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Biomedical subjects

M J Lin

Publications and source records attributed to M J Lin.

15 recordsLinked to original sources

A theoretical analysis of a new drug delivery system: a cylindrical device with a vertical opening on its surface.

A theoretical analysis of a proposed drug delivery device is presented. The device is of cylindrical shape with an opening on its side surface. Analytical expressions for the temporal variations in the amount of drug released and the size of the unreleased portion of the device are derived. The result of numerical simulation reveals that an approximately zero-order mechanism can be obtained, provided that the device is designed appropriately. The applicability of the analytical expressions derived is justified by examining the release of sodium salicylate embedded in polyethylene. The present work is a generalization of analyses suggested previously for some similar devices.

Drug Delivery Systems

[Causes of maternal death. A 10-year case analysis].

The causes of maternal deaths in our hospital from 1981 to 1989 were analysed. There were 12,819 live births and 6 maternal deaths during this period, a maternal mortality rate of 46.69/per 100,000. The main cause of maternal deaths was acute fatty liver of pregnancy (50%), and next cardiac disease, acute hemorrhagic necrotic pancreatitis and hemorrhage of subarachnoid space (each 16.67%). There was no death due to obstetric hemorrhage, pregnancy induced hypertension syndrome or ectopic pregnancy. It is suggested that needle biopsy of the liver should be done for pregnant women with jaundice of unknown cause. Pregnant women with cardiac disease should be under the care of both obstetrician and internist in collaboration and cesarean section is indicated when the woman's cardiac function remains at grade 3 or 4.

Adult

Dynamics and reactivity of HbXL99 alpha. A cross-linked hemoglobin derivative.

Resonance Raman spectroscopy, transient absorption, and fluroescence techniques have been employed to investigate the structure and dynamics of the alpha-cross-linked hemoglobin derivative, HbXL99 alpha. The resonance Raman spectra of the deoxy form of HbXL99 alpha are identical to those of native NbA (VFe-His approximately 222 cm-1), which exhibit a T-state (low affinity) structure regardless of solvent conditions. The resonance Raman spectra of the transient heme photoproduct resulting from CO photolysis from HbXL99 alpha appear to have structures intermediate between deoxy-T and ligand-bound R structures (VFe-His approximately 222 cm-1). Time-resolved resonance Raman data of HbXL99 alpha-CO show that complete CO recombination occurs after approximately 5 ms, with only a small amount of the CO-bound species reforming within approximately 200 ns (geminate recombination). Transient absorption spectra of HbXL99 alpha-O2 indicate that the extent of sub-nanosecond geminate recombination of O2 is also reduced in the cross-linked derivative relative to native HbA. The decrease in tryptophan fluorescence of HbXL99 alpha upon oxygenation further indicates that tertiary structural changes at the alpha 1-beta 2 interface upon ligation are apparently reduced, but not eliminated in the cross-linked derivative relative to HbA.

Aspirin

[Duplex Doppler ultrasound of internal jugular vein ectasia. Case report].

A seven-year-old boy, who complained of painless swelling mass over the right neck on exertion, was diagnosed as right internal jugular vein ectasis by the duplex Doppler ultrasound. The caliber of the right internal jugular vein was prominently dilated when Valsalva maneuver was done, the duplex Doppler ultrasound showed an essentially flat wave from that indicated the swelling mass to be a venous structure. The clinical manifestation, etiology, pathological findings and diagnostic methods of the internal jugular vein ectasia were reviewed with emphasis on the advantages of duplex Doppler ultrasound in confirming the diagnosis.

Child

Estimation of 5-aminosalicylic acid and its metabolite in human serum by front-face fluorometry: a simple and sensitive method.

Salicylazosulfapyridine (SASP), commonly used in the treatment of inflammatory bowel disease, breaks down in the colon into sulfapyridine and 5-aminosalicylic acid (5-ASA), the active moiety of SASP. We report a sensitive method to measure 5-ASA and its known major metabolite acetyl 5-ASA (Ac-5-ASA) directly from the serum without any extraction procedure. Using front-face fluorometry, 5-ASA and Ac-5-ASA were detected at the excitation wavelength of 310 nm with emission maxima at 475 nm and 440 nm, respectively. Standard curves were obtained by adding known amounts of 5-ASA and Ac-5-ASA to several individual and pooled human sera. Presence of sulfapyridine (0 to 20 micrograms/ml) and SASP (0 to 15 micrograms/ml) in the serum did not interfere with the assays. Five microliters of acetic anhydride was added to the serum to convert all 5-ASA to Ac-5-ASA. The difference in the spectrum before and after addition of acetic anhydride represented the concentration of free 5-ASA. The values thus estimated were within 1% of the expected readings from the standard curves. This assay was compared with the organic extraction method for the determination of free and acetylated 5-ASA in sera of patients given olsalazine (azodisalicylate). The results demonstrate that direct analysis of the sera by front-face fluorometry enables us to measure 5-ASA and Ac-5-ASA at levels as low as 0.1 micrograms/ml in serum, making this method at least 10-fold more sensitive than the current available extraction methods.

