Biomedical subjects

J Lee

Publications and source records attributed to J Lee.

At least 325 records · Page 18Linked to original sources

PubMed2001

A deubiquitinating enzyme, UCH/CeUBP130, has an essential role in the formation of a functional microtubule-organizing centre (MTOC) during early cleavage in C. elegans.

BACKGROUND: Deubiquitinating enzymes generate monomeric ubiquitin in protein degradation pathways and are known to be important for the early development in many organisms. RESULTS: RNA interference experiments targeted for a UBP homologue, UCH/CeUBP130, in C. elegans resulted in cell division defective embryos. Immunostaining localized UCH/CeUBP130 in the sperm and at the microtubule-organizing centre (MTOC) during early cleavage. Furthermore, the embryonic lethal phenotype was rescued by mating with wild-type males. CONCLUSIONS: Since it is known that the MTOC in the fertilized embryo is contributed by sperm asters in C. elegans, we suggest that UCH/CeUBP130 and ubiquitin protein degradation pathways may be involved in microtubule-based sperm aster formation. Therefore UCH/CeUBP130 is necessary for the formation of a functional MTOC in the fertilized embryo of C. elegans.

Amino Acid Sequence↗

PubMed2001

Students' perception of medical school stress and their evaluation of a wellness elective.

CONTEXT: Because medical education is known to be demanding and stressful, Case Western Reserve University developed a programme which included a wellness elective which focused on stress reduction and personal wellness. OBJECTIVES: The purpose of this study was to explore students' perceptions of medical school stress and to assess their perspective on the wellness elective. SUBJECTS: The essays of 60 medical students enrolled in the wellness elective were used. METHODS: The essays were analysed using qualitative methodology. Results were validated by questionnaires mailed to the students 2 years later. RESULTS: It was found that the students felt that: (1) wellness issues should be important for physicians; (2) their own wellbeing had been diminished by the burden of information to be learned in medical school; (3) talking to peers was a useful coping mechanism, and (4) the elective gave permission to engage in wellness activities without additional guilt. CONCLUSIONS: Based on the students' responses, a wellness elective could be a useful addition to the first- or second-year medical curriculum.

Adaptation, Psychological↗

PubMed2001

Cassette mutagenesis of lysine 130 of human glutamate dehydrogenase. An essential residue in catalysis.

It has been suggested that reactive lysine residue(s) may play an important role in the catalytic activities of glutamate dehydrogenase (GDH). There are, however, conflicting views as to whether the lysine residues are involved in Schiff's base formation with catalytic intermediates, stabilization of negatively charged groups or the carbonyl group of 2-oxoglutarate during catalysis, or some other function. We have expanded on these speculations by constructing a series of cassette mutations at Lys130, a residue that has been speculated to be responsible for the activity of GDH and the inactivation of GDH by pyridoxal 5'-phosphate (PLP). For these studies, a 1557-bp gene that encodes human GDH has been synthesized and inserted into Escherichia coli expression vectors. The mutant enzymes containing Glu, Gly, Met, Ser, or Tyr at position 130, as well as the wild-type human GDH encoded by the synthetic gene, were efficiently expressed as a soluble protein and are indistinguishable from that isolated from human and bovine tissues. Despite an approximately 400-fold decrease in the respective apparent Vmax of the Lys130 mutant enzymes, apparent Km values for NADH and 2-oxoglutarate were almost unchanged, suggesting the direct involvement of Lys130 in catalysis rather than in the binding of coenzyme or substrate. Unlike the wild-type GDH, the mutant enzymes were unable to interact with PLP, indicating that Lys130 plays an important role in PLP binding. The results with analogs of PLP suggest that the aldehyde moiety of PLP, but not the phosphate moiety, is required for efficient binding to GDH.

Amino Acid Sequence↗

PubMed2001

Iodoacetate protects hippocampal neurons against excitotoxic and oxidative injury: involvement of heat-shock proteins and Bcl-2.

