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Biomedical subjects

J Yu

Publications and source records attributed to J Yu.

At least 109 records · Page 6Linked to original sources
PubMed1997

Phenotypic and functional characterization of a new human macrophage cell line K1m demonstrating immunophagocytic activity and signalling through HLA class II.

A human macrophage line, designated K1m, has been established from peripheral blood. K1m expresses a number of lineage-specific markers as well as a broad array of intercellular adhesion molecules. In particular, K1m expresses high levels of human leucocyte antigen (HLA) class I and class II. In response to ligation of HLA class II (HLA-DR), but not in response to ligation of HLA class 1, K1m forms tighter homotypic aggregates and develops a striking 'stellate' culture phenotype. K1m also expresses Fc receptors for immunoglobulin G (IgG) (CD64, CD32, and CD16) and can be shown to phagocytose polystyrene latex beads, as well as neuroblastoma cells in the presence of tumour-specific monoclonal antibody (mAb). The K1m cell line should therefore prove useful for studying both signalling through macrophage HLA class II and immunophagocytosis.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1997

Cholinergic control of nerve growth factor in adult rats: evidence from cortical cholinergic deafferentation and chronic drug treatment.

It is well documented that nerve growth factor (NGF) plays an important role in maintaining functions of cholinergic basal forebrain neurons. In the present study, we tested the hypothesis that cholinergic activity controls NGF levels in cholinoceptive neurons of the cerebral cortex and hippocampus. To address that question, we used both cholinergic deafferentation of cerebral cortex and hippocampus by cholinergic immunolesion with 192IgG-saporin and chronic pharmacological treatment of sham-treated and immunolesioned rats with the cholinergic agonist pilocarpine and the cholinergic antagonist scopolamine. We observed an increase in NGF protein levels in the cortex and hippocampus after cholinergic immunolesions and also after muscarinic receptor blockade by chronic intracerebroventricular scopolamine infusion in sham-treated rats after 2 weeks. There was no further increase in the accumulation of NGF after scopolamine treatment of immunolesioned rats. Chronic infusion of pilocarpine had no effect on cortical and hippocampal NGF protein levels in sham-treated rats. In rats with cholinergic immunolesions, however, pilocarpine did prevent the lesion-induced accumulation of NGF. There was no effect of cholinergic lesion and drug treatment on cortical or hippocampal NGF mRNA levels, consistent with the importance of NGF retrograde transport as opposed to its de novo synthesis. This study provides strong evidence for the hypothesis that there is cholinergic control of cortical and hippocampal NGF protein but not mRNA levels in adult rats.

Animals↗
PubMed1997

A mathematical model of the intracranial system including autoregulation.

Cerebral autoregulation plays an important role in the dynamic processes of intracranial physiology. This work develops a four-compartment, lumped-parameter model for the interactions of intracranial pressures, volumes, and flows as a test bed for examining the consistent inclusion of explicit autoregulation in mathematical models of the intracranial system. It is hypothesized that autoregulation of the blood supply from the arterioles to the capillary bed can be modeled by allowing the flow resistance at the interface of the artery and capillary compartments in the model to be a function of pressure rather than a constant. The functional dependence on pressure of this resistance parameter is not specified in advance, but emerges naturally from the assumed relationship between pressure differences and flows. Results show that a constant flow from the artery to the capillary compartment can be maintained by a flow resistance which is resistance which is directly proportional to the pressure difference between these two compartments. Oscillatory flow is reestablished in the model at the capillary-cerebrospinal fluid and capillary-venous interfaces.

Animals↗
PubMed1997

Cytokine modulatable signalling through macrophage HLA class II. 1. IFN-gamma upregulates the efficiency of Ca2+ mobilization in response to ligation of macrophage HLA-DP.

The human macrophage line 2MAC, established recently from peripheral blood, expresses a number of lineage-specific markers as well as a broad array of intercellular adhesion molecules, including high levels of HLA class I and class II. We have presented evidence elsewhere that 2MAC can be productively applied to the study of signal transduction through macrophage HLA class II. Namely, we showed that ligation of 2MAC HLA class II, but not HLA class I, by monoclonal antibody (mAb) elicits an increase in free cytoplasmic Ca2+ concentration [Ca2+]i. Moreover, this Ca2+ flux appears to be functionally relevant: ligation of HLA-DR, but not HLA class I, by mAb results in the Ca2+ mobilization-dependent induction of tissue factor, the high-affinity cellular receptor for factor VII/VIIa. Here we show that 2MAC is uniquely valuable for addressing the efficiency of signal transduction through HLA class II. Namely, we show here that prior culture of 2MAC cells with interferon-gamma (IFN-gamma) profoundly upregulates subsequent Ca2+ mobilization in response to ligation of HLA-DP in the absence of increased cell surface HLA-DP expression. Because IFN-gamma has no effect on 2MAC HLA-DP expression, IFN-gamma must upregulate Ca2+ mobilization by increasing the efficiency of signal transduction through HLA class II (HLA-DP), by targeting some other component of the macrophage HLA class II signalling pathway.

