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Biomedical subjects

J Lim

Publications and source records attributed to J Lim.

At least 145 records · Page 8Linked to original sources
PubMed1997

Regulation of amelogenin gene expression.

The amelogenins are found uniquely in enamel, where they constitute the predominant class of secreted matrix proteins and where they play a fundamental role in normal enamel formation. To better understand the high level of tissue-specific expression, we cloned the bovine X and Y chromosomal amelogenin genes and the murine amelogenin gene and determined the DNA sequences for the regions upstream of the transcription start sites. We observed segments of strong homology among species, and identified consensus sequences for the binding of various transcription factors, including the glucocorticoid receptor, AP1, RXR and p53. Although specific sis-elements conferring enhanced transcription have not yet been identified, elements have been localized that have silencing effect in non-ameloblast cells. Conserved sequences are likely to be involved in tissue-specific expression. Transgenic mouse studies have shown that 3.5 kb of upstream region is sufficient but 900 bp is insufficient for specific expression in vivo. Alternative splicing of the primary transcript is an effective mechanism for generating molecular heterogeneity. Amelogenin genes contain seven exons, and exons 3, 4, 5 and most of 6 can be deleted by alternative splicing. However, the pattern of exon splicing varies according to the species, and skipping of bovine exon 3 appears to be developmentally regulated. It will be important to determine whether the relative amounts of translation products differ among species as do the mRNAs, and to correlate the various protein structures with function. These findings also suggest that the regulation of amelogenin gene expression is complex and takes place at several levels.

Alternative Splicing↗
PubMed1997

Role of testis exposure levels in the insensitivity of prepubertal rats to carbendazim-induced testicular toxicity.

Our recent studies have indicated that benomyl (BNL)-induced testicular toxicity is mediated by its major metabolite carbendazim (CBZ). The present study has used CBZ to investigate hypotheses that could explain prepubertal insensitivity to BNL. When CBZ (164 mg/kg intraperitoneally) was administered to postpubertal and prepubertal rats, it caused little testicular damage in prepubertal rats, but in adult rats, sloughing of the seminiferous epithelium resulted. When the inhibitory effect of CBZ on prepubertal testicular microtubule assembly was compared with that on postpubertal assembly, the IC50 values were very similar. Pharmacokinetic studies revealed that blood levels of CBZ were comparable in the two age groups; however, higher levels of CBZ were found in the adult testes (210.52 nmol/g wet wt) in comparison with young testes (67.77 nmol/g wet wt). These data suggest that delivery to and/or retention of CBZ in the testis may play a role in the age-dependent differences in susceptibility to CBZ toxicity. When CBZ was administered intratesticularly to reach levels sufficient to cause damage, the young animals did show an increased incidence of vacuolization and detachment of the seminiferous epithelium; however, in contrast to the older animals, sloughing of the seminiferous epithelium was not observed in the prepubertal animals. Overall, the low levels of CBZ measured in the testes of prepubertal animals offer a partial explanation for the insensitivity of young animals to CBZ-induced testicular toxicity following intraperitoneal administration. A differential responsiveness between the two age groups is also likely, however, since prepubertal animals lack elongated spermatids and it is sloughing of this cell type that characterizes CBZ-induced testicular toxicity in the adult.

Animals↗
PubMed1997

The role of the benomyl metabolite carbendazim in benomyl-induced testicular toxicity.

The present study has investigated the role of benomyl (BNL) vs carbendazim (CBZ) in BNL-induced testicular toxicity. Equivalent molar concentrations of BNL and CBZ were administered to rats intraperitoneally (859 mumol/kg) or by direct injection into the testis (1.37 mumol/testis). Whereas no significant testicular damage was observed both 1 and 2 hr after BNL administration by the ip route, CBZ administration resulted in sloughing of the seminiferous epithelium after 1 hr, which increased in severity at the 2-hr time point. Intratesticular treatment of BNL caused little testicular damage after 1 hr whereas an equimolar amount of CBZ elicited severe disruption of the seminiferous epithelium. Testicular levels of CBZ and BNL were measured at various times after both routes of administration. The AUC from the concentration of CBZ in the testis vs time plot showed an excellent relationship to the number of tubules which exhibited slouging. The BNL AUC also showed a straight-line relationship to severity of lesion. However, when the contribution of CBZ to the BNL response was subtracted, no effect of BNL was discernible. The effect of BNL and CBZ on testicular microtubule assembly was then investigated. IC50 for CBZ was 5 microM and that for BNL was 75 microM. Again, the effect of BNL on microtubule assembly could be largely accounted for by the presence of the CBZ breakdown product. These results strongly suggest that the BNL metabolite CBZ, and not BNL itself, is the mediator of BNL-induced testicular toxicity and inhibitor of testicular microtubule assembly.

