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Biomedical subjects

Z Liu

Publications and source records attributed to Z Liu.

At least 739 records · Page 41Linked to original sources

Intermittent use of copper-silver ionization for Legionella control in water distribution systems: a potential option in buildings housing individuals at low risk of infection.

One copper-silver ionization system was sequentially installed onto the hot-water recirculation lines of two hospital buildings colonized with Legionella pneumophila, serogroup 1. A third building with the same water supply and also colonized with Legionella served as a control. Four weeks after activation of the system, distal site positivity for Legionella in the first test building dropped to zero. After operating for 16 weeks, the system was disconnected and installed onto the second test building. Twelve weeks of disinfection reduced the distal site positivity for Legionella in the second test building to zero. Legionella recolonization did not occur in the first test building for 6-12 weeks and in the second test building for 8-12 weeks after inactivation of the system. The control building remained Legionella-positive throughout the experimental period. A significantly higher copper concentration was found in the biofilm taken from a sampling device than in that from water. This is likely to be the reason that the copper-silver ionization system had the residual effect of preventing early recolonization. Our study raises the possibility that one copper-silver unit could be rotated among several buildings to maintain a Legionella-free environment. Such an approach may be cost-effective for buildings housing individuals at low risk for contracting legionnaires' disease.

Biofilms↗

Least squares interval mapping of quantitative trait loci under the infinitesimal genetic model in outbred populations.

Genetic marker and phenotypic data for a quantitative trait were simulated on 20 paternal half-sib families with 100 progeny to investigate properties of within-family-regression interval mapping of a postulated single quantitative trait locus (QTL) in a marker interval under the infinitesimal genetic model, which has been the basis of the application of quantitative genetics to genetic improvement programs, and to investigate use of the infinitesimal model as null hypothesis in testing for presence of a major QTL. Genetic effects on the marked chromosome were generated based on a major gene model, which simulated a central biallelic QTL, or based on 101 biallelic QTL of equal effect, which approximated the infinitesimal model. The marked chromosome contained 0, 3.3%, 13.3%, or 33.3% of genetic variance and heritability was 0.25 or 0.70. Under the polygenic model with 3.3% of genetic variance on the marked chromosome, which corresponds to the infinitesimal model for the bovine, significant QTL effects were found for individual families. Correlations between estimates of QTL effects and true chromosome substitution effects were 0.29 and 0.47 for heritabilities of 0.25 and 0.70 but up to 0.85 with 33.3% of polygenic variance on the marked chromosome. These results illustrate the potential of marker-assisted selection even under the infinitesimal genetic model. Power of tests for presence of QTL was substantially reduced when the polygenic model with 3.3% of genetic variance on the chromosome was used as a null hypothesis. The ability to determine whether genetic variance on a chromosome was contributed by a single QTL of major effect or a large number of QTL with minor effects, corresponding to the infinitesimal model, was limited.

Chromosome Mapping↗

Epidemiology of drug-resistant tuberculosis in New Jersey from 1991 to 1995.

BACKGROUND: In a nationwide survey in 1991, the proportion of Mycobacterium tuberculosis isolates resistant to both isoniazid and rifampin (MDR-TB) in New Jersey (6.6%) was ranked second highest in the United States. The objectives of this study were to describe drug-resistant TB trend and to investigate risk factors for TB patients with isolates resistant to isoniazid or rifampin or both. METHODS: TB surveillance data in New Jersey from 1991-1995 were analysed. Data on Mycobacterium tuberculosis culture and drug susceptibility testing of all TB isolates were obtained from public health and clinical laboratories. Logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (CI) and to adjust for potential confounders. RESULTS: From 1991 to 1995, the proportion of MDR-TB was 5.7%, 4.1%, 2.7%, 3.3% and 2.6%, respectively. There was 10.6% isoniazid resistance and 4.3% rifampin resistance among TB patients in 1993-1995. As expected, recurrent TB was the most important risk factor for resistance to isoniazid (OR = 4.5, 95% CI: 2.6-7.6), rifampin (OR = 5.5, 95% CI: 2.8-11) or both (OR = 6.1, 95% CI: 2.9-13). HIV infection was significantly associated with MDR-TB (OR = 3.6, 95% CI: 1.5-8.8). Drug resistance was not found to be significantly associated with homelessness, injecting drug use and excess alcohol use. CONCLUSIONS: The proportion of MDR-TB in New Jersey declined significantly from 1991 to 1993, but remained at a plateau from 1993-1995. The results suggest that continuous efforts should be directed at the prevention of MDR-TB among people infected with HIV and at improving the proportion who complete chemotherapy among those with TB.

