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Biomedical subjects

C Yu

Publications and source records attributed to C Yu.

At least 181 records · Page 10Linked to original sources

The time course of psychophysical end-stopping.

This study measured the time course of psychophysical end-stopping and compared it with the time course of masking. For a 10' D6 target on an 18' D6 pedestal, two abutting end-zone masks (each 13.5' long) covering the filter end-zones reduce masking. This facilitatory 'end-stopping' effect was measured over a range of exposure durations and stimulus onset asynchronies (SOAs). We found that psychophysical end-stopping has a delayed onset which is around 70-100 ms after stimulus onset, in contrast to masking which is robust immediately after stimulus onset, suggesting intracortical feedback processes in the generation of psychophysical end-stopping. The development course of psychophysical end-stopping is relatively long and lasts for approximately 150-200 ms after stimulus onset, in contrast to that of masking which lasts for approximately 100-150 ms. Our results also showed that end-stopping occurs only when the center mask and the end-zone masks have sufficient temporal overlap, possibly indicating that the feedback process for generating end-stopping is triggered by the activation of the spatial filter center by the center mask. These results are in tune with current knowledge of intracortical feedback modulating activities of receptive fields, and have been incorporated into our model to describe the temporal dynamics within end-stopped spatial filters.

Adult↗

Tyrosine-PEG-derived poly(ether carbonate)s as new biomaterials. Part I: synthesis and evaluation.

Tyrosine PEG-derived poly(ether carbonate)s were prepared by condensation copolymerization with phosgene. The resulting polymers were random copolymers with weight average molecular weights from 40 000 to 200 000 dalton. Chemical structure and purity were confirmed by NMR and FTIR spectral analysis. General structure property correlations were established. The glass transition temperature decreased with increasing PEG content and increasing pendent chain length. When higher molecular weight PEG blocks were used, the glass transition temperature increased relative to identical polymers having shorter PEG blocks. The tensile modulus increased with decreasing PEG content, decreasing pendent chain length, and when longer PEG blocks were used. Water uptake and the rate of backbone degradation increased with increasing PEG content. Microspheres could be prepared by solvent evaporation techniques from copolymers with low PEG content. Release rate of pNA and FITC-dextran from the microspheres increased with increasing PEG content. While tyrosine-derived polycarbonates were excellent substrates for cell attachment and growth, the presence of only 5 mol% of PEG1000 led to low or no cell attachment in short-term cell culture with both rat lung fibroblasts and osteoblasts. The polymers were non-cytotoxic.

3T3 Cells↗

Tyrosine-PEG-derived poly(ether carbonate)s as new biomaterials. Part II: study of inverse temperature transitions.

Tyrosine-poly(alkylene oxide)-derived poly(ether carbonate)s represent a new group of degradable biomaterials that exhibit inverse temperature transitions. Poly(DTE co 70%PEG,1000 carbonate) was chosen as an example to study this special phase transition behavior of the polymers. The observed transition temperature varied slightly depending on the technique used, e.g. CD always gave a lower temperature than UV/Vis. CD and UV/Vis studies indicated that the transition temperature was both heating rate and concentration dependent. Thermodynamic parameters of the transition (enthalpy, entropy, and free energy) were determined by DSC. The molecularity of the transition was 2.6, as calculated from UV and DSC data. The transition temperature could be varied from 18 to 58 degrees C by changing the polymer structure. The new poly(ether carbonate)s may be used in medical applications such as injectable drug delivery formulations and bioresorbable barriers for the prevention of surgical adhesions.

Biocompatible Materials↗

Sudden and unexpected neonatal death: a protocol for the postmortem diagnosis of fatty acid oxidation disorders.

Fatty acid oxidation (FAO) disorders are frequently reported as the cause of sudden and unexpected death, but their postmortem identification remains difficult. Over a period of 5 years, the authors have identified 44 cases representing five FAO disorders and 19 additional cases without a diagnosis of a specific defect. Among the two groups, 13 patients died in the neonatal period, 10 in the FAO group, and three from the undetermined defect group. This outcome was consistently associated with exclusive breast feeding and presumably poor caloric intake. The diagnosis of FAO disorder in these cases was based on the analysis of postmortem liver and bile. In postmortem liver, informative findings are microvesicular steatosis, elevated fatty acid concentrations, glucose depletion, and low carnitine concentration. Bile carnitine analysis and acylcarnitine profiling have expanded significantly the effectiveness of the initial protocol and could lead, based on preliminary observations, to better identification of patients who may have been missed or left undetermined by the analysis of liver only. If an autopsy is not performed, informative findings can still be obtained by analysis of blood spots collected for newborn screenings and by biochemical testing of parents and asymptomatic siblings.

