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C J Morgan

Publications and source records attributed to C J Morgan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Hydrogen exchange properties of proteins in native and denatured states monitored by mass spectrometry and NMR.

The extent of deuterium labeling of hen lysozyme, its three-disulfide derivative, and the homologous alpha-lactalbumins, has been measured by both mass spectrometry and NMR. Different conformational states of the proteins were produced by varying the solution conditions. Alternate protein conformers were found to contain different numbers of 2H atoms. Furthermore, measurement in the gas phase of the mass spectrometer or directly in solution by NMR gave consistent results. The unique ability of mass spectrometry to distinguish distributions of 2H atoms in protein molecules is exemplified using samples prepared to contain different populations of 2H-labeled protein. A comparison of the peak widths of bovine alpha-lactalbumin in alternate solution conformations but containing the same average number of 2H atoms showed dramatic differences due to different 2H distributions in the two protein conformers. Measurement of 2H distributions by ESI-MS enabled characterization of conformational averaging and structural heterogeneity. In addition, a time course for hydrogen exchange was examined and the variation in distributions of 2H atom compared with simulations for different hydrogen exchange models. The results clearly show that exchange from the native state of bovine alpha-lactalbumin at 15 degrees C is dominated by local unfolding events.

Animals↗
PubMed1997

Leukotrienes are indicated as mediators of hyperoxia-inhibited alveolarization in newborn rats.

We investigated the role of leukotrienes (LT) in hyperoxia-induced changes in lung parenchyma in neonatal rat pups. Rat pups were exposed to 21% O(2) (air) or >95% O(2) from days 4 to 14 after birth and were administered the 5-lipoxygenase (5-LO) inhibitor and LTD4 receptor antagonist Wy-50295, 5-LO-activating protein inhibitor MK-0591, or vehicle from days 3 to 14. All measurements were done on days 12-14. There was a significant (P < 0.05) increase in peptido-LT output from lung slices of animals exposed to O(2) compared with air-exposed animals. Both Wy-50295 and MK-0591 significantly lowered (P < 0.05) peptido-LT output in O(2)-exposed animals. The 6-ketoprostaglandin F(1alpha) output was increased similarly in both vehicle- and drug-treated O(2)-exposed animals. O(2) exposure also caused a significant increase in bronchoalveolar lavage fluid protein and extravascular lung water that could not be ameliorated by Wy-50295 or MK-0591. Hyperoxia-induced inhibition of alveolarization, indicated by a significantly (P < 0.05) lower parenchymal tissue density, specific internal surface area, and airspace perimeter-to-area ratio, and a significantly (P < 0.05) higher mean linear intercept and airspace unit volume than air-exposed animals, was prevented by both Wy-50295 and MK-0591. Although hyperoxia had no effect on septal thickness, Wy-50295 caused significant thickening in both air- and O(2)-exposed pups. Our studies provide evidence that hyperoxia-induced peptido-LT may mediate O(2)-induced inhibition of alveolarization and that this is not caused by an arachidonic acid shunt to cyclooxygenase.

Acute Disease↗
PubMed1996

Defective transfer RNA-queuine modification in C3H10T1/2 murine fibroblasts transfected with oncogenic ras.

tRNA isoacceptors for aspartic acid, asparagine, histidine, and tyrosine are modified in the anticodon wobble position with the deazaguanine analogue queuine. Queuine modification is defective in many tumors and transformed cell lines, and the extent of hypomodification correlates with staging and outcome in numerous human tumors. The molecular role of queuine modification in normal cells and the mechanisms of queuine hypomodification in tumors are unknown. We have characterized nontransformed C3H10T1/2 murine fibroblasts (C3H) and their ras-transfected counterparts (RasC4) with respect to the causes and effects of queuine hypomodification. RasC4 cells are hypomodified for queuine compared with C3H cells, despite increase tRNA-guanine ribosyltansferase activity. Excess exogenous queuine can cause repletion of tRNA queuine levels in RasC4 cells. Queuine modification of both C3H and RasC4 cells can be decreased by treatment with 7-methylguanine. This treatment does not affect growth in monolayer culture but enhances anchorage-independent growth of RasC4 cells greatly. These cell lines may be useful systems for the study of queuine function in normal cells and the causes and consequences of hypomodification for queuine in tumors.

Animals↗
PubMed1996

Limitation of life support: frequency and practice in a London and a Cape Town intensive care unit.

