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Biomedical subjects

M Lim

Publications and source records attributed to M Lim.

At least 73 records · Page 4Linked to original sources

Ultrafast rotation and trapping of carbon monoxide dissociated from myoglobin.

The nature of ligand motion within proteins has been investigated by measuring femtosecond time-resolved infrared (IR) spectra of CO photodissociated from the haem of myoglobin. Upon dissociation, the CO rotates approximately 90 degrees and becomes trapped within a ligand docking site located near the binding site. Two trajectories, distinguished spectroscopically and kinetically with time constants of 0.20 +/- 0.05 ps and 0.52 +/- 0.10 ps, lead to CO located within the docking site with opposite orientations. The protein reorganizes about the "docked' CO with a time constant of 1.6 +/- 0.3 ps and quickly establishes an energetic barrier that inhibits the reverse rebinding process.

Animals↗

Sudden cardiac death in cardiac transplant recipients.

BACKGROUND: Sudden cardiac death (SCD) remains a significant cause of mortality in the general population. Its role in cardiac transplant patients-including its incidence, mechanism, potential risk factors, or influence on survival in this patient population-has not been well described. METHODS AND RESULTS: We undertook a retrospective analysis of the clinical and autopsy records of 257 patient deaths. SCD was analyzed in relation to severity and frequency of rejection episodes, clinical history of arrhythmias, coronary artery disease (CAD), hypertension, diabetes, left ventricular dysfunction, and clinical history of premorbid symptoms. A total of 25 patients were identified as having died of SCD, an incidence of 9.7%: 20% died < or = 12 months after transplantation, 80% died after > 12 months, and 20% died after > or = 60 months. Patient survival ranged from 2.5 to 138 months (mean, 45.7 months). The mean number of rejection episodes per patient was 2.6, most occurring within 12 months after transplantation. Echocardiography or multigated acquisition scan revealed an ejection fraction (EF) > or = 50% in 68% of patients; however, the presence of arrhythmias, primarily atrial, was evident in 68% of patients and was equally distributed between patients with EFs > or = 50% and EFs < 50%. CAD was present in 53% of patients (10 of 19) whose angiograms were available, and the appearance of CAD after transplantation was between 29 and 85 months (mean, 51.4 months). Of the 9 patients with normal cardiac catheterization studies, 6 with available autopsy reports had documented CAD. Autopsy data in 13 of 25 patients revealed CAD in 92% and rejection in 15% (International Society for Heart and Lung Transplantation grade > 3A). Of the deaths, 64% occurred within 3 months of the last endomyocardial biopsy, 96% had normal biopsies, and the only rejection was without hemodynamic compromise. CONCLUSIONS: SCD occurs relatively frequently in the cardiac transplant population, and CAD is present in most of the patients. Because the frequency of arrhythmias is relatively high in this group, more aggressive antiarrhythmic therapy may be beneficial for patients with allograft CAD in the prevention of SCD.

Adult↗

Effects of diminished and conflicting sensory information on balance in patients with cerebellar deficits.

We studied the effects of altered sensory information on standing balance in 25 patients with cortical cerebellar atrophy (CCA), nine patients with olivoponto-cerebellar atrophy (OPCA), and 10 normal subjects. The total sway path and its components, the anteroposterior (AP) sway path and the lateral sway path, were measured under six conditions: (1) standing on a fixed platform with the eyes open and visual surroundings fixed, (2) standing on a fixed platform with the eyes closed, (3) standing on a fixed platform with the eyes open and visual surroundings AP sway referenced, (4) standing on an AP sway-referenced platform with the eyes open and visual surroundings fixed, (5) standing on an AP sway-referenced platform with the eyes closed, and (6) standing on an AP sway-referenced platform with the eyes open and visual surroundings AP sway referenced. Patients swayed more than normal subjects during normal stance (condition 1), when the visual information was absent (condition 2) or distorted (condition 3), and when the proprioceptive information from the ankles was distorted (condition 4). Patients swayed much more than normal, and most fell, when two sensory modalities were affected under condition 5 (proprioceptive information distorted and visual information absent) and condition 6 (both proprioceptive information and visual information distorted). When the patients' sway was normalized to that of the first condition, however, only their lateral sway was greater than the sway in normal subjects. Unlike in normal subjects, the patients' lateral sway varied with the AP sway to approximately the same degree in each condition for conditions 1-5. Clinical ratings of gait and balance were highly correlated with the sway measures. Quantitative testing of standing balance with altered sensory information has better sensitivity than normal stance testing.

Adult↗

Maternal congenital heart disease and pregnancy outcome.

