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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 289 records · Page 16Linked to original sources
PubMed2001

Decreased circulating levels of estrogen alter vaginal and clitoral blood flow and structure in the rabbit.

Aging and menopause related decline in circulating levels of estrogen has been shown to adversely affect female sexual arousal function. Our aim was to study the effects of circulating levels of estrogen on the hemodynamic mechanism of vaginal and clitoral engorgement and on the structure of the vaginal and clitoral cavernosal tissue in the rabbit. New Zealand White female rabbits (3.5-4 kg) were randomly divided into three groups with five rabbits in each group: control; bilateral oophorectomy; bilateral oophorectomy undergoing subcutaneous injection of estrogen (40 microg/kg/day). After 6 weeks, the serum levels of 17 beta-estradiol were measured and systemic blood pressure was monitored. Vaginal and clitoral cavernosal blood flows were measured with laser Doppler flowmeter before and after pelvic nerve stimulation. Cross sections of the clitoris and vagina were processed for histologic examination and histomorphometric image analysis. Serum level of 17 beta-estradiol (pg/ml; mean+/-s.d.) revealed a significant decrease in the oophorectomy group (25.4+/-5.1) compared with the control (38.5+/-7.6) and estrogen replacement (115.9+/-57.3) groups (P<0.05). Nerve stimulation-induced peak vaginal and clitoral intracavernosal blood flows in the oophorectomy group (28.9+/-16.3 and 6.1+/-1.4, respectively) were significantly less than those recorded in the control (48.9+/-6.5 and 11.0+/-2.4, respectively) or estrogen replacement (48.7+/-12.2 and 10.1+/-2.8, respectively) group (P<0.05). In histology, marked thinning of the vaginal epithelial layers, decreased vaginal submucosal microvasculature, and diffuse clitoral cavernosal fibrosis were evident in the oophorectomy group but not in the estrogen supplement and control groups. In histomorphometry, the percentage of clitoral cavernosal smooth muscle in the oophorectomy group (49.6+/-6.2) was significantly decreased compared with the control (56.8+/-2.6) and estrogen replacement (58+/-3.0) groups (P<0.05). Our studies show that decline in circulating levels of estrogen impairs the hemodynamic mechanism of vaginal and clitoral engorgement and leads to histopathologic changes in the vagina and clitoral cavernosal tissue. These observations suggest that decreased circulating levels of estrogen, a physiologic change in the menopausal state, may play a role in the development of female sexual arousal dysfunction.

Animals↗
PubMed2001

Effects of beacon administration on energy expenditure and substrate utilisation in Psammomys obesus (Israeli sand rats).

OBJECTIVE: To investigate whether beacon administration affects substrate utilisation, physical activity levels or energy expenditure in Psammomys obesus. DESIGN: Pairs of age- and sex-matched Psammomys obesus were randomly assigned to either beacon-treated (15 microg/day for 7 days (i.c.v.)) or control (i.c.v. saline) groups. MEASUREMENTS: Indirect calorimetry on day 0 and day 7 to measure oxygen consumption and carbon dioxide production, which were used to calculate fat oxidation, carbohydrate oxidation and total energy expenditure. Physical activity in the calorimeter was measured using an infrared beam system. Food intake and body weight were measured daily. RESULTS: The administration of beacon significantly increased body weight compared to saline-treated control animals. This body weight gain was primarily due to increased body fat content. Average daily food intake tended to be higher in beacon-treated Psammomys obesus, but no effect of beacon administration on substrate oxidation, activity or energy expenditure was detected. CONCLUSION: The effects of beacon on body weight are due to increased food intake, with no detectable effect on nutrient partitioning, physical activity or energy expenditure.

Adipose Tissue↗
PubMed2001

Effects of solar-simulated radiation dose fractionation on CD1a+ Langerhans cells and CD11b+ macrophages in human skin.