Adult↗

Specific suppression of T helper alloreactivity by allo-MHC class I-restricted CD8+CD28- T cells.

Specific suppression of the host's immune response to donor HLA antigens remains the ultimate goal for clinical transplantation. In spite of considerable effort, however, allospecific human suppressor T cells (Ts) have been difficult to generate. Here we show that allospecific and xenospecific Ts can be raised by multiple priming of human T cells in mixed lymphocyte cultures. Ts derive from the CD8+CD28- subset and recognize specifically the MHC class I antigens expressed by antigen-presenting cells (APC) used for in vitro immunization. Allospecific Ts prevent the up-regulation of B7 molecules on target APC, interfering with the CD28-B7 interaction required for T helper (Th) activation. These findings provide a basis for the development of specific immunosuppressive therapy.

Antigen-Presenting Cells↗

Laryngotracheal reconstruction with tracheal patch allografts.

The capacity of tracheal allotransplants in providing optimal tissues for laryngotracheal repair was studied in an animal model. Segments of cervical trachea could be revascularized completely when wrapped in a receptor fascia flap in immunosuppressed rabbits. In phase I the revascularized tracheas were incised longitudinally and transformed into four different patches after a 14-day revascularization period. The blood supply toward the four patch designs was examined with angiography. The patch designs that showed a vascularization over at least 75% of their mucosal surface area were used in phase II to reconstruct extended anterior laryngotracheal defects. The morphologic characteristics of the tracheal patches when used inside laryngotracheal defects were studied using radiographic, angiographic, and histologic techniques. The revascularized allograft patches that were fully supported by tracheal cartilage were most suitable to repair anterior laryngotracheal defects in this animal study. This model allowed us to define the tissue characteristics necessary for obtaining a combination of primary healing and optimal luminal support in the repair of laryngotracheal defects.

Animals↗

Activation of the locus coeruleus after amygdaloid kindling.

PURPOSE: Substantia nigra (SN) and locus coeruleus (LC) neurons are implicated in the propagation and suppression of amygdaloid seizures. Both structures are activated concomitant with amygdaloid seizure discharges. Their mechanisms of activation, however, remain to be elucidated. SN firing is not associated with the induction of Fos immunoreactivity (ir), a marker of excitatory neuronal activation. LC has not been studied. The purpose of this investigation was to determine if amygdala-kindled generalized seizures could induce Fos-ir in the LC. METHODS: Female Sprague-Dawley rats were killed after generalized seizures induced by amygdala electrical stimulation and stained by using Fos immunocytochemistry. The number of Fos-ir neurons was compared between 15 animals with generalized seizures and four implanted, unstimulated controls. RESULTS: LC-ir neurons were significantly (p < 0.05) more prevalent after seizures than in control animals. Their numbers correlated very highly with Fos-ir in the central nucleus of the amygdala (p < 0.0001). No Fos induction was observed in LC in controls or in the SN in either group. CONCLUSIONS: Amygdala-induced generalized seizures result in Fos-ir in the LC but not in the SN. This is consistent with different mechanisms of activation possibly involving disinhibition in the SN and direct excitation in the LC.

Amygdala↗

Abnormalities of electrocardiographic P wave morphology and their relation to electrophysiological parameters of the atrium in patients with sick sinus syndrome.

