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Biomedical subjects

D Song

Publications and source records attributed to D Song.

At least 91 records · Page 5Linked to original sources
PubMed1997

Rapid determination of 1,4-dioxane in water by solid-phase extraction and gas chromatography-mass spectrometry.

A highly sensitive and accurate gas chromatography-mass spectrometry method for rapidly quantitative analysis of dioxane in water samples is described. Dioxane in water sample was extracted by hexane-methylene chloride (80:20, v/v) then transferred to a C18 solid-phase extraction (SPE) cartridge and eluted by acetonitrile. An aliquot of this solution was analyzed by gas chromatography-mass spectrometry with electron impact ionization and selected ion monitoring (dioxane m/z 88) mode. The quantitative limit was set to be 0.05 microgram/ml with an injection volume of 2 microliters and a sample volume of 1 ml. The isotopically labelled [2H8]dioxane (m/z 96) was used as internal standard. Analysis time is approximately 6 min. The results for various kinds of SPE cartridges in this method are also discussed.

Carcinogens, Environmental↗
PubMed1997

Role of phospholipase A2 in the release of free fatty acids during ischemia-reperfusion in the rat cerebral cortex.

Phospholipases are implicated in ischemic damage. In this study, we have examined the time course of changes in free fatty acid (FFA) levels and cytosolic phospholipase A2 (PLA2) activity during 10 or 20 min periods of four vessel occlusion rat cerebral ischemia followed by reperfusion. Ischemia for a duration of 20 min resulted in a biphasic release of FFA in rat cortical superfusates. There was a rapid elevation in the first 10 min followed by a slower release in the next 10 min. Reperfusion for 10 min resulted in another rapid release of FFA and thereafter the levels gradually declined, but did not return to basal levels. Measurements by enzymatic assay and Western blot analysis showed a significant increase in the activity and protein levels of cPLA2 during the ischemic periods. These remained elevated at 10 min of reperfusion, but returned to base line levels after 20 min of reperfusion. The possible role of phospholipase A2 (PLA2) in the release of FFA and ischemic injury to the brain is discussed.

Animals↗
PubMed1997

Protein carbonyl formation in blood plasma by cephalosporins.

Cephalosporin antibiotics caused the formation of carbonyl groups in the plasma proteins both in vivo and in vitro. After the administration of either moxalactam (3 g/day) or cefotaxime (2 g/day) to patients for 7 days, the carbonyl contents in the plasma proteins increased markedly as determined by the 2,4-dinitrophenylhydrazine (DNPH) method. The increase in protein carbonyl groups was also visualized by the conjugation of plasma proteins with fluorescein thiosemicarbazide (FTSC) and subsequent electrophoresis. When blood plasma was incubated with cephalosporins, most of the cephalosporins tested caused the carbonyl formation in plasma proteins to significant degrees in a concentration-dependent manner. Although a number of plasma proteins and other nonplasma proteins could be modified by cephalosporins in vitro, the plasma albumin was most markedly modified in vivo as well as in vitro. The protein carbonyl formation by cephalosporins was inhibited by ascorbic acid, reduced glutathione, and cysteine, but it was not affected by FeSO4, CuSO4, desferrioxamine, EDTA, catalase, superoxide dismutase, uric acid, alpha-tocopherol, and mannitol. Sodium borohydride, when applied to moxalactam-treated plasma proteins, markedly reduced the reactivities of the protein with FTSC or DNPH, indicating that the observed reactivities of the cephalosporin-treated proteins toward FTSC or DNPH are actually due to the protein carbonyl groups. These data suggest that cephalosporins can oxidatively modify proteins in blood plasma and other tissues and that the oxidative modification of proteins may be involved in the adverse reactions observed frequently following cephalosporin therapy.

Antioxidants↗
PubMed1997

Epitope mapping by phage display: random versus gene-fragment libraries.