BACKGROUND: There are few human studies investigating the immunosuppressive effects of exposure to solar-simulated radiation (SSR) and its relationship with sunburn/erythema, and few comparative data on the importance of SSR exposure regimens. OBJECTIVES: To evaluate whether SSR-induced erythema is a reliable end-point for assessing damage to antigen-presenting cells (APCs) in human skin. METHODS: We compared the relationship between SSR-induced erythema and alterations in epidermal CD1a+ Langerhans cells (LCs) and CD11b+ macrophages in human volunteers after single exposures to 0, 0.5, 1, 2 or 3 minimal erythema doses (MED). We also investigated whether SSR exposure leads to an accumulation or accommodation of the same end-points by comparing the effects of a relatively low cumulative SSR dose (3 MED) given in varying daily dose fractions (4 x 0.75 MED, 2 x 1.5 MED and 1 x 3 MED). RESULTS: Single SSR exposures induced a dose-dependent increase in erythema. CD1a+ LCs remaining in the irradiated epidermis showed a dose-dependent increase in cell size and altered morphology. Significant depletion of CD1a+ LCs and presence of CD11b+ macrophages only occurred in sites irradiated with 2 MED and 3 MED. Dose fractionation had no effect on the final erythemal response but the 4 x 0.75 MED and 1 x 3 MED protocols were better tolerated than 2 x 1.5 MED for alterations in CD1a+ LC and CD11b+ cell numbers. In contrast, dose fractionation protected against alterations in CD1a+ LC morphology or cell size. CONCLUSIONS: We found that erythema is a poor indicator of alterations in epidermal APCs and that dose fractionation is an important parameter in the immunological effects of ultraviolet radiation.

Adult↗
PubMed2001

Experimental studies on the antiviral agent famciclovir in Behçet's disease symptoms in ICR mice.

BACKGROUND: Chronic oral aphthae, recurrent genital ulcers and uveitis are the three main manifestations of Behçet's disease (BD). The aetiopathogenesis of BD is still obscure, but herpes simplex virus (HSV) is one of the possible causal factors. Various kinds of drugs, including immunosuppressants and aciclovir have been used in treatment, but effectiveness is variable. OBJECTIVES: To demonstrate the efficacy of famciclovir, an antiviral compound that acts against HSV, varicella-zoster virus and hepatitis B virus, in a murine model of BD. METHODS: Using the HSV-induced BD mouse model, famciclovir was administered variously before and after inoculation or from the day of lesion occurrence, with appropriate controls. Ulceration of the mouth and genital skin and eye involvement were monitored. In addition, spleen cytokine expression was measured by polymerase chain reaction. RESULTS: Pretreatment and concurrent treatment did not affect the occurrence of BD, but treatment from the appearance of lesions was effective in improving BD and preventing recurrence. After famciclovir, interleukin 2 expression correlated with the recurrence of BD symptoms. CONCLUSIONS: This model suggests the possible role of immune response to viral infection in the development and activation of BD. The study provides a rationale for clinical trials of famciclovir in the human form of BD.

2-Aminopurine↗
PubMed2001

An evaluation of serum soluble CD30 levels and serum CD26 (DPPIV) enzyme activity as markers of type 2 and type 1 cytokines in HIV patients receiving highly active antiretroviral therapy.

This study evaluates serum CD26 (dipeptidyl peptidase IV, DPPIV) enzyme activity and serum levels of soluble CD30 as markers of T1 and T2 cytokine environments in HIV patients who achieved immune reconstitution after highly active antiretroviral therapy (HAART). Patients who had experienced inflammatory disease associated with pre-existent opportunistic infections after HAART (immune restoration diseases, IRD) were considered separately. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were compared with IFN-gamma production by PBMC cultured with cytomegalovirus (CMV) antigen in controls and patient groups. High sCD30 levels were associated with low IFN-gamma production after antigenic stimulation in control subjects and, to a lesser extent, in immune reconstituted HIV patients. There was no association between serum CD26 (DPPIV) enzyme activity and IFN-gamma production or sCD30 levels. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were significantly increased in immune reconstituted patients with high HIV viral loads. Patients who had experienced CMV retinitis as an IRD had significantly higher sCD30 levels than all other patient groups. Hence, high sCD30 levels may be a marker of a T2 cytokine environment in HIV patients with immune reconstitution and are associated with higher HIV viral loads and a history of CMV associated IRD.

