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Biomedical subjects

H Chang

Publications and source records attributed to H Chang.

At least 55 records · Page 3Linked to original sources

Differentiation of embryonic stem cell-derived dopaminergic neurons is enhanced by survival-promoting factors.

Here, we describe the generation of viable and dopamine-producing neurons derived from pluripotent mouse embryonic stem cells. Neurotrophic factors in combination with survival-promoting factors, such as interleukin-1beta, glial cell line-derived neurotrophic factor, neurturin, transforming growth factor-beta(3) and dibutyryl-cyclic AMP, significantly enhanced Nurr1 and tyrosine hydroxylase (TH) mRNA levels, whereas En-1, mash-1 and dopamine-2-receptor mRNA levels were not upregulated. In parallel, mRNA levels of the anti-apoptotic gene bcl-2 were found to be upregulated at terminal stages. Double immunofluorescence analysis revealed increased numbers of TH- and dopamine transporter-, but not gamma-aminobutyric acid- and serotonin-positive neurons in relation to synaptophysin-labeled cells by survival-promoting factors. Moreover, high-performance liquid chromatography analysis showed detectable levels of intracellular dopamine. We conclude that survival-promoting factors enhance differentiation, survival and maintenance of dopaminergic neurons derived from embryonic stem cells.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Correlation between 99mTc-pertechnetate uptakes and expressions of human sodium iodide symporter gene in breast tumor tissues.

We investigated a correlation between the expression of human sodium iodide symporter (hNIS) mRNA and the uptake of 99mTc-pertechnetate in 25 breast tumors. 99mTc-pertechnetate scintigraphy revealed positive uptake in 4 patients. The normalized mRNA expression of hNIS was higher in tumors with positive uptake on the scintigraphy (n=4, median 0.97, range 0.78-1.27) than that in negative uptake tumors (n=21, median 0.46, range 0.10-1.03, p < 0.005). 99mTc-pertechnetate uptake is correlated with the hNIS expression in the breast tumor.

Breast Neoplasms↗

A new siglec family member, siglec-10, is expressed in cells of the immune system and has signaling properties similar to CD33.

The siglecs (sialic acid-binding Ig-like lectins) are a distinct subset of the Ig superfamily with adhesion-molecule-like structure. We describe here a novel member of the siglec protein family that shares a similar structure including five Ig-like domains, a transmembrane domain, and a cytoplasmic tail containing two ITIM-signaling motifs. Siglec-10 was identified through database mining of an asthmatic eosinophil EST library. Using the Stanford G3 radiation hybrid panel we were able to localize the genomic sequence of siglec-10 within the cluster of genes on chromosome 19q13.3-4 that encode other siglec family members. We have demonstrated that siglec-10 is an immune system-restricted membrane-bound protein that is highly expressed in peripheral blood leukocytes as demonstrated by Northern, RT-PCR and flow cytometry. Binding assays determined that the extracellular domain of siglec-10 was capable of binding to peripheral blood leukocytes. The cytoplasmic tail of siglec-10 contains four tyrosines, two of which are embedded in ITIM-signaling motifs (Y597 and Y667) and are likely involved in intracellular signaling. The ability of tyrosine kinases to phosphorylate the cytoplasmic tyrosines was evaluated by kinase assay using wild-type siglec-10 cytoplasmic domain and Y-->F mutants. The majority of the phosphorylation could be attributed to Y597 andY667. Further experiments with cell extracts suggest that SHP-1 interacts with Y667 and SHP-2 interacts with Y667 in addition to another tyrosine. This is very similar to CD33, which also binds the phosphatases SHP-1 and SHP-2, therefore siglec-10, as CD33, may be characterized as an inhibitory receptor.

Amino Acid Motifs↗

Doctor discontent. A comparison of physician satisfaction in different delivery system settings, 1986 and 1997.