We present a comparative study on epitope mapping of four monoclonal antibodies directed against four different antigens using alternative phage display techniques and peptide scanning: mAb215 reacts with the largest subunit of RNA polymerase II, mAbBp53-11 with the tumor suppressor protein p53, mAbGDO5 with the Hantaan virus glycoprotein G2 and mAbL13F3 with the Hantaan virus nucleocapsid protein. Epitopes were determined (i) by gene-fragment phage display libraries, constructed by DNaseI digested random gene fragments cloned into the 5' terminus of the pIII-gene of fd phage and (ii) by random peptide phage libraries displaying 6mer and 15mer peptides at the N-terminus of the pIII protein. Using the gene-fragment phage display libraries a single round of affinity selection resulted in the determination of the corresponding epitopes for all monoclonal antibodies tested. In contrast, biopanning of 6mer and 15mer random peptide libraries was only successful for two of the antibodies (mAbBp53-11 and mAbGDO5) after three or four rounds of selection. For the anti-p53 antibody we recovered the epitope from both the 6mer and 15mer library, for mAbGDO5 only the 6mer library displayed the epitope sequence. However, screening of the random peptide libraries with mAb215 and mAbL13F3 failed to yield immunopositive clones. Fine mapping of the epitopes by peptide scan revealed that the minimal epitopes recognized by mAbBp53-11 and mAbGDO5 consist of four and five amino acids, respectively, whereas mAb215 requires a minimal epitope of 11 amino acids for antigen recognition. In contrast, mAbL13F3 did not react with any of the synthesized 15mer peptides. The limits of the different methods of epitope mapping tested in this study are compared and the advantages of the gene-fragment phage display system are discussed.

Amino Acid Sequence↗
PubMed1997

Inhibition by anion channel blockers of ischemia-evoked release of excitotoxic and other amino acids from rat cerebral cortex.

Neuronal and glial cell swelling occurs rapidly in ischemia as part of the cytotoxic response. Astrocytic swelling is known to result in large extracellular increases in certain amino acids, including glutamate, aspartate and taurine, as part of the regulatory volume decrease (RVD) response inherent to these and other cells. RVD in astrocytic cultures is inhibited by anion channel blockers. In this study, we compared the effects of three anion channel blockers on the ischemia/reperfusion-evoked release of amino acids from the in vivo rat cerebral cortex. Twenty minutes of four vessel cerebral ischemia caused significant increases in cortical superfusate levels of aspartate, glutamate, GABA, taurine and phosphoethanolamine. During reperfusion there were delayed increases in the level of glycine, alanine and serine. Glutamine levels were not affected. Cl- channel blockers, 4-acetamido-4'-isothiocyanostrilbene-2,2'-disulfonic acid (SITS, 2 mM), 5-nitro-2-(3-phenyl-propylamino)benzoic acid (NPPB, 350 microM) and dipyridamole (200 microM) depressed basal releases of glutamate and taurine and the ischemia/reperfusion-evoked releases of aspartate, glutamate, taurine and phosphoethanolamine. The results suggest that diffusion of amino acids through an anion channel may be partially responsible for the elevated extracellular levels of excitotoxic and other amino acids that occur during cerebral ischemia/reperfusion.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1997

Modulation of melphalan resistance in glioma cells with a peripheral benzodiazepine receptor ligand-melphalan conjugate.

Peripheral benzodiazepine receptors (PBRs) are located on the outer membrane of mitochondria, and their density is increased in brain tumors. Thus, they may serve as a unique intracellular and selective target for antineoplastic agents. A PBR ligand-melphalan conjugate (PBR-MEL) was synthesized and evaluated for cytotoxicity and affinity for PBRs. PBR-MEL (9) (i.e., 670 amu) was synthesized by coupling of two key intermediates: 4-[bis(2-chloroethyl)-amino]-L-phenylalanine ethyl ester trifluoroacetate (6) and 1-(3'-carboxylpropyl)-7-chloro-1,3- dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (8). On the basis of receptor-binding displacement assays in rat brain and glioma cells, 9 had appreciable binding affinity and displaced a prototypical PBR ligand, Ro 5-4864, with IC50 values between 289 and 390 nM. 9 displayed differential cytotoxicity to a variety of rat and human brain tumor cell lines. In some of the cell lines tested including rat and human melphalan-resistant cell lines, 9 demonstrated appreciable cytotoxicity with IC50 values in the micromolar range, lower than that of melphalan alone. The enhanced activity of 9 may reflect increased membrane permeability, increased intracellular retention, or modulation of melphalan's mechanisms of resistance. The combined data support additional studies to determine how 9 may modulate melphalan resistance, its mechanisms of action, and if target selectivity can be achieved in in vivo glioma models.

Animals↗
PubMed1997

Isocratic high-performance liquid chromatographic determination of thiacetazone by direct injection of plasma into an internal surface reversed-phase column.