Aminosalicylic Acids

[Prognostic nutritional index in hepatobiliary surgery].

Malnutrition has long been recognized as a potential source of increased morbidity and mortality in patients with various disorders, including those undergoing hepatobiliary surgery. To elucidate the role of malnutrition in postoperative complications in hepatobiliary surgery, the nutritional status of 73 patients was evaluated with the Prognostic Nutritional Index (PNI) devised by Dr. Mullen. PNI was calculated based on the following parameters: albumin, transferrin, triceps skin folds and delayed cutaneous hypersensitivity (DH). DH was performed with four skin antigens: candida, trichophyton, streptokinase/streptodornase and PPD. Based on the results the patients were stratified into two groups, a low-risk group with PNI less than 40 and a high-risk group with PNI greater than or equal to 40. Complications occurred in 10 of 34 patients (29%) in the low-risk group and in 15 of 39 patients (38%) in the high-risk group. There were 2 deaths in the latter and none in the former group, the difference was not statistically significant. We conclude that PNI fails to predict postoperative complications in hepatobiliary surgery patients. Either the formula of PNI, which is derived from gastrointestinal surgery patients, is not applicable to patients undergoing hepatobiliary surgery, or factors other than nutrition are involved in the development of postoperative complications in hepatobiliary surgery.

Biliary Tract Diseases

Interaction of zinc protoporphyrin with intact oxyhemoglobin.

In erythropoietic protoporphyria and lead poisoning, free protoporphyrin (PPIX) and zinc protoporphyrin (ZPP), respectively, accumulate in erythrocytes. That PPIX and ZPP bind to human hemoglobin A (Hb4) is established, but the site of binding is still a matter of controversy. We investigated the interaction of ZPP with intact, tetrameric oxy Hb4, using batch microcalorimetry, front-face fluorometry, absorption difference spectroscopy, oxygen equilibrium studies, and isoelectric focusing (IEF). In the presence of oxy Hb4 (pH 7.35, 0.05 M phosphate), the fluorescence emission maximum (excitation at 420 nm) of ZPP immediately shifts from 587 nm (ZPP alone) to 594 nm, as expected when binding to protein. The fluorescence intensity increases with time and is correlated with the ZPP:Hb4 mole ratio. A slow, time-dependent reaction is also observed with microcalorimetry: the rate of heat of reaction exhibits both a fast and a slow component. The heats of reaction range from -2.1 to -14.8 mcal depending upon the ZPP:Hb4 ratio of 4:1 (0.4 mM:0.1 mM) to 38:1 (3.8 mM:0.1 mM), respectively, and are typical of weak, noncovalent protein-ligand interactions. The optical difference spectra are a function of the ZPP:Hb4 molar ratio and also exhibit a slow increase in intensity over time. No time-dependent optical difference spectra are observed with ZPP or with Hb4 alone. The oxygen affinity of Hb4 in the presence of ZPP decreases with increasing mole ratio. During IEF, all ZPP separates from Hb4, consistent with a weak, noncovalent interaction at a non-heme pocket site. We conclude that ZPP binds to intact, tetrameric hemoglobin at non-heme pocket sites in a nonspecific, weak, noncovalent interaction.

Calorimetry

[Quantitative detection of microcirculation and multi-factorial analysis of patients with cardio-cerebrovascular diseases with blood-stasis syndrome].

The studies, which applied the Laser Doppler Micro-detection technique and other multi-factors analysis in patients with cardio-cerebrovascular diseases with blood-stasis syndrome, suggested that the speed of microcirculatory flow were slowed down obviously. The change of this value in patients comparing with healthy adults and the aged showed evident difference accompanied with many changes such as hemorheology, red cell deformability (RCD) and platelet aggregation (PA). Relativity analysis showed that there was linear relativity in degree of microcirculatory obstacle and PA and RCD. Further comparison and analysis with multi-factors for mechanism in microcirculatory obstacles illustrated that those might be the result of many pathological factors' action. In clinical treatment, using anti-platelet drugs and comprehensive measures to enhance RCD and lower viscosity of blood, could be effective in improvement of microcirculatory functions.

Aged

Acceleration of hemoglobin C crystallization by hemoglobin S.