OBJECTIVE: To examine the differences in physician satisfaction associated with open- versus closed-model practice settings and to evaluate changes in physician satisfaction between 1986 and 1997. Open-model practices refer to those in which physicians accept patients from multiple health plans and insurers (i.e., do not have an exclusive arrangement with any single health plan). Closed-model practices refer to those wherein physicians have an exclusive relationship with a single health plan (i.e., staff- or group-model HMO). DESIGN: Two cross-sectional surveys of physicians; one conducted in 1986 (Medical Outcomes Study) and one conducted in 1997 (Study of Primary Care Performance in Massachusetts). SETTING: Primary care practices in Massachusetts. PARTICIPANTS: General internists and family practitioners in Massachusetts. MEASUREMENTS: Seven measures of physician satisfaction, including satisfaction with quality of care, the potential to achieve professional goals, time spent with individual patients, total earnings from practice, degree of personal autonomy, leisure time, and incentives for high quality. RESULTS: Physicians in open- versus closed-model practices differed significantly in several aspects of their professional satisfaction. In 1997, open-model physicians were less satisfied than closed-model physicians with their total earnings, leisure time, and incentives for high quality. Open-model physicians reported significantly more difficulty with authorization procedures and reported more denials for care. Overall, physicians in 1997 were less satisfied in every aspect of their professional life than 1986 physicians. Differences were significant in three areas: time spent with individual patients, autonomy, and leisure time (P < or =.05). Among open-model physicians, satisfaction with autonomy and time with individual patients were significantly lower in 1997 than 1986 (P < or =.01). Among closed-model physicians, satisfaction with total earnings and with potential to achieve professional goals were significantly lower in 1997 than in 1986 (P < or =.01). CONCLUSIONS: This study finds that the state of physician satisfaction in Massachusetts is extremely low, with the majority of physicians dissatisfied with the amount of time they have with individual patients, their leisure time, and their incentives for high quality. Satisfaction with most areas of practice declined significantly between 1986 and 1997. Open-model physicians were less satisfied than closed-model physicians in most aspects of practices.

Adult↗

A challenging treatment for an ischaemic ulcer in a patient with Buerger's disease: vascular reconstruction and local flap coverage.

An ischaemic heel ulcer in a patient with Buerger's disease was reconstructed using an in situ saphenous vein graft combined with a local flap. The bypass was sufficient to restore blood supply to the ischaemic limb but a flap was necessary to cover the persistent heel ulcer, which remained after revascularisation. One month after bypass surgery the ulcer was debrided and the resulting defect was covered with a lateral supramalleolar flap. The postoperative course was uneventful and the flap donor site healed well. When treating ischaemic ulcers in a patient with Buerger's disease, vascular reconstruction should be considered first in order to salvage the limb. After revascularisation, a local flap can be used to cover a persistent defect but very few local flaps have been reported. This report is the first published case of successful local flap transfer after bypass surgery in a patient with Buerger's disease. We think that a local flap is one possible treatment for a non-healing ulcer after revascularisation.

Female↗

Intravenous morphine reduces plasma endothelin 1 concentration through activation of neutral endopeptidase 24.11 in patients with myocardial infarction.

STUDY OBJECTIVE: Morphine has multiple cardiovascular effects, but its action on hydrolysis of endothelin 1 (ET-1) has not been investigated. METHODS: We measured plasma levels of ET-1, C-terminal degradation products of ET-1, and neutral endopeptidase 24.11 (NEP) in 68 patients with acute Q-wave myocardial infarction and 29 control subjects. All the patients underwent blood sampling at initial presentation and 10 minutes later. Thirty-six of those with Q-wave myocardial infarction intravenously received 3 mg of morphine immediately after the first sampling (group 1), and the other 32 received the same after the second sampling (group 2). Twenty-four of the control subjects (group 3) were randomized to the protocol of group 1, and the remaining 5 subjects (group 4) were randomized to the protocol of group 2. RESULTS: The plasma ET-1 levels were significantly higher in groups 1 and 2 than in groups 3 and 4 (control groups). In group 1, the ET-1 level decreased significantly at second blood samplings (2.5+/-0.4 pmol/L versus 1.7+/-0.6 pmol/L, P <.001), whereas there were no definite changes of ET-1 levels in group 2 (2.5+/-0.5 pmol/L versus 2.6+/-0.6 pmol/L, P =not significant). However, the C-terminal degradation products increased significantly at second blood samplings in group 1 (0.8+/-0.2 pmol/L versus 1.3+/-0.4 pmol/L, P <.001), whereas there were no definite changes in group 2 (0.9+/-0.3 pmol/L versus 0.9+/-0.4 pmol/L, P =not significant). There was no significant difference in baseline NEP activities between groups 1 and 2 (5.02+/-1.30 nmol/mg protein versus 5.06+/-1.48 nmol/mg protein, P =not significant). However, the NEP activities at second blood samplings declined significantly in group 1 (9.76+/-1.76 nmol/mg protein, P <.001 versus baseline), whereas no definite changes were observed in group 2 (5.09+/-1.62 nmol/mg protein, P =not significant versus baseline). CONCLUSION: Intravenous morphine may increase NEP activities to accentuate hydrolysis of ET-1.

