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Biomedical subjects

P Gregory

Publications and source records attributed to P Gregory.

At least 37 records · Page 2Linked to original sources
PubMed1996

Immunization with soluble BDC 2.5 T cell receptor-immunoglobulin chimeric protein:antibody specificity and protection of nonobese diabetic mice against adoptive transfer of diabetes by maternal immunization.

The BDC 2.5 T cell clone is specific for pancreatic beta-cell antigen presented by I-Ag7, and greatly accelerates diabetes when injected into 10-21-d-old nonobese diabetic (NOD) mice. The BDC 2.5 T cell receptor (TCR) has been solubilized as a TCR-IgG1 chimeric protein. All NOD mice immunized against BDC 2.5 TCR-IgG1 produced antibodies recognizing TCR C alpha/C beta epitopes that were inaccessible on the T cell surface. 56% of the mice produced antibodies against the BDC 2.5 clonotype that specifically blocked antigen activation of BDC 2.5 cells. We have used the adoptive transfer model of diabetes to demonstrate that maternal immunization with soluble TCR protects young mice from diabetes induced by the BDC 2.5 T cell clone.

Adoptive Transfer↗
PubMed1996

Early complications with external fixation of pediatric femoral shaft fractures.

A retrospective study of 27 pediatric patients with femoral shaft fractures treated by external fixation was made to identify complications and evaluate outcomes. The average age at the time of injury was 8 years, 9 months (range 5 years, 6 months to 13 years, 2 months). Sixteen fractures were isolated, and nine were associated with polytrauma. There was only one open fracture. Data obtained from chart review (n = 27), radiographs (n = 27), physical exam (n = 16), and questionnaire (n = 21) identified eight major complications (30%) in six patients and 29 minor complications (107%) in 20 patients. The major complications included two refractures, two fractures through pin sites, one postimmobilization supracondylar femoral fracture, one persistent pin-tract infection requiring early fixator removal, one malreduction, and one loss of reduction. Both the patient with malreduction and the one who lost reduction had > 10 degrees of varus deformity before adjustment of their frames. Five of the eight major complications (64%) were secondary to errors in operative technique or postoperative treatment. Only one major complication was noted among the 16 patients with isolated injuries. Of the patients with minor complications, 14 had pin-tract infections requiring oral antibiotics, five refused to go to school with the fixator in place, five were dissatisfied with scar appearance, and five had clinically insignificant malunions. A clinically insignificant malunion was considered to be angulation > or = 5 degrees varus or valgus or > or = 10 degrees procurvatum or recurvatum deformity that did not affect the patient's function. The minor complications were considered intrinsic to the procedure and difficult to avoid. Despite these problems, all patients with isolated injuries, except one with a slipped capital femoral epiphysis, had excellent function at the time of final review. If external fixation is chosen as the method of treatment for a pediatric femur fracture, careful attention must be paid to operative technique and postoperative treatment in order to minimize complications.

Adolescent↗
PubMed1996

Ipsilateral fractures of the femur and tibia: treatment with retrograde femoral nailing and unreamed tibial nailing.

Between 1989 and 1995 a total of 47 patients with 50 fractures of the ipsilateral femoral and tibial shafts without significant articular involvement were treated at Tampa General Hospital. Within this group were 24 patients with 26 fractures who were treated with intramedullary fixation of both bones using a technique of retrograde insertion of a femoral nail and unreamed insertion of an interlocking tibial nail. Information concerning the injuries, treatments, and much of the follow-up was gleaned from a trauma registry. Five of the femoral fractures (19%) and 14 of the tibial fractures (54%) were open. Associated injuries were present in 18 of the 24 patients (75%) with injuries of the pelvis, other extremities, and head being most prevalent. The average Injury Severity Score was 14 (range 9-32). The femoral nails were placed either through the medial femoral condyle (n = 14) or the intercondylar notch of the distal femur (n = 12). Twenty patients with 22 extremities had sufficient follow-up at an average of 20 months (range 4-60) postinjury to be included in the review. One patient had died, and three were completely lost to follow-up. Both fractures in 14 extremities had healed or were healing uneventfully at final review. Seven of the tibiae and three of the femora had complications after initial hospitalization. Two patients developed problems in both bones. Three patients had electrical stimulation of a tibia fracture, one of which underwent simultaneous nail dynamization. A total of 18 additional operative procedures were necessary after the primary treatment in six problematic extremities. Thirteen additional operative procedures were required in five complicated tibiae (one nail dynamization, six debridement procedures, five bone grafts, and one muscle flap) after the initial hospitalization. Five additional operative procedures were required in the three complicated femora (two nail dynamizations, one bone graft, and two exchange nailing procedures). Functional results were good or excellent in 13 of the 20 patients (65%) and 15 of the 22 extremities (68%) available at final review. No significant knee problem related to the femoral nailing technique was identified. This method of treatment can be performed using a standard radiolucent table and a single medial parapatellar incision. It is expedient and allows other procedures to be performed simultaneously in this group of severely injured patients.