This report describes the determination of thiacetazone in human and rat plasma by direct-injection high-performance liquid chromatography (HPLC). Plasma filtrate (50 microliters) was injected directly into the internal surface reversed-phase (ISRP) mixed-functional phenyl column (Capcell Pak, 50 x 4.6 mm, 5 microns) and eluted with an aqueous mobile phase containing 7.5% acetonitrile at a flow-rate of 1 ml/min. With UV detection at 322 nm, thiacetazone eluted at 11.0 min whereas endogenous interferences eluted before 5 min. The lower detection limit for a 50-microliter sample at a signal-to-noise ratio of 5 was 63 ng/ml, which was several hundred fold lower than its cytotoxic concentrations determined from in vitro cell line studies. At a concentration range of 0.17 to 2.7 micrograms/ml, the recovery of thiacetazone was 98.0 +/- 4.4% (mean +/- S.D.). The intra- and inter-day coefficients of variation were 3.0 +/- 1.4% and 4.2 +/- 2.1%, respectively. This method was successfully applied to study the pharmacokinetics of thiacetazone in rats. The direct injection method is simple, requires small sample volume and does not require sample extraction, internal standard, or gradient elution.

Animals↗
PubMed1997

Response of cortical oxygen and striatal extracellular dopamine to metabolic acidosis in newborn piglets.

This study determined the relationships of metabolic acidosis, cortical oxygen pressure, and striatal extracellular dopamine in the brain of newborn piglets. After a baseline period of 120 minutes, a 0.6 N HCl solution was infused intravenously to decrease the blood pH to about 7.0-7.05. The metabolic acidosis was then corrected by injecting sodium bicarbonate and measurements were continued for one hour. The results show that decreased blood pH to about 7.2-7.15 does not cause a statistically significant change in mean blood pressure, cortical oxygen pressure or striatal extracellular dopamine. Further decrease in pH caused significant decrease in both blood pressure and cortical oxygen pressure. By the end of the period of acidosis the cortical oxygen pressure decreased from the control value of 43 +/- 4 Torr to 22 +/- 8 Torr. Changes in the extracellular level of striatal dopamine were parallel to changes in cortical oxygen pressure. The extracellular dopamine increased to 1270% of the control on the end of HCl injection. Infusion of bicarbonate to correct the acidosis resulted in an increase of cortical oxygen and progressive decline of dopamine in the extracellular medium. It is suggested that the level of extracellular dopamine in the striatum of newborn piglets was not directly affected by decrease in pH but was dependent on changes in tissue oxygen pressure during metabolic acidosis.

Acidosis↗
PubMed1997

Bladder tissue pharmacokinetics of intravesical taxol.

Our previous studies have suggested that the ineffectiveness of intravesical mitomycin C or doxorubicin therapy against muscle-invading bladder cancer is in part because of the inability of these drugs to penetrate the urothelium (the urothelial drug concentration is < 5% of the concentration in urine). The goal of the present study was to identify agents that are efficiently absorbed across the urothelium. To evaluate the potential use of taxol in intravesical therapy for bladder cancer, we examined the bladder tissue and systemic plasma pharmacokinetics of intravesical taxol in dogs. Animals (approximately 8 kg body weight) were given an instillation of taxol at 500 micrograms in 20 ml water. At 120 min postinstillation, the bladder was emptied and excised, and about 85% of the dose was recovered in the urine. The taxol concentration in the urothelium was about 50% of the concentration in the urine, the concentrations then declined logarithmically in the underlying capillary-perfused tissues. The average tissue concentration (-2 micrograms/g) was two to three times the reported plasma concentration of 0.75 microgram/ml in patients following intravenous infusion of the > 100-fold higher dose of 250 mg/m2. The steady-state plasma concentration was < 0.02% of the average tissue concentration, and was < 0.05% of the maximally tolerated plasma concentration in patients. The octanol:water partitioning coefficients of taxol, doxorubicin, and mitomycin were > 99, 0.52, and 0.41, which parallels the rank order of the partitioning across urothelium, i.e. taxol (approximately 50%) > > doxorubicin approximately mitomycin C (-3%). In summary, the partitioning of taxol across the urothelium was more favorable than the partitioning of mitomycin C and doxorubicin, and the systemic concentration of taxol resulting from intravesical treatment was insignificant in spite of the extensive absorption into the bladder. We conclude that intravesical delivery of taxol provides a significant bladder tissue targeting advantage, and that taxol represents a viable candidate drug for intravesical bladder cancer therapy.