Aged↗

A numerical model of acid-base transport in rat distal tubule.

The purpose of this study is to develop a numerical model that simulates acid-base transport in rat distal tubule. We have previously reported a model that deals with transport of Na(+), K(+), Cl(-), and water in this nephron segment (Chang H and Fujita T. Am J Physiol Renal Physiol 276: F931-F951, 1999). In this study, we extend our previous model by incorporating buffer systems, new cell types, and new transport mechanisms. Specifically, the model incorporates bicarbonate, ammonium, and phosphate buffer systems; has cell types corresponding to intercalated cells; and includes the Na/H exchanger, H-ATPase, and anion exchanger. Incorporation of buffer systems has required the following modifications of model equations: new model equations are introduced to represent chemical equilibria of buffer partners [e.g., pH = pK(a) + log(10) (NH(3)/NH(4))], and the formulation of mass conservation is extended to take into account interconversion of buffer partners. Furthermore, finite rates of H(2)CO(3)-CO(2) interconversion (i.e., H(2)CO(3) &rlharr; CO(2) + H(2)O) are taken into account in modeling the bicarbonate buffer system. Owing to this treatment, the model can simulate the development of disequilibrium pH in the distal tubular fluid. For each new transporter, a state diagram has been constructed to simulate its transport kinetics. With appropriate assignment of maximal transport rates for individual transporters, the model predictions are in agreement with free-flow micropuncture experiments in terms of HCO reabsorption rate in the normal state as well as under the high bicarbonate load. Although the model cannot simulate all of the microperfusion experiments, especially those that showed a flow-dependent increase in HCO reabsorption, the model is consistent with those microperfusion experiments that showed HCO reabsorption rates similar to those in the free-flow micropuncture experiments. We conclude that it is possible to develop a numerical model of the rat distal tubule that simulates acid-base transport, as well as basic solute and water transport, on the basis of tubular geometry, physical principles, and transporter kinetics. Such a model would provide a useful means of integrating detailed kinetic properties of transporters and predicting macroscopic transport characteristics of this nephron segment under physiological and pathophysiological settings.

Acid-Base Equilibrium↗

Arterial anatomy of subdermal plexus of the face.

The subdermal plexus of the face was angiographically investigated using ten fresh cadavers injected with a radio-opaque lead oxide-gelatin mixture over the entire body. The subdermal vessels were unique in each region of the face, and the author classified the vessels into three kinds according to their running forms, shape of their skin territories, and arrangement of the territories. A kind of line by anastomoses of the subdermal vessels which are mutually adjacent or by the quite elongated subdermal vessels was observed. The line depicted by those vessels almost coincided with the relaxed skin tension lines. The author believes that when local flaps in the face are utilized, the flaps should be better designed along the line to obtain better blood supply and aesthetic outcome.

Aged↗

The quality of physician-patient relationships. Patients' experiences 1996-1999.

BACKGROUND: Our objective was to examine how patients of primary care physicians are responding to a changing health care environment. The quality of their relationship with their primary care physicians and their experience with organizational features of care were monitored over a 3-year period. METHODS: This was a longitudinal observational study (1996-1999). Participants completed a self-administered questionnaire at baseline and at follow-up. The questionnaires included measures of primary care quality from the Primary Care Assessment Survey (PCAS). We included insured adults employed by the Commonwealth of Massachusetts who remained with one primary care physician throughout the study period (n=2383). The outcomes were unadjusted mean scale score changes in each of the 8 PCAS over the 3 years and associated standardized difference scores (effect sizes). The 8 PCAS scales measured relationship quality (4 scales: communication, interpersonal treatment, physician's knowledge of the patient, patient trust) and organizational features of care (4 scales: financial access, organizational access, visit-based continuity, integration of care). RESULTS: There were significant declines in 3 of the 4 relationship scales: communication (effect size [ES] = -0.095), interpersonal treatment (ES = -0.115), and trust (ES = -0.046). Improvement was observed in physician's knowledge of the patient (ES = 0.051). There was a significant decline in organizational access (ES = -0.165) and an increase in visit-based continuity (ES = 0.060). There were no significant changes in financial access and integration of care indexes. CONCLUSIONS: The declines in access and 3 of the 4 indexes of physician-patient relationship quality are of concern, especially if they signify a trend.

