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Biomedical subjects

F Lynch

Publications and source records attributed to F Lynch.

At least 19 recordsLinked to original sources

Interleukin-1 beta rapidly inhibits aortic endothelium-dependent relaxation by a DNA transcription-dependent mechanism.

OBJECTIVES: This study examined the effects of interleukin-1 beta on isometric tension development and relaxation in isolated rat aortic rings in response to the alpha-1 adrenergic agonist phenylephrine, the endothelium-dependent vasodilator acetylcholine, and the endothelium-independent vasodilator sodium nitroprusside. DESIGN: Randomized, controlled, paired design. SETTING: Animal laboratory within a university department of physiology. SUBJECTS Paired aortic thoracic aortic rings from specific pathogen-free Sprague-Dawley rats. INTERVENTIONS: Series I examined the potential for interleukin-1 beta to cause early arterial endothelial dysfunction. Paired aortic rings were incubated for 2 hrs with interleukin-1 beta or vehicle. Series II examined the potential for inhibition of DNA transcription to attenuate interleukin-1 beta-mediated endothelial dysfunction. Paired rings received either dactinomycin or vehicle before interleukin-1 beta incubation. Series III quantified the degree to which inhibition of DNA transcription inhibited early interleukin-1 beta-mediated endothelial dysfunction. Paired rings received either dactinomycin pretreatment followed by interleukin-1 beta incubation, or pretreatment and incubation with inert vehicles. Series IV assessed the effects of interleukin-1 beta on responsiveness to an exogenous nitric oxide donor, sodium nitroprusside, in the presence of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester. MEASUREMENTS AND MAIN RESULTS: Incubation with interleukin-1 beta for 2 hrs had no effect on contractile response but attenuated endothelium-dependent relaxation significantly relative to control. Dactinomycin pretreatment inhibited early interleukin-1 beta-mediated endothelial dysfunction. The combination of interleukin-1 beta and dactinomycin produced effects on endothelium-dependent relaxation that were not different from that seen in rings not exposed to interleukin-1 beta. Interleukin-1 beta attenuated responsiveness to sodium nitroprusside relative to control. CONCLUSIONS: Interleukin-1 beta causes an early impairment of endothelium-dependent vasorelaxation with an onset that precedes its effects on systemic contractility. This impairment occurs via a mechanism that is wholly or predominantly dependent on DNA transcription. The altered vasorelaxation induced by interleukin-1 beta is at least partly mediated by a reduction in nitric oxide responsiveness.

Acetylcholine↗

A randomized trial of a group cognitive intervention for preventing depression in adolescent offspring of depressed parents.

BACKGROUND: Adolescent offspring of depressed parents are at high risk for development of depression. Cognitive restructuring therapy holds promise for preventing progression to depressive episodes. METHODS: A randomized, controlled trial was conducted to prevent depressive episodes in at-risk offspring (aged 13-18 years) of adults treated for depression in a health maintenance organization (HMO). Potential adult cases were found by reviewing the HMO pharmacy records for dispensation of antidepressant medication and the mental health appointment system. Medical charts were reviewed for a depression diagnosis. Recruitment letters signed by treating physicians were mailed to adults. Eligible offspring had subdiagnostic depressive symptoms insufficient to meet full DSM-III-R criteria for affective disorder and/or a past mood disorder. These youth were randomized to usual HMO care (n = 49) or usual care plus a 15-session group cognitive therapy prevention program (n = 45). RESULTS: We detected significant treatment-by-time (program) effects for the Center for Epidemiological Studies Depression Scale (P=.005) and the Global Assessment of Functioning scores (P =.04). Survival analysis of incident major depressive episodes during a median 15-month follow-up found a significant advantage (P =.003) for the experimental condition (9.3% cumulative major depression incidence) compared with the usual-care control condition (28.8%). CONCLUSION: A brief, group cognitive therapy prevention program can reduce the risk for depression in the adolescent offspring of parents with a history of depression.

Adolescent↗

Drinking patterns, health care utilization, and costs among HMO primary care patients.

A survey of 8,034 primary care patients in a health maintenance organization examined the relationship between alcohol consumption and health care costs and service use. Costs were estimated from service use data for 1 year before and 2 years after study enrollment. No strong, consistent relationships were identified between multiple indicators of drinking patterns and either health care costs or service use. Compared with total costs among very light drinkers, former drinkers were higher, lifetime abstainers were similar, and persons in the higher drinking levels tended to have lower but not significantly different costs. Drinking patterns did not appear to be an important predictor of short-term health care costs or service use in this setting. Further study of former drinkers is warranted to examine the role of alcohol-related illnesses in the decision to quit drinking.

