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Biomedical subjects

P Fowler

Publications and source records attributed to P Fowler.

At least 19 recordsLinked to original sources
PubMed2001

Brief report: Lack of correlation between age of symptom onset and contemporaneous presentation.

The parents/guardians of 50 individuals were surveyed using a semistructured interview to determine the feasibility of this method and to establish ages of symptom onset. Thirty-eight informants were able to recall sufficient detail to allow categorization of the age of symptom onset. Chi-square analysis confirmed a significant association between investigators' categorization and informants' categorization. Contemporaneous presentation was indexed using Childhood Autism Rating Scale, the Autism Behavior Checklist, the Conners Hyperactivity Index, and the Ritvo-Freeman Real Life Rating Scale for Autism. No significant correlations were determined between any of these indices of symptom severity and age of symptom onset.

Adolescent↗
PubMed2001

Evaluation of ewe vaccination as a tool for increasing bighorn lamb survival following pasteurellosis epizootics.

We conducted field and laboratory experiments to evaluate whether treating pregnant bighorn ewes with a combination of an experimental Pasteurella trehalosi and Mannheimia haemolytica (formerly P. haemolytica) vaccine and a commercially-available bovine P. multocida and M. haemolytica vaccine would increase lamb survival following a pneumonia epidemic. Three free-ranging bighorn herds affected by pasteurellosis outbreaks between November 1995 and June 1996 were included in the field experiment. Post-epidemic lamb survival was low in all three herds in 1996, with November lamb:ewe ratios of < or = 8:100. In March 1997, thirty-six ewes (12/herd) were captured and radiocollared. Half of the ewes captured in each herd were randomly selected to receive both vaccines; the other half were injected with 0.9% saline solution as controls. Lambs born to radiocollared ewes were observed two or more times per week and were considered to have survived if they were alive in October 1997, about 6 mo after birth. Lamb survival differed among herds (range 22% to 100%), and survival of lambs born to vaccinated ewes was lower (P = 0.08) than survival of lambs born to unvaccinated ewes. Bronchopneumonia (pasteurellosis) was the dominant cause of mortality among lambs examined. We concurrently evaluated vaccine effects on survival of lambs born to seven captive ewes removed from the wild during the 1995-96 epidemic. Antibody titers were high in captive ewes prior to vaccination, and vaccines failed to enhance antibody titers in treated captive ewes. None of the captive-born lambs survived. These data suggest that, using existing technology, vaccinating bighorn ewes following pneumonia epidemics has little chance of increasing neonatal survival and population recovery.

Agglutination Tests↗
PubMed2000

Tourniquet versus no tourniquet use in routine knee arthroscopy: a prospective, double-blind, randomized clinical trial.

PURPOSE: The purpose of this study was to determine the effects of tourniquet use for routine knee arthroscopy based on both subjective and objective functional outcome measures. TYPE OF STUDY: The study was a prospective, double-blind, randomized clinical trial. MATERIALS AND METHODS: There were 120 patients randomized to tourniquet inflation (300 mm Hg) or no tourniquet inflation during routine knee arthroscopy. Patients recorded their average pain on a visual analog scale and their narcotic use for the previous 24 hours, for the first 5 postoperative days. Patients also completed a preoperative and postoperative (2 week, 6 week, 3 month) Western Ontario and McMaster University Osteoarthritis Index (WOMAC), 6-minute walk, 30-second stair climb, 1-leg standing vertical leap, range of motion, and isokinetic strength testing. Time to return to work and sport was documented. RESULTS: No statistically significant difference was found between tourniquet-up and tourniquet-down groups for the WOMAC quality of life measure, functional tests, isokinetic muscle strengthening, or time to return to work or sport (t test/repeated measures analysis of variance). However, there was a trend for less early postoperative pain and slightly better isokinetic strength testing at 2 weeks in the tourniquet-down group. Visualization was rated by surgeons to be 3 times better in the tourniquet-up group, although mean operative time did not differ between the groups. CONCLUSION: The use of a pneumatic tourniquet at 300 mm Hg does not significantly effect overall patient quality of life or functional outcome following routine knee arthroscopy.

Adult↗
PubMed2000

The efficacy of femoral nerve block in pain reduction for outpatient hamstring anterior cruciate ligament reconstruction: a double-blind, prospective, randomized trial.