Animals↗
PubMed1997

The anatomical basis of the vascularized pronator quadratus pedicled bone graft.

The vascular supply of the pronator quadratus was studied in 25 cadaveric dissections following coloured latex injections. This showed that the main blood supply of the pronator quadratus came from the anterior interosseous artery. There was, however, a rich anastomosis between the branches of the anterior interosseous artery and those of the radial and ulnar arteries. It was possible to raise a corticocancellous bone graft from the anterior surface of the radial styloid on a pedicle of the lower fibres of the pronator quadratus muscle. This muscle pedicle had a constant branch of the anterior interosseous artery which vascularized the bone graft. Such a vascularized pedicled bone graft may be useful in the treatment of non-union of the scaphoid and Kienböck's disease.

Bone Transplantation↗
PubMed1997

Scintigraphic assessment of drug delivery from the Ultrahaler dry powder inhaler.

A new dry powder inhaler, the Ultrahaler, has been developed to deliver nedocromil sodium for the prophylaxis of asthma. This study was performed to compare the lung deposition of nedocromil sodium inhaled from the Ultrahaler at two different inhaled flow rates with that from a pressurised metered dose inhaler (MDI). A scintigraphic study was conducted in 12 healthy volunteers. On each study day, volunteers received a single 4.2 mg dose of nedocromil sodium from the Ultrahaler, using either an optimal (fast) inhaled flow rate or a suboptimal (slow) inhaled flow rate, or two doses of 2 mg nedocromil sodium from an MDI using an optimal (slow) inhaled flow rate. Used optimally, the Ultrahaler deposited significantly more (p < 0.05) of the metered dose in the lungs than either the Ultrahaler used suboptimally or the MDI used optimally [mean (SD) lung deposition values of 13.3 (4.8)%, 9.8 (3.5)%, and 7.5 (2.9)%, respectively]. Oropharyngeal deposition averaged over 80% of the dose for all three treatment regimens. This scintigraphic study demonstrated in vivo proof of concept for the Ultrahaler dry powder inhaler, and provided quantitative data on the relationship in lung deposition between the Ultrahaler and MDI which differed from that predicted by the in vitro fine particle fraction.

Anti-Asthmatic Agents↗
PubMed1997

Comparison of intranasal triamcinolone acetonide with oral loratadine in the treatment of seasonal ragweed-induced allergic rhinitis.

A double-blind, randomized, multicenter, parallel-group controlled study compared the efficacy and safety of intranasal triamcinolone acetonide (220 micrograms/day) and oral loratadine (10 mg/day) in patients with at least two seasons of ragweed-induced seasonal allergic rhinitis. A 28-day screening period, including a 5-day baseline period, preceded a 4-week treatment period. Reduction in rhinitis symptom scores was evident in both groups as early as day 1, with no significant between-group differences during week 1. At weeks 2, 3, and 4, patients treated with triamcinolone acetonide were significantly (P < 0.05) more improved in total nasal score, nasal itch, nasal stuffiness, and sneezing than were patients treated with loratadine. At weeks 3 and 4, rhinorrhea and ocular symptoms were significantly (P < 0.05) more improved from baseline among triamcinolone acetonide patients compared with loratadine patients. There was no significant between-group difference in relief from postnasal drip at any time point. Physicians' global evaluations significantly (P = 0.002) favored triamcinolone acetonide at the final visit, with moderate to complete relief of symptoms attained by 68% of triamcinolone acetonide patients and 59% of loratadine patients. Over the 4-week treatment period, triamcinolone acetonide patients had significantly greater improvement in total nasal score, nasal itch, nasal stuffiness, sneezing, and ocular symptoms. Both treatments were well tolerated, with headache being the most frequently reported drug-related adverse effect in both the triamcinolone acetonide (15%) and loratadine (11%) groups. These results indicate that triamcinolone acetonide is more effective than oral loratadine in relieving the symptoms of ragweed-induced seasonal allergic rhinitis.