Administration, Intravesical↗
PubMed1997

alpha- and beta-adrenoceptor blockade fail to prevent high sodium diet-induced left ventricular hypertrophy.

High sodium diet (HS, 8% NaCl) induces left ventricular hypertrophy (LVH) in normotensive rats without an increase in pressure or volume load or in resting cardiac sympathetic activity. HS may affect LV adrenoceptors density or affinity or their postreceptor pathways, thereby causing LVH. We therefore assessed the effects of HS with and without blockade of alpha1- or beta-adrenoceptors by terazosin or nadolol, alone or in combination, on resting hemodynamics, LV and right ventricular (RV) weights, and LV dimensions of male WKY rats. HS increased LV weight by 14% to 17%, and the ratio of LV wall thickness to radius by 18% to 23%. Singly or in combination, the adrenoceptor antagonists did not prevent HS-induced LVH, but instead aggravated it. The increased ratio of LV wall thickness to radius and of LV to RV were attenuated by terazosin or nadolol alone. Neither the resting LV peak-systolic or end-diastolic pressures nor the right atrial pressure was changed by HS, either alone or in combination with the blockers. The failure of chronic alpha1- or beta-blockade to prevent HS-induced LVH suggests that adrenoceptor activation is not important in evoking the LVH. However, the blockers shifted the LVH from a concentric to an eccentric form, suggesting an involvement of additional trophic factors during adrenoceptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1997

Free radicals and the ischemia-evoked extracellular accumulation of amino acids in rat cerebral cortex.

The effects of free radical generating systems on basal and ischemia/reperfusion-evoked release of amino acids into cortical superfusates was examined in the rat using the cortical cup technique. Xanthine oxidase plus xanthine significantly enhanced GABA levels 358 fold over controls during 20 min of four vessel occlusion. Glutamate and phosphoethanolamine release following reperfusion were also elevated. Prostaglandin synthase plus arachidonic acid significantly enhanced the ischemia-evoked release of all amino acids (aspartate 360 fold; glutamate 433 fold; glycine 6 fold; GABA 689 fold; phosphoethanolamine 69 fold) and increased the pre-ischemic levels of glutamate, glycine and phosphoethanolamine. Administration of H2O2 plus ferrous sulfate significantly elevated both pre-ischemic amino acid release and ischemia-evoked release. A role for free radical generating systems in the development of ischemic injury is supported by the ability of superoxide dismutase plus catalase to reduce ischemia-evoked amino acid efflux into cortical superfusates. Thus, the species of free radical produced, as well as the amount generated, may after the pattern of amino acid release under both ischemic and non-ischemic conditions.

Animals↗
PubMed1997

Effect of hemorrhagic hypotension on cortical oxygen pressure and striatal extracellular dopamine in cat brain.

This study investigated the relationships between blood pressure, cortical oxygen pressure, and extracellular striatal dopamine in the brain of adult cats during hemorrhagic hypotension and retransfusion. Oxygen pressure in the blood of the cortex was measured by the oxygen dependent quenching of phosphorescence and extracellular dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) by in vivo microdialysis. Following a 2 h stabilization period after implantation of the microdialysis probe in the striatum, the mean arterial blood pressure (MAP) was decreased in a stepwise manner from 132 +/- 2 Torr (control) to 90 Torr, 70 Torr and 50 Torr, holding the pressure at each level for 15 min. The whole blood was then retransfused and measurements were continued for 90 min. As the MAP was lowered there was a decrease in arterial pH, from a control value of 7.37 +/- 0.05 to 7.26 +/- 0.06. The PaCO2 decreased during bleeding from 32.3 +/- 4.8 Torr to 19.6 +/- 3.6 Torr and returned to 30.9 +/- 3.9 Torr after retransfusion. The PaO2 was 125.9 +/- 15 Torr during control conditions and did not significantly change during bleeding. Cortical oxygen pressure decreased with decrease in MAP, from 50 +/- 2 Torr (control) to 42 +/- 1 Torr, 31 +/- 2 Torr and 22 +/- 2 Torr, respectively. A statistically significant increase in striatal extracellular dopamine, to 2,580 +/- 714% of control was observed when MAP decreased to below 70 Torr and cortical oxygen pressure decreased to below 31 Torr. When the MAP reached 50 Torr, the concentration of extracellular dopamine increased to 18,359 +/- 2,764% of the control value. A statistically significant decrease in DOPAC and HVA were observed during the last step of bleeding. The data show that decreases in systemic blood pressure result in decrease in oxygen pressure in the microvasculature of the cortex, suggesting vascular dilation is not sufficient to result in a full compensation for the decreased MAP. The decrease in cortical oxygen pressure to below 32 Torr is accompanied by a marked increase in extracellular dopamine in the striatum, indicating that even such mild hypoxia can induce significant disturbance in brain metabolism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Evidence that the early loss of membrane protein kinase C is a necessary step in the excitatory amino acid-induced death of primary cortical neurons.