OBJECTIVES: To examine the frequency of limiting (withdrawing and withholding) therapy in the intensive care unit (ICU), the grounds for limiting therapy, the people involved in the decisions, the way the decisions are implemented and the patient outcome. DESIGN: Prospective survey. Ethical approval was obtained. SETTING: ICUs in tertiary centres in London and Cape Town. PATIENTS: All patients who died or had life support limited. INTERVENTIONS: Data collection only. RESULTS: There were 65 deaths out of 945 ICU discharges in London and 45 deaths out of 354 ICU discharges in Cape Town. Therapy was limited in 81.5% and 86.7% respectively (p = 0.6) of patients who died. The mean ages of patients whose therapy was limited were 60.2 years and 51.9 years (p = 0.014) and mean APACHE II scores 18.5 and 22.6 (p = 0.19) respectively. The most common reason for limiting therapy in both centres was multiple organ failure. Both medical and nursing staff were involved in most decisions, which were only implemented once wide consensus had been reached and the families had accepted the situation. Inotropes, ventilation, blood products, and antibiotics were most commonly withdrawn. The mean time from admission to the decision to limit therapy was 11.2 days in London and 9.6 days in Cape Town. The times to outcome (death in all patients) were 13.2 h and 8.1 h respectively. CONCLUSIONS: Withdrawal of therapy occurred commonly, most often because of multiple organ failure. Wide consensus was reached before a decision was made, and the time to death was generally short.

APACHE↗
PubMed1996

Definition and detection of alarms in critical care.

Critical care medicine has developed enormously in complexity and even more so in cost over the past twenty years. There has been evidence of remarkable progress in improved outcomes from some conditions, particularly when severely ill patients are treated in well equipped and well managed intensive care units (ICU) which have clear directorship and comprehensive management guidelines and protocols (Zimmermann et al., Crit Care Med 1993; 21:1443-1451). Nevertheless, for some conditions such as severe acute respiratory failure and multiple organ failure, there is considerable debate as to whether there has been any improvement at all (Lee et al., Thorax 1994; 49:596-597. Artigas et al., Adult respiratory distress syndrome, Churchill Livingstone, Edinbugh, London, Madrid, Melbourne, New York, Tokyo, pp. 509-525). Developments in signal processing and monitoring and recording technology have resulted in a vast increase in the quantity of data that is available to clinicians trying to manage critically ill patients (Price, Bailliere's Clin Anaesthesiol 1987; 1:533-556) but there is little evidence that this apparent gain has lead to better clinical decisions or earlier warning of significant instability. One of the tasks of the European Union sponsored IMPROVE group was to attempt to identify significant downward trends in vital parameters sufficiently early to allow clinical intervention to be potent and effective and ultimately improve patient outcome from a wide range of life threatening conditions. The first stage of this task was to define examples of such life threatening deterioration and conduct a survey in representative intensive care units of the incidence of these conditions and the subsequent patient outcomes. This is a preliminary task, the next stage being the gathering of "real time' data from critically ill patients for 24-h sample periods to probe for deteriorating trends and to compile a comprehensive annotated data library of physiological data as a rich resource for future adaptations in signal processing technology and clinical decision support.

Bacterial Infections↗
PubMed1996

Effects of chronic administration and subsequent withdrawal of ethanol-containing liquid diet on rat liver tryptophan pyrrolase and tryptophan metabolism.

An investigation of the effects of chronic administration of ethanol by the liquid diet procedure and its subsequent withdrawal on tryptophan (Trp) metabolism and disposition was performed in rats. Treatment with the control liquid diet caused an enhancement of liver Trp pyrrolase activity and mRNA abundance. These effects are not due to the starvation associated with this feeding procedure, because they occur in rats maintained on the liquid diet ad libitum. Chronic ethanol administration in the liquid diet did not further influence the above increased expression of Trp pyrrolase mRNA but caused inhibition of pyrrolase activity in competition with the effects of the diet. The control liquid diet decreased liver Trp concentration, but exerted no significant effects on other aspects of Trp disposition. The most striking and robust finding was a highly significant elevation in both Trp pyrrolase activity and mRNA expression at 7 h following discontinuation of ethanol availability, at which time there were demonstrable behavioural signs of ethanol withdrawal. The increase in Trp pyrrolase mRNA during alcohol withdrawal may be caused by corticosterone, whose circulating concentration was also increased. The changes in Trp pyrrolase activity during ethanol withdrawal were associated with significant alterations in Trp disposition including decreased brain Trp concentration and 5-hydroxytryptamine synthesis and turnover. These alterations may play a pivotal role in the behavioural manifestations of ethanol withdrawal including the hyperexcitement underlying audiogenic seizures. We suggest that rat Trp pyrrolase gene regulation may be an important biological determinant of the ethanol withdrawal syndrome and requires further study, and that the use of the liquid diet procedure in Trp metabolic studies requires inclusion of adequate controls and special attention to the effects of the liquid diet itself.