Fatty Acids↗

Coping skills training for youths with diabetes on intensive therapy.

The purpose of this study was to determine if a behavioral intervention (coping skills training [CST]) combined with intensive diabetes management can improve the metabolic control and quality of life in adolescents who are implementing intensive therapy. A total of 77 youths (age range, 12.5-20 years) who were beginning intensive insulin therapy were randomly assigned to one of two groups: intensive management with CST or without CST. CST consists of a series of small group efforts designed to teach problem solving skills and communication. Data were collected preintervention and at 3 and 6 months post-intervention by using established clinical and psychosocial indicators. Randomization produced equivalent groups. After 6 months, subjects who received CST had better metabolic control (F = 3.89, p = .02) and better general self-efficacy (F = 4.54, p = 0.01). They reported less negative impact of diabetes on their quality of life (F = 4.55, p = .01) and had fewer worries about diabetes (F = 3.82, p = .02). Thus, nurses may find CST useful in assisting youths with diabetes to achieve metabolic and quality of life goals.

Adaptation, Psychological↗

The Braden Scale for pressure ulcer risk: evaluating the predictive validity in Black and Latino/Hispanic elders.

The purpose of this study was to examine the predictive validity of the Braden scale in predicting pressure sore risk and to determine the physiological and nonphysiological variables associated with the prediction of pressure ulcers in Black and Latino/Hispanic elders. A prospective clinical design ws used to conduct the study. Among 74 patients aged 60 years or older, 24 patients (32%) developed either a stage 1 or stage 2 pressure ulcer. Black elders had a higher incidence rate (21%) than Latino/Hispanic elders (11%). A 2-tailed Fisher's exact test revealed that the Braden scale with a cutoff score of 18 was highly associated with predicting Black elders aged 75 years and older who were at risk of developing pressure ulcers (p < or = .011). Sensitivity was 81% and specificity was 100%. The female gender was also a highly significant factor in the development of pressure ulcers (chi 2(1, N = 49) = 6.4, p < or = .011). Overall, the Braden scale was found to be a valid tool in predicting pressure ulcer risk in Black elders aged 75 years or older when a cutoff score of 18 is used.

Black or African American↗

Genetic tracing of arterial graft flow surface endothelialization in allogeneic marrow transplanted dogs.

In order to trace genetically the source of fallout endothelialization on arterial grafts, six beagle dogs with successful autologous bone marrow transplantation received composite tandem aortic grafts with an isolated, totally impervious Dacron graft and a porous Dacron graft for 12 weeks. For impervious segments, five of 12 fresh tissue samples were Factor VIII/von Willebrand factor + (FVIII/vWF) and seven had faint or negative signals; three of the FVIII/vWF + samples had alpha-actin + smooth muscle cells. Polymerase chain reaction (PCR) study showed eight had a pure donor DNA genotype and four had donor/host mixed, with the donor predominant. Of 12 AgNO3-stained samples, 11 showed pure donor type and one had donor/host mixed, with the donor predominant. For porous segments, all 12 fresh samples had positive flow surface FVIII/vWF and alpha-actin cells. PCR showed all these samples and all 12 AgNO3-stained samples had donor/host mixed type, but the host pattern was predominant. Porous graft healing appears to involve both cellular fallout and tissue ingrowth, and bone-marrow-derived cells may be a source for fallout.

Animals↗

Synthesis and study of peptides with semirigid i and i + 7 side-chain bridges designed for alpha-helix stabilization.