Mild metabolic stress may increase resistance of neurons in the brain to subsequent, more severe insults, as demonstrated by the ability of ischemic pre-conditioning and dietary restriction to protect neurons in experimental models of stroke- and age-related neurodegenerative disorders. In the present study we employed iodoacetic acid (IAA), an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, to test the hypothesis that inhibition of glycolysis can protect neurons. Pre-treatment of cultured hippocampal neurons with IAA can protect them against cell death induced by glutamate, iron and trophic factor withdrawal. Surprisingly, protection occurred with concentrations of IAA (2-200 nM) much lower than those required to inhibit glycolysis. Pre-treatment with IAA results in suppression of oxyradical production and stabilization of mitochondrial function in neurons after exposure to oxidative insults. Levels of the stress heat-shock proteins HSP70 and HSP90, and of the anti-apoptotic protein Bcl-2, were increased in neurons exposed to IAA. Our data demonstrate that IAA can stimulate cytoprotective mechanisms within neurons, and suggest the possible use of IAA and related compounds in the prevention and/or treatment of neurodegenerative conditions.

Adenosine Triphosphate↗

PubMed2001

Increased expression of atrial natriuretic peptide in the kidney of rats with bilateral ureteral obstruction.

BACKGROUND: Whether the postobstructive diuresis can be related to an altered regulation of local atrial natriuretic peptide (ANP) in the kidney was investigated. METHODS: Three groups of rats had both of their ureters obstructed for 48 hours. The kidneys were taken without releasing the obstruction in one group [bilateral ureteral obstruction (BUO)]. The obstruction was released in the other two groups and the animals were kept for 4 and 24 hours thereafter to collect urinary data (BUR-4 and BUR-24, respectively). Plasma and urine ANP levels were measured by radioimmunoassay. The mRNA expression of ANP, natriuretic peptide receptor-A (NPR-A), and NPR-C was determined by reverse transcription-polymerase chain reaction. ANP receptors were also quantitated by in vitro autoradiography. The activity of guanylyl cyclase was determined by the amount of cGMP generated in response to ANP. RESULTS: Urinary volume and sodium excretion increased in BUR-4, along with the ANP mRNA expression in the kidney and the urinary ANP excretion. The ANP excretion positively correlated with the urinary volume and sodium excretion. The mRNA expression of both NPR-A and NPR-C was decreased by BUO, the latter being far more prominently affected. The maximal binding capacity of radiolabeled ANP was decreased in the glomerulus and papilla in BUO. Not only the urinary parameters but also the mRNA expression of ANP, NPR-A, and NPR-C were comparable between BUR-24 and control rats. ANP-stimulated cGMP generation was reduced in the glomerulus and papilla in BUO animals, which was rapidly resumed following the release of the obstruction. CONCLUSIONS: Postobstructive diuresis may be due partially to an increased ANP activity in the kidney.

Animals↗

PubMed2001

Glycolic acid treatment increases type I collagen mRNA and hyaluronic acid content of human skin.

BACKGROUND: Chronic solar irradiation results in both morphologic and functional changes in affected skin. alpha-hydroxy acids, such as glycolic acid, have been shown to improve photodamaged skin. OBJECTIVE: To investigate alterations in collagen gene induction and epidermal and dermal hyaluronic acid production as a result of administered glycolic acid. METHODS: In this study we compared collagen gene expression from skin biopsy specimens, and epidermal and dermal hyaluronic acid immunohistochemical staining between glycolic acid-treated and vehicle-treated skin. Forearm skin was treated with 20% glycolic acid lotion or a lotion vehicle control twice a day for 3 months. RESULTS: Epidermal and dermal hyaluronic acid and collagen gene expression were all increased in glycolic acid-treated skin as compared to vehicle-treated controls. CONCLUSION: Our data suggest that epidermal and dermal remodeling of the extracellular matrix results from glycolic acid treatment. Longer treatment intervals may result in collagen deposition as suggested by the measured increase in mRNA.

Aged↗

PubMed2001

Testicular torsion: a review.

