Biomedical subjects

Q Chang

Publications and source records attributed to Q Chang.

At least 73 records · Page 4Linked to original sources

PubMed1998

Metabolic abnormalities and differential responses to stress associated with hamster cardiomyopathy.

Metabolic differences between cardiomyopathic hamsters (CMHs), as they progress through various physiologic phases before reaching end-stage heart failure (HF), and healthy hamsters (HHs) are often difficult to demonstrate. We suggest that metabolic differences, magnified by application of chronic stress (S: cold immobilization 2 hr/day for 5 days) followed by acute stress (AS: 55 min global ischemia /30 min reperfusion), can be used to characterize different stages in this cardiomyopathic process. High performance liquid chromatography (HPLC) and 31P NMR methods were used to monitor the effects of acute stress applied to nonstressed (NS) and previously stressed CMHs (NS-2.5-month NS-5-month; S-2.5-month, S-5-month) and HHs (NS-HH, S-HH). Cardiac tissue extracts from nonstressed and stressed hamsters were analyzed for ATP and PCr at baseline and after completion of ischemia/reperfusion (AS) using HPLC. In nonstressed hamsters, ATP and PCr were 12% lower in CMHs (both NS-2.5- and NS-5-month) than in NS-HHs. After exposure to stress, ATP was 26% lower in CMHs (S-2.5- and S-5-month) compared to S-HHs, whereas there were minimal differences in PCr between the groups. 31P NMR monitoring of metabolism in the perfused beating heart during application of acute stress produced similar changes (%) in ATP and PCr in all groups (NS and S), whereas Pi increase was less in NS-5-month (118%) compared to NS-2.5-month (179%) and NS-HHs (306.8%), P < 0.05; and in S-5-month (148%) compared to S-2.5-month (216%) and S-HHs (222%). The changes in myocardial pH were inversely related to changes in Pi: NS-5-month (-13.5%); NS-2.5-month (-9.7%); NS-HH (-17.7%). pH changes in stressed cardiomyopathic hamsters were similar to those of S-HHs. The postischemic recovery of ATP and Pi return closer to baseline values in cardiomyopathic hamsters (both NS and S) compared to healthy hamsters. The data suggest that cardiomyopathic hamsters have baseline metabolic abnormalities, and their responses to chronic cold immobilization stress, acute ischemia, and chronic cold immobilization stress plus acute ischemia are different from those in HHs. These responses may help to characterize specific stages of disease.

Adenosine Triphosphate↗

PubMed1998

A pathological study of in situ thrombosis of small pulmonary arteries and arterioles in autopsy cases of chronic cor pulmonale.

OBJECTIVE: To investigate the incidence of in situ thrombosis of small pulmonary arteries and arterioles during the exacerbation stage of chronic cor pulmonale. METHODS: 49 autopsy cases died from the exacerbation of chronic cor pulmonale were chosen as the study group, while 103 other autopsy cases without chronic cor pulmonale and disseminated intravascular coagulation (DIC) as control group. Morphologic and morphometric studies were taken on lung tissues and other organs with focus on the thrombi in small pulmonary arteries and arterioles. RESULTS: 44 cases of the study group had multiple thrombi in small pulmonary arteries and arterioles, the incidence is 89.8%, and in 9 of them, thrombi in proximal pulmonary arteries co-existed, the incidence is 18.4%. 80% of the thrombi existed in pulmonary arterioles. In the control group, only 3 cases had thrombi in small pulmonary arteries and arterioles, the incidence is 2.9%. All thrombi adhered to endangium, implying that they were in situ thrombi. No intravascular thrombosis was found in other organs. chi 2 test showed that the incidence of thrombosis and the number of thrombi in small pulmonary arteries and arterioles in cases with chronic cor pulmonale were significantly higher than those of the control group (P < 0.01). CONCLUSIONS: Multiple in situ thrombosis in small pulmonary arteries and arterioles is a prominent and common pathological change during the exacerbation stage of chronic cor pulmonale. The study suggests a new diagnostic and therapeutic concept and gives a morphological and theoretical basis for the clinical application of anticoagulants or even the thrombolytic agents for the cases of chronic cor pulmonale in the exacerbation stage.

