Biomedical subjects

Samuel A Lee

Publications and source records attributed to Samuel A Lee.

7 recordsLinked to original sources

PubMed2006

Signs and symptoms of sleep-disordered breathing in trauma survivors: a matched comparison with classic sleep apnea patients.

Chronic posttraumatic sleep disturbance may include sleep-disordered breathing (SDB), but this disorder of sleep respiration is usually not suspected in trauma survivors. Sleep breathing signs and symptoms were studied in 178 adults-all with SDB-including typical sleep clinic patients (N = 89) reporting classic snoring and sleepiness and crime victims (N = 89) with insomnia and posttraumatic stress. Significant differences (p < 0.0001) were common between groups. Sleep breathing complaints, loud snoring, marked obesity, and obstructive sleep apnea were prevalent in sleep clinic patients; crime victims reported more insomnia, nightmares, poor sleep quality, leg jerks, cognitive-affective symptoms, psychotropic medication usage, and less snoring but more upper airway resistance syndrome. Both groups reported high rates of fatigue or sleepiness, nocturia, morning dry mouth, and morning headaches. Awareness of these clinical features might enhance detection of SDB among trauma survivors.

Adult↗

PubMed2005

Intracellular trafficking of fluorescently tagged proteins associated with pathogenesis in Candida albicans.

Proteins that enter the secretory pathway play important roles in virulence and pathogenesis in Candida albicans, but our understanding of the trafficking of these proteins is in its early stages. In Saccharomyces cerevisiae, dominant negative alleles of YPT1 and SEC4 interrupt secretory traffic at pre- and post-Golgi steps, respectively. We therefore used a dominant negative genetic approach to examine the intracellular trafficking of several proteins associated with virulence or azole resistance. When the dominant negative ypt1(N121I) allele of C. albicans was overexpressed, yellow-fluorescent protein (YFP) tagged forms of two plasma membrane transporters (Cdrlp and Ftrlp) and the vacuolar membrane ABC transporter Mltlp accumulated in intracellular structures that appeared related to the ER, but localization of Cdc10p and Int1p was unaffected. When the dominant negative sec4(S28N) allele of C. albicans was overexpressed, Cdrlp and Ftrlp accumulated intracellularly, and localization of Mltlp, Cdc10p and Int1p was unaffected. These results imply that (i) Cdrlp and Ftrlp are transported to the plasma membrane by the general secretory pathway, (ii) Mlt1p enters the secretory pathway but is diverted to the vacuole at an early post-Golgi step, and (iii) like Cdc10p, Int1p does not enter the general secretory pathway.

ATP-Binding Cassette Transporters↗

PubMed2004

Refractory insomnia and sleep-disordered breathing: a pilot study.

OBJECTIVE: To assess an uncontrolled, open-label trial of sleep-disordered breathing (SDB) treatment on two different samples of chronic insomnia patients. METHOD: In Study 1 (Retrospective), data from one diagnostic and one continuous positive airway pressure (CPAP) titration polysomnogram were compiled from 19 chronic insomnia patients with SDB. Objective polysomnogram indicators of sleep and arousal activity and self-reported sleep quality were measured. In Study 2 (Prospective), clinical outcomes were assessed after sequential cognitive-behavioral therapy (CBT) and SDB therapy (CPAP, oral appliances, or bilateral turbinectomy) were provided to 17 chronic insomnia patients with SDB. Repeat measures included the Insomnia Severity Index, Functional Outcomes of Sleep Questionnaire, Pittsburgh Sleep Quality Index, and self-reported insomnia indices and CPAP use. RESULTS: In Study 1, seven objective measures of sleep and arousal demonstrated or approached significant improvement during one night of CPAP titration. Sixteen of 19 patients reported improvement in sleep quality. In Study 2, Insomnia Severity Index, Functional Outcomes of Sleep Questionnaire, and Pittsburgh Sleep Quality Index improved markedly with CBT followed by SDB treatment and achieved an average outcome equivalent to curative status. Improvements were large for each treatment phase; however, of 17 patients, only 8 attained a nonclinical level of insomnia after CBT compared with 15 patients after SDB therapy was added. Self-reported insomnia indices also improved markedly, and self-reported SDB therapy compliance was high. CONCLUSIONS: In one small sample of chronic insomnia patients with SDB, objective measures of insomnia, arousal, and sleep improved during one night of CPAP titration. In a second small sample, validated measures of insomnia, sleep quality, and sleep impairment demonstrated clinical cures or near-cures after combined CBT and SDB therapies. These pilot results suggest a potential value in researching the pathophysiological relationships between SDB and chronic insomnia, which may be particularly relevant to patients with refractory insomnia.

Chronic Disease↗

PubMed2003

An analysis of the Candida albicans genome database for soluble secreted proteins using computer-based prediction algorithms.