AIDS-Related Opportunistic Infections↗
PubMed2001

Analysis of steroid-induced genes in the rat preoptic area-anterior hypothalamus using a differential-display reverse transcriptase-polymerase chain reaction.

Steroid hormones modulate a variety of physiological functions in the hypothalamus. We attempted to identify steroid-regulated genes in the rat preoptic area-anterior hypothalamus by comparing differentially expressed mRNAs. Adult female rats were ovariectomized and, 1 week later, a silastic capsule containing 17beta-oestradiol (180 microg/ml) was subcutaneously implanted. After 2 days, a single injection of progesterone (1 mg) was administered at 10.00 h and rats were killed at 17.00 h on the same day. Differential-display polymerase chain reaction followed by Northern blot analysis showed that 10 clones were differentially regulated. Using homology search in Genbank, three genes were identified as sodium, potassium-ATPase beta1, protein kinase C-binding Nell-homologue protein and evectin-1. Further characterization of 10 clones showed that the expression patterns were tissue-specific and differentially regulated during puberty. Among these, mRNAs for protein kinase C-binding Nell-homologue protein, evectin-1 and human CGI-118 protein-like gene were induced after vagina opening, and differentially expressed during the oestrous cycle. Taken together, several steroid-regulated genes identified in the present study may play an important role in regulating hypothalamic functions, including puberty and the oestrous cycle.

Animals↗
PubMed2001

Pattern analysis of sleep-deprived human EEG.

Progress during the past decade in non-linear dynamics and instability theory has provided useful tools for understanding spatio-temporal pattern formation. Procedures which apply principle component analysis (using the Karhunen-Loeve decomposition technique) to the multichannel electroencephalograph (EEG) time series have been developed. This technique shows localized changes of cortical functioning; it identifies increases and decreases of the activity of localized cortical regions over time while the subject performs a simple task or test. It can be used to demonstrate the change in cortical dynamics in response to a continuous challenge. Using 16 EEG electrodes, the technique provides spatio-temporal information not obtained with power spectrum analysis, and includes the weighted information given with omega complexity. As an application, we performed a pattern analysis of sleep-deprived human EEG data in 20 healthy young men. Electroencephalograph recordings were performed on subjects for <2 min, with eyes closed after normal sleep and after 24 h of experimentally-induced sleep deprivation. The significant changes in the eigenvector components indicated the relative changes of local activity in the brain with progressive sleep deprivation. A sleep deprivation effect was observed, which was hemispherically correlated but with opposite directional dynamics. These changes were seen in the temporo-parietal regions bilaterally. The application of the technique showed that the simple test task was performed with a limited unilateral hemispheric involvement at baseline, but needed a much larger cortical participation with decreased frontal activity and increased coherence and bilateral hemispheric involvement. The calculations performed demonstrated that the same weighted changes as those obtained with omega complexity were shown, but the technique had the added advantage of showing the localized directional changes of the principle eigenvector at each studied electrode, pointing out the cortical localized region affected by the sleep deprivation and toward which direction the environmental challenge induced the spatial change. This methodology may allow the evaluation of changes in local dynamics in brain activity in normal and pathological conditions.

Adult↗
PubMed2001

Phosphatidic acid activates a wound-activated MAPK in Glycine max.

Many plant species demonstrate a systemic increase in phosphatidic acid (PA) levels after being wounded (Lee et al., 1997). To understand the role of PA in wound signal transduction, we investigated if PA can activate protein kinases in soybean (Glycine max L.). We found that a MAPK is activated in soybean seedlings in both wounded and neighboring unwounded leaves. The wound-activated soybean kinase is specifically recognized by an antibody against the alfalfa MAPK, SIMK. When PA production is inhibited with n-butanol, an inhibitor of phospholipase D, the wound-induced activation of the MAPK is suppressed, suggesting that an elevation in PA levels is essential for its activation. Supporting this is the observation that exogenous PA activates the MAPK in suspension-cultured soybean cells. Activation of the 49 kDa MAPK occurs almost exclusively by PA, as other lipids are unable to or can only weakly activate the kinase. PA-induced activation of the MAPK is not a direct effect on the kinase but is mediated by upstream kinases. Our results suggest that PA acts as a second messenger in wound-induced MAPK signaling in plants.