Adolescent↗
PubMed1996

Cholecystokinin-8 and vasoactive intestinal polypeptide stimulate exocrine pancreatic secretion via duodenally mediated mechanisms in the conscious pig.

The effects of local and peripheral administration of cholecystokinin-8 (CCK-8) and vasoactive intestinal polypeptide (VIP) on basal pancreatic secretion were investigated in conscious pigs. Five pigs (20 +/- 2 kg, mean +/- S.E.M.) were chronically fitted with a T-shaped cannula in the duodenum, and catheters in the pancreatic duct, jugular vein, and right gastroepiploic artery. The arterial catheter was inserted against the bloodstream with its tip opposite the duodenal branch(es) of the right gastroepiploic artery, so that all injected peptides would reach the duodenal arterial circulation excluding the pancreas. Pancreatic secretion during basal conditions (i.e. after an overnight fast) exhibited a characteristic cyclic pattern (cycle duration, 70 +/- 4.2 min). Secretion volume oscillated between 0.2 +/- 0.04 and 4.0 +/- 0.9 ml kg-1 h-1 (P < 0.001), trypsin output between 9.6 +/- 1.9 and 29.1 +/- 4.1 U kg-1 h-1 (P < 0.001) and protein output between 0.36 +/- 0.08 and 9.2 +/- 1.7 mg kg-1 h-1 (P < 0.001). Infusion into the jugular vein for 1 min, during the trough of pancreatic secretion, of either CCK-8 (15 pmol kg-1 min-1) or VIP (7 pmol kg-1 min-1) did not stimulate pancreatic secretion. However, local infusion of an identical dose of CCK-8 or VIP into the duodenal arterial circulation increased the volume, protein output and trypsin output of the pancreatic juice (P < 0.05 to < 0.001). These results indicate that CCK-8 and VIP can stimulate the exocrine pancreas by a duodenally mediated mechanism.

Animals↗
PubMed1996

Tandem duplication in ermC translational attenuator of the macrolide-lincosamide-streptogramin B resistance plasmid pSES6 from Staphylococcus equorum.

A tandem duplication of 23 bp in the ermC gene translational attenuator of plasmid pSES6 from Staphylococcus equorum which mediated constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics was identified. This duplication included the ribosome binding site for the ermC gene as well as the first 5 bp of the ermC coding sequence. It was postulated that this sequence duplication affects the possible RNA conformations so that the ribosome binding site for ErmC synthesis is readily accessible to the ribosomes and thus constitutive expression of the ermC gene occurs.

Amino Acid Sequence↗
PubMed1996

Ipsilateral fractures of the talus and calcaneus.

Nine ipsilateral fractures of the talus and calcaneus were treated at Tampa General Hospital between 1991 and 1994 and entered into the trauma registry of this level 1 trauma center. During this same period, a total of 78 talar fractures and 334 calcaneal fractures were entered into the registry. The patients who sustained this rare combined injury were studied retrospectively to characterize the fractures that occurred, examine the treatments instituted, and determine outcomes. Four patients had severe intra-articular damage of the subtalar joint surfaces and underwent either primary or delayed arthrodesis. This subgroup of patients was followed for an average of 39 months (range, 25-45 months), and all had excellent or good outcome as assessed by the Maryland Foot Score. Three patients had nondisplaced or avulsion-type fractures of both bones, which were treated with immobilization. These all healed well. One patient had a Hawkins type 2 talus fracture with an extra-articular avulsion fracture of the Achilles tendon. This patient did well with open reduction and internal fixation of both fractures. The final patient had a crushed lower extremity in association with her hindfoot injury, which resulted in primary below-knee amputation. In general, we believe each individual fracture in this combined injury can be addressed with standard treatment regimens.

