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Biomedical subjects

P Hsu

Publications and source records attributed to P Hsu.

At least 19 recordsLinked to original sources
PubMed2005

Electromagnetically induced magnetochiral anisotropy in a resonant medium.

Chirality has been extensively studied for well over a century, and its potential applications range from optics to chemistry, medicine, and biology. Ingenious experiments have been designed to measure this naturally small effect. Here we discuss the possibility of producing a medium having a large chiral effect by using the ideas of coherent control. The coherent fields resonant with appropriate transitions in atomic or molecular systems can be used to manipulate the optical properties of a medium. We demonstrate experimentally very large magnetochiral anisotropy by using electromagnetic fields in atomic Rb vapors.

Journal Article↗
PubMed2001

Basic fibroblast growth factor and fibroblast growth factor receptors in adult olfactory epithelium.

Basic fibroblast growth factor (FGF2) stimulates proliferation of the globose basal cells, the neuronal precursor in the olfactory epithelium. The present study investigates the expression of basic fibroblast growth factor and fibroblast growth factor receptors in the adult olfactory epithelium. FGF2 immunoreactivity was expressed widely in the olfactory epithelium, with the highest density of immunoreactivity in the supporting cells. In contrast, most cells in the epithelium expressed FGF2 mRNA. Fibroblast growth factor receptor-1 (FGFr1) immunoreactivity was densest in the basal cell and neuronal layers of the olfactory epithelium and on the apical surface of supporting cells. In the lamina propria FGF2 immunoreactivity and mRNA were densest in cells close to the olfactory nerve bundles. FGFr1 immunoreactivity was heaviest on the olfactory ensheathing cells. Using reverse transcriptase-polymerase chain reaction analysis, the olfactory epithelium was shown to express only three receptor splice variants, including one (FGFr1c) with which basic fibroblast growth factor has high affinity. Other receptor splice variants were present in the lamina propria. Taken together, these observations indicate endogenous sources of FGF2 within the olfactory epithelium and lamina propria and suggest autocrine and paracrine pathways via which FGF2 might regulate olfactory neurogenesis. The observation of only three receptor splice variants in the olfactory epithelium limits the members of the fibroblast growth factor family which could act in the olfactory epithelium. The widespread distribution of receptors suggests that fibroblast growth factors may have roles other than proliferation of globose basal cells.

Age Factors↗
PubMed2000

A computer-aided design mammography screening system for detection and classification of microcalcifications.

This paper presents a prototype of a computer-aided design (CAD) diagnostic system for mammography screening to automatically detect and classify microcalcifications (MCCs) in mammograms. It comprises four modules. The first module, called the Mammogram Preprocessing Module, inputs and digitizes mammograms into 8-bit images of size 2048x2048, extracts the breast region from the background, enhances the extracted breast and stores the processed mammograms in a data base. Since only clustered MCCs are of interest in providing a sign of breast cancer, the second module, called the MCCs Finder Module, finds and locates suspicious areas of clustered MCCs, called regions of interest (ROIs). The third module, called the MCCs Detection Module, is a real time computer automated MCCs detection system that takes as inputs the ROIs provided by the MCCs Finder Module. It uses two different window sizes to automatically extract the microcalcifications from the ROIs. It begins with a large window of size 64x64 to quickly screen mammograms to find large calcified areas, this is followed by a smaller window of size 8x8 to extract tiny, isolated microcalcifications. Finally, the fourth module, called the MCCs Classification Module, classifies the detected clustered microcalcifications into five categories according to BI-RADS (Breast Imaging Reporting and Data System) format recommended by the American College of Radiology. One advantage of the designed system is that each module is a separate component that can be individually upgraded to improve the whole system. Despite that it is still is a prototype system a preliminary clinical evaluation at TaiChung Veterans General Hospital (TCVGH) has shown that the system is very flexible and can be integrated with the existing Picture Archiving and Communications System (PACS) currently implemented in the Department of Radiology at TCVGH.

Algorithms↗
PubMed2000

Latino physician supply in California: sources, locations, and projections.