Administration, Intranasal↗
PubMed1997

Uncommon lesions presenting as tumors of the internal auditory canal and cerebellopontine angle.

OBJECTIVE: The aim of this study was to identify distinguishing characteristics of uncommon lesions of the cerebellopontine angle (CPA) and internal auditory canal (IAC) in order to attain the correct diagnosis and thus formulate an appropriate therapeutic protocol. STUDY DESIGN: A retrospective chart analysis was performed on all patients with surgically managed lesions of the IAC and CPA referred to neuropathology from January 1985 to April 1996. SETTING: All patients were treated by New York University faculty at a tertiary referral center. PATIENTS: Among 426 surgical cases identified, 384 patients (90.1%) with acoustic neuromas and 18 patients (4.2%) with meningiomas were excluded. The remaining 24 cases, involving 17 women and seven men with a median age of 34 years, were analyzed. INTERVENTION: Most patients underwent audiovestibular evaluations, as well as magnetic resonance imaging (MRI) and computed tomographic (CT) scanning, and all patients underwent neurotologic surgery as part of their management protocol. MAIN OUTCOME MEASURES: Correlating patient presentation, preoperative imaging, and surgical findings often identified distinguishing characteristics of unusual CPA and IAC lesions. RESULTS: Unusual lesions identified at the CPA and IAC included: four epidermoids, four lipomas, two facial neuromas, two arachnoid cysts, two choroid plexus papillomas, two metastatic adenocarcinomas, one metastatic neuroblastoma, one ependymoma, one lymphoma, one cholesterol cyst, one angioleiomyoma, one venous hemangioma, one cavernous angioma, and one pontine glioma. CONCLUSIONS: Preoperative tumor differentiation based on the patient history, physical examination, audiovestibular testing, CT, and MRI help the surgeon to formulate an appropriate treatment protocol.

Adult↗
PubMed1996

Chemical modification of porcine kidney aminopeptidase P indicates the involvement of two critical histidine residues.

Aminopeptidase P (AP-P), purified to homogeneity from porcine kidney membranes, was completely inactivated by treatment with 0.2 mM diethylpyrocarbonate (DEP) at pH 7.0. Treatment of the modified enzyme with 20 mM hydroxylamine resulted in recovery of AP-P activity. The differential absorption of native and modified AP-P at 240 mm showed that DEP modified two histidyl residues per mol of AP-P. The substrates, bradykinin(1-5) and Gly-Pro-Hyp, and also the inhibitor, apstatin, could protect against DEP inactivation. These results suggest that histidine residues are critical for AP-P activity.

Aminopeptidases↗
PubMed1996

Effect of felbamate on the pharmacokinetics of lamotrigine.

To assess the possible interaction between lamotrigine and felbamate, a double-blind, randomized, placebo-controlled, two-way crossover study was conducted in 21 healthy male volunteers. Volunteers were given lamotrigine (100 mg every 12 hours) and felbamate (1,200 mg every 12 hours) or matching placebo for 10 days during each period of the crossover. After morning administration on day 10, blood samples were obtained over 12 hours for measurement of lamotrigine. Felbamate increased the maximum concentration (Cmax) and and area under the concentration-time curve from time 0 to 12 hours (AUC0-12) of lamotrigine by 13% and 14%, respectively, compared with placebo. The 90% confidence intervals of the log-transformed pharmacokinetic parameters were within the 80-125% bioequivalance limits, however. Felbamate had no significant effect on the urinary excretion of lamotrigine (total), unconjugated lamotrigine, or the N-glucuronide. One volunteer discontinued the study after developing a rash while taking lamotrigine and placebo. All other adverse events were primarily related to the central nervous system and gastrointestinal tract, with a higher incidence reported during coadministration of lamotrigine and felbamate than with placebo. Overall, felbamate appears to have no clinically relevant effects on the pharmacokinetics of lamotrigine.

Adult↗
PubMed1996

Dexamethasone-induced impairment in skeletal muscle glucose transport is not reversed by inhibition of free fatty acid oxidation.