We previously reported that circulating hemoglobin (Hb) CC erythrocytes contain oxygenated HbC crystals with little or no HbF and that HbF inhibits in vitro crystallization of HbC. We now report that HbS accelerates in vitro crystallization of HbC. Crystals were formed in 1.8 mol/L potassium phosphate buffer, pH 7.4, at 30 degrees C and were counted in several time intervals with a hematocytometer. The hemoglobin composition of Millipore-isolated crystals and supernatant were also analyzed. Under the conditions selected, 100% HbS formed needle-shaped crystals only after two hours. Pure HbC does not form crystals within 15 minutes, whereas a ratio of 10% HbS:90% HbC forms 1,100 crystals/mm3, 20% HbS:80% HbC forms 370 crystals/mm3, and 30% HbS:70% HbC forms 5 crystals/mm3. Crystals formed in the presence of HbS are tetragonal, as are pure HbC crystals. As compared with 100% HbC, HbA or albumin mixed with HbC showed a decreased number of crystals as a result of dilution. Analysis of the Hb content of isolated crystals by citrate agar gel electrophoresis showed that HbS was rapidly incorporated into the crystal in the same ratio over time. These results demonstrate that HbS accelerates crystallization of HbC with respect to the rates of crystallization of any of these two Hbs separately, through a mechanism that involves cocrystallization. These results may be significant in understanding SC disease.

Crystallization

Effects of ligand size on pH and organic phosphate-dependent affinity changes in carp hemoglobin as measured by isonitrile binding.

The equilibria of the binding of methyl and ethyl isonitrile to carp hemoglobin have been measured at three pH values in the presence and absence of inositol hexaphosphate. The binding of methyl isonitrile is characterized by a higher overall dissociation constant, C1/2, and a higher Hill coefficient, n, than that of the ethyl derivative. The former is consistent with the greater hydrophobicity of ethyl isonitrile, and the latter is probably due to a greater intrinsic difference or heterogeneity in the binding affinities of the alpha- and beta-chains for the larger ligand. Changes in log C1/2 which result from alterations in pH or addition of organic phosphate are the same for both ligands within experimental error. This result is not consistent with affinity changes being the result of steric interactions between the protein and the ligand. At pH 6 in the presence of inositol hexaphosphate, equilibrium parameters estimated from overall rates of ligand binding and dissociation are in good agreement with direct equilibrium measurements. This is consistent with the protein being in a low-affinity, T-like state even when saturated with ligand under these conditions, resulting in a loss of cooperativity in ligand binding. At high pH, ligand binding remains cooperative, as evidenced by n values greater than unity, a general lack of agreement between measured equilibrium parameters and those estimated from overall kinetic constants, and differences in the kinetics of ligand binding as observed by rapid-mixing and flash photolysis techniques. Thus, the deoxygenated state of carp hemoglobin at high pH does not appear to be a good model of a deoxygenated R quaternary structural state.

Animals

The inhibition of hemoglobin C crystallization by hemoglobin F.

We have reported that circulating CC erythrocytes containing HbO2 C crystals exhibit little or no Hb F suggesting that Hb F may inhibit the crystallization of Hb C. We report now that Hb F inhibits in vitro crystallization of HbO2 and HbCO C when compared to the effect of Hb A in a wide range of mixture proportions. For example, while HbCO C solutions form tetragonal C crystals within 25 min, no crystals form within 2 h with 30% Hb F, whereas 550 crystals/mm3 form with 30% Hb A. Furthermore, an increase in the percent of Hb A is correlated with a greater number of orthorhombic crystal formation rather than the tetragonal morphology observed with 100% Hb C. We also report that Hb A2 (containing delta chains that exhibit 10 sequence differences with beta chains) and Hb Lepore Boston-Washington (a fusion mutant of delta and beta chains that contains only six of these differences) both inhibit Hb C crystallization. By comparing the sequences of the three inhibitory hemoglobins, we conclude that position Gln-87 in the gamma chains is, at least partially, the cause of the inhibitory effect of Hb F on the crystallization of Hb C.

Amino Acid Sequence

The role of the subependymal plate in glial tumorigenesis.

We have studied the sequential morphological events of glial tumorigenesis in neonatal dogs, using high titer subgroup C Bratislava-77 Avian Sarcoma Virus, given as 0.01 ml by intraventricular inoculation. The cells of the subependymal plate are those which seem to form the gliomas; cytoplasmic alterations are evident within 24 h after inoculation and microfoci of gliomas, contiguous with the subependymal plate of the lateral ventricles, are visible within 7 days. Independent tumors are present by the 10th post-inoculation day. These studies support the hypothesis of Globus and Kuhlenbeck, which implicates the cells of the subependymal palte in glial tumorigenesis.

Animals