PURPOSE: To determine the number of Latino physicians in California, identify the schools and countries where they were educated, determine the percentage located in Latino areas, and project the supply of Latino physicians to 2020. METHOD: From a 1999 list of 74,345 licensed physicians, the authors identified Latino U.S. medical graduates (USMGs) by "heavily Hispanic" surnames and Latino international medical graduates (IMGs) by country and school of graduation. The 1999 license addresses of all physicians in Los Angeles County were analyzed against 1998 Latino-population data by zip code. A baseline projection of the supply of Latino physicians was based on the ten-year (1986 to 1995) average annual production of Latino physicians educated in California, out of state, and in Latin America. A worst-case projection assumed the continuation of recent trends: a 32% decrease in California-educated Latino USMGs, a 19% decrease in out-of-state Latino USMGs, and a reduction of Latino IMGs to five per year. RESULTS: In 1999, 3,578 Latino physicians comprised 4.8% of all Californian physicians. In contrast, Latinos made up 30.4% of the state's population. Latino physicians were more likely than non-Latinos to have addresses in a heavily Latino zip code. In the baseline projection, while the overall supply of Latino physicians will increase by nearly 30% by 2020, that growth will be dwarfed by the 74% growth in the Latino population over the same time. In the worst-case projection, the actual number of Latino physicians will decrease from the 1999 figure of 3,578 to 3,448 by 2020, while the Latino population continues to grow. CONCLUSIONS: (1) The Latino USMG supply must be markedly increased in the number of first-year matriculants in both California and out-of-state schools. (2) The issue of Latino IMGs requires special attention, and may provide a temporary solution to the Latino physician shortfall. (3) Non-Latino physicians need to be prepared to be culturally effective with a large and growing Latino patient population.

California↗
PubMed1999

HIV-1 genotypic resistance patterns predict response to saquinavir-ritonavir therapy in patients in whom previous protease inhibitor therapy had failed.

BACKGROUND: Tests for resistance to HIV drugs are available for clinical use; however, their predictive value has not been fully assessed. OBJECTIVES: To determine HIV-1 genotypic predictors of a virologic response to saquinavir-ritonavir therapy in patients in whom at least one previous protease inhibitor-containing regimen had failed and to compare the predictive value of baseline genotype with that of standard clinical evaluation. DESIGN: Retrospective clinical cohort study. SETTING: University-based HIV clinic. PATIENTS: 54 HIV-1-infected adults treated with saquinavir-ritonavir who had experienced virologic failure while receiving a protease inhibitor-containing regimen for at least 3 months. MEASUREMENTS: HIV-1 reverse transcriptase and protease gene sequences, CD4 cell counts, clinical characteristics, detailed antiretroviral treatment history, and plasma HIV-1 RNA levels at baseline and at three follow-up time points (median, 4, 12, and 26 weeks). Virologic failure was defined as a plasma HIV RNA level greater than 1000 copies/mL. RESULTS: In 22 patients (41%), a plasma HIV-1 RNA level less than 500 copies/mL was achieved by week 12; in 15 patients (28%), this response was maintained through week 26. Clinical characteristics predicting a poorer response included a diagnosis of AIDS, lower CD4 cell count, and higher plasma HIV RNA level (P<0.03). Number of previous nucleoside reverse transcriptase inhibitors, previous protease inhibitor therapy, and duration of previous protease inhibitor therapy were predictors of poorer response (P<0.01). Multivariate regression models revealed that protease mutations present at the initiation of saquinavir-ritonavir therapy were the strongest predictors of virologic response. A model of clinical features explained up to 45% of the variation in virologic outcomes by week 12, whereas the explained variance was 71% when genotypic predictors were included. CONCLUSIONS: In patients in whom protease inhibitor-containing antiretroviral therapy fails, HIV-1 genotype is predictive of virologic response to subsequent therapy. This predictive capacity adds to that of standard clinical evaluation.

Adult↗
PubMed1999

Identification of biased amino acid substitution patterns in human immunodeficiency virus type 1 isolates from patients treated with protease inhibitors.

Human immunodeficiency virus type 1 (HIV-1) amino acid substitutions observed during antiretroviral drug therapy may be caused by drug selection, non-drug-related evolution, or sampling error introduced by the sequencing process. We analyzed HIV-1 sequences from 371 untreated patients and from 178 patients receiving a single protease inhibitor. Amino acid substitution patterns during treatment were compared with inferred substitution patterns arising evolutionarily without treatment. Our results suggest that most treatment-associated amino acid substitutions are caused by selective drug pressure, including substitutions not previously associated with drug resistance.