Torsion of the testis, also referred to as torsion of the spermatic cord, is a subject of debate among physicians and surgeons. Testicular torsion is an acute vascular event causing the rotation of the vascular pedicle of the testis, thereby impeding the blood flow to the testis and the scrotal contents. It could be either within or outside the tunica vaginalis. Testicular torsion causes immediate circulatory changes and long-term sequelae such as testicular function and fertility. It is considered a surgical emergency, as a delay causes irreversible testicular damage. The diagnosis and treatment of testicular torsion are discussed in this review, which also illustrates an algorithm and a scoring system for the diagnosis and management of this condition based on current literature.

Journal Article↗

PubMed2001

Acetazolamide in women with catamenial epilepsy.

PURPOSE: Catamenial epilepsy is a condition characterized by an increase in seizures during particular phases of the menstrual cycle. The incidence of catamenial epilepsy varies widely, partly because of a lack of a universally adopted definition. Specific treatment options for these patients are limited. The use of acetazolamide (AZ) has been based largely on anecdotal reports demonstrating efficacy in small or poorly characterized populations. The purpose of this study was to analyze retrospectively the efficacy, safety profile, and tolerability of AZ in women with catamenial epilepsy. METHODS: Women with catamenial epilepsy identified from 1990 through 1999 were invited to participate in a retrospective telephone questionnaire addressing the relationship of seizures and the menstrual cycle and the use, efficacy, and adverse effects of AZ. Seizure outcome was classified as: seizure free (SF), significantly improved (SI), or not significantly improved (NSI). Responses to AZ were compared in women with different types of epilepsy and comparing continuous versus intermittent dosing using Fisher's exact tests. RESULTS: Twenty women were identified who had received or were currently taking AZ. The drug was given continuously in 55% and intermittently in 45% of patients. A > or =50% decrease in the seizure frequency was reported by 40% of subjects. Response rates were similar in generalized and focal epilepsy and in temporal and extratemporal epilepsy. There was no significant difference in effectiveness comparing continuous with intermittent dosing. A loss of efficacy over 6-24 months was reported by 15% of women. CONCLUSIONS: Despite our small sample and retrospective design, AZ appears to demonstrate efficacy for catamenial epilepsy.

Acetazolamide↗

PubMed2001

The effects of lamotrigine on sleep in patients with epilepsy.

PURPOSE: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in REM, slow-wave sleep (SWS) and sleep latency, and increased percentage of light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of lamotrigine (LTG) on sleep. METHODS: Ten adults with focal epilepsy, in whom the decision was made to add LTG to either phenytoin (PHT) or carbamazepine (CBZ) for control of seizures, were the subjects of this study. Patients underwent pre- and posttreatment polysomnography (PSG) and completed sleep questionnaires. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon sign rank test. RESULTS: Seven patients were taking CBZ, and three were treated with PHT. All subjects were titrated to an LTG dose of 400 mg/day. Treatment with LTG produced a significant decrease in SWS and an increase in stage 2 sleep percentage. No significant difference in ESS or any of the other polygraphic variables was observed. However, LTG treatment was associated with a reduction in arousals and stage shifts and an increase in REM periods. No subjects reported insomnia with treatment. CONCLUSIONS: LTG appears to be less disruptive to sleep than some of the older AEDs.

Adult↗

PubMed2001

Stability of the lumbar spine after intradiscal electrothermal therapy.