Aged↗

PubMed1998

In vitro pulsatile flow visualization on extracardiac conduits for the right ventricular outflow tract reconstruction: qualitative considerations.

Valved homograft conduits play an important role in the right ventricular outflow tract (RVOT) reconstruction for the surgical treatment of complex congenital heart disease. An excellent immediate rather than long-term outcome could be obtained. The hemodynamics for late failure, however, remained unclear. In vitro pulsatile flow visualization was not conducted before. A simplified right heart duplicator system was set up and driven under physiologic conditions. Polystyrene of 0.18 mm in diameter was applied as the tracing particle. Flow characteristics of models of normal pulmonary circulation as well as pulmonary artery atresia with the RVOT reconstructed utilizing valved and non-valved extracardiac conduits were observed. Flow patterns in the normal pulmonary circulatory model were mainly of axial flow associated with small scope of flow disturbances. A single vortex in the right ventricle was noted in diastole. In the pulmonary artery atresia model, a couple of vortexes were found in the right ventricle, a secondary flow in the main pulmonary artery, and a stronger secondary flow than in the normal pulmonary circulatory model in the two branches in both systole and diastole. A secondary flow was found in the proximal, an axial flow was observed in the distal portion of the extracardiac conduit with normal bioprosthetic valves and a secondary flow was observed in the entire conduit with stenotic bioprosthetic valves. The secondary flow intensity became stronger with the development of the stenosis. Severe insufficiency occurred in the bileaflet ceramic tilting-disc prosthesis during the entire cardiac circle, i.e., the prosthesis was in a maximum open position. Severe reverse flow could be found in the extracardiac conduit in the deceleration phase. Concavity of the crank shaft was found by examination to be filled with tracing particles and the prosthesis became stuck. Model of RVOT reconstruction with non-valved conduit yielded reverse flow inside the extracardiac conduit as well. Secondary flow may occur in normal or diseased extracardiac conduit for RVOT reconstruction. If micro-thrombus of over 0.18 mm in diameter attached in the concave of the crank shaft of a bileaflet tilting-disc prosthesis under a condition of resistance as occurred in the present study, the prosthesis may become stuck. Model of RVOT reconstruction with non-valved extracardiac conduit yielded reverse flow inside the conduit, of which the flow pattern was of greater energy consumption. Thus, a non-valved conduit should be avoided in clinical practice as far as possible.

Heart Defects, Congenital↗

PubMed1997

Long-lifetime metal-ligand pH probe.

We describe the synthesis and fluorescence spectral characterization of a pH-sensitive metal-ligand complex, [Ru(deabpy)(bpy)2]2., where deabpy is 4,4'-diethylaminomethyl-2,2'-bipyridine. This metal-ligand complex (MLC) was found to display pH-dependent intensities, emission spectra, and decay times, with the changes centered near the physiological useful pH value of 7.5. The apparent pKa values were not found to be dependent on ionic strength. The compound was found to be useful for lifetime-based sensing by phase-modulation fluorometry. Global analysis of the intensity decays over a range of pH values revealed two decay times of 235 and 380 ns, associated with the protonated and unprotonated forms, respectively. Because of its long decay time, optical pH measurements could be accomplished by phase-modulation fluorometry with a conveniently low modulation frequency of 700 kHz. The lifetime data were obtained with either a amplitude-modulated laser or with an amplitude-modulated blue-light-emitting diode. This pH-sensitive complex also displays a modest spectral shift with change in pH, allowing its use as a wavelength-ratiometric MLC probe. One can imagine lifetime sensors for a variety of blood cations and point-of-care assays based on long-lifetime metal-ligand complexes and simple solid-state light sources and detectors.

2,2'-Dipyridyl↗

PubMed1997

Nip and tuck at the neuromuscular junction: a role for proteases in developmental synapse elimination.

