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Biomedical subjects

L Lee

Publications and source records attributed to L Lee.

At least 217 records · Page 12Linked to original sources
PubMed1993

Speech breathing in patients with lung disease.

Lung volumes and breathing patterns used during speech differ from those of quiet respiration and may be expected to vary with different types of lung disease. To test this possibility, 41 patients with asthma, emphysema, or sarcoidosis and 16 healthy subjects completed a speech protocol. Volumes, times, and flow rates were recorded during conversation and during a counting task. A total of 16 measured variables were derived for each breath and analyzed statistically. Alterations in speech breathing were disease and task specific. Discriminant function analysis applied to data from either speech task could correctly classify subjects with more than 50% accuracy, showing that different patterns were significantly disease specific. Compared with healthy subjects during conversation, all patients averaged a more rapid respiratory rate and increased the proportion of time spent on inspiration (Ti/Ttot). During counting, patient groups showed a variety of patterns, most commonly subordinating metabolic need to communication drive and sounding more breathless to observers. Regression analysis was used to determine how strongly changes in measured speech variables related to degree of physiologic impairment. The effect of severity of disease on speech production is distinguishable from the effect of the diagnostic category.

Adult↗
PubMed1993

Processing interactions between segmental and suprasegmental information in native speakers of English and Mandarin Chinese.

The processing interactions between segmental and suprasegmental information in native speakers of English and Mandarin Chinese were investigated in a speeded classification task. Since in Chinese, unlike in English, tones convey lexically meaningful information, native speakers of these languages may process combinations of segmental and suprasegmental information differently. Subjects heard consonant-vowel syllables varying on a consonantal (segmental) dimension and either a Mandarin Chinese or constant-pitch (non-Mandarin) suprasegmental dimension. The English listeners showed mutual integrality with the Mandarin Chinese stimuli, but not the constant-pitch stimuli. The native Chinese listeners processed these dimensions with mutual integrality for both the Mandarin Chinese and the constant-pitch stimuli. These results were interpreted in terms of the linguistic function and the structure of suprasegmental information in Chinese and English. The results suggest that the way listeners perceive speech depends on the interaction between the structure of the signal and the processing strategies of the listener.

Adolescent↗
PubMed1993

Transcriptional activation domains of elk-1, delta elk-1 and SAP-1 proteins.

elk-1, an ets related gene codes for a sequence specific DNA binding transcriptional activator which in association with serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE). Recently the C-terminal region of both elk-1 and delta elk-1 proteins was shown to undergo phosphorylation by MAP kinases and function as an activator of MAP kinases. Here we show that delta elk-1 and two other elk-1 related proteins SAP-1a and SAP-1b, like elk-1, can function as transcriptional activators. In this report we have localized the transcriptional activation domain of the SAP-1 proteins (STA) to a large portion of the carboxy terminal region and have identified two autonomous transcriptional activation domains in the elk-1 protein, one at the amino (ETA-1) and the other at the carboxy terminal region (ETA-2). delta elk-1 protein contains only the ETA-2 domain indicating differential usage of activation domains as a result of alternative splicing. We can speculate that the ETA-1 domain can function in vivo independent of ETA-2, but the ETA-2 domain can function either in the absence of ETA-1 (as seen in delta elk-1) or in the presence of accessory proteins like SRF. The role of SRF in the activation of the ternary complex might be to bind to the ETA-1 domain, somehow conceal it's activation domain and in the process unmask the ETA-2 domain (for phosphorylation by MAP kinases) and activate transcription. The ETA-1 domain may be functioning as a negative regulatory transcriptional activation domain for ETA-2. These observations suggest that the elk-1 family of proteins may not only regulate fos and MAP kinases but also other elk-1 target genes that are essential for cellular growth control.

Animals↗
PubMed1993

The Rb gene suppresses the growth of normal cells.