Adult↗

Switching doctors: predictors of voluntary disenrollment from a primary physician's practice.

BACKGROUND: Our objective was to evaluate 8 interpersonal and structural features of care as predictors of patients' voluntary disenrollment from their primary care physician's practice. METHODS: We performed a longitudinal observational study in which participants completed a validated questionnaire at baseline (1996) and follow-up (1999). The questionnaire measured 4 elements of the quality of physician-patient relations (communication, interpersonal treatment, physician's knowledge of the patient, and patient trust) and 4 structural features of care (access, visit-based continuity, relationship duration, and integration of care). Study participants were insured adults who reported having a regular personal physician at baseline and who completed both baseline and follow-up questionnaires (n=4108). The outcome measured was voluntary disenrollment from the primary physician's practice between baseline and follow-up. RESULTS: One fifth of the patients voluntarily left their primary physician's practice during the study period. When tested independently, all 8 scales significantly predicted voluntary disenrollment (P <.001), with somewhat larger effects associated with the 4 relationship quality measures. In multivariable models, a composite relationship quality factor most strongly predicted voluntary disenrollment (odds ratio [OR]=1.6; P<.001), and the 2 continuity scales also significantly predicted disenrollment (OR=1.1; P<.05). Access and integration did not significantly predict disenrollment in the presence of these variables. CONCLUSIONS: These findings highlight the importance of relationship quality in determining patients' loyalty to a physician's practice. They suggest that in the race to the bottom line medical practices and health plans cannot afford to ignore that the essence of medical care involves the interaction of one human being with another.

Adult↗

Characteristics of patients at a Taipei summer rock concert festival.

BACKGROUND: Rock concerts are popular mass gatherings in Taiwan. Millions of fans participate in rock concerts in Taiwan each year. However, there were no reports on the characteristics of the patients seen in rock concerts in Taiwan. METHODS: Medical care for a summer rock concert festival held in an outdoor stadium in Taipei was coordinated by emergency physicians of a medical center. About 50,000 attendees participated in the two-night concert. Three stations were set up to provide advanced medical care. A standardized form was used to collect information about patients. RESULTS: A total of 28 cases visited the medical stations, fourteen cases each day. They were aged from 13 to 40 years, with an average of 20.8 +/- 6.4. Twenty-one cases were female and seven were male. Twenty-two (79%) were spectators, five (18%) were on-duty staff, and one was a by-stander. Based on an estimation of totally 50,000 participants in the stadium for this two-night festival, the medical use rate was roughly 5.6 PPTT (patients per ten thousand attendees). The most common major problem was fainting which accounted for 13 cases (46%). Of these 13 cases, three cases (23%) lost consciousness and 12 cases (92%) were female. Sixteen cases (57%) were classified as requiring ALS (advanced life support) and 12 cases (43%) as requiring BLS (basic life support). Most cases improved and were discharged after onsite treatment. Only one case was transferred by ambulance due to persistent chest pain. However, she recovered several hours later. CONCLUSIONS: By this preliminary data, first reported in Taiwan, we found that the most common problem was fainting. More than half of the cases seen at the concert required advanced life support. A well-designed emergency medical service (EMS) system is mandatory to provide services for these events.

Adolescent↗

Cyclical mechanical stretching increases the expression of vascular endothelial growth factor in rat vascular smooth muscle cells.