During late embryonic and early postnatal development, synaptic connections are extensively modified so that some functional connections are weakened and eliminated from a neural circuit while others are strengthened and maintained. The mechanisms that underlie synapse elimination are beginning to be understood from studies of the neuromuscular junction. A recent paper provides some intriguing insights into the role proteases may play in the developmental disassembly of neuromuscular synapses.

Endopeptidases↗

PubMed1997

Counterflow centrifugal elutriation as a method of T cell depletion may cause loss of immature CD34+ cells.

Counterflow centrifugal elutriation (CCE) is capable of separating cells on the basis of size. CCE has been used successfully to deplete allogeneic bone marrow (BM) grafts of T lymphocytes to decrease the risk of acute graft-versus-host disease. Previous studies have shown that more immature CD34+ cells in human BM tend to be smaller than more mature CD34+ cells. Human BM was subjected to CCE with the 4 ml standard chamber at constant rotor speed (2300 r.p.m.) and increasing flow-rate (14-23 ml/min, rotor-off). The eleven fractions collected were assayed for CD34+ and CD3+ cells, and for CFU-GM, HPP-CFC and long-term culture initiating cells (LTC-IC). The CD3+ T cells were enriched in the early (small-cell) fractions 14-17 ml/min. CD34+ cells were enriched in fractions 17-21 ml/min, and CFU-GM were concentrated in the same fractions. HPP-CFC and LTC-IC showed nearly identical CCE profiles, with enrichment in fractions 16-18 ml/min. When fraction < or = 17 ml/min was chosen as cut-off, the small-cell fraction contained 94.0% of all CD3+ cells, 44.4% of total cells, 33.2% of CD34+ cells and 34.7% of CFU-GM; however, 67.6% of HPP-CFC and 72.4% of LTC-IC were recovered in this small-cell fraction. These data suggest that T cell depletion through CCE as used by us, while losing only minor proportions of CD34+ cells and CFU-GM, carries the risk of losing the majority of more immature progenitor cells. This may lead to an increased risk of graft failure, in particular in HLA-mismatched transplants.

Antigens, CD34↗

PubMed1997

Effects of topical N-methyl-D-aspartate on blood-brain barrier permeability in the cerebral cortex of normotensive and hypertensive rats.

This study was performed to examine if blood-brain barrier (BBB) permeability could be increased by N-methyl-D-aspartate (NMDA) in the cerebral cortex, and to compare the degree of alteration of BBB permeability in normotensive and in chronic hypertensive rats. Twenty- to 22-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were anesthetized with isoflurane. After craniotomy in 7 animals in each group (SHR and WKY group), an NMDA patch (10 mM) was placed on one cortex (ipsilateral cortex: IC), and a normal saline patch was placed on the other cortex (control cortex: CC). The other 7 rats in each group were pretreated with MK-801 before placing NMDA and normal saline patches (SHR.MK-801 and WKY.MK-801 group). The BBB transfer coefficient (Ki) was determined using 14C-alpha-aminoisobutyric acid. The mean arterial pressures of the SHR and the SHR.MK-801 group were about 65% higher than those of the WKY and the WKY.MK-801 groups. In the WKY group, the Ki of the IC was significantly higher than that of the CC (IC: 10.0 +/- 2.7, CC: 6.2 +/- 2.4 microliters g-1 min-1). In the WKY.MK-801 group, the Ki was similar in both cortices (IC: 8.6 +/- 4.0, CC: 8.2 +/- 3.3). In the SHR group, the Ki of the IC was significantly higher than that of the CC (IC: 9.5 +/- 3.7, CC: 6.5 +/- 3.4), and the Ki of each cortex was similar to that of the corresponding cortex of the WKY group. In the SHR.MK-801 group, the Ki was similar in both cortices (IC: 7.2 +/- 1.5, CC: 7.1 +/- 2.7), and was also similar to those of the WKY.MK-801 group. Our data suggest that NMDA is involved in increasing BBB permeability. In chronic hypertension, the response of the BBB to NMDA is not altered when compared with normotension.