Alcohol Withdrawal Delirium↗
PubMed1996

Prevention by cycloheximide of the audiogenic seizures and tryptophan metabolic disturbances of ethanol withdrawal in rats.

Cycloheximide (20 mg/kg body wt, given intraperitoneally at-1 and 3 h after withdrawal of an ethanol-containing liquid diet) prevents the activation of liver tryptophan pyrrolase, the consequent inhibition of synthesis of brain 5-hydroxytryptamine, and the audiogenic seizures observed at 7 h after alcohol withdrawal. We suggest that a rapidly-turning-over protein mediates the alcohol withdrawal syndrome and discuss the possible role of liver tryptophan pyrrolase.

Acoustic Stimulation↗
PubMed1996

The localisation and characterisation of insulin-like growth factor-I receptors and the investigation of melatonin receptors on the hair follicles of seasonal and non-seasonal fibre-producing goats.

To define the hormonal influences that are directly involved in the hair follicle cycles of animals with differing patterns of fibre growth and moulting, we have investigated the possible presence of IGF-I and melatonin receptors on the dermis and hair follicles of cashmere and Angora goats, sampled in February. March and June, using quantitative in vitro autoradiography. The presence of IGF-I receptors in the dermis of both breeds of goat was determined using cryostat sections incubated with 50 pM 125I-labelled IGF-I in the presence or absence of 50 nM IGF-I. Sections of the growing tip of deep antlers concerning the cartilaginous zone, a tissue known to contain high concentrations of specific IGF-I receptors, were used as a positive control. As the production of antler velvet uniquely involves the generation of hair follicles de novo, the presence of IGF-I receptors in the velvet-producing region was also investigated. In both breeds of goat, specific 125I-IGF-I binding was localised over the inner and outer root sheath, the matrix, the germinal matrix, the dermal papilla and the sebaceous glands and satisfied the basic kinetic criteria considered to be representative of a specific IGF-I receptor. Analysis of saturation isotherms using a one-site binding model revealed dissociation constants (Kd) in the range 0.1-0.9 nM and theoretical maximal numbers of binding sites (Bmax) between 21.4 and 45.6 fmol/mg tissue. Kd and Bmax values derived from cashmere and Angora goats sampled at different times of the year did not differ significantly between breeds or sampling times. Specific 125I-IGF-I binding was also localised to the developing follicles on the deer antler dermis. The presence of melatonin receptors within the goat dermis was also investigated. Sections were incubated with 100 pM 2-[125I]iodomelatonin with or without 0.1 microM melatonin, along with sections of sheep pars tuberalis which are known to contain high levels of high-affinity melatonin receptors. No displaceable 2-[125I]iodomelatonin binding was found on any sections of the cashmere or Angora skin analysed. It is therefore concluded that melatonin receptors are not present on the hair follicles or associated structures. IGF-I receptors are present on the hair follicle and sebaceous gland and may be involved in the growth of both seasonally and non-seasonally produced fibre and in the development of antler velvet.

Animals↗
PubMed1995

Decrease in circulating tryptophan availability to the brain after acute ethanol consumption by normal volunteers: implications for alcohol-induced aggressive behaviour and depression.

Acute ethanol consumption by fasting male volunteers decreases circulating trytophan (Trp) concentration and availability to the brain as determined by the ratio of (Trp) to the sum of its five competitors ([Trp]/[CAA]ratio). These effects of alcohol are specific to Trp, because levels of the 5 competitors are not increased. The decrease in circulating (Trp) is not associated with altered binding to albumin and may therefore be due to enhancement of hepatic Trp pyrrolase activity. It is suggested that, under these conditions brain serotonin synthesis is likely to be impaired and that, as a consequence, a possible strong depletion of brain serotonin in susceptible individuals may induce aggressive behaviour after alcohol consumption. The possible implications of these findings in the relationship between alcohol and depression are also briefly discussed.