The purpose of this study was to assess the efficacy of intraoperative femoral nerve block (FNB) in the reduction of postoperative pain following anterior cruciate ligament (ACL) hamstring reconstruction. Patients undergoing primary ACL reconstruction with hamstring tendon graft under general anesthetic who had signed an informed consent were included in the study. Patients were stratified to 4 surgeons and randomized to FNB with 0.25% bupivacaine or placebo of normal saline injected into the femoral nerve sheath before reversal of the general anesthetic. All patients received an intra-articular injection of bupivacaine at the beginning of their operative procedure. A single technique that included the use of a peripheral nerve stimulator was used for all FNBs. All patients were discharged on the day of surgery and given prescriptions for Tylenol 3. The Short-Form McGill Pain Questionnaire (SF-MPQ), a visual analog scale (VAS) for pain, and a medication diary recording Tylenol 3 usage were completed by patients in the recovery room, on the night of surgery, and on postoperative days 1, 2, and 3. There were complete data for 61 patients (FNB, 29; placebo, 32). An analysis of variance (ANOVA) test of the data showed no significant difference between the FNB and placebo group for pain reduction over the combined study period for both the SF-MPQ and VAS. However, the ANOVA does suggest that, on the night of surgery, there was a significant reduction in pain as measured with the VAS in the FNB group. A Student t test performed on the night of surgery data (SF-MPQ, P = .131; VAS, P = .0114; Tylenol 3, P = .076) showed a statistically significant difference between the FNB (39.4+/-21.0 mm) and placebo (56.8+/-24.6 mm) measured by VAS. Because this represented a difference of only 1.74 cm on a 10-cm VAS, it is unlikely to be clinically relevant. No difference was found in the amount of analgesic required on any day postoperatively. In conclusion, FNB may reduce pain on the night of surgery. However, this may not be clinically significant. FNB is not recommended at this time for use in outpatient ACL reconstruction with hamstring graft.

Adolescent↗
PubMed1999

Compartment pressure monitoring during anterior cruciate ligament reconstruction.

A prospective double blind randomized study was carried out using 20 healthy males with anterior cruciate ligament (ACL) insufficiency undergoing bone-patellar tendon-bone ACL reconstruction. The subjects were randomized into either water or saline irrigation and then underwent identical reconstructive procedures using an arthroscopic pump. Continuous preoperative, intraoperative, and postoperative pressures were monitored using the slit catheter technique. Blood pressure and compartment pressure measurements were continuously recorded and noted at all stages of the procedure. Mean preoperative anterior and posterior compartment pressures were similar in both groups. No significant differences were noted between the anterior and posterior compartments of each group. No difference between water and saline irrigation was identified throughout the procedure. In both groups, postoperative pressures were slightly lower in the anterior and posterior compartments compared with preoperative pressures, but not significantly.

Adolescent↗
PubMed1999

The effect of bracing on varus gonarthrosis.

BACKGROUND: The purpose of this study was to compare a custom-made valgus-producing functional knee (unloader) brace, a neoprene sleeve, and medical treatment only (control group) with regard to their ability to improve the disease-specific quality of life and the functional status of patients who had osteoarthritis in association with a varus deformity of the knee (varus gonarthrosis). METHODS: The study design was a prospective, parallel-group, randomized clinical trial. Patients who had varus gonarthrosis were screened for eligibility. The criteria for exclusion included arthritides other than osteoarthritis; an operation on the knee within the previous six months; symptomatic disease of the hip, ankle, or foot; a previous fracture of the tibia or femur; morbid obesity (a body-mass index of more than thirty-five kilograms per square meter); skin disease; peripheral vascular disease or varicose veins that would preclude use of a brace; a severe cardiovascular deficit; blindness; poor English-language skills; and an inability to apply a brace because of physical limitations such as arthritis in the hand or an inability to bend over. Treatment was assigned on the basis of a computer-generated block method of randomization with use of sealed envelopes. The patients were stratified according to age (less than fifty years or at least fifty years), deformity (the mechanical axis in less than 5 degrees of varus or in at least 5 degrees of varus), and the status of the anterior cruciate ligament (torn or intact). The patients were randomly assigned to one of three treatment groups: medical treatment only (control group), medical treatment and use of a neoprene sleeve, or medical treatment and use of an unloader brace. The disease-specific quality of life was measured with use of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the McMaster-Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR), and function was assessed with use of the six-minute walking and thirty-second stair-climbing tests. The primary outcome measure consisted of an analysis of covariance of the change in scores between the baseline and six-month evaluations. RESULTS: One hundred and nineteen patients were randomized. The control group consisted of forty patients (thirty-one men and nine women; mean age, 60.9 years); the neoprene-sleeve group, of thirty-eight patients (twenty-seven men and eleven women; mean age, 58.2 years); and the unloader-brace group, of forty-one patients (twenty-eight men and thirteen women; mean age, 59.5 years). Nine patients withdrew from the study. At the six-month follow-up evaluation, there was a significant improvement in the disease-specific quality of life (p = 0.001) and in function (p< or =0.001) in both the neoprene-sleeve group and the unloader-brace group compared with the control group. There was a significant difference between the unloader-brace group and the neoprene-sleeve group with regard to pain after both the six-minute walking test (p = 0.021) and the thirty-second stair-climbing test (p = 0.016). There was a strong trend toward a significant difference between the unloader-brace group and the neoprene-sleeve group with regard to the change in the WOMAC aggregate (p = 0.062) and WOMAC physical function scores (p = 0.081). CONCLUSIONS: The results indicate that patients who have varus gonarthrosis may benefit significantly from use of a knee brace in addition to standard medical treatment. The unloader brace was, on the average, more effective than the neoprene sleeve. The ideal candidates for each of these bracing options remain to be identified.