A rapid loss of protein kinase C (PKC) activity is a prognostic feature of the lethal damage inflicted on neurons by cerebral ischemia in vivo and by hypoxic and excitotoxic insults in vitro. However, it is not known if this inactivation of PKC is incidental or is an essential part of the neurodegenerative process driven by such insults. To address this issue, the effects of glutamate on PKC activity and neurotoxicity were studied in immature [8 days in vitro (DIV)] and mature (15-20 DIV) embryonic day 18 rat cortical neuronal cultures. Exposing 16 DIV neurons to as little as 20-50 microM glutamate for 15 min was neurotoxic and induced a rapid (approximately 1-2 h) Ca(2+)-dependent inactivation of membrane PKC. By contrast, neurons 8 DIV were resistant to > 800 microM glutamate, and no evidence of PKC inactivation was observed. Reverse transcription-polymerase chain reaction analysis of NMDA and AMPA receptor subtypes and fluorometric intracellular Ca2- concentration measurements of the effects of NMDA, AMPA, kainate, and metabotropic glutamate receptor activation demonstrated that this striking difference in vulnerability was not due to an absence of functional glutamate receptors on neurons 8 DIV. However, 8 DIV neurons became highly vulnerable to low (< 20 microM) concentrations of glutamate when PKC activity was inhibited by 50 nM staurosporine, 1 microM calphostin C, 5 microM chelerythrine, or chronic exposure to 100 nM PMA. A 15-min coapplication of 50 nM staurosporine with glutamate, NMDA, AMPA, or kainate killed between 50 and 80% of 8 DIV cells within the ensuing 24 h. Moreover, cell death was observed in these cells even when PKC inactivation was delayed up to 4 h after glutamate removal. The evidence indicates that a loss of PKC activity is an essential element of the excitotoxic death of neurons 8 DIV and that cellular event(s) responsible for linking glutamate-mediated Ca2+ influx to PKC inactivation in vulnerable neurons 16 DIV are undeveloped in resistant cells 8 DIV. These results also suggest that the loss of neuronal PKC activity observed in cerebral ischemia may indeed be an important part of the neurodegenerative process. The 8 DIV/16 DIV cortical cell model may prove to be valuable in discerning those intracellular signaling events critical to glutamate-mediated neuronal death.

Alkaloids↗
PubMed1997

Primary structure and functional expression of heavy- and light-chain variable region genes of a monoclonal antibody specific for human fibrin.

The immunoglobulin heavy- and light-chain variable region (VH and VK) genes were isolated from 8E5 hybridoma cells, which secreted monoclonal antibody against human fibrin by RT-PCR. An expression vector pOPE51-8E5 was constructed for the recombinant VH-VK scFv expression. The primary sequence of the variable regions was determined. Expression product was found in the periplasmic space and inclusion bodies by SDS-PAGE and immunoblotting. It was a 30 KDa single chain fragment (scFv) with the antigen-binding specificity of the parental monoclonal antibody. A light chain shuffling with an unspecific VL did not result in a loss of fibrin binding specificity.

Amino Acid Sequence↗
PubMed1997

Optimal dose of nicardipine for maintenance of hemodynamic stability after tracheal intubation and skin incision.