A search for conformational constraints on the peptide alpha-helical conformation indicated that para-substituted amino acid derivatives of a benzene ring might be suitable for linking pairs of side chains that are separated by two turns of the helix. A 14-residue synthetic, amphiphilic alpha-helical peptide model system has been used to study the helix stabilizing effects of a series of four such bridges having constitutionally isomeric structures. These bridges were used to link positions 3 and 10 of the model peptides. The peptides were synthesized in good yield by standard solid-phase methods, including cyclization on the solid support. They were then studied for their solution conformations and melting behavior by circular dichroism (CD) spectropolarimetry, and for their elution behavior on reversed-phase HPLC columns. In aqueous solution and in 50% (v/v) trifluoroethanol, the most effective bridge for helix stabilization consisted of a 4-(aminomethyl)phenylacetic acid residue (AMPA) linked by amide bonds to the side chain functional groups of a (S)-2,3-diaminopropionic acid residue (Dap) in position 3 of the model peptide and an aspartic acid residue in position 10. This Dap3(AMPA), Asp10 bridge was about as effective as two Lys(i), Asp(i+4) lactam bridges incorporated linking residues 3 and 7, and 10 and 14, in the same model peptide sequence. This suggests that it is worth about 1 kcal/mol of helix stabilization energy.

Chromatography, High Pressure Liquid↗

Myeloablation by intravenous busulfan and hematopoietic reconstitution with autologous marrow in a canine model.

We have previously described pharmacokinetic studies with a dimethylsulfoxide-based intravenous busulfan preparation in a canine model and in preliminary clinical trials. Using the same intravenous busulfan preparation, we carried out a dose escalation study to determine a marrow-ablative dose and to test the ability of autologous marrow to reconstitute hematopoiesis in dogs so treated. Busulfan was given intravenously at doses of 3.75 to 40 mg/kg. Marrow ablation was achieved at 20 mg/kg given either as a single dose or in four daily increments of 5 mg/kg each. There was a relative sparing of lymphocytes. A busulfan dose of 40 mg/kg resulted in severe central nervous system toxicity. Otherwise, nonhematopoietic toxicity was minimal and restricted to mild hepatic abnormalities. Four dogs were given busulfan at 20 mg/kg followed 30 hours later by infusion of autologous marrow, and all showed prompt and complete hematopoietic reconstitution. The area under the curve (AUC) determined by busulfan concentration in plasma over time was dose dependent, ranging from 12 to 100 microg x h/mL for busulfan doses of 3.75-20 mg/kg. There was a suggestion that the plasma half-life increased at the highest busulfan doses used. Intravenous administration of busulfan circumvented differences in bioavailability; nevertheless, considerable variations in the pharmacokinetic parameters were observed between individual animals. Thus, intravenous busulfan can be given safely and is effective in ablating hematopoiesis. However, factors other than absorption influence the AUC, and individualization of dosing may be required even with intravenous administration of the drug.

Animals↗

NB1-C16-insulin: site-specific synthesis, purification, and biological activity.

PURPOSE: To develop a simple and efficient method for the synthesis and purification of NB1-lipid-modified-insulin without the use of protecting agents. METHODS: Bovine insulin was allowed to react with cis-9-hexadecenal in an aqueous-organic medium in the presence of NaBH3CN at room temperature overnight. HPLC and ESI LC/MS coupled with dithiothreitol and trypsin treatment were employed for product identification and optimization. The product was purified by a differential C18 solid-phase extraction. The biological effects of the modified insulin were evaluated by receptor binding assay and hypoglycemic effect measurement. RESULTS: NB1-cis-9-hexadecenyl insulin was synthesized by a one-step reductive alkylation in sodium salicylate and isopropanol solution in high yield (80%). The site selectivity and yield of the reaction were found to be affected by pH, medium, and insulin-to-aldehyde ratio. After solid phase extraction, the purity was found to be approximately 98%. This derivative showed a Kd to the insulin receptor of 5.72x10(-9) M and a significantly slower glucose lowering rate than insulin. CONCLUSIONS: NB1-hexadecenyl insulin was synthesized by reductive alkylation without the use of protective agents in high yield. NB1-hexadecenyl insulin retained significant binding affinity to insulin receptor and showed a pronounced hypoglycemic effect.

Alkylation↗

Influence of disulfide bonds on the induction of helical conformation in proteins.