OBJECTIVE: To study the obstetrics and neonatal outcome of women with congenital heart disease. METHOD: This is a retrospective study of 85 women with congenital cardiac disease. Data collected include maternal characteristics, New York Heart Association Class, cardiac complications and obstetric and neonatal outcome. RESULTS: The maternal and neonatal outcomes were excellent with no maternal and perinatal mortality. The main cardiac lesions were mitral valve prolapse (60.8%), atrial septal defect (8.6%), ventricle septal defect (6.5%) and aortic regurgitation (4.3%) and 2.1% each of tricuspid regurgitation, pulmonary regurgitation, Ebstein's anomaly, coarctation of aorta, patent ductus arteriosus, and Eisenmenger's syndrome. Six deliveries were associated with New York Heart Association deterioration. Compared to the general obstetric population, more women in the study group were primigravida, had pregnancy induced hypertension, underwent instrumental vaginal deliveries and caesarean sections and had more babies with lower birth weights. CONCLUSION: Despite potential difficulties and complications associated with congenital heart disease, careful cardiac and obstetric management in a tertiary referal centre resulted in good maternal and fetal outcomes.

Adolescent↗

C4 and 21-hydroxylase gene deletions in nasopharyngeal carcinoma among the Chinese.

Deletions around the C4 and 21-hydroxylase (21-OH) gene region occur among the Chinese, and C4B together with 21-OHA deletion is the most common. This deletion was found to be strongly associated with human leucocyte antigen (HLA) B58 DRB1*0301, particularly with DRB1*0301. The initial observation of a high frequency of this deletion in nasopharyngeal carcinoma (NPC) was secondary to the B58 DR3 association with NPC. A deletion of 21-OHA alone was observed to be associated with HLA B13 DRB1*1501.

Asian People↗

Denture plaque distribution and the effectiveness of a perborate-containing denture cleanser.

Formation of plaque on the surfaces of dentures is a common problem among denture wearers. A study was conducted to determine the distribution of plaque on dentures. The plaque material was disclosed with a dye solution and measured with a modified Quigley-Hein scale. A photographic method was used to determine the distribution of plaque on the dentures of a group of complete-denture wearers. The effectiveness of a perborate soak-type cleanser was also measured by studying the precleaned and postcleaned states of the denture. Denture plaque was more evident on the fitting surfaces of the dentures than on areas of the flange, teeth, and palate. The use of the soak-type cleanser alone may not be completely effective for the control of heavy plaque.

Aged↗

Binding of CO to myoglobin from a heme pocket docking site to form nearly linear Fe-C-O.

The relative orientations of carbon monoxide (CO) bound to and photodissociated from myoglobin in solution have been determined with time-resolved infrared polarization spectroscopy. The bound CO is oriented < or = 7 degrees from the heme normal, corresponding to nearly linear FE-C-O. Upon dissociation from the Fe, CO becomes trapped in a docking site that orientationally constrains it to lie approximately in the plane of the heme. Because the bound and "docked" CO are oriented in nearly orthogonal directions CO binding from the docking site is suppressed. These solutions results help to establish how myoglobin discriminates against CO, a controversial issue dominated by the misconception that Fe-C-O is bent.

Binding Sites↗

Upregulation of the 72-kDa type IV collagenase in epithelial and stromal cells during rat tracheal gland morphogenesis.

Submucosal glands secrete most of the mucus that lubricates the tracheal surface and protects it from irritants and infection. These glands develop postnatally in the rat, permitting convenient study of the mechanisms controlling this process. One such mechanism involves degradation of the supportive connective tissue matrix at the front of the growing glands. We recently showed that tracheal gland cell invasion of collagen gels in vitro is dependent on secretion of a 72-kDa type IV collagenase. In the present study, we show that the activity of this enzyme (also referred to as matrix metalloproteinase-2 or gelatinase A) is elevated at the time of gland development in vivo. That this increase is at least partly mediated at the level of steady-state mRNA was indicated by semiquantitative PCR analysis of gland-enriched, microdissected tissue samples. Immunohistochemistry revealed that the enzyme was present at the interface between the glands and extracellular matrix. In situ hybridization revealed that the cognate mRNA was present in epithelial cells of glands undergoing morphogenesis (particularly Postnatal Day 7) but not in those of adult glands or the surface epithelium. At all ages, stromal cells below the surface epithelium were labeled; labeling intensity was highest at the time and location of gland morphogenesis. These findings suggest that the 72-kDa type IV collagenase is developmentally regulated in gland and stromal cells at the level of steady-state mRNA and plays a role in the degradation of extracellular matrix during tracheobronchial gland morphogenesis.

Animals↗

Comparison of techniques for transscleral diode photocoagulation in the rabbit.