Alcohol Drinking↗

Trends in the prescribing of psychotropic medications to preschoolers.

CONTEXT: Recent reports on the use of psychotropic medications for preschool-aged children with behavioral and emotional disorders warrant further examination of trends in the type and extent of drug therapy and sociodemographic correlates. OBJECTIVES: To determine the prevalence of psychotropic medication use in preschool-aged youths and to show utilization trends across a 5-year span. DESIGN: Ambulatory care prescription records from 2 state Medicaid programs and a salaried group-model health maintenance organization (HMO) were used to perform a population-based analysis of three 1-year cross-sectional data sets (for the years 1991, 1993, and 1995). SETTING AND PARTICIPANTS: From 1991 to 1995, the number of enrollees aged 2 through 4 years in a Midwestern state Medicaid (MWM) program ranged from 146,369 to 158,060; in a mid-Atlantic state Medicaid (MAM) program, from 34,842 to 54,237; and in an HMO setting in the Northwest, from 19,107 to 19,322. MAIN OUTCOME MEASURES: Total, age-specific, and gender-specific utilization prevalences per 1000 enrollees for 3 major psychotropic drug classes (stimulants, antidepressants, and neuroleptics) and 2 leading psychotherapeutic medications (methylphenidate and clonidine); rates of increased use of these drugs from 1991 to 1995, compared across the 3 sites. RESULTS: The 1995 rank order of total prevalence in preschoolers (per 1000) in the MWM program was: stimulants (12.3), 90% of which represents methylphenidate (11.1); antidepressants (3.2); clonidine (2.3); and neuroleptics (0.9). A similar rank order was observed for the MAM program, while the HMO had nearly 3 times more clonidine than antidepressant use (1.9 vs 0.7). Sizable increases in prevalence were noted between 1991 and 1995 across the 3 sites for clonidine, stimulants, and antidepressants, while neuroleptic use increased only slightly. Methylphenidate prevalence in 2- through 4-year-olds increased at each site: MWM, 3-fold; MAM, 1.7-fold; and HMO, 3.1-fold. Decreases occurred in the relative proportions of previously dominant psychotherapeutic agents in the stimulant and antidepressant classes, while increases occurred for newer, less established agents. CONCLUSIONS: In all 3 data sources, psychotropic medications prescribed for preschoolers increased dramatically between 1991 and 1995. The predominance of medications with off-label (unlabeled) indications calls for prospective community-based, multidimensional outcome studies.

Attention Deficit Disorder with Hyperactivity↗

Hypercapnia-induced contraction in isolated pulmonary arteries is endothelium-dependent.

It has been demonstrated previously that isohydric hypercapnia (IH) does not affect agonist-induced tension development in pulmonary arteries. The aim of the present study was to examine the effects of IH on depolarisation-induced, steady state tension in the isolated rat pulmonary artery. Rings were submaximally contracted with high KCl under control conditions (5% CO(2)-95% air). IH was achieved by switching to a modified PSS (isosmotic substitution of NaHCO(3) for NaCl), equilibrated with 10% CO(2) in air. On switching to IH, a significant increase in mean (+/-SEM) tension (25.3+/-6.3% Tmax) was observed in endothelium intact rings (n=6). Endothelial removal significantly reduced this response. Non-specific inhibition of nitric oxide synthase (NOS) isoenzymes (L-NAME, 10(-3) M) abolished the IH-induced increase in tension while inhibition of neuronal NOS (TRIM, 10(-5) M) was without effect. The relaxant response to the nitric oxide donor sodium nitroprusside was similar in IH and control conditions. These results suggest that IH caused an endothelium-dependent increase in depolarisation-induced tension by reducing NO production.

Acetylcholine↗

Laparoscopic appendectomy for simple and perforated appendicitis in children: the procedure of choice?