The effect(s) of TFE (2,2,2-trifluoroethanol) on three different conformational states (native, denatured, and carboxymethylated) of CTX III and RNase A has been examined. Contrary to the general belief, the results of the present study reveal that TFE can induce helical conformation in a protein which has no sequence propensity to form a helix. It is found that the helix induction in TFE is intricately related to the destabilization of the tertiary structural conformation in proteins. More importantly, the disulfide bonds in proteins are found to have significant influence on the TFE-mediated helix induction. The results obtained in this study strongly suggest that information pertaining to the influence of disulfide bonds on helix induction need to be considered to improve the accuracy of secondary structure prediction algorithms.

Circular Dichroism↗

Phosphorylation-dephosphorylation of retinoblastoma protein not necessary for passage through the mammalian cell division cycle.

Phosphorylation of the retinoblastoma protein (Rb) during the G1-phase of the mammalian cell division cycle is currently believed to be a controlling element regulating the passage of cells into S-phase. We find, however, that the suspension-grown cell lines U937, L1210, and MOLT-4 contain exclusively hyperphosphorylated Rb. Furthermore, when adherent NIH3T3 cells are grown at very low densities to avoid overgrowth and contact inhibition, they also contain only hyperphosphorylated Rb. NIH3T3 cells exhibit hypophosphorylation when the cells are grown at moderate to high cell densities. We propose that cultures of adherent cells such as NIH3T3, when grown to moderate cell densities, are made up of two populations of cells: (a) cells that are relatively isolated and therefore growing exponentially without contact inhibition, and (b) cells that are growth-inhibited by local cell density or contact inhibition. The common observation in adherent cell lines, that Rb is both hyper- and hypophosphorylated in the G1-phase and only hyperphosphorylated in the S- and G2-phases, is explained by the effects of cell density and contact inhibition. Thus, phosphorylation-dephosphorylation of Rb protein during the G1 phase is not a necessary process during the NIH3T3, L1210, MOLT-4, and U937 division cycles. We propose that phosphorylation-dephosphorylation of Rb is independent of the division cycle and is primarily determined by growth conditions throughout the division cycle.

3T3 Cells↗

Gamma knife radiosurgery for metastatic melanoma: an analysis of survival, outcome, and complications.

OBJECTIVE: Although the mainstays for treatment of metastatic brain disease have been surgery and/or external beam radiation therapy, an increasing number of patients are being referred for stereotactic radiosurgery as the primary intervention for their intracranial pathological abnormalities. The lack of efficacy and cognitive and behavioral consequences of whole brain irradiation have prompted clinicians to select patients for alternative therapies. This study analyzes the effectiveness of Leksell gamma unit therapy for metastatic melanoma to the brain. METHODS: We present our experience with 59 Leksell gamma unit treatment sessions in 45 consecutive patients who presented with metastatic melanoma to the brain. Five of these procedures were performed as salvage therapy for patients who needed second radiosurgical treatment for new lesions that were remote from the previous targets and were not included in the overall analyses. RESULTS: The population included 78% male patients. The mean patient age was 53 years (age range, 24-80 yr). The mean time from diagnosis of primary melanoma to discovery of brain metastasis was 43 months (median, 27.5 mo; range, 1-180 mo). At the time of diagnosis of brain disease, 35.5% of the patients (16 of 45 patients) had neurological symptoms, 77.7% (35 of 45 patients) had known visceral metastases, and 11.1% (5 of 45 patients) had seizure disorders. Eighty-six percent of the lesions (80 of 93 lesions) were cortical, 12% (11 of 93 lesions) were cerebellar, 1% (1 of 93 lesions) were pontine, and 1% (1 of 93 lesions) were thalamic. Fifty-seven percent of the sessions (31 of 54 sessions) were performed for a single lesion, 24.1% (13 of 54 sessions) for two lesions, 9.2% (5 of 54 sessions) for three lesions, 7.4% (4 of 54 sessions) for four lesions, and 1.8% (1 of 54 sessions) for five lesions. The mean treatment volume was 5.6 cc, with a mean prescription of 21.6 Gy to the 56.0% mean isodose line. The median survival time of the patients in our population, using Kaplan-Meier curves, was 43 months from the time of diagnosis of primary melanoma (range, 3-180 mo) and 8 months (range, 1-20 mo) from the time of gamma knife treatment. Complications included seizures within 24 hours of the procedure in four patients, with transient nausea and vomiting in three patients, transient worsening of preprocedure paresis responsive to steroids in three patients, and increased confusion in one patient. All 45 patients were located for follow-up (mean follow-up duration, 1 yr). After gamma knife treatment, 78% of the patients (35 of 45 patients) experienced either improved or stable neurological symptomatology before death or at the time of the latest follow-up examination. There were 26 deaths (58%). The cause of death was determined to be neurological in only 2 of 45 patients (7.7%). Follow-up magnetic resonance images revealed a 97% local tumor control rate of gamma knife-treated lesions, with 28% radiographic disappearance (9 of 32 cases). Six patients developed new lesions remote from radiosurgical targets and underwent second procedures. CONCLUSION: Although metastatic melanoma to the brain continues to have a foreboding prognosis for long-term survival, gamma knife radiosurgery seems to be a relatively safe, noninvasive, palliative therapy, halting or reversing neurological progression in 77.8% of treated patients (35 of 45 patients). The survival rate matches or exceeds those previously reported for surgery and other forms of radiotherapy. Only 7.7% of the patients in our study population who died as a result of metastatic melanoma (2 of 26 patients) died as a result of neurological disease. The routine use of therapeutic level antiseizure medication is emphasized, considering the findings of our review.