The suppression of tumor formation, first demonstrated by somatic cell hybrid and microcell fusion experiments, suggests the existence of a class of genes that selectively suppress the growth of tumor cells but not normal cells. The reintroduction of these genes into tumor cells presumably renders the cells responsive to in vivo growth inhibitory environment. As the inheritance of a defective retinoblastoma gene (Rb-1) allele results in a predisposition to the development of various cancers, and since inactivation of both alleles are observed in tumor cells, the Rb gene has been suspected to have the ability to suppress tumor growth. Data presented here demonstrated that different types of normal cells, which have a limited life span, were also growth arrested by a transfected Rb gene. Cell lines which are resistant to the growth suppression effect of the Rb gene in vitro, retain the ability to form tumors in nude mice even in the presence of a stable and highly expressed wild type Rb protein. We conclude that while the Rb gene can suppress the growth of many tumor cell lines, its growth suppression effect is not tumor specific.

3T3 Cells↗
PubMed1993

Characterization of the DNA binding and transcriptional activation domains of the erg protein.

erg, an ets related gene encodes a sequence specific DNA binding transcriptional activator protein. We have identified four functional domains of erg protein that are responsible for DNA binding, transcriptional activation and negative regulation of transcriptional activation. Deletion analysis revealed that the 3'-ets domain of the erg protein is sufficient for DNA binding activity. Analysis of these deletion mutants also revealed the presence of two autonomous transcriptional activation domains, one at the amino and the other at the carboxyterminal region. This aminoterminal transcriptional activator domain (5'-ets domain) is conserved in six of the ets genes suggesting that it (ETA, ets Transcriptional Activation domain) may contribute to a common function among these genes. The transcriptional activation function of the carboxy terminal transcriptional activation domain (CTA) was inhibited by the presence of a Negative Regulatory Transcriptional activation domain (NRT), which is located at the amino terminal region of erg DNA binding domain. These results may help in understanding the structure/function relationship of other erg/ets related proteins.

3T3 Cells↗
PubMed1992

A recombinant, soluble, single-chain class I major histocompatibility complex molecule with biological activity.

Heterodimeric class I major histocompatibility complex molecules, which consist of a 45-kDa heavy-chain and a 12-kDa beta 2-microglobulin (beta 2m) light chain, bind endogenously synthesized peptides for presentation to antigen-specific T cells. We have synthesized a gene encoding a single-chain, soluble class I molecule derived from mouse H-2Dd, in which the carboxyl terminus of beta 2m is linked via a peptide spacer to the amino terminus of the heavy chain. The chimeric protein is secreted efficiently from transfected L cells, is thermostable, and when loaded with an appropriate antigenic peptide, stimulates an H-2Dd-restricted antigen-specific T-cell hybridoma. Thus, functional binding of peptide does not require the complete dissociation of beta 2m, implying that a heavy chain/peptide complex is not an obligate intermediate in the assembly of the heavy-chain/beta 2m/peptide heterotrimer. Single-chain major histocompatibility complex molecules uniformly loaded with peptide have potential uses for structural studies, toxin or fluor conjugates, and vaccines.

Animals↗
PubMed1992

32P-postlabeling of acrolein-deoxyguanosine adducts in DNA after nuclease P1 digestion.

In order to study the relationship between the level of acrolein-DNA adducts and their biological effects, sensitive methods are needed to quantitate DNA adducts. 32P-postlabeling is one such method that has been widely used and we have adapted the technique to detect acrolein-deoxyguanosine adducts. Adducts formed by the reaction of acrolein and deoxyguanosine-3'-monophosphate were isolated by HPLC. Based on their UV spectra and cochromatography with standards after dephosphorylation with acid phosphatase, these adducts were identified as the nucleotide equivalents of cyclic 1,N2-propanodeoxyguanosine adducts formed by acrolein that have been described by Chung et al. [15]. As nucleotides, the adducts were good substrates for polynucleotide kinase-mediated transfer of phosphate from ATP and were able to be detected by 32P-postlabeling. These adducts were resistant to the activity of nuclease P1 and dinucleoside monophosphates in the form d(G*pN) where G* is the acrolein-guanine adduct also resisted digestion by nuclease P1. Digestion of DNA by nuclease P1 and acid phosphatase resulted in the conversion of normal nucleotides to nucleosides and selective enrichment of the adducts as dinucleoside monophosphates. Using nuclease P1/acid phosphatase digestion, followed by 32P-postlabeling and TLC separation, levels of the two adducts in acrolein-treated DNA were found to be about 6185 and 19,222 nmol/mol.