We examined the incidence of long P wave duration in lead II and increased P terminal force in lead V1 (PTFV1), and their relationship to electrophysiological findings of atrial muscle in 34 patients with sick sinus syndrome (SSS). Patients were divided into three groups: Group I, consisting of 20 patients with various cardiac arrhythmias other than SSS and paroxysmal atrial fibrillation (PAF) who served as controls; Group II, consisting of 18 patients with SSS but without PAF; and Group III consisted of 16 patients with SSS and PAF. P wave duration was significantly longer in Group III (122 +/- 11 ms, mean +/- SD, P < 0.0001) and Group II (111 +/- 15 ms, P < 0.002) than in Group I (98 +/- 10 ms). PTFV1 was greater in Group III (0.052 +/- 0.025 ms) than in Group I (0.028 +/- 0.011 ms, P < 0.05). P wave duration and PTFV1 had significantly and/or borderline correlations with longest duration of right atrial electrograms (r = 0.84, P < 0.0001 and 0.47, P < 0.02, respectively), maximal number of fragmented deflections of atrial electrograms (r = 0.69, P < 0.0001 and r = 0.51, P < 0.02, respectively), repetitive atrial firing zone (RAFZ) (r = 0.81, P < 0.0001 and 0.48, P < 0.05, respectively) and fragmented atrial activity zone (FAAZ)(r = 0.53, P < 0.01 and r = 0.45, P = 0.06, respectively). We concluded that long P wave duration and increased PTFV1 are electrocardiographic indicators for coexistence of electrophysiological abnormalities in the atria in SSS without recognizable heart disease.

Adult↗

Efficient class II major histocompatibility complex presentation of endogenously synthesized hepatitis C virus core protein by Epstein-Barr virus-transformed B-lymphoblastoid cell lines to CD4(+) T cells.

The induction of an efficient CD4(+) T-cell response against hepatitis C virus (HCV) is critical for control of the chronicity of HCV infection. The ability of HCV structural protein endogenously expressed in an antigen-presenting cell (APC) to be presented by class II major histocompatibility complex molecules to CD4(+) T cells was investigated by in vitro culture analyses using HCV core-specific T-cell lines and autologous Epstein-Barr virus-transformed B-lymphoblastoid cell lines (B-LCLs) expressing structural HCV antigens. The T- and B-cell lines were generated from peripheral blood mononuclear cells derived from HCV-infected patients. Expression and intracellular localization of core protein in transfected cells were determined by immunoblotting and immunofluorescence. By stimulation with autologous B-LCLs expressing viral antigens, strong T-cell proliferative responses were induced in two of three patients, while no substantial stimulatory effects were produced by B-LCLs expressing a control protein (chloramphenicol acetyltransferase) or by B-LCLs alone. The results showed that transfected B cells presented mainly endogenously synthesized core peptides. Presentation of secreted antigens from adjacent antigen-expressing cells was not enough to stimulate a core-specific T-cell response. Only weak T-cell proliferative responses were generated by stimulation with B-LCLs that had been pulsed beforehand with at least a 10-fold-higher amount of transfected COS cells in the form of cell lysate, suggesting that presentation of antigens released from dead cells in the B-LCL cultures had a minimal role. Titrating numbers of APCs, we showed that as few as 10(4) transfected B-LCL APCs were sufficient to stimulate T cells. This presentation pathway was found to be leupeptin sensitive, and it can be blocked by antibody to HLA class II (DR). In addition, expression of a costimulatory signal by B7/BB1 on B cells was essential for T-cell activation.

Animals↗

Secretion imbalance between tumour necrosis factor and its inhibitor in inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF) alpha and TNF-beta are soluble ligands binding to TNF receptors with similar activities; soluble TNF receptors neutralise TNF activity by acting as inhibitors. Little is known about the cytokine/soluble receptor role in inflammatory bowel disease (IBD). AIMS: To test the hypothesis that an imbalance in secretion between TNF and TNF inhibitors plays a role in gut inflammation in patients with IBD. METHODS: The secretion of TNF-alpha, TNF-beta, and soluble TNF receptors was compared in the culture supernatants of colonic biopsy specimens and isolated lamina propria mononuclear cells from patients with active colonic IBD. RESULTS: Spontaneous secretion of TNF-alpha in involved IBD mucosa was higher than in normal control and self limited colitis mucosa. Secretion of TNF-beta was higher in patients with Crohn's disease than in those with ulcerative colitis. Soluble TNF receptor in IBD mucosa inhibited TNF activity. Type 2 soluble receptor release from IBD mucosa was increased in active inflammation; release from lamina propria cells was not increased. Mucosal TNF-alpha production correlated with severity of disease. CONCLUSIONS: Results showed enhanced secretion of TNF-alpha but failure to release enhanced amounts of soluble TNF receptor in lamina propria mononuclear cells of patients with IBD. An imbalance in secretion between TNF and TNF inhibitor may be implicated in the pathogenesis of IBD.