Adult↗
PubMed1995

Dietary satisfaction correlated with adherence in the Modification of Diet in Renal Disease Study.

OBJECTIVE: To measure satisfaction with modified protein eating patterns and the relationship of satisfaction to adherence and sociodemographic factors in a clinical trial. DESIGN: Participants completed the Dietary Satisfaction Questionnaire at baseline, at 6-month follow-up visits, at annual visits, and at the final visit. Satisfaction with diet was rated on a visual analog scale from 1 (dislike extremely) to 5 (like very much). Adherence to protein goals was assessed using urine urea nitrogen excretion from monthly 24-hour urine samples. SUBJECTS: 840 adults with chronic renal disease. INTERVENTION: Individual participants, randomly assigned to a usual-protein, low-protein, or very-low-protein group, received monthly counseling from a dietitian for an average of 26 months. STATISTICS: Analyses of variance and two-sample t tests compared, among study/diet groups, satisfaction with diet, its relationship to adherence and sociodemographic characteristics, and changes in satisfaction over time. Paired t tests compared changes within diet groups from baseline to final visit. RESULTS: From the baseline visit to the final visit, satisfaction with the prescribed eating pattern increased slightly in the usual-protein group, declined slightly in the low-protein group, and declined significantly in the very-low-protein group. Participants in all of the eating pattern groups who were more satisfied at the final visit had mean protein intakes closer to their assigned protein goals. This relationship was significant in the low-protein group (P < .05). In men, satisfaction with diet declined significantly from baseline to the final follow-up visit in the very-low-protein group. APPLICATIONS: The Modification of Diet in Renal Disease Study Dietary Satisfaction Questionnaire may be useful in other research and clinical settings to assess and enhance dietary adherence.

Adult↗
PubMed1995

Adolescent femoral shaft fractures: rigid versus flexible nails.

Twenty-one skeletally immature patients between 11 and 16 years of age were treated operatively for a unilateral femoral shaft fracture. Eleven patients underwent fixation with flexible nails and 10 with rigid nails. The patients were studied retrospectively to determine the similarity of the groups. Each method of fixation was then compared to determine the technical ease and final outcome. Both methods gave excellent final radiographic alignment with minimal complications. Flexible nailing required much less operative time and less fluoroscopy time. Estimated cost of using Ender nails is much less than using Russell-Taylor interlocking nails.

Adolescent↗
PubMed1995

The treatment of closed, unstable tibial shaft fractures with unreamed interlocking nails.

Forty-seven closed, unstable tibial shaft fractures were treated with locked intramedullary nailing without reaming at the authors' institution. Fifty-three percent of the fractures were in polytraumatized patients. Followup was possible for 38 (81%) fractures. Thirty-three fractures healed within 6 months (87%). All patients had unlimited ambulation without assistive devices, and the ability to climb stairs in a normal fashion. Range of motion of the knee, ankle, and subtalar joints at final followup was normal, except in those patients who had concomitant joint injuries. There were 2 delayed unions (5%) and 3 nonunions (8%). Three patients had angular deformities. There were no broken nails in this series (0%), but 12 of 80 screws were bent or broken. There was 1 (2.6%) superficial infection, and 1 (2.6%) case of osteomyelitis. Interlocked, intramedullary nailing inserted in an unreamed manner has become the treatment of choice for the closed, unstable tibial shaft fracture in the polytraumatized patient in the authors' institution. A high union rate, coupled with a lack of compartment syndromes or peroneal palsy, makes this procedure an attractive alternative to reamed nailing. This study was not able to prove any superiority over reamed nail insertion in closed, isolated, unstable tibial shaft fractures.

Adolescent↗
PubMed1995

Injuries of the shoulder girdle.

Shoulder girdle injuries occur infrequently, but can lead to high rates of morbidity and mortality if these high energy injuries are underdiagnosed or mistreated. Most injuries can be treated conservatively, but a high index of suspicion and aggressive physical and radiographic evaluations should be used to evaluate patients with polytrauma. This article discusses these injuries, their associated pathoanatomy, and current management.

Acromioclavicular Joint↗
PubMed1995

The management of severe fractures of the lower extremities.