Cross Reactions↗
PubMed2001

Point mutations in KEL exon 8 determine a high-incidence (RAZ) and a low-incidence (KEL25, VLAN) antigen of the Kell blood group system.

BACKGROUND AND OBJECTIVES: The molecular basis of two Kell blood group antigens, RAZ (provisionally KEL27) and VLAN (KEL25), were determined. MATERIALS AND METHODS: The DNA sequences of the open reading frames and the flanking intron regions of the 19 KEL exons from RAZ and VLAN probands were compared with that of common KEL. Genotyping assays were designed to confirm and detect RAZ and VLAN phenotypes. RESULTS: A homozygous G865A mutation, encoding lysine instead of glutamic acid at amino acid position 249 of Kell protein, defines the RAZ phenotype, while a heterozygous G863A mutation in KEL, encoding an arginine to glutamine substitution at amino acid 248, characterizes the VLAN phenotype. CONCLUSION: Point mutations G865A and G863A, in adjacent codons of KEL exon 8, which cause amino acid substitutions, characterize the RAZ and VLAN Kell blood group phenotypes.

Antigens↗
PubMed2001

Determination of binding constant of transcription factor AP-1 and DNA. Application of inhibitors.

The equilibrium binding and association kinetics of the fos-jun dimer (basic and leucine zipper domain) to the AP-1 DNA were studied using a quantitative assay. The basic-region and leucine zipper (bZip) domain of c-fos was expressed as a fusion protein with glutathione S-transferase, and it was bound to glutathione-agarose. The GST-fused fos bZip region was allowed to form a heterodimer with the bZip domain of c-jun, to which radiolabeled AP-1 nucleotides were added. After thorough washing, the gel-bound radioactivity was counted. The binding and dissociation rate constants (k(1) and k-(1)) of the fos-jun dimer and DNA could be obtained from a time-course experiment. The association binding constant (K(1)) was determined using both a thermodynamic equation and kinetic parameters. Nordihydroguaiaretic acid (NDGA), momordin I, natural product inhibitors of the fos-jun/DNA complex formation, was applied to this jun-GST-fused fos system and it was found to decrease the apparent equilibrium binding of dimer and DNA. The thermodynamic constant of dimer and inhibitor binding was also determined.

Cloning, Molecular↗
PubMed2001

Localization and coexistence of calcium-binding proteins and neuropeptides in the vagal ganglia of the goat.

This study was performed to investigate the neurochemical characteristics of the vagal ganglia of the goat by immunohistochemical methods using calbindin D-28k (CB), calretinin (CR). parvalbumin (PA), substance P (SP). calcitonin generelated peptide (CGRP) and galanin (GAL) antibodies. In the proximal vagal ganglia (jugular ganglia), CGRP- (57.1%), SP- (48.2%), GAL- (8.6%), PA- (8.7%), CB- (8.5%) and CR-like (5.3%) immunoreactive cells were observed. In the distal vagal ganglia (nodose ganglia), CGRP- (40.5%), SP- (30.20%), CB- (22.0%) and CR-like (18.10%) immunoreactive cells were present. The double immunohistochemical study showed, that in the proximal vagal ganglia, CGRP immunoreactivity was co-localized in SP- (84.8%), GAL-(100%), CB- (5.6%) and CR- (5.7%) immunoreactive cells: SP immunoreactivity was co-localized in the CGRP- (80.0%), GAL- (100%). CB- (5.3%) and CR- (5.6%) immunoreactive cells; GAL immunoreactivity coexisted in the CGRP- (4.4%) and SP- (19.8%) immunoreactive cells, but not in calcium-binding proteins (CBP)-immunoreactive cells; PA immunoreactivity was absent in the CGRP- and SP-immunoreactive cells; CB and CR immunoreactivities were seen in the CGRP-(0.8%) and SP-immunoreactive (0.9%) cells. On the other hand, in the distal vagal ganglia, CGRP immunoreactivity appeared in SP- (66.6%), CB- (1.0%) and CR- (1.2%) immunoreactive cells; SP immunoreactivities were observed in the CGRP- (44.1%), CB- (1.0%) and CR- (1.2%) immunoreactive cells; CB immunoreactivities were present in the CGRP- (0.5%) and SP- (0.8%) immunoreactive cells; CR immunoreactivities were contained in the CGRP- (0.5%) and SP- (0.8%) immunoreactive cells. These findings indicate that the goat is distinct from other mammalian species in the distribution and localization of neurochemical substances in the vagal ganglia. and suggest that these differences may be related to physiological characteristics, particular those of the ruminant digestive system.