Adolescent↗

Metabotropic glutamate receptors depress vagal and aortic baroreceptor signal transmission in the NTS.

We sought to determine whether metabotropic glutamate receptors contribute to frequency-dependent depression of vagal and aortic baroreceptor signal transmission in the nucleus of the solitary tract (NTS) in vivo. In alpha-chloralose-anesthetized rabbits, we determined the number of extracellular action potentials synaptically evoked by low (1 Hz)- or high-frequency vagal (3-20 Hz) or aortic depressor nerve (ADN) (6-80 Hz) stimulation and postsynaptically evoked by the ionotropic glutamate receptor agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The metabotropic glutamate receptor agonist (2S,1'S, 2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I) attenuated NTS responses monosynaptically evoked by 1-Hz vagus stimulation by 34% (n = 25; P = 0.011), while augmenting AMPA-evoked responses by 64% (n = 17; P = 0.026). The metabotropic glutamate receptor antagonist alpha-methyl-4-phosphonophenylglycine (MPPG) did not affect NTS responses to low-frequency vagal stimulation (n = 11) or AMPA (n = 10) but augmented responses to high-frequency stimulation by 50% (n = 25; P = 0.0001). MPPG also augmented NTS responses to high-frequency ADN stimulation by 35% (n = 9; P = 0.048) but did not affect responses to low-frequency stimulation (n = 9) or AMPA (n = 7). The results suggest that metabotropic glutamate receptors, presumably at presynaptic sites, contribute to frequency-dependent depression of vagal and aortic baroreceptor signal transmission in NTS.

Action Potentials↗

Limb reduction defects in endothelial nitric oxide synthase-deficient mice.

Nitric oxide synthases are a family of enzymes capable of converting L-arginine to L-citrulline with the subsequent release of nitric oxide (NO). NO has been shown to have multiple biologic effects depending on the isoform responsible for its production and its tissue of origin. Murine endothelial nitric oxide synthase (eNOS) is encoded by Nos3, located on mouse chromosome 5. NO produced from this isoform causes vascular smooth muscle relaxation. Other investigators have shown that the administration of nonspecific inhibitors of nitric oxide synthases to pregnant rats induces limb reduction defects. However, mice deficient in Nos3 have not previously been noted to show such abnormalities. To explore the importance of eNOS during development, we produced mice deficient in eNOS using embryonic stem cell technology. Limb reduction defects were seen in approximately 10% of the null animals. We also observed increased neonatal loss of homozygous deficient pups. One functional copy of Nos3 eliminates the risk of limb defects observed in our mouse strain. These findings have implications for understanding genetic predisposition to sporadic limb reduction defects in humans.

Acetylcholine↗

Acute and chronic increases in excitability in rat hippocampal slices after perinatal hypoxia In vivo.

We have previously shown that hypoxia induces both acute and chronic epileptogenic effects that are age dependent. Global hypoxia (3-4% O2) induces seizure activity in the developing brain [postnatal day (P)10-12] but not at younger or older ages. Adult rats with prior seizures induced by hypoxia at P10 show increased seizure susceptibility to chemical convulsants compared with controls. In the present study, we tested the hypothesis that acute and chronic epileptogenic effects of hypoxia are demonstrable in hippocampus both in vivo and in vitro. Depth electrode recordings confirmed the presence of ictal activity within hippocampus in P10 rats during global hypoxia. Hippocampal slices prepared from P10 pups killed at 10 min after recovery from hypoxia showed evidence of increased excitability. Extracellular field recordings revealed that the amplitude and duration of long-term potentiation (LTP) was increased significantly in area CA1 of hippocampal slices removed from hypoxic pups. In addition, extracellular recordings within areas CA1 and CA3 showed significantly longer afterdischarge durations in response to kindling stimuli in slices from hypoxic pups compared with controls. To evaluate whether there were also long-term changes in hippocampal excitability, hippocampal slices were prepared from adult rats that had underwent hypoxia at P10 and compared with slices from adult litter-mate controls. A Mg2+-free medium was superfused to induce epileptiform activity within the slices. Extracellular recordings from stratum pyramidale of area CA1 showed that Mg2+-free media induced significantly more frequent ictal discharges in slices from previously hypoxic rats compared with controls. These results provide evidence that the naturally occurring stimulus of hypoxia can result in both acute and chronic changes in the excitability of the CA1 neuronal network. These results parallel our previous in vivo studies demonstrating that global hypoxia acutely increases excitability in the immature brain and that hypoxia during the age window approximately P10 results in long-lasting increases in seizure susceptibility within hippocampus. Our results suggest that the age-dependent epileptogenic effects of hypoxia are in part mediated by a direct and permanent effect on neuronal excitability within hippocampal neuronal networks.