Administration, Topical↗

PubMed1997

Lineage commitment of HLA-DR/CD38-defined progenitor cell subpopulations in bone marrow and mobilized peripheral blood assessed by four-color immunofluorescence.

We used four-color fluorescence analysis to compare lineage antigen expression in relationship to CD38 and HLA-DR on CD34+ progenitor cells in adult human bone marrow and mobilized peripheral blood. Each of four progenitor cell subpopulations defined by HLA-DR and CD38 intensity (CD38-/HLA-DR-, CD38-/HLA-DR+, CD38+/HLA-DR+, and CD38+/HLA-DR-) were present in both progenitor cell sources in similar ratios. The most prevalent subpopulation consisted of cells that expressed both CD38 and HLA-DR. Virtually all progenitor cells that lacked CD38 also lacked lineage antigens regardless of their HLA-DR expression. In contrast, the majority of the cells within both CD38+ progenitor cell subpopulations possessed either lineage antigens or the proliferation-associated antigen, CD71. Furthermore, CD71 was expressed on three times the number of CD38+/HLA-DR- cells when compared with the CD38-/HLA-DR- subpopulation. Within CD34+ progenitor cell subpopulations defined by the expression of CD38 and HLA-DR, the CD38+/HLA-DR- component appears to be the most mature, based on the expression of CD71 and various lineage-associated antigens, including representative markers characterizing early lymphoid, myeloid, and erythroid precursors. Thus, selection of the most immature CD34+ progenitor cells based solely on the lack of HLA-DR expression results in isolation of two distinct cell populations with markedly different maturation status and resultant growth characteristics.

ADP-ribosyl Cyclase↗

PubMed1997

Effects of nitric oxide on blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats.

We performed this study to evaluate the effects of changing the level of nitric oxide (NO) on disruption of the blood-brain barrier (BBB) by hyperosmolar mannitol. Under isoflurane anesthesia, control rats (control group, n = 6) were given infusions with 25% mannitol into the internal carotid artery before measuring the transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid (14C-AIB). In the CAS group (n = 6), [3-(cis-2,6-dimethyl piperidino)-sydnonimine] (CAS 754), a NO donor, was injected to decrease the mean arterial pressure (MAP) to 55 mm Hg and in the L-NAME group (n = 6), NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, was injected before administering mannitol. In additional control animals (control + P group, n = 6) and additional CAS 754-treated animals (CAS + P group, n = 6), phenylephrine was infused to keep MAP at 130 mm Hg during the experimental period. In the control group, with mannitol injection, the Ki of the ipsilateral cortex (IC) where mannitol was injected increased to 4.3 times that of the contralateral cortex (CC) (17.2 +/- 2.9 vs 4.0 +/- 2.6 microliters.g-1.min.1). Without blood pressure control, the Ki of the IC of the CAS group (7.0 +/- 4.5) was lower and that of the L-NAME group (26.2 +/- 12.7) was higher than that of the control animals. At the same MAP, the Ki of the IC of the CAS + P group (9.6 +/- 3.1) was significantly lower than that of the control + P group (21.3 +/- 14.5) or that of the L-NAME group. There was no significant difference in the Ki of the IC between the control + P and the L-NAME groups. In conclusion, L-NAME worsened BBB disruption induced by hyperosmolar solution, which may be due to the pressure effect of L-NAME. CAS 754 was effective in attenuating disruption of the BBB caused by hyperosmolar mannitol. This effect is apparently not due to decreased MAP.

Aminobutyrates↗

PubMed1997

[Experimental study of the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and its mechanism on the vascular cell components--the possible relationship between PACAP and atherosclerosis].

By using cultured vascular endothelial cell (EC) and smooth muscle cell (SMC) as model, the morphological and functional effects of PACAP on EC and SMC in normal and hyper-lipid culture circumstances as well as its possible mechanism of action were studied. The results showed that (1) PACAP may partly counteract the morphologic injury of EC and SMC produced by high lipid. (2) PACAP significantly increased the production of anti-AS substances by EC. (3) PACAP inhibited the proliferation of SMC. (4) PACAP reduced significantly the production of lipid peroxide by EC and SMC in hyperlipid circumstances. The present study suggests that PACAP has cytoprotective effect on EC and SMC and thus it is possible that PACAP has an anti-AS effects.