Animals↗
PubMed2001

Reactive perforating collagenosis: a condition that may be underdiagnosed.

Reactive perforating collagenosis is a perforating disorder developing in adults, usually in association with diabetes mellitus or renal failure. We present three cases diagnosed at the Royal Prince Alfred Hospital in a 5 month period. All three patients had long-standing diabetes mellitus, hypertension, hypercholesterolaemia and ischaemic heart disease. Each patient presented with generalized pruritus and a papular eruption across the trunk and limbs. More than one biopsy or multiple levels were needed before the diagnostic histological features were seen. The first patient responded to 0.5% phenol with 10% glycerine in sorbolene cream. The second patient did not respond to topical betamethasone diproprionate 0.5 mg/g cream and antihistamines (hydroxyzine 25 mg nocte) and required narrow-band ultraviolet (UV) B. The third patient, having failed to respond to topical betamethasone diproprionate 0.5 mg/g cream and wet dressings, antihistamines (hydroxyzine 25 mg tds and doxepin 50 mg nocte) and UVB required acitretin 25 mg orally per day. Because reactive perforating collagenosis responds to treatment, we believe this condition should be considered in patients with diabetes mellitus or renal failure presenting with pruritus and that biopsy of intact lesions may need multiple levels to help establish the diagnosis.

Acitretin↗
PubMed2001

The lateral distally based adipofascial flap of the lower limb.

Several authors have reported the advantages of adipofascial flaps. We describe a series of flaps based exclusively on the perforator of the peroneal artery. This is an axially patterned distally based adipofascial flap useful for small and medium-sized defects over the distal fibula, lateral malleolus, the Achilles region or the dorsum of the foot. It can be an excellent alternative to fasciocutaneous or free flaps, with minimum donor-site morbidity, good cosmesis and an excellent functional result.

Adult↗
PubMed2001

The impact of intraoperative hypotension on the development of wound haematoma after breast reduction.

A wound haematoma occurring after breast reduction may need to be drained surgically, and may prolong both hospital stay and the total recovery time following surgery. Intraoperative hypotension has been implicated in the development of various complications, but has not been previously studied in relation to breast reduction. A retrospective analysis of 238 breast reductions was performed with the aim of identifying risk factors for the development of wound haematoma after breast reduction. The operative time was divided into three equal periods and, in our experience, haemostasis was achieved in the middle period. In our series, 16 patients developed a postoperative wound haematoma; only four patients required operative evacuation (1.7%). Subcutaneous heparin prophylaxis, the level of the surgical team and the weight of tissue resected did not significantly affect the likelihood of wound haematoma. The lowest and the peak values of systolic blood pressure and the mean blood pressure (diastolic + 1/3 pulse) were significantly lower in the middle period of the operation in patients who developed a haematoma P values: 0.012, 0.021 and 0.005, respectively). Univariate logistic regression analysis showed the same significant findings (P values: 0.0014, 0.021 and 0.0059, respectively). Multivariate stepwise logistic regression showed that the lowest systolic blood pressure in the middle period was significantly lower in the haematoma group than in the non-haematoma group (P= 0.0007). Intraoperative hypotension in the middle period of the operation, which is usually the period when haemostasis is achieved, is associated with the development of postoperative wound haematoma.

Adolescent↗
PubMed2001

Enabling the diagnosis of occult psychiatric illness in the emergency department: a randomized, controlled trial of the computerized, self-administered PRIME-MD diagnostic system.