Bone Diseases, Developmental↗
PubMed1998

Polyclonality and multispecificity of the CTL response to a single viral epitope.

The molecular anatomy of an immunodominant, Ld restricted CTL epitope located between residues 28-39 in hepatitis B surface Ag was defined to explore the immunologic constraints on mutational escape from the CTL response during a viral infection. Using a panel of hepatitis B surface Ag residue 28-39-specific CTL clones, the response to this epitope was found to be extremely diverse at the level of TCR fine specificity and beta-chain usage. Although each clone recognized shared as well as unique residues within the epitope as TCR contact sites, even the shared residues were recognized differently by different TCRs. Despite these differences, all clones were comparably cytolytic following Ag stimulation and produced similar amounts of antiviral cytokines previously shown to inhibit HBV replication. These results demonstrate that the CTL response to individual viral epitopes can be markedly polyclonal and multispecific, such that mutational inactivation of a single TCR contact site will not usually lead to viral escape from all CTL clones of the same epitope specificity. Given these constraints and the fact that the CTL response is usually directed against several different epitopes during most viral infections, mutational inactivation of a single epitope is not likely to be sufficient to cause viral persistence.

Amino Acid Substitution↗
PubMed1998

Dendritic cell immunization breaks cytotoxic T lymphocyte tolerance in hepatitis B virus transgenic mice.

Hepatitis B virus (HBV) transgenic mice that are immunologically tolerant to HBV-encoded Ags represent a model of chronic HBV infection suitable for the development of therapeutic immunization strategies before testing in humans. Five lineages of HBV transgenic mice were immunized with plasmid DNA that encodes hepatitis B surface Ag (HBsAg) or with cytokine-activated bone marrow-derived dendritic cells (DCs) in an attempt to break tolerance to HBsAg at the B and T cell levels. DNA immunization stimulated an Ab response but not a cytotoxic T lymphocyte response to HBsAg in two of the five transgenic lineages studied. In contrast, infusion of activated transgenic or nontransgenic DCs stimulated a splenic CTL response in all three transgenic lineages immunized in this manner at precursor frequencies comparable to those in nontransgenic mice, indicating that DC function is normal, and HBsAg-specific CTLs are present but functionally silent in these transgenic animals. Importantly, none of the animals developed hepatitis or displayed suppressed viral gene expression or replication following either DNA immunization or DC administration even in the presence of anti-hepatitis B surface (HBs) Abs and HBs-specific CTLs. These results indicate that Ag presentation by cytokine-activated DCs can break tolerance and trigger an anti-viral CTL response in HBV transgenic mice, and they suggest that this strategy is more efficient than DNA immunization in this setting. Nonetheless, more efficient immunization strategies are needed to stimulate an immune response of sufficient quality and magnitude to achieve an immunotherapeutic antiviral effect.