Animals↗

PubMed1997

Differences in CD34+ cell subpopulations between human bone marrow and "mobilized" peripheral blood as determined with counterflow centrifugal elutriation.

Engineering of hematopoietic progenitor cells (HPCs) from bone marrow (BM) or "mobilized" peripheral blood (MoPB) is becoming increasingly important. Counterflow centrifugal elutriation (CCE) has been used to separate cells on the basis of their size. In this study, CCE was applied to evaluate BM and MoPB for differences in their HPC populations. Using a standard 4-mL elutriation chamber at 2300 rpm, CD34+ cells from BM peaked at a flow rate of 19 mL/minute, with 85% of all CD34+ cells recovered from fractions 15-22 mL/minute. The CD34+ cells from MoPB, mobilized with chemotherapy and granulocyte colony-stimulating factor (G-CSF), peaked at 22 mL/minute, with 90% of all CD34+ cells recovered from fraction 19-26 mL/minute. Colony-forming cells (colony-forming units granulocyte/macrophage [CFU-GM] + burst-forming unit-erythroid [BFU-E] + multipotent colony-forming units [CFU-GEMMs]) followed the distribution of CD34+ cells very closely, also with a shift to higher flow-rates for MoPB compared with BM. The lower flow-rate fractions of both BM and MoPB contained an increased proportion of CD34+ cells that did not express HLA-DR and/or CD38 on their surface, suggesting that the earliest CD34+ cells were enriched in the low-flow rate fractions. Although CFU-GMs, BFU-Es, and CFU-GEMMs from BM all peaked in the same fraction (19 mL/minute), high-proliferative potential colony-forming cells (HPP-CFCs) were concentrated in fraction 17 mL/minute, indicating that these earlier progenitor cells were slightly smaller. With MoPB, HPP-CFCs did not appear to be smaller than BFU-Es or CFU-GEMMs. CCE appears to be an attractive method for separating HPCs from BM or MoPB into populations of different maturity. Differences in CD34+ cell populations between BM and MoPB may help explain the differences in repopulation kinetics observed after transplantation.

Antigens, CD34↗

PubMed1997

[An attempt on the normalization of the moduli spectrum of pulmonary pressure and flow waveforms in canine].

There is no reference of the standard function as the input and/or output control for the pressure and flow waveforms employed by a circulation duplicator or a computational fluidddynamics investigator. The author suggested a hypothesis that the Fourier series with limited terms should be the normalization function of ventricular and great artery pressure and flow waveforms in every cardiac cycle when sinus rhythm is normal, and that the square root of the amplitudes at each harmonic of the heart rate equals to C1-C2 square root of n, where n is the ratio of harmonic/heart rate, C1 and C2 are constants. This article is to provide some procves. The main pulmonary pressure and flow waveforms of 9 mongrel canines were divided into a single cardiac cycle, electrocardiography accordingly, then harmonic was expanded by using a Fourier series with 15 harmonic terms, and the moduli and phrase spectrum of each waveform was obtained respectively and statistically processed. The results support the hypothesis. We also found that the phrases of the pressure and flow waveforms have less variation at the basic harmonic of heart rate, but the higher the frequency of the harmonics comes out, the more variable the phrases appear.

Animals↗

PubMed1996

Growth factor induction of cytosolic protein tyrosine kinase activity in human haemopoietic progenitor cells isolated by flow cytometry.