BACKGROUND/PURPOSE: Whether laparoscopic appendectomy (LA) is superior to open appendectomy (OA) for simple (SA) and perforated appendicitis (PA) in children is debatable. The operative experience of 4 senior pediatric surgeons at a single institution was studied over a 6-year period during a transition from OA in all cases to LA in all cases, to answer this question. METHODS: All appendectomies from December 1993 to December 1999 were reviewed for operative technique (OA, LA), presence of perforation (SA, PA), operating time (OT), length of stay (LOS), morbidity, and mortality. RESULTS: There were 1,128 appendectomies in children aged 14 months to 19 years, including 955 LA (653 in SA, 302 in PA) and 173 OA (86 in SA, 87 in PA). OT was equal for LA and OA in SA (52 minutes), but has dropped to less than 40 minutes for LA in the past year. OT in PA was slightly longer in LA versus OA (68 v. 58 minutes; P < .001) but recently has dropped in LA to less than 60 minutes. LOS in SA was 2 days for LA and 3 days for OA; in PA, LOS was 7 days in both LA and OA, but has dropped to 5 days for LA recently. Postoperative abscess rates and incidence of bowel obstruction did not differ between LA and OA in either group. There was no mortality. CONCLUSIONS: LA is at least as safe and effective as, if not superior to, OA for both simple and perforated appendicitis. Postoperative pain is less, and recovery is faster, thereby reducing LOS and overall cost. The growing demand for this procedure can be satisfied without increase in cost, morbidity, or mortality. Laparoscopic appendectomy is our procedure of choice in children.

Acute Disease↗

Management of pediatric liver injuries: a 13-year experience at a pediatric trauma center.

PURPOSE: This study of traumatic liver injuries (LI) in children reviews the authors' management and identifies the indications for surgical intervention. METHODS: A total of 11,761 admissions over 13 years to a regional pediatric trauma center were surveyed. RESULTS: LI were identified in 328 children. Mechanisms included 39% pedestrians struck by a vehicle, 34% motor vehicle occupants, 13% falls or discrete blows to the abdomen, 5% bicycle injuries, 5% child abuse, and 4% penetrating injuries. Eighty-seven of patients with LI were treated nonoperatively with a mortality rate of 17%. Six percent of deaths were attributed to the LI and massive hemorrhage, all of which presented with cardiopulmonary resuscitation (CPR) in progress, with the remainder of deaths attributed to massive head, neck, or chest injuries (HNCI, 90%) and sepsis (4%). Surgery was performed in 13% of all LI and included major hepatic vascular injury (MHVI) repairs (34%), hepatorrhaphies (34%), lobectomies (27%), and biliary repairs (4%). Excluding the nonoperative group deaths, the need for blood transfusion of more than 25 mL/kg in the first 2 hours as an indicator of surgical necessity or a MHVI had, respectively, a sensitivity of 34% and 67%, specificity of 98% and 97%, positive predictive value of 79% and 53%, negative predictive value of 89% and 98%, and prediction accuracy of 88% and 95%. In the surgical management group, the mortality rate was 23% with 40% of deaths attributed to MHVI, 30% a combination of MHVI and HNCI, 20% massive HNCI, and 10% sepsis. CONCLUSIONS: The majority of pediatric LI are not associated with hemodynamic instability and can be successfully managed nonoperatively (72%). Hemodynamic instability, as defined by the need for blood transfusion in excess of 25 mL/kg within the first 2 hours, was a strong indicator of a MHVI, which was often a lethal injury (70%).

Adolescent↗

Developing a culture of lifelong learning in a library environment.

Between 1995 and 1996, the Annette and Irwin Eskind Biomedical Library (EBL) at Vanderbilt University Medical Center (VUMC) radically revised the model of service it provides to the VUMC community. An in-depth training program was developed for librarians, who began to migrate to clinical settings and establish clinical librarianship and information brokerage services beyond the library's walls. To ensure that excellent service would continue within the library, EBL's training program was adapted for library assistants, providing them with access to information about a wide variety of work roles and processes over a four to eight-month training period. Concurrently, customer service areas were reorganized so that any question--whether reference or circulation--could be answered at any of four service points, eliminating the practice of passing customers from person to person between the reference and circulation desks. To provide an incentive for highly trained library assistants to remain at EBL, management and library assistants worked together to redesign the career pathway based on defined stages of achievement, self-directed participation in library-wide projects, and demonstrated commitment to lifelong learning. Education and training were the fundamental principles at the center of all this activity.

Career Mobility↗

Separation of omphalopagus twins: unique reconstruction using syngeneic cryopreserved tissue.