Acid Phosphatase↗
PubMed1992

Marek disease virus encodes a basic-leucine zipper gene resembling the fos/jun oncogenes that is highly expressed in lymphoblastoid tumors.

Marek disease virus (MDV) is a herpesvirus of chickens that induces T lymphomas within 3 weeks of infection. The short latency and polyclonal nature of MDV-induced tumors have suggested that the virus may encode one or more direct-acting oncogenes. To date, however, no MDV-specific tumor antigens or candidate transforming genes have been demonstrated. In this paper, we report the identification of a MDV gene encoding a protein with homology to the leucine-zipper class of nuclear oncogenes. It also contains a proline-rich domain characteristic of another class of transcription factors. This gene, designated meq, maps to the long repeat of MDV and is one of the few genes that are highly expressed in MDV-induced T-cell tumors. To our knowledge, a herpesvirus gene closely related to the fos/jun family of oncogenes has not been reported previously.

Amino Acid Sequence↗
PubMed1992

Cardiogenic shock complicating acute myocardial infarction: the use of coronary angioplasty and the integration of the new support devices into patient management.

Conventional therapy for cardiogenic shock complicating acute myocardial infarction continues to be associated with a high in-hospital mortality rate. Hemodynamic support with new mechanical devices and emergency coronary revascularization may alter the long-term prognosis for patients with this complication. Between July 1985 and March 1990, 68 patients presented to the University of Michigan with acute myocardial infarction and cardiogenic shock. Interventions performed included thrombolytic therapy (46%), intraaortic balloon pump counterpulsation (70%), cardiac catheterization (86%), coronary angioplasty (73%), emergency coronary artery bypass grafting/ventricular septal defect repair (15%), Hemopump insertion (11%), percutaneous cardiopulmonary support (4%) and ventricular assist device (3%). The 30-day survival rate was significantly better in patients who had successful angioplasty of the infarct-related artery than in patients with failed angioplasty (61% vs. 7%, p = 0.002) or no attempt at angioplasty (61% vs. 14%, p = 0.003). This difference was maintained over the 1-year follow-up period. The only clinical variable that predicted survival was age less than 65 years. The early use of the new support devices in 10 patients was associated with death in 8 (80%), but this poor outcome may reflect a selection bias for an especially high risk population. Collectively, these recent data continue to suggest that emergency revascularization with angioplasty may reduce the mortality rate, but further study is required to define optimal utilization and integration of new support devices.

Aged↗
PubMed1992

Synthesis and secretion of interphotoreceptor retinoid-binding protein (IRBP) and developmental expression of IRBP mRNA in normal and rd mouse retinas.

The synthesis and secretion of interphotoreceptor retinoid-binding protein (IRBP) was quantitatively assessed in retinas of normal and rd mutant mice using short-term organ culture with [35S]methionine. Retinas were studied at ages P9-P12, time points prior to and immediately after the onset of the degeneration of the rd retina. Soluble proteins of the retinal pellet and the incubation medium were subjected to SDS-polyacrylamide gel electrophoresis. Analysis of labeled protein bands utilized a radioactivity scanning system to quantify [35S]methionine incorporation into newly synthesized IRBP. The synthesis and secretion into the incubation medium of IRBP by rd mouse retinas was comparable to normal retinas at P9-P10 but decreased by more than 50% by P12. IRBP mRNA levels were evaluated in retinas of normal and rd mice ages P7-P14. Although IRBP mRNA expression increased in the rd mouse through P10, it decreased markedly thereafter. Previously reported immunocytochemical studies suggested that IRBP was not secreted in the rd mouse retina. The results of this study indicate, however, that rd mouse retinas, when removed from the eye, have the capacity to synthesize and secrete IRBP.