Adoptive Transfer↗
PubMed1998

Immune pathogenesis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common complication of chronic hepatitis B virus (HBV) infection. The pathogenetic mechanisms potentially responsible for HCC during chronic HBV infection are not well defined. This study demonstrates that chronic immune-mediated liver cell injury triggers the development of HCC in the absence of viral transactivation, insertional mutagenesis, and genotoxic chemicals. These results strongly suggest that the immune response to HBV is both necessary and sufficient to cause liver cancer during chronic HBV infection, and that all other procarcinogenic events associated with HCC are probably dependent on this process.

Animals↗
PubMed1997

Human histocompatibility leukocyte antigen-binding supermotifs predict broadly cross-reactive cytotoxic T lymphocyte responses in patients with acute hepatitis.

The present study was designed to determine if highly conserved hepatitis B virus (HBV)-derived peptides that bind multiple HLA class I alleles with high affinity are recognized as cytotoxic T lymphocyte (CTL) epitopes in acutely infected patients. Peripheral blood mononuclear cells from 67 patients with acute hepatitis B, and 12 patients convalescent from acute hepatitis B, were stimulated with three panels of peptides, each of which bind with high affinity to several class I alleles from the HLA-A2-, HLA-A3-, or HLA-B7-supertypes. In these patients, 8 of the 19 peptides tested were found to represent CTL epitopes recognized by two or more alleles in each supertype. Two sets of nested peptides were recognized in the context of alleles with completely unrelated peptide binding specificities. Finally, promiscuous recognition by the same CTL of a given peptide presented by target cells expressing different A2 subtypes was also commonly observed. In conclusion, several HBV-specific CTL epitopes, recognized by acutely infected or convalescent patients in the context of a wide range of HLA alleles have been identified. These results demonstrate the functional relevance of the supertype grouping of HLA class I molecules in a human viral disease setting. Furthermore, they represent a significant advance in the development of a totally synthetic vaccine to terminate chronic HBV infection and support the feasibility of a systematic approach to development of similar vaccines for prevention and treatment of other chronic viral infections.

Acute Disease↗
PubMed1997

Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy.

OBJECTIVE: To investigate whether leptin is linked to reproduction, circulating levels were measured longitudinally throughout spontaneous menstrual cycles and during pregnancy in normal women. DESIGN: Longitudinal blood samples were collected from normal volunteers, either during regular menstrual cycles or during successful singleton pregnancies. PATIENTS: Six healthy, regularly cycling, women volunteers (31.5 +/- 3.0 years old, BMI = 21.6 +/- 0.5) were recruited for serial venous blood sampling throughout one complete menstrual cycle. In addition, five healthy, women (31.8 +/- 1.2 years old, pregnant BMI = 30.0 +/- 3.1) provided serial venous blood samples throughout one complete singleton pregnancy. MEASUREMENTS: Circulating venous oestradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), leptin and (pregnant group only) human chorionic gonadotrophin (hCG). RESULTS: In spontaneously cycling women, changes in circulating leptin levels were associated with menstrual phase (P < 0.001) and correlated with progesterone levels (P < 0.05). Peak leptin concentrations were recorded during the luteal phase (P < 0.01), coincident with maximal progesterone levels (P < 0.05). Leptin concentrations were elevated throughout gestation (P < 0.05), and especially during the second trimester (P < 0.05). Post-partum, circulating leptin levels fell sharply to below pregnant values. Leptin correlated with oestradiol (P < 0.05) and human chorionic gonadotrophin (hCG, P < 0.01) levels during pregnancy. First trimester (P < 0.05) and postpartum (P < 0.05) oestradiol concentrations and post-partum hCG levels exhibited the greatest correlation with circulating leptin. CONCLUSIONS: We conclude that the relationship between body mass index and circulating leptin varies during the course of spontaneous cycles in women, the best correlation occurring during the luteal phase when progesterone and leptin concentrations are highest. This, together with the correlation between circulating oestradiol, hCG and leptin levels during pregnancy, strongly suggests a dynamic relationship between leptin and reproductive events in women.

Adult↗
PubMed1997

Functional knee braces and dynamic performance: a review.