BACKGROUND AND PURPOSE: Mechanical forces have profound effects on vascular smooth muscle cells (VSMCs). The mechanism by which mechanical stimuli regulate vascular endothelial growth factor (VEGF) expression and regulation has yet to be elucidated. We investigated the effect of cyclical mechanical stretching on regulation of the VEGF gene in VSMCs. MATERIALS AND METHODS: Cultured rat VSMCs grown on a flexible membrane base were stretched by applying a vacuum at 60 cycles/minute. VEGF concentration in the cultured media was determined by enzyme-linked immunoassay. VEGF gene expression was determined by Western blot and Northern blot. The location of VEGF in the VSMC was studied immunohistochemically. Chimeric constructs of the VEGF promoter were deleted and the promoter activity was determined by luciferase activity. RESULTS: VEGF concentration increased by 21 to 32% as early as 10 minutes after stretching and remained at this level for up to 12 hours. The concentration of VEGF reached a maximum of 2.8-fold over that in control cells by 2 hours after stretching and declined slightly thereafter. The amount of VEGF mRNA in stretched cells increased as early as 1 hour after stretching, reached a maximum of 3.2-fold over the amount in control cells by 2 hours, and remained at this level for up to 6 hours after stretching. Immunohistochemical study confirmed increased VEGF expression in VSMCs after stretching. Stretched cells transfected with a Sac-Nhe fragment showed only 46% of the luciferase activity of unstretched control cells. However, stretched cells transfected with chimeric plasmids containing a Spe-Nhe fragment showed 2.8-fold luciferase activity over that in control cells. CONCLUSIONS: Cyclical mechanical stretching upregulates expression of the VEGF gene in VSMCs at the transcription level. The VEGF 5'-flanking region contains a negative stretch-response element located in the 0.4-kb Sac-Pst fragment and a positive stretch-response element located in the 0.6-kb Spe-Sac fragment.

Animals↗

Clinical evaluation of a new non-isotopic leptin immunoassay.

OBJECTIVE: Evaluate the new Active human leptin ELISA available through Diagnostic Systems Laboratories Inc for use in clinical research laboratories. DESIGN: Fasting plasma samples for this study were obtained randomly from human subjects. Precision, linearity, recovery, and interference studies were performed, in addition to method comparison with the conventional leptin RIA method and comparison between laboratories. SETTING: University of Hawaii at Manoa, Division of Medical Technology and the Native Hawaiian Health Research-RCMI laboratory. PARTICIPANTS: Native Hawaiians were selected for this study since this population has consistently demonstrated a higher incidence rate of obesity and Type 2 diabetes and thus, potentially have high leptin levels. RESULTS: At leptin concentrations of 2.3, 16.6, and 45.6 ng/ mL, within-run imprecision (n = 5) ranged from 3.1%, 1.6%, and 4.2%, and the between-run imprecision (n = 10) ranged from 6.8%, 4.1%, and 2.7%. The comparison-of-method gave a linear regression equation of y = 0.92x + 1.6 mg/dL (r = 0.96, n = 74, S(y/x) 2.0) when compared to the Linco human leptin RIA method. The dilution curve showed acceptable linearity within the reportable range of the assay, and the recovery was 88.5% to 112%. No interference was detected with hemoglobin up to 1 g/dL, and with triglyceride, up to 1.8 g/dL. However, bilirubin, 10 mg/dL, did show significant interference. CONCLUSION: Overall, we feel that the new Active Human Leptin assay offers a safe and rapid alternative method appropriate for clinical research laboratories and epidemiological studies.

Enzyme-Linked Immunosorbent Assay↗

T Cell Receptor Binding to a pMHCII Ligand Is Kinetically Distinct from and Independent of CD4.

Immune recognition of pMHCII ligands by a helper T lymphocyte involves its antigen-specific T cell receptor (TCR) and CD4 coreceptor. We have characterized the binding of both molecules to the same pMHCII. The D10 alphabeta TCR heterodimer binds to conalbumin/I-A(k) with virtually identical kinetics and affinity as the single chain ValphaVbeta domain module (scD10) (Kd = 6-8 microm). The CD4 ectodomain does not alter either interaction. Moreover, CD4 alone demonstrates weak pMHCII binding (Kd = 200 microm), with no discernable affinity for the alphabeta TCR heterodimer. Hence, rather than providing a major contribution to binding energy, the critical role for the coreceptor in antigen-specific activation likely results from transient inducible recruitment of the CD4 cytoplasmic tail-associated lck tyrosine kinase to the pMHCII-ligated TCR complex.