Adult↗
PubMed1995

Expansion of mucin-reactive T-helper lymphocytes from patients with colorectal cancer.

The ability to identify and expand effector cells with reactivity against tumor-associated antigens (TAA) is critical for effective adoptive cellular therapy. The purpose of this study was to assess lymph node lymphocytes sensitized in vivo to the shed TAA TAG-72 as a potential source of cells for adoptive cellular therapy. Lymph nodes containing microscopic tumor and/or shed TAG-72+ mucin were localized using radiolabeled CC49 monoclonal antibody and a gamma detector at the time of exploratory colorectal surgery. Lymph nodes containing microscopic tumor and shed mucin exhibited approximately 40-fold expansion in short-term (< 21 days) cultures with either IL-2 or IL-1 plus IL-2; the combination of IL-2/anti-CD3 monoclonal antibody (mAb) resulted in significantly higher expansion. Cultures generated with IL-2 alone favored the expansion of CD8+ and CD56+ cells, whereas addition of IL-1 or anti-CD3 mAb to IL-2 promoted outgrowth of CD4+ T-cells. The IL-2/anti-CD3 expanded cells exhibited low levels of cytolytic activity in vitro against autologous and allogeneic colon tumor targets. However, CD4+ cells expanded in IL-2/anti-CD3 retained the ability to proliferate in response to TAG-72 mucin-expressing autologous tumor as well as bovine submaxillary mucin (BSM) a soluble TAG-72+ mucin. In addition, CD4+ cells expressed mRNA for IL-2, IL-4, tumor necrosis factor-beta and IFNg, and retained the ability to secrete IL-2 after expansion. Thus, noncytolytic, cytokine-secreting, mucin-reactive T- cells can be expanded from lymph nodes of patients with colorectal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed1995

Difficulties in predicting outcome in cardiac surgery patients.

OBJECTIVE: To evaluate a novel combination of preoperative, intraoperative, and postoperative variables (including the Parsonnet, and the Acute Physiology and Chronic Health Evaluation II and III [APACHE II and III] scores) in cardiac surgery patients in order to predict hospital outcome, complications, and length of stay. DESIGN: Prospective survey. SETTING: Adult intensive care unit (ICU) at a tertiary care cardiothoracic surgery center. PATIENTS: All cardiac surgery patients admitted to the ICU over a 1-yr period. INTERVENTIONS: Medical history, Parsonnet score, intraoperative data (including bypass and ischemic times), APACHE II and III scores, complications, and outcome were collected for each patient. MEASUREMENTS AND MAIN RESULTS: One thousand eight patients were entered into the study. The mean Parsonnet score was 7.8 (range 0 to 33), mean APACHE II score 11.8 (range 2 to 33), and mean APACHE III score 42.5 (range 9 to 132). ICU mortality rate was 2.7% and hospital mortality rate was 3.8%. The mean APACHE II predicted risk of dying was 5.31%, which gave a standardized mortality ratio of 0.71. The above scores were all statistically well correlated with hospital mortality. Further, a logistic regression model was developed for the probability of hospital death. This model (which included bypass time, need for inotropes, mean arterial pressure, urea, and Glasgow Coma Scale) had an area under the receiver operating characteristic curve of 0.87, while the Parsonnet score had an area of 0.82 and the APACHE II risk of dying had an area of 0.84. CONCLUSIONS: Cardiac surgery remains a difficult area for outcome prediction. A combination of intraoperative and postoperative variables can improve predictive ability.

APACHE↗
PubMed1994

6-Thioguanine-induced growth arrest in 6-mercaptopurine-resistant human leukemia cells.