Our previous studies suggested a possible role for the glucose-free fatty acid (FFA) cycle, ie, preferential utilization of FFA by muscle at the expense of glucose, in dexamethasone (DEX)-induced insulin resistance. To determine whether this resistance could be reversed by inhibiting FFA utilization, we used etomoxir, a potent inhibitor of mitochondrial FFA oxidation. Male Sprague-Dawley rats were injected subcutaneously with 1 mg/kg DEX or the vehicle every other day for 10 days, and half of each group was administered 10 mg/kg etomoxir by gavage once per day and 1 hour before the experiment. As expected, etomoxir treatment increased serum FFA levels and inhibited FFA oxidation by diaphragm in vitro. Administration of etomoxir decreased serum glucose and insulin concentrations under basal conditions in both control and DEX-treated animals, implying enhanced insulin sensitivity. DEX treatment significantly increased endogenous glucose production and decreased whole-body glucose disposal, as well as 2-deoxyglucose (2-DG) uptake by skeletal muscle during euglycemic-hyperinsulinemic clamps. Administration of etomoxir led to small but significant increases in glucose disposal rates of both control (14%) and DEX (23%) groups, but had no effect on residual endogenous glucose production. Thus, DEX-induced insulin resistance was marginally ameliorated but not completely reversed by etomoxir. Depressed 2-DG uptake by individual muscle tissues observed in the present study in conjunction with the absence of free intracellular glucose in muscle tissue following glucose-insulin infusion strongly suggests that the primary defect in glucose metabolism is at the level of transport. Neither overall abundance of the insulin-sensitive glucose transporter (GLUT-4) in skeletal muscle nor its distribution between intracellular stores and plasma membrane were modified by DEX treatment, either, under basal conditions or in response to acute insulin stimulus. These results suggest a defect(s) in the inherent activity of plasma membrane-bound GLUT-4 as the likely mechanism for DEX-induced insulin resistance.

Animals↗
PubMed1996

Comparison of triamcinolone acetonide nasal inhaler with astemizole in the treatment of ragweed-induced allergic rhinitis.

BACKGROUND: Few clinical trials have directly compared the efficacy of antihistamines with topical nasal corticosteroids. OBJECTIVE: The study was performed to compare the efficacy and safety of triamcinolone acetonide nasal spray at a dose of 110 micro g in each nostril once daily with 10 mg of oral astemizole once daily for the treatment of seasonal allergic rhinitis. METHODS: A multicenter, double-blind, parallel-group study was conducted in 239 patients who were randomized to receive either triamcinolone acetonide or astemizole. A 5-day, drug-free, lead-in period was followed by 4 weeks of double-blind treatment. One hundred four patients treated with triamcinolone acetonide and 105 patients treated with astemizole could be evaluated. RESULTS: Overall, triamcinolone acetonide was more effective than astemizole in reducing total nasal symptoms, nasal stuffiness, nasal itching, and sneezing (p </= 0.01). Triamcinolone acetonide was superior to astemizole at weeks 1, 2, and 3 in reduction of the total nasal symptom score (p </= 0.0401) and in reduction of nasal stuffiness (p </= 0.05). Improvements in individual nasal symptoms (itching, postnasal drip, runny nose, and sneezing) were greater for triamcinolone acetonide at week 2 (p </= 0.01). Ocular symptoms improved from baseline in both groups. When pollen counts were correlated to mean nasal rhinitis scores, the triamcinolone acetonide group showed continued improvement from week 1 to week 2 in nasal symptoms when pollen counts were at their highest. During the same period, patients treated with astemizole failed to show improvement from week 1 to week 2. This study demonstrated that once daily administration of triamcinolone acetonide was more effective than astemizole for controlling nasal symptoms of seasonal allergic rhinitis, especially during the peak pollination period.

Administration, Intranasal↗
PubMed1996

Elimination of both E1 and E2 from adenovirus vectors further improves prospects for in vivo human gene therapy.