This review is designed to address the problem of severe fractures of the lower extremities that often accompany the patient who is polytraumatized. Although open fractures occupy a predominant place in the subsequent discussion, closed fractures also may be associated with a significant crush component, a vascular lesion, a degloving injury, or a compartment syndrome. It is of paramount importance that the treating physician understand the implications of the potential or actual soft tissue damage to maximize the outcome after these devastating injuries.

Ankle Injuries↗
PubMed1995

Operative treatment of intra-articular fractures of the calcaneus.

Displaced intra-articular fractures of the calcaneus remain a diagnostic and therapeutic dilemma. The classification of these fractures has been frustrated in the past by limitations of radiographic technique. Because of our need to consistently analyze our results, a CT scan classification was developed, based on the number and location of articular fracture fragments. The authors have treated displaced intra-articular calcaneal fractures according to an operative protocol using a modified lateral approach, a new plate and lag screws, all without the use of bone graft. This article will discuss in depth the treatment options available as well as the controversies that surround them.

Arthritis↗
PubMed1994

Insulin activates a novel adipocyte mitogen-activated protein kinase kinase kinase that shows rapid phasic kinetics and is distinct from c-Raf.

Treatment of adipocytes with insulin or phorbol 12-myristate 13-acetate (PMA) results in transient activation of mitogen-activated protein kinase kinase (MEK) (Tmax = 90 s) and mitogen-activated protein kinase (MAPK) (Tmax = 300 s). We have identified a novel insulin-stimulated MEK kinase (I-MEKK) in the 100,000 x g infranatant that shows rapid phasic kinetics that temporally precede that of MEK. Maximal activation of I-MEKK occurs within 20 +/- 5 s (S.D., n = 3) followed by complete inactivation by 30 +/- 10 s (S.D., n = 3). I-MEKK was characterized by anion-exchange and gel filtration chromatography and separated into two distinct activities of approximately 56 kDa that phosphorylated and activated MEK. I-MEKKs did not co-elute on anion exchange with c-Raf or 73-kDa MEK kinase (MEKK), suggesting they are distinct enzymes. Protein phosphatase 2A inactivated both I-MEKKs in vitro and in the intact cell okadaic acid blocked inactivation in the presence of insulin. These results suggest activation of I-MEKK involves phosphorylation on serine or threonine residues. I-MEKK was not activated by PMA, suggesting that in adipocytes the enzyme represents a divergence point between signal transduction pathways mediated by insulin and those activating protein kinase C.

Adipocytes↗
PubMed1994

Breast capsule contracture: is fibroblast activity associated with severity?

Factors responsible for breast capsule contracture remain elusive. Using an in vitro model of wound contraction, the fibroblast-populated collagen lattice (FPCL), breast capsule fibroblasts and control dermal fibroblasts from ten patients were analyzed. Comparison was made to determine (1) if the activity of dermal fibroblasts on a collagen lattice correlated with the activity of breast capsule fibroblasts or if capsular fibroblasts are unique, and (2) if the degree of fibroblast-driven collagen contraction correlated with clinical severity of breast capsule contracture. If so, a preoperative predictor of breast capsule contracture would be available. Dermal fibroblasts and breast capsule fibroblasts were cultured and mixed with media and collagen to form a matrix, and then the degree of lattice contraction was measured. A correlation between breast capsule fibroblasts and control dermal fibroblasts with respect to collagen matrix contraction was confirmed. Collagen lattice contraction coordinated by fibroblasts derived from breast capsules did not correlate with clinical severity of capsular contracture. These results indicate that the degree of breast capsule contracture can not be predicted by fibroblast activity alone. An interaction between inflammatory cells, extracellular matrix, and fibroblasts is hypothesized. Further work is needed to delineate the mechanisms responsible for breast capsule contracture.

Breast↗
PubMed1994

Fetal fibroblast contraction of collagen matrices in vitro: the effects of epidermal growth factor and transforming growth factor-beta.