We employed a highly sensitive method to assay protein tyrosine kinase activity in extracts of subpopulations of CD34+ bone marrow progenitor cells isolated by fluorescence activated cell sorting in an attempt to better define how growth-factor induction of enzymatic activity relates to progenitor cell maturation. FACS analysis confirmed that, under the conditions employed, essentially all of the CD34+ cells in adult human marrow that lacked the CD38 antigen were devoid of the myeloid maturation marker CD33 as well as the lineage antigens: CD10, 13, 14, 15, 16, 19, 71 and glycophorin A. A variable portion (50-90%) of these CD34+, CD38- progenitor cells expressed HLA-DR. CD34+, CD38- cells that did not express HLA-DR were found to lack detectable levels of either membrane or cytosolic tyrosine kinase activity. HLA-DR+ progenitor cells that lacked CD38 possessed elevated levels of cytosolic tyrosine kinase activity but only low levels of plasma membrane activity. In contrast, CD34+ cells that expressed CD38 (and HLA-DR) possessed high levels of membrane-associated tyrosine kinase activity. A cocktail of haemopoietic growth factors that included IL-3, IL-6 and stem cell factor effectively induced tyrosine kinase activity in CD34+, CD38-, HLA-DR- progenitor cells. Growth factor induction of tyrosine kinase activity in these cells was not inhibited by actinomycin D or cyclohexamide. Most of the tyrosine kinase activity induced by these growth factors was recovered from the cytosolic fraction of disrupted cells. Thus, induction of cytosolic tyrosine kinase activity is an early event in the response of uncommitted haemopoietic cells to haemopoietic growth factors. Subsequent activation of membrane tyrosine kinases may initiate key transduction processes as these cells begin to differentiate.

Antigens, CD↗

PubMed1996

Testicular blood flow following spinal cord injury in the Sprague Dawley rat.

The causes of poor semen quality following spinal cord injury (SCI) are unknown. One possible mechanism is decreased testicular blood flow. Chronic testicular ischemia in non-SCI animals has been shown to have significant adverse impact on spermatogenesis. This study was designed to evaluate testicular blood flow following SCI in the Sprague Dawley rat. Testicular blood flows were determined in 11 rats with SCI at thoracic level nine (T9) and six sham control rats three days prior and three days and 14 days after SCI. Testicular blood flow velocity was measured with a Doppler flow probe. Blood flows were compared between groups using T-tests. There were no significant changes in blood flow in the sham operated rats three or 14 days after surgery. However, three days after SCI, blood flow had decreased in the SCI rats to 78 +/- 5 percent of the pre-SCI flow (t = -4.65 with 10 df, p < 0.001). At 14 days after SCI, blood flow was still decreased to 77 +/- 8 percent, (t = -3.40 with 3 df, p < 0.05). This study established that following SCI, testicular blood flow decreases in the Sprague Dawley rat.

Animals↗

PubMed1996

Electrophysiological evidence for the broad distribution of specific odorant receptor molecules across the olfactory organ of the channel catfish.

To determine if there is a spatial segregation of responsiveness to odorants within the olfactory epithelium, microelectrode recordings were obtained from small populations of olfactory receptor neurons located across different lamellar sensory regions of the olfactory organ of the channel catfish, lctalurus punctatus. Stimuli included L-alanine, L-methionine, L-arginine hydrochloride, L-glutamic acid, ATP and a mixture of bile salts-odorants previously reported to stimulate independent receptor sites in aquatic species. The peak integrated olfactory receptor responses at each recording site were standardized to the response to L-alanine. The relative stimulatory effectiveness of the stimuli was preserved across the 10 olfactory lamellae recording sites. These data support previous molecular biological results of a broad distribution of receptor neurons that express specific receptor genes across the olfactory organ of the channel catfish.

Adenosine Triphosphate↗

PubMed1996

The role of stressor intensity in influencing the course of heart disease in cardiomyopathic hamsters.