Adult↗

TLD dose measurement: a simplified accurate technique for the dose range from 0.5 cGy to 1000 cGy.

A simplified TLD technique characterized by high precision and reproducibility of dose measurement is presented. One hundred eighty LiF TLD rods 1 mm diam x 3 mm length as obtained from the manufacturer were annealed for 1 h at 400 degrees C followed immediately by 2 h at 105 degrees C. After exposure to a dose of 1 Gy of 4 MV x rays, TLDs were annealed for 15 min at 105 degrees C, then read out. TLDs were then sorted into five groups, ranging from 26 to 50 rods each with approximately equal sensitivity after correcting for the drift in the sensitivity of the TLD reader during the readout session. Maintaining group identity, the TLDs were again annealed, irradiated and read out. Fewer than 10% of the TLDs were removed from each group because the corrected readings differed from the respective group mean by more than 3.5%. The standard deviation of the readout was approximately 1.5% within each group. The planchet heater was not flushed with nitrogen gas. Various tests were performed to assess the stability of the group sorting technique and the linearity of TLD dose response. After reannealing, five TLDs were randomly drawn from one of the presorted groups, and subjected to various dose of 4 MV radiation over the range from 0.5 to 1000 cGy. This resulted in an average readout standard deviation of 1.2%. Response per unit dose was almost flat over the range from 0.5 cGy to 100 cGy, and increased by 15% over the range from 100 cGy to 1000 cGy. TLD sensitivity was affected by the duration of the anneal, but was virtually independent of the various time delays between irradiation, prereadout anneal, and readout. The group annealing and sorting (GAS) procedure provides a simple, reliable, precise, convenient, and accurate method for TLD measurements.

Biophysical Phenomena↗

Carbon monoxide and cerebral microvascular tone in newborn pigs.

The present study addresses the hypothesis that CO produced from endogenous heme oxygenase (HO) can dilate newborn cerebral arterioles. HO-2 protein was highly expressed in large and small blood vessels, as well as parenchyma, of newborn pig cerebrum. Topically applied CO dose-dependently dilated piglet pial arterioles in vivo over the range 10(-11)-10(-9) M (maximal response). CO-induced cerebrovascular dilation was abolished by treatment with the Ca2+-activated K+ channel inhibitors tetraethylammonium chloride and iberiotoxin. The HO substrate heme-L-lysinate also produced tetraethylammonium-inhibitable, dose-dependent dilation from 5 x 10(-8) to 5 x 10(-7) M (maximal). The HO inhibitor chromium mesoporphyrin blocked dilation of pial arterioles in response to heme-L-lysinate. In addition to inhibiting dilation to heme-L-lysinate, chromium mesoporphyrin also blocked pial arteriolar dilations in response to hypoxia but did not alter responses to hypercapnia or isoproterenol. We conclude that CO dilates pial arterioles via activation of Ca2+-activated K+ channels and that endogenous HO-2 potentially can produce sufficient CO to produce the dilation.