OBJECTIVE: The purpose of the present review was to examine current experimental research on the effectiveness of functional knee braces (FKBs) used by patients with anterior cruciate ligament injury during dynamic performance tests. DATA SOURCES: Twelve studies published in peer-reviewed journals and listed in the Excerpta Medica system were reviewed. STUDY SELECTION: All studies compared braced and unbraced tests performed by the same subjects, using tests characterized by weight bearing/axial loading. DATA EXTRACTION: Studies were reviewed independently by three investigators. DATA SYNTHESIS: Tests included one-leg hop, figure-of-eight run, stair climbing, walking, cutting, agility runs, straight running, and bicycle ergometry. Experimental situations were classified as follows: (a) maximal effort tests, which compared overall measures of performance such as the distance hopped and the time to run a specific distance; and (b) matched submaximal effort tests, which compared specific variables such as electromyography, range of motion, ground reaction forces, and energy costs. Bracing was found to be advantageous in three of the 16 maximal effort situations, disadvantageous in two, and of no measurable effect in 11. Six of the 10 matched effort situations reported differences in the criterion measurements when braced, while four reported no differences. CONCLUSIONS: If FKB prescription is to be based solely on empirical evidence of efficacy from performance tests, then further investigation is required to provide this evidence. Future research needs to examine the subjective and psychological aspects of FKB usage along with the results of objective performance tests.

Braces↗
PubMed1996

A biomechanical analysis of joint contact forces in the posterior cruciate deficient knee.

The approach to the posterior cruciate deficient knee is controversial. The purpose of this study is to document the biomechanical changes in the static cadaveric knee model with simulated physiological loads. Nine fresh cadaveric knees from young donors (aged under 45 years) were mounted on a materials testing machine. Loading was carried out at 0 degrees, 30 degrees and 60 degrees to 1.5 kN with low-pressure sensitive Prescale film (Fuji; Tokyo, Japan) inserted through arthrotomies into the medial and lateral compartments. Computerized analysis of the imprints on the film was then carried out. Tests were then repeated after cutting the posterior cruciate ligament (PCL). Results demonstrate a statistically significant posterior subluxation of the tibia on the femur at 60 degrees flexion. This causes a significant increase in contact pressure and pressure concentration on the medial compartment of the knee after cutting the PCL. This may help explain the long-term degenerative changes observed in the medial femoral condyle after cutting the PCL.

Adult↗
PubMed1996

Identification of gonadotrophin surge-inhibiting factor (GnSIF)/attenuin in human follicular fluid.

Evidence from several laboratories suggests that the ovaries of many species produce a non-steroidal factor called gonadotrophin surge-inhibiting or attenuating factor (GnSIF) which may regulate the response of the pituitary to gonadotrophin-releasing hormone (GnRH) and as such, may modulate the timing and/or amplitude of the luteinizing hormone (LH) surge. We have recently isolated a candidate GnSIF from porcine follicular fluid (PFF). Porcine GnSiF is a 69 kDa protein which has undetectable inhibin and follistatin immunological and biological activity. The present study was designed to purify and identify GnSIF from human follicular fluid. GnSIF activity was measured as suppression of GnRH-stimulated LH secretion from rat pituitary cells in primary culture. Human follicular fluid (approximately 500 ml) was recovered from patients undergoing in-vitro fertilization (IVF). GnSIF was purified by heparin-sepharose, Q-sepharose, S-sepharose, and hydrophobic interaction chromatography followed by isoelectric focusing. Gel electrophoresis and Western blot were used to identify human GnSIF and compare it with porcine GnSIF. Using these steps, we obtained a highly-purified preparation of GnSIF that manifests in-vitro bioactivity and chromatography characteristics similar to those observed for porcine GnSIF and that hybridizes with a porcine GnSIF antibody. Following treatment with human chorionic gonadotrophin/human menopausal gonadotrophin (HMG/HCG), human follicular fluid contained roughly 25% of the GnSIF (per mg protein) present in porcine follicular fluid. We conclude that GnSIF is present in human follicular fluid and may participate in the regulation of gonadotrophin secretion in this species.

Animals↗
PubMed1996

Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women.