The thiopurines 6-thioguanine (6TG) and 6-mercaptopurine (6MP) are cytotoxic to proliferating cells by a mechanism involving incorporation into DNA via the purine salvage pathway, and resistance to these agents can be conferred by lack of the salvage pathway enzyme hypoxanthine-guanine phosphoribosyltransferase. However, human and murine hypoxanthine-guanine phosphoribosyltransferase-deficient leukemia cell lines have been shown to respond to 6TG by growth arrest and differentiation by a mechanism apparently not involving incorporation of 6TG into DNA. If so, leukemia cells resistant to 6MP should still respond to 6TG by growth arrest via an undescribed epigenetic mechanism. To test this, polyclonal 6MP-resistant variants were produced from three human leukemia cell lines, HL-60, U937, and CCRF-CEM. Treatment of both sensitive and resistant cells with 6TG induced growth arrest. The effect of 6TG in the 6MP-sensitive HL-60 and U937 cells was associated with significant loss of viability and DNA fragmentation. In contrast, the 6TG-treated 6MP-resistant cells exhibited a slower decline in viability and no DNA fragmentation. To identify the mechanism by which 6TG may induce growth arrest, tRNA was isolated from 6MP-resistant cells cultured for 48 h with 6TG. 6TG was found to be incorporated into tRNAs normally containing queuine in the anticodon wobble position. These studies may provide a basis for the development of new therapeutic regimens for the treatment of leukemia.

Apoptosis↗
PubMed1994

Transmission of hepatitis C by kidney transplantation--the risks.

The use of cadaveric organ donors with positive serologic tests for hepatitis C (HCV) has caused considerable debate. We have reviewed the clinical course of 43 EIA1 HCV-negative recipients who received kidney transplants from EIA1 HCV-positive donors (Study). We have attempted to define the rate of HCV-RNA transmission and to determine the frequency of HCV disease transmission as determined by abnormalities in liver function tests. Viral transmission was assessed using serologic assays for HCV antibody formation (EIA1, EIA2, and Matrix--an automated multiple antigen immunoblot assay) and with PCR testing for the presence of HCV-RNA on recipient sera. Liver function was followed longitudinally in the Study patients and compared with a group of 103 kidney recipients of organs from EIA1 HCV-negative donors (Control). Of the Study patients, 56% became PCR-positive for HCV-RNA, suggesting the transmission of HCV-RNA from the HCV-positive donor. Interpretation of serologic tests for HCV was complex. Currently available first (EIA1) and second (EIA2) generation serologic assays were always negative. The multiple antigen immunoblots assay (Matrix) had a high positive predictive value (93%) for the presence of HCV-RNA transmission, but one-third of Matrix-negative Study patients were PCR-positive (sensitivity = 66%). Currently, only 38% of recipients have HCV-RNA, suggesting that the virus may have been cleared by one-third of Study recipients who had circulating virus. Traditional tests of liver function (ALT, AST, AP, and GGT) were of limited use in predicting HCV-RNA transmission. Average AST, AP, and GGT were similar in the two groups. Average ALT was increased (93 I/U and 47 I/U) in Study and Control patients, respectively, but this difference was not significant. Episodes of abnormal liver function (ALT 60-99 IU for > or = 14 days) occurred in 22% of Study and 10% of Control patients (P = NS) and lasted longer in Study compared with Control patients (301 vs. 138 days; P < 0.02). Hepatitis (ALT > or = 100 IU for > 14 days) occurred with an equal frequency (6.5%) in both groups. The presence of HCV-RNA did not predict episodes of abnormal liver function. Fulminant hepatitis or rapidly progressive cirrhosis did not occur in the recipients of organs from HCV-positive donors. These data demonstrate a high efficiency of transfer of HCV-RNA by kidney transplantation from an HCV-positive donor to an HCV-negative recipient. A majority of the patients have asymptomatic HCV infection.(ABSTRACT TRUNCATED AT 400 WORDS)

Cadaver↗
PubMed1994

Alloantigenicity of human endothelial cells. IV. Derivation, characterization, and utilization of gonadal vein endothelia to control endothelial alloantigenicity during lymphocyte-endothelial interactions.

Most previous studies to evaluate endothelial cell-T lymphocyte interactions have used human peripheral blood as a source of T lymphocytes and human umbilical vein endothelial cells as a source of endothelia. Implicit in this experimental system are allogeneic lymphocyte-endothelial interactions, which are largely ignored. To overcome this problem, we isolated gonadal vein endothelial cells (GVEC) along with matched splenic macrophages and T lymphocytes from cadaveric donors, thus providing a completely autologous series of cells for experimentation. First, GVEC were analyzed for morphology, surface phenotype, and cytokine mRNA expression, and found to be indistinguishable from human umbilical vein endothelial cells. Using this system, we observed that irradiated GVEC were able to promote a 2- to 3-fold increase in the proliferation of matched autologous splenic T cells after PHA stimulation. This indicates that the costimulator activity of endothelial cells reported by others is an intrinsic property of endothelial cells, and is not a consequence of endothelial alloantigens. We also used this system to assess the relative abilities of GVEC and macrophages obtained from the same donor to stimulate the proliferation of purified allogeneic CD3+ PBL. We found the following hierarchy of alloantigenicity in this experimental system: splenic macrophages > IFN-gamma-treated GVEC >> untreated GVEC = TNF alpha-treated GVEC. These studies demonstrate that allogeneic macrophages are intrinsically more antigenic than endothelial cells derived from the same donor. Furthermore, they illustrate the utility of this experimental system to obtain data regarding lymphocyte-endothelial interactions that are otherwise unobtainable.