Omphalopagus twin girls were admitted for evaluation of possible separation and repair at age 7 days. Prenatal sonographic diagnosis occurred late in the third trimester and was followed by cesarean section delivery shortly thereafter. Results of extensive evaluation over the next 7 days including x-rays, computed tomography and ultrasound scan of the head and torso, and cardiac catheterization showed: the gastrointestinal tracts were separate and normal, the livers were joined but had separate biliary and vascular systems, and the hearts were separate with vastly different anatomy and function. One twin (twin A) had a normal heart with a small insignificant VSD. Twin B had a single ventricle, an incompetent A-V valve, stenotic pulmonic valve, ASD, PDA, and congenital heart block. Hemodynamic support of twin B was almost entirely from twin A. The vascular communications between the two consisted of a major connection between the internal mammary arteries and large arterial and venous connections traversing the joined livers. Because of continued deterioration of twin B, separation was undertaken at age 15 days. The separation included dividing the liver and the multiple large vascular connections. Two teams then reconstructed each twin separately. Twin B began showing signs of cardiac decompensation shortly after separation in spite of placement of a pacemaker, pulmonary artery banding, and ligation of the PDA. Cardiac function rapidly deteriorated and she died. Tissue from her chest wall was cryopreserved and placed in the tissue bank. Twin A underwent closure of her abdomen, and received a temporary bovine pericardial patch over the chest defect. She subsequently underwent placement of a graft of twin B's rib cage to bridge the bony chest defect and skin flap closure. She is presently taking a normal diet and thriving at home at age 18 months. The use of cryopreserved tissue from a syngeneic source provides a unique method of reconstruction in this situation.

Abdomen↗

Intramedullary pressure and pulmonary function during total knee arthroplasty.

Twenty-eight patients who underwent unilateral total knee arthroplasty and 20 patients who underwent simultaneous bilateral total knee arthroplasties participated in this study and were randomized to have either a fluted or round 10-mm diameter femoral intramedullary alignment rod used during surgery. The intramedullary rods were cannulated and connected with pressure tubing to a monitor which provided measurements of pressure at the tip of each rod. Arterial blood gas measurements on room air were obtained before and on the morning after surgery. An arterial line was placed and an arterial blood gas measurement was obtained at the time of skin incision and again after tourniquet release. Pulmonary shunt was calculated from the arterial blood gas measurements. Intramedullary pressure during rod insertion was significantly higher for the groups of patients having the round compared with the fluted rod. The change in pulmonary shunt during surgery was lowest for the patients in the unilateral group having the fluted rod and highest for the patients in the bilateral group having the round rod. A fluted rather than a round intramedullary alignment rod should be used to minimize intramedullary pressure and pulmonary shunting during unilateral and bilateral total knee arthroplasties.

Analysis of Variance↗

Split tolerance to the MHC class I molecule H-2Dd in animals transgenic for its soluble analog.

To determine whether the function of MHC molecules in tolerance and education is related to cell surface expression, we have produced two strains of transgenic mice in the C57Bl/6 background that express soluble analogs of the H-2D(d) class I protein. The transgenes were stably integrated and genetically transmitted in a Mendelian fashion. Messenger RNA for the hybrid genes was detected in all tissues analyzed in a class I-like pattern of expression, with the highest levels in lymphoid tissues. All mice bearing the transgenes expressed relatively high levels (0.1 mg/ml) of the encoded protein in their serum as assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Gel filtration chromatography showed that the soluble H-2D(d) protein exists as a heterodimer with beta2-microglobulin and as higher order multimers in serum. Lymphoid cells from the transgenic mice showed no cell surface expression of the soluble class I protein in indirect immunofluorescence assays. Splenocytes from two independently derived transgenic lines generated primary cytotoxic and proliferative responses directed against membrane H-2D(d) antigens. Mice of both strains rejected tail skin from donors that differed from the B6 background at the H-2D(d) locus only, but with delayed kinetics compared to nontransgenic littermate controls. Mice expressing the transgenic protein on immunization did not produce antibodies that recognized soluble H-2D(d) in ELISA, whereas B6 mice generated strong antibody responses to challenge with splenocytes bearing cell surface H-2D(d). Thus, transgenic mice expressing soluble H-2D(d) were partially tolerant to stimulation by membrane-bound H-2D(d). As with the activation of T-cells, the induction and maintenance of immunologic tolerance apparently displayed different requirements depending upon the T-cell subpopulation involved.

Animals↗

Effect of total hip arthroplasty on cardiovascular fitness.