Amino Acid Sequence↗
PubMed1997

Timing of the expression of enamel gene products during mouse tooth development.

In order to understand the mechanisms involved in tooth development it is important to define the timing for tissue-specific gene expression. A consequence of ameloblast cell differentiation is the sequential expression of tissue-specific genes whose products form the enamel extracellular matrix. The ameloblast phenotype has been characterized as consisting of two major classes of proteins: amelogenins and non-amelogenin proteins such as anionic enamel proteins (enamelins, tuft proteins, tuftelin, sulfated proteins) and enamel proteases. The postulated functions for the anionic enamel proteins are as nucleators for hydroxyapatite crystal formation while amelogenins control the crystal size, growth and orientation. While the amelogenins have been well characterized, detailed knowledge for anionic enamel proteins has been sparse. In the present study, we designed experiments to characterize one of the anionic enamel proteins from mouse molars, tuftelin, and to determine the timing of expression of this protein during molar tooth development. Our results showed the initial detection of tuftelin transcripts within proliferating inner enamel epithelial cells at very early stages of tooth development (13 days of embryonic development equivalent to the bud stage of tooth development). These data provide direct evidence that invalidates previous dogmas that enamel proteins were synthesized by polarized, non-dividing, fully differentiated ameloblast cells. In addition, tuftelin was found to be synthesized also by dental papilla mesenchyme cells suggesting that this protein is not enamel-specific. These data taken together open the possibility that the tuftelin present in the dentino-enamel junction could be secreted by both, preodontoblast cells and preameloblast cells. It might also suggest a possible different role for tuftelin than nucleator of hydroxyapatite crystals.

Amelogenin↗
PubMed1996

Identification of the site in the substance P (NK-1) receptor for modulation of peptide binding by sulfhydryl reagents.

Substance P (SP) is a peptide neurotransmitter that is involved in multiple responses in both the central and the peripheral nervous systems through a G-protein-coupled contains a number of conserved cysteine residues. To localize and identify the cysteine residues that participate in receptor binding, intact Chinese hamster ovary cells expressing the SP receptor were treated with various sulfhydryl reagents and the effect of these reagents on radioiodinated SP binding affinity and dissociation rate was determined. We used a series of amphiphilic maleimide derivatives in which the reactive maleimide group penetrates to different depths within the plane of membrane. Only the maleimide derivatives with intermediate chain lengths modified receptor binding properties, indicating that the reactive sulfhydryl group is located within a transmembrane domain of the receptor close (within 1.7 nm) to the extracellular border. Since peptide binding to a mutant receptor C199S, in which Cys-199 was replaced by a serine, was found to be insensitive to modulation by sulfhydryl reagents, this reactive sulfhydryl group is on Cys-199 of the receptor. Receptor occupancy by SP protects Cys-199 from modification and thus this residue is either located at or conformationally linked to the SP binding site.

Alkylation↗
PubMed1996

Genotypic analysis of primary head and neck squamous carcinoma by combined fluorescence in situ hybridization and DNA flow cytometry.

Concurrent DNA flow cytometric (FCM) and fluorescence in situ hybridization (FISH) analyses were prospectively performed on 24 primary untreated head and neck squamous carcinomas for characterization of the genotypic and phenotypic DNA aberrations of these neoplasms. Eleven tumors (42.0%) manifested DNA diploidy (DI = 1.00) and 15 (58.0%) had DNA aneuploidy (DI < or > 1.00) by FCM. Fluorescence in situ hybridization results showed aneusomy in the majority of DNA diploid and in all DNA aneuploid tumors. The extent of the abnormalities for individual chromosomes and the number of involved chromosomes in a given DNA diploid or aneuploid tumor were significantly different. Overall, a statistical correlation between the FCM DNA index (DI) and the magnitude of the chromosomal aberration by FISH was found. Our results also show a significant association between the DI and histologic differentiation and stage of disease in these neoplasms. In conclusion, (1) chromosomal aneusomy characterizes most DNA diploid (DI = 1.00) and all DNA aneuploid (DI < or > 1.00) head and neck squamous carcinomas; (2) polysomy is the most prevalent finding; (3) loss of the Y chromosome in tumors from male patients is a consistent feature; (4) the FCM DI reflects net chromosomal gains or losses in these neoplasms; and (5) DNA aneuploidy is associated with tumor aggressiveness.