STUDY OBJECTIVE: Undiagnosed mental illness is highly prevalent and produces needless morbidity. Emergency department patients with vague or longstanding complaints are at risk for occult mental illness, but are seldom diagnosed. We conducted this study to determine whether a previously validated, self-administered, computerized psychiatric interview (Primary Care Evaluation of Mental Disorders [PRIME-MD]) could increase the detection of occult psychiatric illness in the ED. METHODS: This was a randomized, controlled trial of consecutive patients enrolled during convenient times at a university teaching hospital ED with an annual census of 38,000. ED house staff and attending physicians participated. Patients were those with nonspecific complaints potentially associated with occult psychiatric illness (eg, long-standing headache, abdominal or back pain). Exclusion criteria were known psychiatric illness, complaint, or medication; and straightforward reason for the ED visit. Consenting subjects completed the PRIME-MD questionnaire in the waiting room, and were randomly assigned to either the "report" (report results given to physician) or "no-report" groups. PRIME-MD results were clipped to the front of the chart of report group patients. There was no other intervention. The main outcome measures were the percentage of all patients and percentage of patients with a PRIME-MD diagnosis who received a psychiatric diagnosis, consultation, or referral from the emergency physician. RESULTS: A total of 339 (5.1%) of all patients were approached; 230 consented to participate in the study, and 218 completed the PRIME-MD session and were randomly assigned to study groups. Ninety-two patients in the report group and 98 cases in the no-report group were analyzed. Patients were omitted for the following reasons: left without being seen (8), mistakenly enrolled (10), or unretrievable medical records (10). Seventy-nine (42%) patients received a psychiatric diagnosis from PRIME-MD and 9 (5%) from the physician. The frequencies of physician psychiatric diagnosis and referral did not differ between groups (diagnosis: report 9%, no report 9%, Delta 0%, 95% confidence interval [CI] -13, 14; referral: report 9%, no report 7%, Delta 2%, 95% CI -11, 16). CONCLUSION: ED patients willingly completed the PRIME-MD questionnaire (in a median time of 7 minutes), which frequently diagnosed psychiatric conditions. Despite this, physicians rarely diagnosed or treated these conditions regardless of whether they were provided with the PRIME-MD diagnoses.

Adult↗
PubMed2001

Molecular mechanisms of aortic wall remodeling in response to hypertension.

OBJECTIVE: The molecular basis of vascular response to hypertension is largely unknown. Both cellular and extracellular components are critical. In the current study we tested the hypothesis that there is a balance between vascular cell proliferation and cell death during vessel remodeling in response to hypertension. METHODS: A midthoracic aortic coarctation was created in rats to induce an elevation of blood pressure proximal to the coarctation. The time course was 1 and 3 days and 1, 2, and 4 weeks for the study of the proximal aorta. Ribonuclease protection assay and Western blot analysis were used to evaluate gene expression of growth and apoptosis-related cytokines with two sets of multiple probes, rCK-3 and rAPO-1. Cell proliferation was determined with BrdU (5-bromo-2'-deoxyuridine) incorporation. Apoptosis was examined with TUNEL (transferase-mediated dUTP nick end-labeling). Morphometry was performed on histologic sections. RESULTS: Coarctation produced hypertension in the proximal aorta, 118 +/- 9 mm Hg versus 94 +/- 6 mm Hg in controls (P <.002). Both messenger RNA and protein levels of transforming growth factor (TGF)-beta1 and TGF-beta3 were increased (P <.005 vs controls). Messenger RNA and protein of Bcl-xS and Fas ligand, known as proapoptotic factors, were both reduced after coarctation (P <.005 vs controls). There was increased BrdU incorporation at 3 days and 1 and 2 weeks (P <.001 vs controls). There were no remarkable changes in the apoptosis rate until 4 weeks later. CONCLUSION: Cell proliferation was stimulated at 3 days, and apoptosis was halted until 4 weeks. These changes were associated with upregulation of TGF-beta and downregulation of Bcl-xS and Fas ligand gene expression. These findings suggest that a coordinated regulation of cell proliferation and cell death contributes to arterial remodeling in response to acute sustained elevation of blood pressure. Cell proliferation precedes apoptosis by 2 weeks in this procedure.

Animals↗