OBJECTIVE: To assess the stability of the human lumbar cadaveric spinal motion segment before and after treatment with intradiscal electrothermal therapy (IDET). DESIGN: An in vitro biomechanic analysis of 5 human cadaveric spinal motion segments by using nondestructive biomechanic testing in flexion/extension, lateral bending, and axial rotation with loads of 0N, 600N, and 1200N. SETTING: University-based hospital research center. CADAVERS: Spinal unit specimens (upper and middle lumbar) from 5 human cadavers (age range, 39-79yr). INTERVENTIONS: A spinal catheter consisting of a thermal-resistive heating coil was placed circumferentially into the outer annulus by using the standard extrapedicular discographic technique through a 17-gauge introducer needle. The disc was then heated in a saline bath (37 degrees C) from 65 degrees C up to 90 degrees C for a total of 17 minutes. MAIN OUTCOME MEASURE: The stability of the spinal segments was measured before and shortly after IDET. Stability of the spine was measured as the compliance of the spine (the angular deformation afforded by the spine under applied bending moments). RESULTS: With increasing preloads, there is a decrease in motion of the spinal segment in all planes of testing. However, there was no significant difference (p >.05) in the stability of the lumbar spine before and after treatment with IDET. CONCLUSIONS: IDET does not destabilize the spinal motion segment in vitro.

Adult↗

PubMed2001

Intradiskal electrothermal therapy: a preliminary histologic study.

OBJECTIVE: To characterize descriptively the histologic and temperature effects of intradiskal electrothermal annuloplasty on human cadaveric lumbar disks. DESIGN: In vitro histologic study. SETTING: Hospital-based soft-tissue research laboratory. CADAVERS: Six human cadaveric lumbar disks, from 5 cadavers aged 39 to 79 who died from nonspine-related causes. INTERVENTIONS: Intradiskal electrothermal therapy (IDET) by using a standard high-temperature heating protocol with the temperature of the probe gradually increased from 65 degrees C to 90 degrees C over 16.5 minutes. Disks were stained and examined by light microscopy and electron microscopy. MAIN OUTCOME MEASURES: Temperatures in outer annulus, gross macroscopic changes, and histologic damage. RESULTS: Gross inspection showed a small circumferential area of tissue alteration localized to the posterior annulus but not extending to the endplates. Light microscopy of the posterior aspect of the lumbar disks showed denaturation, shrinkage, and coalescence of annular collagen; the anterior portions, which served as internal controls, showed no evidence of damage. The endplates were structurally preserved and showed no evidence of damage. Electron microscopy showed extensive collagen disorganization, decreased quantity of collagen, collagen fibril shrinkage, and chondrocyte damage when compared with a control portion. The temperature curves showed parallel changes in temperature at the level of the probe and at the posterior portion of the disk. CONCLUSIONS: IDET raises temperatures sufficiently to induce collagen denaturation and coalescence. These histologic changes may play a substantial role in the clinical efficacy of IDET.

Adult↗

PubMed2001

Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat.

BACKGROUND & AIMS: Cholestasis results in adaptive regulation of bile salt transport proteins in hepatocytes that may limit liver injury. However, it is not known if changes also occur in the expression of bile salt transporters that reside in extrahepatic tissues, particularly the kidney, which might facilitate bile salt excretion during obstructive cholestasis. METHODS: RNA and protein were isolated from liver and kidney 14 days after common bile duct ligation in rats and assessed by RNA protection assays, Western analysis, and tissue immunofluorescence. Sodium-dependent bile salt transport was also measured in brush border membrane vesicles from the kidney. RESULTS: After common bile duct ligation, serum bile salts initially rose and then declined to lower levels after 3 days. In contrast, urinary bile salt excretion rose progressively over the 2-week period. By that time, the ileal sodium-dependent bile salt transporter messenger RNA and protein expression in total liver had increased to 300% and 200% of controls, respectively, while falling to 46% and 37% of controls, respectively, in the kidney. Sodium-dependent uptake of (3)H-taurocholate in renal brush border membrane vesicles was decreased. In contrast, the multidrug resistance-associated protein 2 expression in the kidney was increased 2-fold, even 1 day after ligation. Immunofluorescent studies confirmed the changes in the expression of these transporters in liver and kidney. CONCLUSIONS: These studies show that the molecular expression of bile salt transporters in the kidney and cholangiocytes undergo adaptive regulation after common bile duct obstruction in the rat. These responses may facilitate extrahepatic pathways for bile salt excretion during cholestasis.