A novel recombinant adenovirus vector, Av3nBg, was constructed with deletions in adenovirus E1, E2a, and E3 regions and expressing a beta-galactosidase reporter gene. Av3nBg can be propagated at a high titer in a corresponding A549-derived cell line, AE1-2a, which contains the adenovirus E1 and E2a region genes inducibly expressed from separate glucocorticoid-responsive promoters. Av3nBg demonstrated gene transfer and expression comparable to that of Av1nBg, a first-generation adenovirus vector with deletions in E1 and E3. Several lines of evidence suggest that this vector is significantly more attenuated than E1 and E3 deletion vectors. Metabolic DNA labeling studies showed no detectable de novo vector DNA synthesis or accumulation, and metabolic protein labeling demonstrated no detectable de novo hexon protein synthesis for Av3nBg in naive A549 cells even at a multiplicity of infection of up to 3,000 PFU per cell. Additionally, naive A549 cells infected by Av3nBg did not accumulate infectious virions. In contrast, both Av1nBg and Av2Lu vectors showed DNA replication and hexon protein synthesis at multiplicities of infection of 500 PFU per cell. Av2Lu has a deletion in E1 and also carries a temperature-sensitive mutation in E2a. Thus, molecular characterization has demonstrated that the Av3nBg vector is improved with respect to the potential for vector DNA replication and hexon protein expression compared with both first-generation (Av1nBg) and second-generation (Av2Lu) adenoviral vectors. These observations may have important implications for potential use of adenovirus vectors in human gene therapy.

Adenoviridae↗
PubMed1996

Detection of faking on the MMPI-2: differentiation among faking-bad, denial, and claiming extreme virtue.

The purpose of this study was (a) to evaluate the ability of the existing validity indices of the Minnesota Multiphasic Personality Inventory (MMPI-2) in detecting faking. bad and faking-good profiles, (b) to differentiate between two strategies for faking-good (denial and claiming extreme virtue), (c) to determine the effectiveness of the new MMPI-2 validity scale, the S scale, in detecting people's tendency to present themselves in a superlative manner, and (d) to explore the response strategy under conditions in which individuals we known to be distorting their responses to the MMPI-2 Participants were 167 undergraduate, college students who were administered the test under different conditions, and 50 hospitalized, psychiatric patients. Mean profile configurations and optimal cutoff scores obtained in this study were similar to those reported in previous studies. Accurate identification of faked profiles was achieved. The new S scale and its subscales, especially S2 (Serenity), S3 (Contentment With Life), and S5 (Denial of Moral Flaws), showed particular promise in detecting faking-good (denial and claiming extreme virtue) profiles, Participant's debriefing provided valuable information about the participants' understanding of the instructions and their deception strategies. The attempts to differentiate between two strategies for faking-good, denial and claiming extreme virtue, were not successful, However, these results should not be taken to indicate that the particular strategies assessed in this study cannot be differentiated. Methodological issues reviewed suggest that further research might yield more understanding of the nature of any deception efforts made by respondents. In addition, future, research is needed to discover if the findings from this study generalize to other clinical settings and populations.

Journal Article↗
PubMed1996

Correlates of osteopenia in patients with cystic fibrosis.

OBJECTIVE: As the expected survival improves for individuals with cystic fibrosis, these individuals face myriad medical complications. The goals of this study were to examine the prevalence of osteopenia in children and adults with cystic fibrosis and to elucidate the risk factors associated with deficits in bone mineral. METHODOLOGY: We compared bone mineral levels in 49 patients (30 female and 19 male) ages 8 through 48 years with those of age- and sex-matched control subjects. Lumbar spine, femoral neck, and whole-body bone mineral were measured by dual-energy radiographic absorptiometry and expressed in terms of bone mineral content, areal bone density (BMD), and bone mineral apparent density (BMAD), which corrects for differences in bone size. Clinical variables were evaluated as potential correlates of bone mineral. RESULTS: Patients with cystic fibrosis had significantly less bone mineral than did control subjects at all sites using all expressions of bone mass. Mean BMD z scores were -1.7 (lumbar spine), -1.9 (femoral neck), and -1.2 (whole body). BMAD z scores also were significantly low for age and gender. Twenty-six of the 49 patients (8 adolescents) had significant osteopenia according to their BMD z scores; 14 of the 45 patients (5 adolescents) with available BMAD z scores had significantly low values at one or more sites. Age, pubertal stage, body mass, caloric expenditure, illness severity, glucocorticoid therapy, and gonadal function predicted bone mineral status. Serum parathyroid hormone and calcium, carbohydrate intake, and weight-bearing activity had limited predictive value. Daily calcium intake and cystic fibrosis transmembrane regulator genotype did not predict bone mineral status. CONCLUSIONS: Osteopenia is common at all ages in cystic fibrosis, suggesting that inadequate bone mineral accretion as well as increased bone loss contribute to the deficits in bone mineral observed. Several clinical factors seem to contribute to these deficits.

Absorptiometry, Photon↗