Mifepristone interrupts folliculogenesis in women but the mechanism is not clear. Previous studies have investigated the effect of this compound on gonadotrophin secretion and have provided conflicting results. To study further the effect of mifepristone on basal and gonadotrophin-releasing hormone (GnRH)-induced gonadotrophin secretion, 12 normally ovulating women were investigated during two consecutive menstrual cycles, comprising an untreated cycle (control) and a cycle treated with mifepristone. All women were treated with mifepristone on days 2-8 at the dose of 100 mg (group 1, eight women) or 10 mg per day (group 2, six women). Two women were treated with both regimens in two different cycles. On day 8 of both cycles, the women received two GnRH pulses of 10 micrograms each 2 h apart. Blood samples in relation to the first GnRH pulse were taken at-15, 0, 30, 60, 120, 150, 180 and 240 min. In group 1, the increase in luteinizing hormone (delta LH) in response to GnRH was significantly attenuated from 30 to 180 min, while the increase in follicle stimulating hormone (delta FSH) was attenuated only in response to the second GnRH pulse. No significant decrease in delta LH and delta FSH response to GnRH was seen during treatment with the 10 mg dose (group 2). In group 1, serum oestradiol and inhibin-A concentrations after day 8 were lower than in the control cycles and the LH peak was postponed by 7 days on average. Basal LH values increased significantly on day 8 in both groups, while FSH values did not change significantly compared with the control cycles. A significant increase in serum progesterone and cortisol values occurred during the treatment only in group 1. Mid-luteal values of inhibin-A were significantly lower in cycles treated with 100 mg mifepristone than in the control cycles. We conclude that the disruption of folliculogenesis by mifepristone cannot be explained by a decrease in basal FSH concentrations during the critical period of follicle recruitment and selection. It is possible that mifepristone exerts its effect at the level of the ovary. It is also suggested that progesterone during the follicular phase of the cycle may participate in the control of the self-priming action of GnRH on the pituitary.

Estradiol↗
PubMed1995

The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis.

Cytotoxic T lymphocytes (CTL) are thought to contribute to viral clearance and liver cell injury during hepatitis B virus (HBV) infection. Using a strategy involving the in vitro stimulation of peripheral blood mononuclear cells (PBMC) with HBV-derived synthetic peptides containing HLA-A2.1, -A31, and -Aw68 binding motifs, we have previously described CTL responses to several epitopes within the HBV nucleocapsid and envelope antigens in patients with acute hepatitis. In this study we define six HLA-A2-restricted CTL epitopes located in the highly conserved reverse transcriptase and RNase H domains of the viral polymerase protein, and we show that the CTL response to polymerase is polyclonal, multispecific, and mediated by CD8+ T cells in patients with acute viral hepatitis, but that it is not detectable in patients with chronic HBV infection or uninfected healthy blood donors. Importantly, the peptide-activated CTL recognize target cells that express endogenously synthesized polymerase protein, suggesting that these peptides represent naturally processed viral epitopes. DNA sequence analysis of the viruses in patients who did not respond to peptide stimulation indicated that CTL nonresponsiveness was not due to infection by viral variants that differed in sequences from the synthetic peptides. CTL specific for one of the epitopes were unable to recognize several naturally occurring viral variants, except at high peptide concentration, underlining the HBV subtype specificity of this response. Furthermore, CTL responses against polymerase, core, and envelope epitopes were detectable for more than a year after complete clinical recovery and seroconversion, reflecting either the persistence of trace amounts of virus or the presence of long lived memory CTL in the absence of viral antigen. Finally, we demonstrated that wild type viral DNA and RNA can persist indefinitely, in trace quantities, in the serum and PBMC after complete clinical and serological recovery, despite a concomitant, vigorous, and sustained polyclonal CTL response. Since viral persistence is not due to escape from CTL recognition under these conditions, the data suggest that HBV may retreat into immunologically privileged sites from which it can seed the circulation and reach CTL-inaccessible tissues, thereby maintaining the CTL response in apparently cured individuals and, perhaps, prolonging the liver disease in patients with chronic hepatitis.

Acute Disease↗
PubMed1995

Induction in vitro of a primary human antiviral cytotoxic T cell response.

We report herein the successful priming of human anti-viral cytotoxic T cells (CTL) in vitro using two induction strategies based on the stimulation of peripheral blood mononuclear cells isolated from uninfected donors with synthetic viral peptides. The peptides used contain HLA-A2 binding motifs and have been identified as HLA-A2-restricted CTL epitopes in patients infected by the hepatitis B and C viruses. One approach uses repetitive long-term stimulation and the other uses bulk cultures containing large numbers of naive peripheral blood mononuclear cells. Both approaches successfully induce HLA-A2-restricted CTL specific for several viral epitopes. Some CTL recognize endogenously synthesized antigen on target cells infected with recombinant vaccinia virus expressing the corresponding viral proteins. This simple technique permits easy analysis of the primary human CTL repertoire, and may be exploitable for production of specific CTL effector cells for adoptive immunotherapy and dissection of the cellular and molecular requirements for priming of naive human CTL.

Amino Acid Sequence↗