Adaptation, Physiological↗

PubMed2001

The watershed labral lesion: its relationship to early arthritis of the hip.

This study examined the hypothesis that labral lesions contribute to early degenerative hip disease. Between 1993 and 1999, 436 consecutive hip arthroscopies were performed by the senior author (J.C.M.). In addition, 54 acetabula were harvested from human adult cadavers and 10 hips underwent microangiography to determine labral blood supply. Of the 436 arthroscopic patients, 241 (55.3%) had a total of 261 labral tears, all located at the articular, not capsular, margin of the labrum. Stereomicroscopic examination of the 54 cadaver acetabula revealed a total of 52 labral lesions. Overall, there was no significant difference between the arthroscopic and cadaver populations in terms of the incidence of labral tears (P=.315). There was a high association between labral lesions and adjacent acetabular chondral damage. Arthroscopic and anatomic observations support the concept that labral disruption and degenerative joint disease frequently are part of a continuum of joint pathology.

Acetabulum↗

PubMed2001

On the investigation of homeopathic potencies using low resolution NMR T2 relaxation times: an experimental and critical survey of the work of Roland Conte et al.

We have attempted to reproduce differences in low resolution nuclear magnetic resonance (NMR) T2 spin-spin relaxation times between homeopathically potentised and unpotentised Nitric acid (nit-ac) solutions previously reported by Conte, et al. Using similar instrumentation and experimental protocols, we have shown that it is likely that Conte's original results are attributable to experimental artifact originating in the glassware used for the manufacture of the NMR tubes.

Homeopathy↗

PubMed2001

Amphotericin B decreases adenylyl cyclase activity and aquaporin-2 expression in rat kidney.

The present study was intended to examine whether the amphotericin-induced urinary concentration defect can be related to an altered regulation of aquaporin (AQP) water channels in the kidney. Male Sprague-Dawley rats were injected with amphotericin B (6 mg/kg/d, IP ) for 21 days. The protein expression of AQP1-3, Gsalpha, and adenylyl cyclase was determined in the kidney. To further specify the primary point of dysregulation of AQP channels that are activated by the arginine vasopressin/cyclic adenosine monophosphate (AVP/cAMP) pathway, different components of adenylyl cyclase complex were separately examined for their cAMP-generating activities. Amphotericin treatment resulted in kidney failure associated with decreased tubular water reabsorption and increased urinary flow rate. The expression of AQP2 proteins was significantly decreased in the outer medulla and inner medulla but not in the cortex. The expression of AQP2 proteins in the membrane fraction changed in parallel with that in the cytoplasmic fraction, suggesting a preserved targeting. Neither the expression of AQP1 nor that of AQP3 was significantly affected in the cortex, outer medulla, or inner medulla. The cAMP generation in response to AVP or sodium fluoride was decreased, whereas that to forskolin was not significantly altered. The expression of Gsalpha proteins was decreased in the inner medulla, whereas that of adenylyl cyclase VI remained unaltered. These findings indicate that the amphotericin-induced urinary concentration defect may in part be causally related to a reduced abundance of AQP2 channels in the kidney. It is also suggested that the primary impairment in the pathway leading to the activation of AQP channels that are regulated by the AVP/cAMP pathway lies at the level of G proteins.

Adenylyl Cyclases↗

PubMed2001

The prevalence of uveitis in juvenile rheumatoid arthritis.

BACKGROUND: Because asymptomatic uveitis has been an important cause of visual loss in children with juvenile rheumatoid arthritis, periodic ophthalmologic screenings of such patients have been recommended. Recently, some authors have found a decreased prevalence of uveitis in children with juvenile rheumatoid arthritis. METHODS: We studied a total of 76 patients (63 girls and 13 boys, aged 1 to 16 years), referred to 3 pediatric ophthalmology practices between March 1976 and October 1999. Follow-up examinations were performed at intervals of 3 to 6 months according to current guidelines, during the following 6 months to 23 years (mean, 55 months). RESULTS: Uveitis developed in 10 children (13%). Of these 10 children, 2 were symptomatic (blurred vision, discomfort) and 7 were diagnosed with uveitis at the initial visit. Only 1 patient had asymptomatic uveitis after initial negative findings on screening examination. Final visual acuity for all the compliant children in the uveitis group was better than 20/30. DISCUSSION: The prevalence of uveitis in our study is similar to rates found by other recent authors. This decrease may reflect a tendency for systemic medications to prevent the development of ocular inflammation. We believe that screening guidelines should be reevaluated, especially for asymptomatic children with negative findings on initial examinations.