Base Sequence↗
PubMed1994

Detection of human tRNAs with antisense oligonucleotides.

Regulated expression and modification of tRNA isoacceptors may play an important role in the control of gene expression during such processes as differentiation and immune activation. However, the development of techniques for the identification and quantitation of multiple tRNA isoaccepting species has been hindered by the relative physicochemical similarity among individual isoacceptors and their high degree of post-transcriptional modification. We have used antisense DNA oligonucleotides derived from the T stem to acceptor stem region of six human tRNAs and one murine tRNA to detect individual tRNA isoacceptors in slot blots, Northern blots, and dot blots of human tRNA. This hybridization protocol was used in combination with tRNA fractionation by electrophoresis on a partially denaturing gel by reversed-phase low pressure chromatography and reversed-phase HPLC to identify multiple tRNA isoacceptors in a single sample of tRNA. Using this technique, it should be possible to monitor changes in the cellular tRNA repertoire that may be involved in the regulation of gene expression.

Amino Acid Sequence↗
PubMed1994

Adult respiratory distress syndrome: has there been a change in outcome predictive measures?

BACKGROUND: Studies suggest that the mortality in adults with acute respiratory distress (ARDS) has not changed over the past two decades, despite the introduction of new therapeutic techniques and sophisticated ventilatory support devices. Mortality and physiological variables that might predict outcome in patients with ARDS were therefore assessed. METHODS: A retrospective survey was undertaken in 41 patients with ARDS. RESULTS: Mortality was 66%. Only the presence of sepsis predicted death. CONCLUSION: Mortality from ARDS is unchanged. Currently available severity scoring systems are not helpful in predicting outcome.

Adolescent↗
PubMed1993

Cellular localization of CD4 in the human placenta. Implications for maternal-to-fetal transmission of HIV.

CD4 is a 55-kDa glycoprotein that serves as an important cellular differentiation Ag and cell signaling protein on T lymphocytes, as well as a principal receptor for HIV-1 on a variety of cell types including lymphocytes. CD4 receptor expression in syncytiotrophoblasts, the principal cellular barrier in the human placenta, has not been clearly defined. Knowledge concerning the expression of the CD4 receptor on placental trophoblasts is important to define potential mechanisms of transmission of the virus between maternal blood and fetal tissues. Both mature and immature placenta (n = 10) were examined using an avidin D-based immunohistochemical procedure that permits clear morphologic distinction of cell types in placental sections. Syncytiotrophoblasts were defined using anti-cytokeratin mAb (AE1/3), whereas endothelial cells in placental villi were distinctly identified using a mAb directed to CD31. Placental Hofbauer cells (macrophages) and other leukocytes were identified by mAb staining of leukocyte common Ag (CD45). CD4 expression (identified by staining with three separate anti-CD4 mAb) was exclusively localized using this immunohistochemical method to leukocytes in placental villi (e.g., Hofbauer cells); however, no CD4 staining was evident in syncytiotrophoblasts, cytotrophoblasts, or villus endothelial cells. Furthermore, immunoaffinity-purified trophoblasts were negative for CD4 receptor expression. CD4 RNA was not identified in purified trophoblasts using both Northern blot assay and a sensitive polymerase chain reaction method to identify CD4 RNA. In addition, time course studies of purified trophoblasts immediately after purification and at 24, 48, and 72 h in culture indicated that CD4 RNA was not present as a transient, but labile transcript in trophoblasts. These data indicate that the transmission of HIV-1 across syncytiotrophoblasts may occur by mechanisms other than by binding the CD4 receptor and that tissue leukocytes (in particular Hofbauer cells) are likely the principal CD4+ cellular target of HIV-1 in the placenta.

Base Sequence↗