Aging↗

Effect of truncated forms of the steroidogenic acute regulatory protein on intramitochondrial cholesterol transfer.

It has been proposed that the steroidogenic acute regulatory (StAR) protein controls hormone-stimulated steroid production by mediating cholesterol transfer to the mitochondrial inner membrane. This study was conducted to determine the effect of wild-type StAR and several modified forms of StAR on intramitochondrial cholesterol transfer. Forty-seven N-terminal or 28 C-terminal amino acids of the StAR protein were removed, and COS-1 cells were transfected with pCMV vector only, wild-type StAR, N-47, or the C-28 constructs. Lysates from the transfected COS-1 cells were then incubated with mitochondria from MA-10 mouse Leydig tumor cells that were preloaded with [3H]cholesterol. After incubation, mitochondria were collected and fractionated on sucrose gradients into outer membranes, inner membranes, and membrane contact sites, and [3H]cholesterol content was determined in each membrane fraction. Incubation of MA-10 mitochondria with wild-type StAR containing cell lysate resulted in a significant 34.9% increase in [3H]cholesterol content in contact sites and a significant 32.8% increase in inner mitochondrial membranes. Incubations with cell lysate containing N-47 StAR protein also resulted in a 16.4% increase in [3H]cholesterol in contact sites and a significant 26.1% increase in the inner membrane fraction. In contrast, incubation with the C-28 StAR protein had no effect on cholesterol transfer. The cholesterol-transferring activity of the N-47 truncation, in contrast to that of the C-28 mutant, was corroborated when COS-1 cells were cotransfected with F2 vector (containing cytochrome P450 side-chain cleavage enzyme, ferridoxin, and ferridoxin reductase) and either pCMV empty vector or the complementary DNAs of wild-type StAR, N-47 StAR, or C-28 StAR. Pregnenolone production was significantly increased in both wild-type and N-47-transfected cells, whereas that in C-28-transfected cells was similar to the control value. Finally, immunolocalization studies with confocal image and electron microscopy were performed to determine the cellular location of StAR and its truncated forms in transfected COS-1 cells. The results showed that wild-type and most of the C-28 StAR protein were imported into the mitochondria, whereas most of N-47 protein remained in the cytosol. These studies demonstrate a direct effect of StAR protein on cholesterol transfer to the inner mitochondrial membrane, that StAR need not enter the mitochondria to produce this transfer, and the importance of the C-terminus of StAR in this process.

Animals↗

Atrial conduction curves in patients with and without atrial fibrillation.

In order to quantify underlying atrial conduction properties in patients with atrial fibrillation (AF) using clinical electrophysiology techniques, atrial conduction curves relating intra-atrial conduction times to extrastimulus prematurities during programmed atrial stimulation were drawn. Based on the presence or absence of AF episodes, 95 subjects were divided into 2 groups: control (n=42); and AF (n=53). During programmed stimulation introduced from the right atrial appendage, an atrial conduction curve was drawn for each patient. For most of the control subjects, when the extrastimulus prematurity was increased by 10-ms steps, the intra-atrial conduction times also increased gradually; the maximum stepwise prolongation in intra-atrial conduction time was 11.0+/-3.4 msec. For patients with AF, a 10-msec increase in extrastimulus prematurity often produced a sudden marked prolongation in the intra-atrial conduction time; the maximum stepwise prolongation of intra-atrial conduction time was 21.4+/-5.9 msec. In contrast to the gradual atrial conduction curves recorded in control subjects, the sudden prolongation of intra-atrial conduction time was remarkable on the curves obtained in patients with AF. Statistical significance was clearly established (p<0.0001). This difference could be related to differences in the underlying conduction properties in patients with and without AF.