Animals↗
PubMed1992

The use of high dose rate endobronchial brachytherapy to palliate symptomatic endobronchial recurrence of previously irradiated bronchogenic carcinoma.

Thirty-eight patients were treated with high dose rate endobronchial brachytherapy to palliate symptoms (cough, hemoptysis, fever, and/or shortness of breath) caused by endobronchial of previously irradiated (greater than or equal to 5000 cGy) bronchogenic carcinoma. The dose per fraction was 600 cGy at a radius of 1 cm from the center of the linear path of the source, and each patient received three fraction, each fraction separated by a 1-week interval. Twenty-nine patients (76%) had symptomatic improvement, 16 with complete and 13 with partial relief of symptoms. The likelihood of symptom relief was greater in those patients who had extra-bronchial tumor measuring less than 5 cm (15/15) compared to those with extra-bronchial tumor measuring greater than or equal to 5 cm (2/8). The median duration of symptom relief was 7.5 months. Repeat bronchoscopy done 3 months after brachytherapy revealed that 41% (11/27) had complete tumor regression and another 41% (11/27) had partial regression. Nine of 14 patients with post-obstructive atelectasis/pneumonitis had radiographic improvement. Twelve patients (32%) died from massive hemoptysis occurring 2-56 weeks (median 10 weeks) after brachytherapy. Location of the recurrence was the most important predictor of pulmonary hemorrhage. It occurred only in patients with recurrence in the right upper lobe, right mainstem, or left upper lobe bronchus. Whether this high rate of fatal pulmonary hemorrhage was a real phenomenon or a statistical fluke of small numbers remains an unanswered question.

Brachytherapy↗
PubMed1992

Isolation of Neurospora crassa A mating type mutants by repeat induced point (RIP) mutation.

In the filamentous fungus, Neurospora crassa, mating type is regulated by a single locus with alternate alleles, termed A and a. The mating type alleles control entry into the sexual cycle, but during vegetative growth they function to elicit heterokaryon incompatibility, such that fusion of A and a hypha results in death of cells along the fusion point. Previous studies have shown that the A allele consists of 5301 bp and has no similarity to the a allele; it is found as a single copy and only within the A genome. The a allele is 3235 bp in length and it, too, is found as a single copy within the a genome. Within the A sequence, a single open reading frame (ORF) of 288 amino acids (mt A-1) is thought to confer fertility and heterokaryon incompatibility. In this study, we have used repeat induced point (RIP) mutation to identify functional regions of the A idiomorph. RIP mutations in mt A-1 resulted in the isolation of sterile, heterokaryon-compatible mutants, while RIP mutations generated in a region outside of mt A-1 resulted in the isolation of mutants capable of mating, but deficient in ascospore formation.

Alleles↗
PubMed1992

Experimental tests of the cortical imaging technique--applications to the response to median nerve stimulation and the localization of epileptiform discharges.

In a previous paper a method for simulating the electric potentials on the surface of the brain was introduced. This method consisted of the construction of a layer of radially oriented current dipoles in a conducting sphere that simulated the head so that the voltages generated by the layer would take the values measured on the surface of the medium (the scalp). The harmonic potential function for this layer was then evaluated in the interior of the medium in an attempt to approximate the potentials that would be generated by the actual neural sources but which could not be observed without recourse to invasive recording techniques. This method, the cortical imaging technique (CIT), has been previously tested by applying it to artificially generated data where the "cortical surface" potentials were known and could be compared with CIT-generated potentials. In this paper the method is tested by applying it to the scalp-recorded potentials evoked by right median nerve stimulation, where direct cortical recordings are available for comparison, and to the scalp-recorded epileptiform discharges from two patients where the spike foci were well defined. The effects of varying the "noise ratio," an input parameter in CIT which allows one to account for noise in scalp-recorded data, is discussed.

Cerebral Cortex↗