We sought to identify all genes in the Candida albicans genome database whose deduced proteins would likely be soluble secreted proteins (the secretome). While certain C. albicans secretory proteins have been studied in detail, more data on the entire secretome is needed. One approach to rapidly predict the functions of an entire proteome is to utilize genomic database information and prediction algorithms. Thus, we used a set of prediction algorithms to computationally define a potential C. albicans secretome. We first assembled a validation set of 47 C. albicans proteins that are known to be secreted and 47 that are known not to be secreted. The presence or absence of an N-terminal signal peptide was correctly predicted by SignalP version 2.0 in 47 of 47 known secreted proteins and in 47 of 47 known non-secreted proteins. When all 6165 C. albicans ORFs from CandidaDB were analysed with SignalP, 495 ORFs were predicted to encode proteins with N-terminal signal peptides. In the set of 495 deduced proteins with N-terminal signal peptides, 350 were predicted to have no transmembrane domains (or a single transmembrane domain at the extreme N-terminus) and 300 of these were predicted not to be GPI-anchored. TargetP was used to eliminate proteins with mitochondrial targeting signals, and the final computationally-predicted C. albicans secretome was estimated to consist of up to 283 ORFs. The C. albicans secretome database is available at http://info.med.yale.edu/intmed/infdis/candida/

Algorithms↗

PubMed2003

Therapy of cutaneous leishmaniasis.

There have been many treatment modalities used for the therapy of cutaneous leishmaniasis. Although treatment need not be given for cosmetically insignificant lesions, which are often self-limited, therapy is usually indicated for larger, cosmetically significant and disfiguring lesions, and lesions which progress. This review summarizes the published evidence in support of the numerous therapeutic options that have been employed for cutaneous leishmaniasis.

Animals↗

PubMed2002

Sleep Dynamic Therapy for Cerro Grande Fire evacuees with posttraumatic stress symptoms: a preliminary report.

BACKGROUND: Sleep disturbance is common among disaster survivors with posttraumatic stress symptoms but is rarely addressed as a primary therapeutic target. Sleep Dynamic Therapy (SDT), an integrated program of primarily evidence-based, nonpharmacologic sleep medicine therapies coupled with standard clinical sleep medicine instructions, was administered to a large group of fire evacuees to treat posttraumatic insomnia and nightmares and determine effects on posttraumatic stress severity. METHOD: The trial was an uncontrolled, prospective pilot study of SDT for 66 adult men and women, 10 months after exposure to the Cerro Grande Fire. SDT was provided to the entire group in 6, weekly, 2-hour sessions. Primary and secondary outcomes included validated scales for insomnia, nightmares, posttraumatic stress, anxiety, and depression, assessed at 2 pretreatment baselines on average 8 weeks apart, weekly during treatment, posttreatment, and 12-week follow-up. RESULTS: Sixty-nine participants completed both pretreatment assessment, demonstrating small improvement in symptoms prior to starting SDT. Treatment and posttreatment assessments were completed by 66 participants, and 12-week follow-up was completed by 59 participants. From immediate pretreatment (second baseline) to posttreatment, all primary and secondary scales decreased significantly (all p values < .0001) with consistent medium-sized effects (Cohen's d = 0.29 to 1.09), and improvements were maintained at follow-up. Posttraumatic stress disorder subscales demonstrated similar changes: intrusion (d = 0.56), avoidance (d = 0.45), and arousal (d = 0.69). Fifty-three patients improved, 10 worsened, and 3 reported no change in posttraumatic stress. CONCLUSION: In an uncontrolled pilot study, chronic sleep symptoms in fire disaster evacuees were treated with SDT, which was associated with substantive and stable improvements in sleep disturbance, posttraumatic stress, anxiety, and depression 12 weeks after initiating treatment.

Clinical Protocols↗

PubMed2001

Overexpression of a dominant-negative allele of YPT1 inhibits growth and aspartyl protease secretion in Candida albicans.

To investigate the pre-Golgi secretion pathway in the pathogenic yeast Candida albicans, we cloned the C. albicans homologue of the Saccharomyces cerevisiae protein secretion gene YPT1. The C. albicans YPT1 ORF contained a 624 bp intronless ORF encoding a deduced protein of 207 aa and 2.3 kDa. This deduced protein was 77% identical to S. cerevisiae Ypt1 protein (Ypt1p) and it contained GTP-binding domains that are conserved among all known ras-like GTPases. Multicopy plasmids containing C. albicans YPT1 complemented the temperature-sensitive S. cerevisiae ypt1 (A136D) mutation. One chromosomal YPT1 allele in C. albicans CAI4 was readily disrupted by homologous gene targeting, but attempts to disrupt the second allele yielded no viable null mutants. Since this suggested that C. albicans YPT1 may be essential, a mutant ypt1 allele was constructed encoding the amino acid substitution analogous to the N121I substitution in a known trans-dominant inhibitor of S. cerevisiae Ypt1p. Next, a GAL1-regulated plasmid was used to express the mutant ypt1(N121I) allele in C. albicans CAI4. Ten of 11 transformants tested grew normally in glucose and poorly in galactose, and plasmid curing restored growth to wild-type levels. When these transformants were incubated in galactose, secretion of aspartyl proteinase (Sap) was inhibited and membrane-bound secretory vesicles accumulated intracellularly. These results imply that C. albicans YPT1 is required for growth and protein secretion, and they confirm the feasibility of using inducible dominant-negative alleles to define the functions of essential genes in C. albicans.

Alleles↗