Adult↗

Distraction bone healing versus osteotomy healing: a comparative biochemical analysis.

This study investigates the biochemical changes in a canine tibia lengthening model in comparison with a nonlengthened osteotomy model. The lengthened and the osteotomized callus and a contralateral corresponding segment were analyzed for their mineralization profile, collagen content, osteocalcin, insulin-like growth factor I (IGF-I), and transforming growth factor beta1 (TGF-beta1). Examinations of bone samples were performed using specimens excised at different time intervals (respectively at 3, 5, 7, 9, and 13 weeks postoperatively). Several serum parameters (alkaline phosphatase [ALP], osteocalcin, IGF-I, and TGF-beta1) were also measured during the experimental period. A progressive increase in mineral parameters was noticed in both the lengthened and the osteotomized areas. A higher level of hydroxyproline and TGF-beta1 was observed in the lengthened area compared with the osteotomized area. IGF-I showed a significant increase in both the lengthened and contralateral control area at the later stage of the experimental period in the lengthened group. In serum, a high level of TGF-beta1 and a progressively increasing osteocalcin concentration were observed in the lengthened dogs in comparison with the osteotomized dogs. Serum ALP was significantly increased in both models during the experimental period. Serum IGF-I was increased in the lengthened models during the distraction period and decreased in the osteotomized models at the early stage of the experimental period. These results suggest that the mechanical strain induced by the Ilizarov distraction procedure stimulates osteoblast proliferation and promotes biosynthesis of bone extracellular matrix in distracted callus. Our data furthermore show that this process is different compared with normal fracture healing.

Alkaline Phosphatase↗

Initial drug regimens for the treatment of tuberculosis: evaluation of physician prescribing practices in New Jersey, 1994 to 1995.

STUDY OBJECTIVE: To evaluate physician prescribing practices for the initial therapy for tuberculosis (TB) according to the recommendations of the Centers for Disease Control and Prevention (CDC) and American Thoracic Society (ATS). DESIGN: Cross-sectional study. SETTING: Statewide TB surveillance system in New Jersey, 1994 to 1995. PATIENTS: We studied 1,230 culture-positive TB patients who were alive at diagnosis and whose isolates were tested for isoniazid susceptibility. RESULTS: Almost all TB patients (98%) were reported from counties with an isoniazid-resistant proportion of 4% or more, which is the minimum level for implementation of an initial four-drug regimen recommended by CDC/ATS. Overall, 36% of the 1,230 patients were not initially treated with four or more drugs. Multivariate analyses found that non-Hispanic white patients were more likely to be treated with fewer than four drugs than were non-Hispanic black patients. Private practitioners and physicians at chest clinics were about five times more likely to prescribe fewer than four drugs initially than were physicians at the hospital where a national TB center is located. CONCLUSION: A substantial proportion of physicians did not initially treat their TB patients according to the CDC/ATS recommendations. The results suggest that New Jersey physicians should be better informed about the recommendation and the high level of drug resistance in the communities they serve to assure that TB patients receive appropriate initial therapy.

Adolescent↗

Distinct trends in tuberculosis morbidity among foreign-born and US-born persons in New Jersey, 1986 through 1995.

OBJECTIVES: This study evaluated tuberculosis (TB) morbidity trends among foreign-born and US-born persons. METHODS: TB surveillance data in New Jersey from 1986 to 1995 were analyzed. RESULTS: The overall TB incidence rate in New Jersey declined 15% from 1992 to 1995 after 7 years of increase. However, the incidence rate of TB in foreign-born persons increased 75% from 1986 through 1995. The proportion of foreign-born persons with TB increased from 20% in 1986 to 37% in 1995. CONCLUSIONS: TB morbidity among foreign-born persons has continued to increase, despite the decline in overall TB morbidity since 1992. Targeted TB prevention and control strategies should be developed to effectively reduce TB morbidity in foreign-born persons.

Adolescent↗