Thirty patients who underwent total hip arthroplasty and 18 patients with medically treated arthritis participated in this study. Both groups of patients underwent a cardiovascular fitness exercise test on entering the study and 6 months, 1 year, and 2 years later. Fitness was assessed by patient performance on a graded maximal exercise test using a bicycle ergometer and metabolic cart. In the group of total hip arthroplasty patients, significant improvements in exercise duration (P = .011), maximum workload (P = .0013), peak oxygen consumption (P = .0036), and percentage of predicted maximum oxygen uptake achieved (P = .0002) were observed during the follow-up evaluation. In the group of control patients, decreases in exercise duration (P = .0001), maximum workload (P = .0001), and workload at anaerobic threshold (P = .0108) occurred without a significant change in the other measures of cardiovascular fitness. The results indicate that resumption of routine physical activities after total hip arthroplasty is associated with a corresponding improvement in cardiovascular fitness.

Activities of Daily Living↗

Affinity purification and comparative analysis of two distinct human uracil-DNA glycosylases.

Evidence is presented on two forms of uracil-DNA glycosylase (UDG1 and UDG2) that exist in human cells. We have developed an affinity technique to isolate uracil-DNA glycosylases from HeLa cells. This technique relies on the use of a uracil-DNA glycosylase inhibitor (Ugi) produced by the Bacillus subtilis bacteriophage, PBS2. Affinity-purified preparations of uracil-DNA glycosylase, derived from total HeLa cell extracts, reveal a group of bands in the 36,000 molecular weight range and a single 30,000 molecular weight band when analyzed by SDS-PAGE and silver staining. In contrast, only the 30,000 molecular weight band is seen in HeLa mitochondrial preparations. Separation of HeLa cell nuclei from the postnuclear supernatant reveals that uracil-DNA glycosylase activity is evenly distributed between the nuclear compartment and the postnuclear components of the cell. Immunostaining of a nuclear extract with antisera to UDG1 indicates that the nuclear associated uracil-DNA glycosylase activity is not associated with the highly conserved uracil-DNA glycosylase, UDG1. With the use of Ugi-Sepharose affinity chromatography, we show that a second and distinct uracil-DNA glycosylase is associated with the nuclear compartment. Immunoblot analysis, utilizing antisera generated against UDG1, reveals that the 30,000 molecular weight protein and a protein in the 36,000 range share common epitopes. Cycloheximide treatment of HeLa cells indicates that upon inhibition of protein synthesis, the higher molecular weight species disappears and is apparently post-translationally processed into a lower molecular weight form. This is substantiated by mitochondrial import studies which reveal that in vitro expressed UDG1 becomes resistant to trypsin treatment within 15 min of incubation with mitochondria. Within this time frame, a lower molecular weight form of uracil-DNA glycosylase appears and is associated with the mitochondria. Antibodies generated against peptides from specific regions of the cyclin-like uracil-DNA glycosylase (UDG2), demonstrate that this nuclear glycosylase is a phosphoprotein with a molecular weight in the range of 36,000. SDS-PAGE analysis of Ugi affinity-purified and immunoprecipitated UDG2 reveals two closely migrating phosphate-containing species, indicating that UDG2 either contains multiple phosphorylation sites (resulting in heterogeneous migration) or that two distinct forms of UDG2 exist in the cell. Cell staining of various cultured human cell lines corroborates the finding that UDG1 is largely excluded from the nucleus and that UDG2 resides mainly in the nucleus. Our results indicate that UDG1 is targeted to the mitochondria and undergoes proteolytic processing typical of resident mitochondrial proteins that are encoded by nuclear DNA. These results also indicate that the cyclin-like uracil-DNA glycosylase (UDG2) may be a likely candidate for the nuclear located base-excision repair enzyme.

Affinity Labels↗

Improvement in cardiovascular fitness after total knee arthroplasty.

