarcoma virus, nerve growth factor receptor, Rous sarcoma and mouse mammary tumor virus, and beta-amyloid precursor protein) expressed low levels of beta-gal. These results were consistent for eight different cell types. A particularly attractive model is the stem cell, P19; cultures differentiating into progeny consisting predominantly of cholinergic neurons could be readily transfected with expression vectors using liposomes and expressed beta-gal without significant morphologic changes of the differentiated neurons. The systems should be useful for the study of promoters and various expressed proteins, including those involved in axonal transport.

Animals↗

Selective neurotoxicity of COOH-terminal fragments of the beta-amyloid precursor protein.

The primary component of amyloid deposits found in the brains of patients with Alzheimer's disease is the beta-amyloid protein, a derivative of a much larger precursor protein (beta PP). We have previously reported that overexpression of carboxyl (COOH)-terminal fragments of beta PP from an integrated DNA construct leads to degeneration of neuronally differentiating mouse embryonic stem cells and that the neuronal degeneration is related to approximately 14- and 15-kDa COOH-terminal fragments of the precursor protein. We here demonstrate that these putative cytotoxic fragments contain intact beta-amyloid protein. When such transformed cell lines are treated with dimethyl sulfoxide to induce differentiation into muscle cells, however, the resulting muscle cells remain viable (as do control non-transformed cells), despite the production of comparable amounts of the 14- and 15-kDa fragments. These results are consistent with the hypothesis that particular COOH-terminal fragments of beta PP are amyloidogenic and neurotoxic.

Amyloid beta-Protein Precursor↗

Polymyositis associated with ulcerative colitis.

An elderly woman with chronic ulcerative colitis who developed proximal muscle weakness, increased serum creatine phosphokinase activity, and histological and electromyographic abnormalities characteristic of polymyositis is described. Treatment with corticosteroids and 5-acetylsalicylic acid was followed by a remission in bowel symptoms, improvement in muscle power, and reversal of electromyographic changes. An autoimmune link between the two disorders seems likely.

Aged↗

Physiological analysis of motor reorganization following lower limb amputation.

It is now known that amputation results in reorganization of central motor pathways, but the mechanism for the changes is unclear. One possibility is alteration of the excitability of the alpha motoneurons. We studied motor reorganization and excitability of alpha motoneurons to Ia input in 6 subjects with unilateral lower limb amputation. A Cadwell MES-10 stimulator was used to deliver transcranial magnetic stimuli through a circular coil centered on the sagittal axis 4 cm anterior to Cz and through an 8-shaped coil positioned over scalp locations 1 cm apart along the coronal axis. Surface EMG was recorded bilaterally from quadriceps femoris, the first muscle immediately proximal to the site of amputation. Excitability of the spinal alpha motoneuron pool to Ia afferents was assessed by determining the ratio of the maximal H reflex to the maximal M response (H/M ratio) elicited in the quadriceps femoris. Stimuli of equal intensity delivered to optimal scalp positions recruited a larger percentage of the alpha motoneuron pool in muscles ipsilateral to the stump than in those contralateral to the stump (P less than 0.01). Mean onset latencies of motor evoked potentials were shorter in ipsilateral muscles than in contralateral muscles (P less than 0.01). Muscles ipsilateral to the stump showed a trend toward activation from a larger number of scalp positions than those contralateral to the stump (P = 0.06). There was no difference in the quadriceps H/M ratios (7.2% ipsilateral vs. 10.9% contralateral). The absence of changes in the excitability of the alpha motoneuron pool in the presence of motor reorganization targeting muscles proximal to the stump suggests that reorganization occurs proximal to the alpha motoneuron level.

Adult↗