PURPOSE: To assess the optimum probe design and treatment parameters for transscleral diode laser retinopexy. METHODS: Transscleral diode photocoagulation was performed on the eyes of Dutch-belted rabbits using three different transscleral probes: a straight, 400-microns diameter probe; a prism-tipped 400-microns diameter probe; and a prism-tipped 900-microns diameter probe. RESULTS: Transscleral diode photocoagulation with all three probe types was an effective method of ablating the retina and creating chorioretinal adhesions. Both the burn diameter and the mean radiant output energy requirement increased as the burn duration and probe aperture diameter was increased. Explosive retinal holes were encountered in 12% of the burns created with the straight probe. The use of the prism-tipped probes significantly reduced the incidence of retinal holes to < 4% (P < 0.005). Histopathologically, all burns were grade III in intensity with severe choroidal injury. In many of the burns, there was histopathologic evidence of thermal injury to the inner sclera. The frequency of these inner scleral changes was reduced with a long burn duration (5 seconds). CONCLUSION: This study confirms that diode transscleral photocoagulation is a feasible method of thermal retinopexy. The use of the prism-tipped probes and long duration burns resulted in the fewest adverse reactions.

Animals↗

Diet measurement in Vietnamese youth: concurrent reliability of a self-administered food frequency questionnaire.

Dietary patterns of Asian Americans change with increasing acculturation, leading to increased consumption of Western foods including those high in fat. Strategies to preserve the healthy aspects of traditional diets need to be developed and dietary assessment methods evaluated. Little is known about reliability of brief dietary measures in the general population or among minority youth. The concurrent reliability of a brief food frequency questionnaire (FFQ) was determined among Vietnamese youth using diet reports. Students in a bilingual high school program were given a FFQ. Students then completed daily diet reports one day each week over seven weeks. The data from the FFQ were compared to the daily food reports. The reliability of the FFQ was highest for frequently eaten food types like rice (r = 0.626, P < 0.01), fruit (r = 0.513, P < 0.01), meat (r = 0.525, P < 0.01) and vegetables (r = 0.474, P < 0.01) and was lower for less commonly eaten types including fish/shellfish (r = 0.227, P = 0.20) and fried foods (r = 0.310, P = 0.07). These results suggest that a few simple FFQ items, particularly for indicator foods such as rice, are reliable for dietary assessment in this population.

Adolescent↗

Differential susceptibility of plasma proteins to oxidative modification: examination by western blot immunoassay.

Plasma proteins are exposed to oxidants in a variety of circumstances in vivo, such as during tissue injury and inflammation. In this report, the relative susceptibility of each of the major plasma proteins to oxidative modification was assessed by exposing whole plasma to a metal-catalyzed radical generating system and detecting oxidation (protein carbonyl groups) using a novel Western blot immunoassay. Proteins were derivitized with dinitrophenylhydrazine, separated by SDS-gel electrophoresis, and screened with antibodies against dinitrophenyl groups. As little as 1 pmol of protein-associated carbonyls could be detected (100 ng of a 50 kD protein containing 0.5 mol carbonyl/mol protein). Individual plasma proteins were identified by their comigration with standards, crossreactivity with specific antibodies, and by comparison of plasma to serum. Using this approach, we found that plasma fibrinogen was much more susceptible to oxidative modification compared to the other major plasma proteins, albumin, immunoglobulins, and transferrin. The results emphasize the utility of this method for studying oxidation of proteins in cell extracts and tissues and indicate that experiments on the effects of oxidation on fibrinogen function are merited.

Animals↗

Phase 1 clinical trial of chimeric monoclonal anti-CD4 antibody in multiple sclerosis.

We conducted an open trial of cM-T412, a chimeric monoclonal anti-CD4 antibody, in 29 patients with MS. This antibody caused a prompt and long-lasting depletion of circulating CD4 (helper/inducer) lymphocytes. The mean (+/- SE) CD4 count for the group decreased from 870 (+/- 66) cells/mm3 at baseline to 76 (+/- 11) 3 hours after treatment, and then increased to 425 (+/- 38) at 1 month after treatment and 475 (+/- 39) at 6 months after treatment. Numbers of CD8 (cytotoxic/suppressor) lymphocytes, B lymphocytes, granulocytes, and monocytes changed transiently but showed no significant long-term effects. The most common side effects were headache, nausea, myalgia, fever, and tachycardia occurring in the first few hours after treatment. No serious or unexpected infections or other significant adverse effects occurred. Kurtzke EDSS scores remained stable, and MRI scans showed less contrast enhancement 1 week after treatment. We conclude that treatment of MS patients with cM-T412 chimeric anti-CD4 antibody is well tolerated at the doses tested and produces a long-lasting, selective depletion of CD4 lymphocytes.