Our earlier work showed that stress had progressively more serious consequences in a hamster model of congestive heart failure as the magnitude of heart failure worsened. Based on that study, we hypothesized that the intensity of the stressor used might play an important part in determining this outcome as well as in influencing coronary reactivity to arginine vasopressin (AVP). Cardiomyopathic (2.5, 6.5, and 10 months) hamsters (CMHs) were stressed with a 2-hr period of supine immobilization for five consecutive days. Stressor intensity was increased by exposing the hamsters to progressively longer periods at 4 degrees C: the low stress group was never put in the cold; the moderate stress group was exposed to cold for 1 hr, and the high stress group for 2 hr. CMHs were anesthetized and sacrificed 5 days after stress, and their hearts were perfused using a modified Langendorff system. Maximum +/- dP/dt, developed pressure, ventricular relaxation time, (T), and coronary vascular resistance (CVR) were recorded, and CVR was also measured following coronary infusion of AVP. Stressor intensity had no effect on cardiac mechanics in 2.5-month CMHs. In 6.5-month CMHs, only the high-intensity stressor impaired ventricular mechanics (decreased maximum +/- dP/dt and developed pressure, increased T; P < 0.05), while low and moderate stress produced no effects. In 10-month CMHs, stress at all intensities exacerbated ventricular dysfunction (decreased maximum +/- dP/dt and developed pressure; P < 0.05). These results support our first hypothesis that stressor intensity interacts multiplicatively with severity of the underlying disease to influence the course of heart failure. However, our second hypothesis was not supported, because stress-regardless of intensity-affected reactivity of the coronary vasculature to AVP only in 2.5-month CMHs. A further test of the relation of stressor intensity and coronary vascular reactivity requires study of additional groups of CMHs during the period of their disease characterized by coronary vasospasm.

Analysis of Variance↗

PubMed1996

Immunomagnetic CD4+ and CD8+ cell depletion for patients at high risk for severe acute GVHD.

Acute GVHD remains a major problem in allogeneic BMT, in particular when donors other than HLA-identical siblings are used. To determine the efficacy of an immunomagnetic method for depletion of CD4+ and CD8+ lymphocytes from the marrow graft, a series of 15 patients was studied. Thirteen patients had matched unrelated donors, and two patients had related donors. Cyclosporine was used as GVHD prophylaxis in combination with CD4+ and CD8+ depletion, which removed 94.1 +/- 3.2%, 97.0 +/- 5.1%, and 96.7 +/- 3.1% of CD3+, CD4+ and CD8+ cells, respectively. All patients engrafted promptly with AGC > 500/mm3 after a median of 16 days post-BMT. Acute GVHD grade II-IV developed in 0/2 related transplants and 4/13 MUD transplants; only one patient had grade III-IV acute GVHD. No late graft failure was observed. Three patients relapsed; two had advanced disease at the time of BMT. Seven patients are alive and in CCR after a median of 497 days; actuarial survival is 39% at 24 months. The fever syndrome observed with selective CD8+ cell depletion was not seen with the combined CD4+ and CD8+ cell depletion. Immunomagnetic CD4+ and CD8+ cell depletion of marrow grafts, in combination with in vivo cyclosporine, is a simple, reproducible and effective method to decrease the incidence and severity of acute GVHD in patients at high risk for this complication after allogeneic BMT.

Acute Disease↗

PubMed1995

A lifetime-based fluorescence resonance energy transfer sensor for ammonia.

A lifetime-based optical NH3 sensor based on the principle of fluorescence resonance energy transfer was developed. The sensor consisted of sulforhodamine 101 as the donor, bromocresol green as the acceptor, ethyl cellulose as the polymer support, and tributyl phosphate as the plasticizer. When the concentration of NH3 changed, it caused a change in the decay time of the SR101, which was measured by phase-modulation fluorometry. At 100 MHz, increasing the concentration of NH3 from 0 to 175 ppm resulted in a decrease in phase angle of about 31 degrees and an increase in modulation of about 18%. Oxygen and carbon dioxide did not interfere with the sensor. However, a 30% relative humidity could cause a downward shift of the response by 5 degrees, while additional increase in the relative humidity to 100% showed little further effect. For a film thickness of 40 microns, the typical response and recovery times for 90% of total signal change were 1 and 2.5 min, respectively. The phase angle measurements for the same sample were reproducible for 5 days, with no special care of the film sample.

Ammonia↗