Adult↗
PubMed1996

An "atomic" approach to dis/ability assessment.

Disability assessment is a complex process that requires consideration of both work demands and clinical conditions. It is commonly practiced in two very distinct fashions. First, poorly specified processes are used to reach decisions about highly specific situations; second, broad generalizations are often applied, which may be poorly applicable to specific situations. A new approach allows the integration of these two methods. The "atomic" approach has two phases: "disaggregation" into the smallest possible meaningful knowledge units (atoms) and then "reintegration" (reassembly). Individual information units may be applicable to a wide variety of different situations, providing an efficient system. The atomic approach includes two tracks that merge to produce the dis/ability assessment: Clinical track (diagnosis-->confirmation test; diagnosis-->impact assessment test-->test result-->physiologic/anatomic limitation; and the job demand track (job-->task-->sub task-->functional work demand index-->empiric data). The approach describe offers advantages of rationality, empiric and face validity, and efficiency. The logic is fully explicable, and most information units (atoms) can be used in many ways to cover new situations. It is applicable to both individual case situations and to large-scale system development.

Disability Evaluation↗
PubMed1996

Age dependence of cerebrovascular response mechanisms in domestic pigs.

Hypercapnia-induced cerebral vasodilation in the newborn pig is a prostanoid-associated response. In some adult models, hypercapnic cerebral vasodilation is associated with the generation of nitric oxide (NO). Acetylcholine (ACh) produces a NO-dependent cerebral vasodilation in many adult models, but topical ACh is a prostanoid-associated cerebral vasoconstrictor in the newborn pig. We hypothesized that mediators influencing cerebral response can be age dependent. Juvenile domestic pigs were compared with newborn pigs, and pial arteriolar diameters were measured by use of a closed cranial window during hypercapnia and topical ACh (10(-5) M). Four different conditions were explored: control, topical N omega-nitro-L-arginine (L-NNA, 10(-3) M), indomethacin (5 mg/kg i.v.), and both L-NNA and indomethacin. All animals were anesthetized with alpha-chloralose. As opposed to the complete block in the newborn, indomethacin only partially attenuated the hypercapnic cerebral vasodilation in the juvenile pig.L-NNA, which had no effect on the response of the newborn, produced a partial attenuation of the hypercapnic response of the juvenile. The combination of indomethacin and L-NNA blocked the response in both age groups. Topical ACh in both age groups initially produced cerebral vasoconstriction, but, in the juvenile, this was followed by a sustained cerebral vasodilation. Indomethacin blocked the early vasoconstriction in both age groups. L-NNA, which had no effect in the response of the newborn to ACh, blocked the vasodilation seen in the juvenile. The combination of both inhibitors blocked all response to ACh in the juvenile. These data indicate that although the cerebral vascular responses to ACh and hypercapnia are prostanoid associated and NO independent in the newborn pig, NO assumes an increasing role in dilatory responses with development.

Acetylcholine↗
PubMed1996

pHi in piglet cerebral microvascular endothelial cells: recovery from an acid load.