Adult↗

Tine test cards for TB screening: rates of return and associated factors.

OBJECTIVE: Screening for tuberculosis in children can be done with the multiple-puncture Tine test. Determination of the extent of induration following the test may be reported by a child's caregiver via a mailed Tine card. We report the rate of return of these cards, and factors associated with return, in a family medicine health center. METHODS: Retrospective review of the medical charts of 152 mother and child pairs seen in the health center over a two-year period. RESULTS: Of the 98 children who had received a Tine test by age one, 16.3% of their Tine cards were returned to the health center. Children whose delivery was insured by Medicaid were less likely to have a Tine card returned than were those without Medicaid (OR for non-return = 4.3, 95% CI = 1.2, 15.4). Physicians often documented a tuberculosis screening result without a Tine card. CONCLUSIONS: Given the low return rates, health care professionals responsible for tuberculosis screening should be cautious when relying on caregivers to interpret, record and return tuberculosis screening results, particularly in the most disadvantaged populations. More valid data are likely to be obtained from a clinical reading of tuberculosis tests.

Data Interpretation, Statistical↗

Nonexponential protein relaxation: dynamics of conformational change in myoglobin.

The picosecond evolution of the tertiary conformation of myoglobin (Mb) after photodissociation of MbCO was investigated at room temperature by probing band III, a weak iron-porphyrin charge-transfer transition near 13,110 cm-1 (763 nm) that is sensitive to the out-of-plane displacement of the iron. Upon photolysis, the iron moves out of the plane of the porphyrin, causing a blue-shift of band III and a concomitant change in the protein conformation. The dynamics for this functionally important motion are highly nonexponential, in agreement with recent molecular dynamics simulations [Kuczera, K., Lambry, J.-C., Martin, J.-L. & Karplus, M. (1993) Proc. Natl. Acad. Sci. USA 90, 5805-5807]. The conformational change likely affects the height of the barrier to ligand rebinding and may explain nonexponential NO rebinding.

Circular Dichroism↗

A prospective randomised study of local versus general anaesthesia for cataract surgery.

One hundred and sixty-nine patients (aged 65-98 years) were randomised to receive either local or general anaesthesia for cataract surgery. Cognitive function was assessed using a battery of psychometric tests performed pre-operatively, and at 24 h, 2 weeks and 3 months postoperatively. Oxygen saturation, blood pressure and heart rate were monitored and the results recorded throughout the anaesthetic and immediate recovery period. In the general anaesthetic group, 19% of patients experienced at least one episode of oxygen desaturation during the procedure compared with none in the local anaesthetic group. Pulse rate and blood pressure were stable in the local anaesthetic group compared with the general anaesthetic group where marked fluctuations were noted; 61% of patients in the general anaesthetic group experienced falls in systolic blood pressure greater than 30% of the pre-induction value. No evidence of long-term postoperative cognitive dysfunction was detected and there was no significant difference between the performances of the two groups.

Aged↗

Expression of granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor genes in human astrocytoma cell lines and in glioma specimens.

Expression of granulocyte (G) and granulocyte-macrophage (GM) colony stimulating factor (CSF) genes in human cells of astroglial lineage was studied. Primers for CSFs were used to analyze RNA transcripts in 5 cultured human astrocytoma cell lines and 8 fresh brain specimens by polymerase chain reaction. Constitutive expression of mRNA transcripts of GM-CSF could be detected in all astrocytoma and one neuroblastoma cell lines, and two out of 5 unstimulated astrocytomas, U87MG and U138 MG, expressed G-CSF genes. After stimulation with interleukin (IL)-1 beta + tumor necrosis factor (TNF)-alpha, all cell lines expressed G-CSF. In addition to the cultured cells, we examined gene expression within human malignant astrocytoma, peritumoral brain and autopsied normal brains. The results show that some of the tumor and its surrounding reactive lesions express G- and GM-CSF genes but normal brains do not. The concentration of G- and GM-CSF in supernatants of cultured cells was assessed at the protein level by ELISA. A low level of GM-CSF activity was constitutively present in all astrocytomas. G-CSF was detected in unstimulated U87MG and U138MG and other cell lines could synthesize G-CSF after the stimulation of IL-1 beta and TNF-alpha at the level of mRNA. Furthermore, the concentration of CSFs increased markedly upon stimulation with IL-1 beta and/or TNF-alpha in both a time- and dose-dependent fashion. From these results, it is suspected that astroglial cell-derived CSFs may participate in local immune reactions accompanying infection, degeneration and malignancies in the brain.

Astrocytoma↗