Adolescent↗

PubMed2001

Endovascular exclusion of descending thoracic aortic aneurysms and chronic dissections: Initial clinical results with the AneuRx device.

OBJECTIVE: The objective of this study was to analyze a single-center experience in which descending thoracic aortic aneurysms (TAAs) were treated with a new self-expanding endovascular prosthesis (Medtronic AVE). METHODS: Twenty-six patients (13 men, 13 women) with American Society of Anesthesiology grades II to IV and ages ranging from 53 to 92 years (average, 74 years) consented as part of a Phase I Food and Drug Administration-approved trial. Treated lesions included TAAs that were 5 to 10 cm in diameter, 12 diffuse dilations or fusiform aneurysms, and four saccular aneurysms. There were also nine chronic dissections (2 aneurysmal dilations and 7 symptomatic acute recurrent dissections). Three patients (2 with diffuse/fusiform and 1 with dissection) presented with hemothorax, contrast extravasation, or both. RESULTS: Twenty-five of the 26 patients who consented (96% technical success) were treated successfully with no surgical conversions. Eighteen patients have been followed up from 1 to 22 months (average, 9 months). One patient is lost to follow-up, and six patients have died (24%). One procedure-related death (4%) occurred within the 30-day postoperative period and was caused by diffuse embolization. There were no device-related deaths. Five additional patients (20%) have died during the study of comorbid conditions. Complications included one massive myocardial infarction 24 hours after the procedure requiring balloon counterpulsation and long-term dialysis, one cardiac tamponade resulting from central line placement before the procedure, one progression of aneurysm dilation proximal to the device at 1 year, and one bilateral lower extremity paralysis occurring 12 hours after successful deployment. Seven patients (5 women) had femoral artery reconstructions or iliac artery grafts to repair injuries during deployment catheter passage. Other significant parameters included average procedure time (2 hours 40 minutes; range, 1 hour 30 minutes to 5 hours 30 minutes), 450 cc average blood loss (n = 25; 100-3000 cc) being replaced by means of autotransfusion with only two patients receiving banked blood products, and an average 2 days to resumption of normal diet, 1 day in the intensive care unit, and 5 days' hospitalization postprocedure in uncomplicated cases (n = 22). One patient had an endoleak immediately after the procedure that sealed without treatment. Follow-up of all patients ranging from 1 to 22 months (average, 9 months; n = 18) demonstrates continued exclusion of the aneurysm with no endoleaks and either stable or decreasing aneurysm volume, except in one patient with volume increase and no obvious etiology who continues to be investigated. CONCLUSIONS: The study suggests that endovascular prosthesis exclusion of TAAs with an AneuRx self-expanding tubular device may be effective in many patients who are at significant risk for open surgical repair and substantiates further clinical investigation to confirm these findings.

Aged↗

PubMed2001

Botulinum toxin to the lateral rectus for the treatment of esotropia with paradoxical diplopia.

A retrospective review of six patients with paradoxical diplopia in the presence of esotropia was carried out. All patients were treated with botulinum toxin to the lateral rectus of the affected side. Five patients had no diplopia post toxin and the remaining patient had diplopia which could be ignored. The number of injections per patient ranged between 3 and 34. Three patients went on to have surgery to increase the angle of esotropia, with relief of diplopia. We conclude that botulinum toxin has a role in the treatment of esotropic patients with paradoxical diplopia.

Adolescent↗