Animals↗

Contribution of endogenous carbon monoxide to regulation of diameter in resistance vessels.

Endogenous carbon monoxide was proposed to subserve vasodepressor functions. If so, inhibition of heme oxygenase may be expected to promote vascular contraction. This hypothesis was examined in large and small arteries and in isolated first-order gracilis muscle arterioles of rat. The heme oxygenase inhibitors chromium mesoporphyrin (CrMP) and cobalt protoporphyrin (0.175-102 micromol/l) decreased the diameter of pressurized (80 mmHg) gracilis muscle arterioles, whereas magnesium protoporphyrin, a weak heme oxygenase inhibitor, did not. CrMP also elicited development of isometric tension in the muscular branch of the femoral artery but not in the aorta or femoral artery. Arteriolar constrictor responses to CrMP varied in relation to the intravascular pressure, were blunted in preparations exposed to exogenous carbon monoxide (100 micromol/l), and were unaffected by an endothelin receptor antagonist. Importantly, CrMP amplified the constrictor response to increases of pressure in gracilis arterioles. Accordingly, the constrictor effect of heme oxygenase inhibitors is attributable to magnification of myogenic tone due to withdrawal of a vasodilatory mechanism mediated by endogenous carbon monoxide. The study suggests that the vascular carbon monoxide system plays a role in the regulation of basal tone in resistance vessels.

Animals↗

Stereotactic radiosurgery in the treatment of metastatic disease to the brain.

We review 190 consecutive patients with 434 metastatic tumors treated by gamma knife stereotactic radiosurgery, from August 1994 to February 1999. Median actuarial survival for all patients was 34 weeks. Factors correlated with significantly improved survival included controlled systemic disease and nonmelanoma histology. We found that no significant survival benefit could be discerned from adjuvant whole brain radiotherapy in this patient group. Survival was not statistically different for patients initially presenting with 1-4 metastases at initial treatment.

Brain Neoplasms↗

Hemodialysis-related nodulocystic acne treated with isotretinoin.

Some hemodialysis patients, without taking any acnegenic agents, developed severe nodulocystic acne with unknown causes. Because nodulocystic acne poorly responds to conventional acne therapy and increases the black pigmentation in the face, it severely interferes with the quality of life of these patients. To investigate whether isotretinoin is effective in treating hemodialysis patients with severe nodulocystic acne, we undertook a prospective, randomized, single-blind study. A total of 20 patients with nodulocystic acne participated in the study, of whom 18 completed it. Ten patients received isotretinoin 10 mg/day (5 mg/capsule) for 3 months as a study group and the other 10 took placebo for 3 months as a control group. The severity of acne and treatment-related side effects were evaluated monthly by a questionnaire and laboratory evaluation which included liver function tests, blood lipids and blood platelet counts. The results showed isotretinoin treatment significantly reduced the severity of acne of the study group patients after 1 month (scales of acne severity: 4.0 +/- 0.0 vs. 3.13 +/- 0.35, p < 0. 01) and 3 months (4.0 +/- 0.0 vs. 1.5 +/- 0.76, p < 0.01) of follow-up. In addition, the severity of acne of the study group patients was significantly less than that of the control group patients after 1 month (3.13 +/- 0.35 vs. 3.80 +/- 0.42, p < 0.01) and 3 months (1.5 +/- 0.76 vs. 3.70 +/- 0.48, p < 0.001) of treatment. Only mild side effects were noted. No significant changes of biochemical evaluation were found except that a mild elevation of aspartate aminotransferase was noted in the study group patients. However, two study group patients withdrew from the trial because of isotretinoin-related side effects and toxic hepatitis. In summary, our study first demonstrated that the small dose of isotretinoin effectively treated nodulocystic acne of hemodialysis patients and the side effects were mild. This result suggests that isotretinoin may be the treatment of choice for nodulocystic acne in end-stage renal disease patients with renal replacement therapy. The liver function and other isotretinoin-related side effects in these patients should be carefully monitored.

Acne Vulgaris↗