Cerebral microvascular endothelial cells form a barrier between the blood and brain, which is critical for normal neuronal functions. These endothelial cells can be challenged by metabolic and respiratory acidosis, especially in newborn babies. We investigated mechanism(s) by which cerebral endothelial cells recover intracellular pH (pHi) when challenged with an intracellular acid load. pHi in piglet cerebral microvascular endothelial cells in primary culture was monitored using the pH-sensitive fluorescent dye BCECF (2',7'-bis-2-carboxyethyl-5(6)-carboxy-fluorescein acetoxymethyl ester), with dual wavelength fluorescence spectroscopy. Endothelial cells attached to coverslips and continuously superfused with HCO3-/CO2 containing medium (25 mM HCO3-, 5% CO2; pH 7.40) have a steady state of pHi of 7.18 +/- 0.02. Under basal conditions, amiloride (100 microMol) and H2DIDS (0.5 mM) decreased pHi 0.12 +/- 0.01 and 0.05 +/- 0.01 pH units, respectively. Removal of external Na+ lowered pHi 0.18 +/- 0.02pH units, while Cl- free medium decreased pHi 0.16 +/- 0.03pH units. These data suggest the presence of an amiloride-sensitive Na+-H+ exchanger and a Na+-dependent HCO3- -Cl- anion exchanger in endothelial cells. Propionate and high PCO2 cause rapid intracellular acidification at constant pH. The cells recover to control pHi over 10 min. Recovery from propionate was largely inhibited by amiloride, slightly inhibited by H2DIDS, and completely prevented by the combination. pHi recovery during elevated PCO2 was blocked by amiloride, H2DIDS, or Na+-free media. These results indicate that recovery from intracellular acidosis can involve amiloride-sensitive Na+-H+ exchange and a Na+-dependent HCO3-/Cl- anion exchange. Relative contributions of pumps and their independence appears to depend on the nature of the acid load.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Isocitrate dehydrogenase from bovine heart: primary structure of subunit 3/4.

Bovine NAD(+)-dependent isocitrate dehydrogenase was shown previously to contain four subunits of approx. 40 kDa (subunits 1-4) possessing different peptide maps and electrophoretic properties [Rushbrook and Harvey (1978) Biochemistry 17, 5339-5346]. In this study the heterogeneity is confirmed using enzyme purified by updated methods and from single animals, ruling out allelic variability. Subunits 1 and 2 were differentiated from each other and from subunits 3 and 4 by N-terminal amino acid sequencing. Subunits 3 and 4 (subunits 3/4) were identical in sequence over 30 residues. The N-terminal residues of subunits 1 and 2 were homologous but not identical with the beta- and gamma-subunits respectively of the comparable pig heart enzyme. Subunits 3/4 were identical over 30 residues with the N-terminus of the pig heart alpha-subunit. Full-length sequence, including that for mitochondrial import, is presented for a protein with the processed N-terminus of subunits 3/4, deduced from cloned cDNA obtained utilizing the N-terminal sequence information. The derived amino acid sequence for the mature protein contains 339 amino acids and has a molecular mass of 36,685 Da. Complete identity with N-terminal and Cys-containing peptides totalling 92 residues from the alpha-subunit of the pig heart enzyme [Huang and Colman (1990) Biochemistry 29, 8266-8273] suggests that maintenance of a particular three-dimensional structure in this subunit is crucial to the function of the enzyme. An electrophoretic heterogeneity within the pig heart alpha-subunit, similar to that shown by bovine subunits 3/4, was demonstrated. One reordering of the Cys-containing peptides of the pig heart alpha-subunit is indicated. Sequence comparison with the distantly related NADP(+)-dependent enzyme from Escherichia coli, for which the three-dimensional structure is known [Stoddard, Dean and Koshland (1993) Biochemistry 32, 9310-9316] shows strong conservation of residues binding isocitrate, Mg2+ and the NAD+ moiety of NADP+, consistent with a catalytic function.

Amino Acid Sequence↗
PubMed1995

The effect of misoprostol on indomethacin-induced renal dysfunction in well-compensated cirrhosis.

BACKGROUND/AIMS: Indomethacin has been shown to have adverse effects on renal function in patients with well-compensated alcoholic cirrhosis. The aim of this study was to determine whether an oral prostaglandin E1 analogue, misoprostol, could prevent this indomethacin-induced renal dysfunction. METHODS: Six patients with well-compensated alcoholic cirrhosis were studied. Renal hemodynamics and tubular function were assessed by clearance techniques before and after an oral dose of (i) 50 mg of indomethacin alone (I50), and (ii) a combination of I50 and 200 micrograms of misoprostol. RESULTS: I50 produced a significant reduction in glomerular filtration rate, a fall in effective renal plasma flow and an increase in renal vascular resistance. Two hundred micrograms of misoprostol was able to abolish the deleterious renal effects of indomethacin totally, yielding an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance as well as an increase in urinary volume and urinary sodium excretion. These beneficial effects were maximal in the hour immediately following medication, but were only transient, and this may be a limiting factor in its clinical use. CONCLUSIONS: If the beneficial renal effects of misoprostol could be confirmed after chronic administration, then the vasodilatory, natriuretic and diuretic potential of 200 micrograms of misoprostol could be of potential therapeutic value in patients with well-compensated alcoholic cirrhosis who require non-steroidal anti-inflammatory drug therapy.