Patients who have osteoarthrosis involving weight-bearing joints typically have a gradual decline in physical activity, which is often associated with cardiovascular deconditioning. After joint replacement, many patients resume routine walking and recreational activities, which may improve aerobic capacity. The purpose of the present study was to determine the effect of total knee arthroplasty on cardiovascular fitness. Nineteen patients who had had total knee arthroplasty (the arthroplasty group) performed an exercise test for cardiovascular fitness preoperatively. Sixteen of these patients were tested again at one year postoperatively and thirteen, at two years postoperatively. Sixteen patients in whom osteoarthrosis of the knee was being treated medically (the control group) were tested at the time of enrollment in the study and one year later. Nine of these patients also were tested two years after enrollment. All of the patients completed the Arthritis Impact-Measurement Scales (AIMS) at each examination. Fitness was assessed by the performance of a progressive maximum exercise test with use of a bicycle ergometer and a metabolic cart. All patients achieved the anaerobic threshold. One year postoperatively, the patients in the arthroplasty group demonstrated an increase, which approached significance, in maximum oxygen consumption (measured in milliliters of oxygen per minute) (p = 0.07), maximum oxygen consumption corrected for body weight (p = 0.08), and percentage of predicted maximum uptake of oxygen (p = 0.06). Two years after the total knee arthroplasty, the patients had a significant improvement with regard to all three parameters (p = 0.008, 0.005, and 0.005, respectively). The patients in the control group demonstrated a significant decrease in duration of exercise and in maximum workload at one year (p = 0.003 and 0.005, respectively) and at two years (p = 0.008 for both parameters). Physical activity had increased in the arthroplasty group but not in the control group, as demonstrated by the results of the Arthritis Impact-Measurement Scales. These findings demonstrate a trend toward improvement in cardiovascular fitness one year after total knee arthroplasty and a significant improvement two years postoperatively for patients who had been able to resume routine functional activities because of the arthroplasty. These improvements compared favorably with the static pattern or the decline in the measures of fitness that were observed in the control group. Our results should be considered preliminary because of the relatively small number of patients who were studied.

Aged↗

Varus migration of PCA stems.

Forty-seven patients with cementless, porous-coated anatomic hip replacements were evaluated after a minimum 2-year follow up with specific attention to varus migration of the stem. A cadaver study was done to define a relationship between projected size of the lesser trochanter seen radiographically, rotation of the femur, and stem position. Seven (15%) of the stems migrated into varus with the distal tip moving laterally. Thigh pain occurred in patients with varus migration and those with no change in stem position. A lower percent canal fill was seen on the lateral radiograph (P < .001) and larger average width of radiodense lines in zone 1 superolateral, and zone 6, midstem medial (P < .005) in the patients with varus migration. Poor distal stability associated with a lower percent canal fill at the stem tip seen on the lateral radiograph may result in varus migration.

Biomechanical Phenomena↗

Osteolysis associated with cemented total knee arthroplasty. A case report.

Osteolysis induced by particulate debris occurs within 5 years after cementless total knee arthroplasty, but has not been reported to be a problem after cemented total knee arthroplasty. It has been suggested that the bone-cement interface may form a barrier to polyethylene-debris migration, thereby limiting bone loss. The authors have observed osteolysis in a 75-year-old woman 9 years after cemented total knee arthroplasty. An osteolytic area appeared to return to an area of normal bone architecture 3 years after the removal of synovium and particulate debris without implant revision.

Aged↗

Fatal massive adrenal hemorrhage after bilateral total knee arthroplasty.

Adrenal hemorrhage can occur in association with postoperative stress, trauma, myocardial infarction, infection, and chronic medical illness. Other risk factors for the development of spontaneous adrenal hemorrhage include a thromboembolic state and anticoagulation therapy, although it has rarely been observed following orthopedic surgery. The authors report the case of an otherwise healthy 61-year-old woman who died suddenly 9 days after bilateral total knee arthroplasty. The only abnormality found on postmortem examination was massive bilateral adrenal hemorrhage with destruction of nearly all adrenal tissue. Surgeons should be aware of this complication that, if recognized early, can be treated with steroid replacement.

Adrenal Gland Diseases↗

Gamma delta T cells promote CD4 and CD8 expression by SCID thymocytes.

Molecular studies of the gamma delta TCR, which is expressed by a minor subpopulation of T lymphocytes in all vertebrate species, have defined a subset which expresses a receptor with extreme junctional diversity and a second subset, most commonly found in epithelia, which expresses a receptor of very limited diversity. In the developing murine thymus, gamma delta T cells appear in an ordered sequence of specific V rearrangements, V gamma 3V delta 1 on day 14, V gamma 2V delta 1 on day 17, and subsequently V gamma 4V delta 5, V delta 6, or V delta 7. We demonstrate that the transfer of expanded populations of gamma delta cells from newborn thymus and cell lines expressing the invariant V gamma 3V delta 1 receptor into SCID mice, which lack T and B cells, results in the appearance of CD3-CD4+CD8+ thymocytes. Thus, one role of the early appearing V gamma 3V delta 1 T cells in thymic development in vivo is to promote CD4 and CD8 surface expression on precursor cells.

Animals↗