Calcium↗
PubMed1997

Magnetic resonance imaging-histomorphologic correlation studies on paramagnetic metalloporphyrins in rat models of necrosis.

RATIONALE AND OBJECTIVES: The authors intended to confirm previous findings that paramagnetic porphyrins are avid only for intratumoral nonviable tissues, but not for viable tumor cells, and to test the hypothesis that necrosis, regardless of location and origin, can be visualized by metalloporphyrin enhanced magnetic resonance imaging (MRI). METHODS: Intravenous administrations of gadolinium mesoporphyrin (Gd-MP), manganese tetraphenylporphyrin (Mn-TPP), manganese methylpyrroporphyrin-gadopentetate dimeglumine complex (Mn-MPP-Gd) and manganese tetra(4-sulfonatophenyl)porphyrin (MnTPPS4) at 0.05 mmol/kg were compared with those of gadopentetate dimeglumine (Gd-DTPA) at 0.1 mmol/kg in 38 rats with cholestatic liver necrosis, alcohol- and laser-induced coagulation necrosis in liver, and skeletal muscle, reperfused hepatic infarction, and segmental renal infarction. T1-weighted spin echo MRI (TR/TE = 300/15 mseconds) was acquired before and as long as 48 hours after injection, matched with histologic findings, and correlated with Gd/ Mn tissue content measurements. RESULTS: Both Gd-DTPA and the four metalloporphyrins initially caused a similar nonspecific negative contrast enhancement in the necrosis. However, a strong and persisting positive enhancement (necrosis-to-normal contrast ratio ranging from 1.5 to 2.0) developed only with metalloporphyrins in all types of necrosis. In liver and kidney, Gd and Mn concentrations at 24 hours were comparable in necrotic and normal tissues. In muscle, the concentrations were more than eight times higher in necrotic than in normal tissue. CONCLUSIONS: The implied affinity of metalloporphyrins for necrosis with presumably increased relaxivity suggests a possible mode of targetability for MRI contrast media that may elicit novel applications.

Animals↗
PubMed1997

Infections in craniofacial surgery: a combined report of 567 procedures from two centers.

This retrospective review of infectious complications was undertaken at two craniofacial centers (Dallas and Philadelphia). Fourteen infections were identified over a 6.5-year period in 567 intracranial procedures primarily for craniosynostosis. There were no infections in infants under 13 months of age and no cases of meningitis. The overall infection rate was 2.5 percent, and 85 percent of infections occurred in secondary reoperative cases. Tracheostomies were not identified as a risk factor for infection. No difference was found in infection rates between patients with shaved and unshaved scalps. Candida and Pseudomonas were the two most common organisms identified, and 28 percent of our infections involved yeast. The average time to diagnose infection was 11.5 days (excluding three patients who averaged 5 months). Thirteen of the fourteen infections were treated surgically with placement of a subgaleal irrigation/drainage system. Initial bony debridement was kept to a minimum. Based on our findings, recommendations are made to further lower infection rates, particularly those caused by opportunistic organisms.

Antibiotic Prophylaxis↗
PubMed1997

The value of preoperative mammograms in nononcologic breast surgery.

It remains unclear whether preoperative mammograms are necessary in young patients having nononcologic breast surgery. Various authors have recommended mammography in all such cases, in conflict with guidelines from the American Cancer Society. We conducted a retrospective study to determine the utility of preoperative mammograms in young women. From 1989 through 1994, 208 patients under 35 years of age had elective breast surgery in our institution. Fifty-one (24.5%) had preoperative mammography. No malignancies were diagnosed. We believe mammograms are not routinely needed before elective breast surgery in patients under 35 years of age.

Adolescent↗
PubMed1997

In vivo regulation of amyloid precursor protein secretion in rat neocortex by cholinergic activity.