Administration, Oral↗
PubMed1995

An expert system based preventive medicine examination adviser.

Periodic preventive medicine examinations generally rely on a standardized approach. In addition, they are often performed by physicians with only limited training in preventive medicine. Evaluation of a corporate-based program led to the prototype development of an artificial intelligence (AI)-based expert system to collect information from employees and make very specific recommendations for primary practitioners. Unique features include the customizing of questions for each subject and the selection of information to be acquired, both based on answers to previous questions. Recommendations are highly person specific and fall into four categories: laboratory testing, primary physician testing, counseling, and referral. The AI approach allows for easy updating of recommendations in order to meet changes in local preventive resources and national recommendations.

Artificial Intelligence↗
PubMed1995

Mechanisms of hypercapnia-stimulated PG production in piglet cerebral microvascular endothelial cells.

High CO2 stimulates dilator prostanoid (prostaglandin; PG) synthesis by piglet cerebral microvascular endothelial cells, but the mechanism of stimulation is unclear. We address the hypothesis that intracellular pH (pHi) and Ca2+ signaling are involved. When extracellular pH (pHe) and PCO2 were constant and pHi was rapidly reduced (propionate or nigericin), PG synthesis was stimulated. When pHe was lowered by reducing NaHCO3, pHi fell slowly, but PG synthesis was not altered. When pHe was decreased by increasing PCO2 or returned to 7.4 by increasing NaHCO3, with a constant PCO2 of 100 mmHg, pHi dropped quickly and PG synthesis was stimulated. When pHi was reduced slowly by changing CO2 slowly, or by stepwise addition of propionate, PG synthesis was increased regardless of pHe, suggesting that the rapid decline of pHi plays a central role in mediating the PG synthesis. Ca2+ signaling is a potential mechanism by which pHi increases PG synthesis. However, extracellular Ca2+ removal did not affect PG synthesis induced by propionate or hypercapnia. Furthermore, neither rapid nor slow decreases of pHi altered cytosolic free Ca2+ concentration. Therefore, Ca2+ signals do not appear to be involved in the CO2 stimulation of PG synthesis.

Acids↗
PubMed1995

Temperature sensitive simian virus 40 large T antigen immortalization of murine odontoblast cell cultures: establishment of clonal odontoblast cell line.

During tooth formation instructive epithelial-mesenchymal interactions result in the cytodifferentiation of ectomesenchymal cells into odontoblasts which produce the dentin extracellular matrix (DECM). The purpose of our study was to establish a stable murine odontoblast cell line by immortalization of odontoblasts using retrovirus transfection. In order to accomplish this goal, we utilized a previously characterized odontoblast monolayer cell culture system supportive of odontoblast cytodifferentiation from dental papilla mesenchyme (DPM), expression and secretion of a DECM and dentin biomineralization. First mandibular molars from E-18 Swiss Webster mice were dissected, the DPM isolated, and pulp cells dissociated. Pulp cells (5 x 10(5)/well) were plated as monolayers and grown in alpha-MEM supplemented with 10% FCS, 100 units/ml penicillin and streptomycin, 50 micrograms/ml ascorbic acid. Cultures were maintained for 6 days at 37 degrees C in a humidified atmosphere of 95% air and 5% CO2, with media changes every two days. Immortalization was performed using a recombinant defective retrovirus containing the temperature sensitive SV-40 large T antigen cDNA and the neomycin (G418) resistance gene recovered from CRE packaging cells. Cultures were infected for 24 h with CRE conditioned medium containing 8 micrograms/ml of polybrene, the media was replaced with selective media containing 300 micrograms/ml of G418, and the cultures incubated at 33 degrees C for one month with media changes every 3-5 days. Neomycin resistant cells were cloned by serial dilution to single cells in 96-well culture plates and grown in selection medium at 33 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