Antigen Presentation↗

Retro-dental reactive lesions related to development of myelopathy in patients with atlantoaxial instability secondary to Os odontoideum.

STUDY DESIGN: A retrospective analysis of 13 patients with atlantoaxial instability secondary to Os odontoideum who underwent posterior atlantoaxial fusion. OBJECTIVE: To assess the relationships between the development of myelopathy and plain radiographic parameters in patients with atlantoaxial instability secondary to Os odontoideum and to determine whether the pathologic structures, which compress the spinal cord, are visualized using magnetic resonance imaging. SUMMARY OF BACKGROUND DATA: The development of myelopathy, which is the most serious complication associated with Os odontoideum, was thought to be related to either the degree of instability or direction of instability, or a decrease in the space available for the cord. However, such indirect radiographic parameters measured using plain radiographs cannot provide direct information concerning the causes of myelopathy in patients with atlantoaxial instability secondary to Os odontoideum. METHODS: Thirteen patients who underwent posterior atlantoaxial fusion for clinical symptoms due to Os odontoideum were classified into two groups depending on whether they had (n = 9) or did not have (n = 4) myelopathy. Four radiographic parameters were measured using flexion and extension lateral radiographs; the degree of instability, the direction of instability, and the space available for the cord in flexion and extension. MRI was performed on all patients in the myelopathy group. The radiologic and clinical data were compared for the two groups. RESULTS: There were no significant statistical differences in the degree of instability (6.83 vs. 7.38, P = 0.816), space available for the cord in flexion (6.94 vs. 7.13, P = 0.938), and space available for cord in extension (7.56 vs. 5.75, P = 0.434) between the two groups. There was a poor agreement between the direction of instability and the development of myelopathy (kappa = 0.268, P = 0.308). Magnetic resonance imaging did demonstrate, however, cord compression caused by retro-dental reactive lesions in the myelopathy; cystic masses were present in two patients; and fibrocartilaginous masses were present in seven. CONCLUSION: The current study suggests that the value of plain radiographic parameters should be reevaluated as a means of evaluating myelopathy in patients with atlantoaxial instability secondary to Os odontoideum, and that retro-dental reactive lesions should be considered as the potential cause of myelopathy.

Adult↗

A mesoscale phytoplankton bloom in the polar Southern Ocean stimulated by iron fertilization.

Changes in iron supply to oceanic plankton are thought to have a significant effect on concentrations of atmospheric carbon dioxide by altering rates of carbon sequestration, a theory known as the 'iron hypothesis'. For this reason, it is important to understand the response of pelagic biota to increased iron supply. Here we report the results of a mesoscale iron fertilization experiment in the polar Southern Ocean, where the potential to sequester iron-elevated algal carbon is probably greatest. Increased iron supply led to elevated phytoplankton biomass and rates of photosynthesis in surface waters, causing a large drawdown of carbon dioxide and macronutrients, and elevated dimethyl sulphide levels after 13 days. This drawdown was mostly due to the proliferation of diatom stocks. But downward export of biogenic carbon was not increased. Moreover, satellite observations of this massive bloom 30 days later, suggest that a sufficient proportion of the added iron was retained in surface waters. Our findings demonstrate that iron supply controls phytoplankton growth and community composition during summer in these polar Southern Ocean waters, but the fate of algal carbon remains unknown and depends on the interplay between the processes controlling export, remineralisation and timescales of water mass subduction.

Atmosphere↗

Breast-cancer diagnosis with nipple fluid bFGF.

Early diagnosis of breast cancer is the key to extending survival of breast-cancer patients. We found that the concentrations of nipple fluid bFGF (basic fibroblast growth factor) was significantly increased in breast-cancer patients compared with concentrations in controls (1717 ng/L [SD 706] vs 19 ng/L [19]; Student's t test p=0.027). Measurement of bFGF in nipple fluid could be a useful diagnostic tool for breast cancer, and deserves further study.

Biomarkers, Tumor↗

Amino acid transporters in plants.

Amino acid transporters are essential participants in the resource allocation processes that support plant growth and development. Recent results have identified several new transporters that contribute to a wide array of physiological activities, and detailed molecular analysis has provided fundamental insights into the structure, function and regulation of these integral membrane proteins.

Amino Acid Transport Systems↗