The proteolytic cleavage of the amyloid precursor protein (APP) has been shown to be modulated through specific muscarinic receptor activation in vitro in both transfected cell lines and native brain slices, whereas a demonstration of receptor-mediated control of APP processing under in vivo conditions is still lacking. To simulate alterations in muscarinic receptor stimulation in vivo, we have (i) specifically reduced the cortical cholinergic innervation in rats using partial immunolesions with 192IgG-saporin, and (ii) restored cholinergic function in lesioned rats by transplantation of nerve growth factor producing fibroblasts. While total APP levels in cortical homogenates were unaffected by cholinergic deafferentation, we observed a significant reduction in the abundance of secreted APP and a concomitant increase in membrane-bound APP. These changes were reversed in immunolesioned rats with nerve growth factor-producing fibroblasts. There was a strong positive correlation between the ratio of secreted APP to membrane-bound APP and the activity of choline acetyltransferase and M1 muscarinic acetylcholine receptor density (measured by [3H]pirenzepine binding) in experimental groups. Additionally, we observed a transient decrease in the ratio of cortical APP transcripts containing the Kunitz protease inhibitor domain (APP 770 and APP 751) versus APP 695 in rats with cholinergic hypoactivity. The data presented suggest that cortical APP processing is under basal forebrain cholinergic control, presumably mediated through M1 muscarinic acetylcholine receptors on cholinoceptive cortical target cells.

3T3 Cells↗
PubMed1997

avnA, a gene encoding a cytochrome P-450 monooxygenase, is involved in the conversion of averantin to averufin in aflatoxin biosynthesis in Aspergillus parasiticus.

Recent studies have shown that at least 17 genes involved in the aflatoxin biosynthetic pathway are clustered within a 75-kb DNA fragment in the genome of Aspergillus parasiticus. Several additional transcripts have also been mapped to this gene cluster. A gene, avnA (previously named ord-1), corresponding to one of the two transcripts identified earlier between the ver-1 and omtA genes on the gene cluster was sequenced. The nucleotide sequence of the avnA gene contains a coding region for a protein of 495 amino acids with a calculated molecular mass of 56.3 kDa. The gene consists of three exons and two introns. Disruption of the avnA gene in the wild-type aflatoxigenic A. parasiticus strain (SU1-N3) resulted in a nonaflatoxigenic mutant which accumulated a bright yellow pigment. Thin-layer chromatographic studies with six different solvent systems showed that the migration patterns of the accumulated metabolite were identical to those of averantin, a known aflatoxin precursor. Precursor feeding studies with this mutant showed that norsolorinic acid and averantin were not converted to aflatoxin whereas 5'-hydroxyaverantin, averufanin, averufin, versicolorin A. sterigmatocystin, and O-methylsterigmatocystin were converted to aflatoxins. Southern blot analysis of the wild-type strain and avnA-disrupted mutant strain indicated that the avnA gene was disrupted in the mutant strain. A search of the GenBank database for similarity indicated that the avnA gene encodes a cytochrome P-450-type monooxygenase, and it has been assigned to a new P-450 gene family named CYP60A1. We have therefore concluded that the avnA gene encodes a fungal cytochrome P-450-type enzyme which is involved in the conversion of averantin to averufin in the aflatoxin biosynthetic pathway in A. parasiticus.

Aflatoxins↗
PubMed1997

The transmission of parent/adult-child drinking patterns: testing a gender-specific structural model.

A structural model on parent/adult-child alcohol use patterns was examined. Three analytical blocks were specified: adult-children's alcohol use onset by types of alcoholic beverage, their current use of these alcoholic beverages, and parents' drinking patterns. The model was examined with data collected from drunken driving offenders in California and Maryland treatment programs. The findings indicate that parent/child alcohol use transmission is more gender specific than race specific; fathers' drinking tends to affect sons' drinking and mothers' drinking tends to affect daughters' drinking. Beer use onset is the earliest and more effective in influencing future alcohol use than the onset of wine or liquor.

Accidents, Traffic↗
PubMed1997

Dynorphin A (1-8) analog, E-2078, is stable in human and rhesus monkey blood.

E-2078 is a dynorphin A (1-8) analog, [N-methyl-Tyr1, N-methyl-Arg7-D-Leu8] Dyn A (1-8) ethylamide. Its biochemical stability against enzymatic degradation in vitro in human and rhesus monkey blood, and in vivo in rhesus monkey blood was studied using matrix-assisted laser desorption/ionization mass spectrometry. In vitro studies were carried out in freshly drawn human and rhesus monkey blood, incubated at 37 degrees C for various time periods. In vivo studies were conducted by E-2078 i.v. injection to rhesus monkeys, and blood samples were collected at various time points after the injection. It was found that E-2078 was stable against enzymatic degradation in vitro in freshly drawn human and rhesus monkey blood. Minor biotransformation products from E-2078, such as E (1-4), E (1-5) and E (3-6), were detected in vitro in some human and rhesus monkey blood, but they made up less than 5% of the total starting E-2078 peptide. No biotransformation products were detected in the blood samples from in vivo studies. The apparent half-life of elimination of E-2078 in vivo from the rhesus monkey blood was determined to be 44.0 min.