UNLABELLED: To determine the optimal dose of nicardipine (N) for maintenance of hemodynamic stability during the postinduction period, we designed a randomized, double-blind, placebo-controlled, dose-ranging study using four different doses of N administered after a standardized anesthetic induction sequence. A total of 106 patients were assigned to one of the following treatment groups: saline (control), N 0.5 mg (N0.5), N 1 mg (N1), N 2 mg (N2), and N 4 mg (N4). The study medication was administered intravenously (I.V.) in 2.5 mL of saline over 30 s 2 min before laryngoscopy. Mean arterial pressure (MAP) and heart rate (HR) were recorded at 1-min intervals for 15 min after tracheal intubation and for 5 min after skin incision. After intubation, the peak MAP values differed from the preinduction baseline MAP values by 21% +/- 20%, 9% +/- 12%, 1% +/- 13%, -10% +/- 12%, and -15% +/- 13% (mean +/- SD) in the control, N0.5, N1, N2, and N4 groups, respectively. However, the percent change in the pre- to postintubation MAP values (37% to 47%) was similar in all five groups. The highest postintubation HR values were recorded in the N4 group (P < 0.05 versus the other groups). However, the increases in MAP values after skin incision were the least in the N4 group. In conclusion, N1 I.V., administered 2 min before laryngoscopy provides optimal control of arterial blood pressure during the postinduction period. IMPLICATIONS: Acute increases in blood pressure during anesthesia are undesirable in patients with preexisting cardiovascular diseases. This double-blind study found that the calcium-channel blocker, nicardipine, 1 mg intravenously 2 min before tracheal intubation maintained hemodynamic stability during the intraoperative period.

Adult↗
PubMed1997

Titration of volatile anesthetics using bispectral index facilitates recovery after ambulatory anesthesia.

BACKGROUND: The bispectral (BIS) index has previously been shown to be a quantifiable measure of the sedative and hypnotic effects of anesthetic drugs. This study was designed to assess the effect of BIS monitoring on the utilization of volatile anesthetics and their recovery profiles after ambulatory surgery. METHODS: Sixty consenting women undergoing outpatient laparoscopic tubal ligation procedures were randomly assigned to one of four treatment groups. After a standardized induction, anesthesia was maintained with either desflurane (Groups I and II) or sevoflurane (Groups III and IV) in combination with nitrous oxide, 65%, and fentanyl. In the control groups (Groups I and III), the anesthesiologists were blinded to the BIS value, and the volatile anesthetics were administered according to standard clinical practice. In Groups II and IV, the volatile anesthetics were titrated to maintain the BIS value at 60. The volatile anesthetic usage and the times from discontinuation of anesthesia to verbal response, orientation, and home-readiness were recorded. RESULTS: During the maintenance period, the BIS values were significantly lower in the control groups (mean, 42) compared with the BIS-titrated groups (mean, 60). The volatile anesthetic usage in the BIS-titrated groups was 30-38% lower (P < 0.05) compared with the control groups. Similarly, the times to verbal responsiveness were 30-55% shorter in the BIS-titrated (vs. control) groups. CONCLUSIONS: Titrating desflurane and sevoflurane using the BIS monitor decreased their utilization and contributed to a faster emergence from anesthesia in outpatients undergoing laparoscopic tubal ligation procedures.

Adult↗
PubMed1997

Timing of lymphocyte activation in neonates infected with human immunodeficiency virus.

Human immunodeficiency virus (HIV) infection in children is associated with qualitative and quantitative changes in the peripheral lymphocyte surface phenotype beyond the normal maturational changes. Neonates, however, have been reported to have a delayed immune response to HIV compared to HIV-infected adults. We prospectively performed immunophenotyping of T lymphocytes by three-color immunofluorescent labeling and laser flow cytometry to determine the timing of phenotypic alterations in 112 neonates born to HIV-infected mothers. Serial testing was performed at birth (cord blood) and at 2, 6, and 12 weeks of age. Data were divided retrospectively for analysis into those for HIV-infected (n = 14) infants and those for exposed, uninfected infants. Our results show that both infected and uninfected infants had a decline in the percentages and numbers of CD4 cells beginning at 2 weeks of age but that the decline was greater in the HIV-infected group. The activation and differentiation of CD8 T cells in HIV+ infants were shown by a significant increase in CD45RA- CD45RO+ CD8+ cells by 6 weeks of age and by increases in CD8+ S6F1+ CD3+ cells and HLA-DR+ CD38+ CD8+ cells by 2 weeks of age. These results indicate that HIV-infected neonates show alterations in T-cell phenotype reflecting those reported for older HIV-infected children. Most importantly, neonatal T cells are able to respond to HIV within the first weeks of life.

Antigens, CD↗