Adult↗
PubMed1997

Paroxysmal nocturnal hemoglobinuria: new insights from murine Pig-a-deficient hematopoiesis.

A large fraction of the hematopoietic cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) are deficient in membrane expression of glycosylphosphatidylinositol-anchored proteins (GPI-APs). Current evidence suggests that this deficiency is sufficient to account for the hemolytic and thrombotic manifestations of this disease but not for its frequent association with aplastic anemia, an autoimmune disorder in which the patients' own hematopoietic progenitor cells are the target. Mutations in X-linked gene PIG-A, encoding one of several enzymes required for the biosynthesis of the glycophosphatidylinositol anchor, have been found in all PNH patients studied to date. Recent experiments with murine Pig-a knock-out embryonic stem cells show that although embryogenesis is critically dependent on normal GPI-AP expression, Pig-a-deficient cells can undergo apparently normal hematopoietic differentiation if they develop in a GPI-AP-replete environment. Thus, in an in vitro mouse model of PNH, Pig-a mutations confer no gross proliferative or differentiative advantage or disadvantage, suggesting an unidentified process selecting for these mutations in the bone marrow of patients with the PNH-aplastic anemia syndrome. The rescue of hematopoiesis observed in chimeric cultures of knock-out and normal cells was accompanied by intercellular transfer of GPI-AP, suggesting exciting new possibilities for future therapeutic manipulations in PNH patients.

Animals↗
PubMed1997

Latex allergy in hospital employees.

The purpose of this study was to investigate the prevalence and risk factors of latex-allergy in hospital personnel and the presence of latex-specific IgE in a latex-allergic group in Taiwan. A total of 1,021 hospital employees were initially screened for latex allergy with a questionnaire, which included sex, age, job categories, number of years of employment, daily working hours, frequency of latex glove wearing, symptoms of immediate reactions to latex gloves and history of previous atopic diseases. Among them, 70 hospital employees (6.8%; 95% confidence interval 1.9%-11.8%) had symptoms associated with glove wearing. The frequencies in different job categories were 28.3% of surgical nurses, 9.2% of surgeons, 5.8% of regular floor nurses, 5.2% of technicians, 4.6% of physicians, and 4.5% of laboratory researchers. The symptoms were significantly related to the frequency of latex glove exposure, surgical work, current hand eczema and history of atopic dermatitis. In contrast, the number of years of employment, daily working hours and previous history of hand eczema were not correlated with the symptoms of latex allergy. Latex-specific IgE was assayed by the dot blot method in 36 hospital employees of the latex allergic group (positive rate, 55.6%). We concluded that the prevalence of latex-allergy among hospital personnel was 6.9% and certain predisposing factors such as atopic dermatitis, current hand eczema ad surgical work may play a critical role in triggering and aggravating the symptoms.

Adult↗
PubMed1997

Dynorphin A (1-8) analog, E-2078, crosses the blood-brain barrier in rhesus monkeys.

E-2078 is a dynorphin A (1-8) analog, [N-methyl-Tyr1, N-methyl-Arg7-D-Leu8] dynorphin A (1-8) ethylamide. Its ability to cross the blood-brain barrier was examined in rhesus monkeys using matrix-assisted laser desorption/ionization mass spectrometry. In vivo studies were carried out by i.v. injecting E-2078, 10 mg/kg, a dose that had been found to be antinociceptive, to rhesus monkeys. Blood and cerebrospinal fluid samples were collected at various time points after the injection. It was found that E-2078 was stable in vivo in rhesus monkey blood. No biotransformation products were detected in the blood. Mass spectrometric analysis of the cerebrospinal fluid samples collected after E-2078 injection detected the presence of E-2078, indicating that E-2078 had crossed the blood-brain barrier. These findings are consistent with the possibility that systemically administered E-2078 could produce centrally mediated behavioral and physiological effects.

Analgesics, Non-Narcotic↗
PubMed1997

Study of mathematical model for product formation with recombinant microbes expressed IFN.

Based on the known molecular interactions of aporepressor, corepressor, and inducer, a mathematical model of product formation about the Trp operon regulated recombinant microbes has been proposed. The linear relation of the overall transcription rate constant and overall translation rate constant on the specific growth rate has been suggested. We used experimental data where engineered microorganisms express interferon (IFN). Decay constant of IFN, mRNA transcription rate constant, and IFN expression rate constant have been estimated. An equation related to IFN concentration in fermentation on specific growth rate and Trp concentration has been obtained. By application of the equation, the expression of IFN is calculated based on Trp concentration and specific growth rate in fermentation. Also, the optimum overall culture time can be determined.

Escherichia coli↗