Wound contraction is an important component of healing but, in the extreme, may lead to excessive scar formation and pathological wound contracture. Fetal rabbit wounds heal without contraction or scarring, whereas excisional fetal sheep wounds have been shown to contract, but no scarring or pathological wound contracture is noted. We used an in vitro model, the fibroblast-populated collagen lattice, to study the ability of fetal fibroblasts to coordinate contraction of a collagen matrix and the modulating effects of epidermal growth factor and transforming growth factor-beta 1 on this contraction. With increasing gestational age, fibroblasts increased the degree of collagen lattice contraction. Epidermal growth factor inhibited contraction by fetal fibroblasts, whereas transforming growth factor-beta 1 stimulated it. These findings suggest that while intrinsic differences between fetal and adult fibroblasts exist, polypeptide growth factors may operate at the site of tissue repair to alter cell phenotype. Further work is underway to delineate the role of soluble protein factors responsible for the absence of scarring and contracture seen in the fetal wound.

Animals↗
PubMed1994

Sex differences in the management and long-term outcome of acute myocardial infarction. A statewide study. MIDAS Study Group. Myocardial Infarction Data Acquisition System.

BACKGROUND: We wished to evaluate whether differences in the rate of invasive cardiac procedures between men and women with acute myocardial infarction are associated with different short- and long-term mortality. METHODS AND RESULTS: The database (Myocardial Infarction Data Acquisition System, MIDAS) included all discharges for the years 1986 and 1987 with the diagnosis of acute myocardial infarction in New Jersey, based on the New Jersey hospital discharge data system (MIDS/UB-82). Accuracy of the data was evaluated by auditing 726 randomly selected charts. The variables examined included age, sex, race, comorbidity (anemia, chronic liver disease, cancer, chronic obstructive pulmonary disease, diabetes, hypertension, prior myocardial infarction), complications (left ventricular dysfunction, arrhythmias, conduction defects), insurance status, performance of cardiac catheterization, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery, and survival up to 3 years. Women were older, had longer hospital stay, and were more likely than men to have anemia, diabetes, hypertension, left ventricular dysfunction, and Medicare or Medicaid insurance coverage. They were less likely than men to be admitted to a hospital equipped to perform invasive procedures or to have chronic obstructive pulmonary disease, chronic liver disease, prior myocardial infarction, or arrhythmias. After adjustment for these differences, women were less likely than men to have cardiac catheterization. Cardiac catheterization was associated with lower mortality. Women up to age 70 had higher 3-year death rates than men after adjustment for age, race, comorbidity, complications, and insurance type. This difference between men and women was somewhat diminished after the performance of cardiac catheterization and revascularization was taken into account. Unadjusted mortality was high in this study group. CONCLUSIONS: Women with acute myocardial infarction are less likely to have invasive cardiac procedures and have higher 3-year adjusted death rate up to age 70 than men.

Aged↗
PubMed1993

Gamma-phosphate-linked ATP-sepharose for the affinity purification of protein kinases. Rapid purification to homogeneity of skeletal muscle mitogen-activated protein kinase kinase.

Recently, Sowadski and colleagues [Knighton, D.R., Zheng, J., Eyck, L.F.T., Ashford, V.A., Xuong, N., Taylor, S.S. & Sowadski, J.M. (1991) Science 407, 407-420] reported the structure of a ternary complex of the catalytic subunit of cAMP-dependent protein kinase (cyclic A kinase), MgATP and a 20-residue inhibitor peptide, at a resolution of 0.27 nm. This structure has since been refined to 0.2-nm resolution and the orientation of the nucleotide and interactions of MgATP with numerous conserved residues at the active site defined [Zheng, J., Knighton, D.R., Eyck, L.F.T., Karlsson, R., Xuong, N., Taylor, S.S. & Sowadski, J.M. (1993) Biochemistry, in the press]. These studies revealed that the adenosine portion of ATP is buried deep within the catalytic cleft, with the alpha, beta and gamma phosphates protruding towards the opening of the cleft. The unique spatial positioning of MgATP within the catalytic cleft of cyclic A kinase and its interactions with conserved amino acids found in all protein kinases, led us to reconsider the use of ATP as an affinity ligand for the purification of these enzymes. In this paper, we describe a straightforward method for the synthesis of [gamma-32P]adenosine-5'-(gamma-4-aminophenyl)triphosphate for the covalent linkage of ATP to Sepharose through its gamma phosphate. In the presence of 20 microM ATP, adenosine-5'-(gamma-4-aminophenyl)triphosphate exhibited apparent Ki values of 103.6, 75.18, 176.28 and 120.00 microM against cyclic A kinase, mitogen-activated protein kinase (p42mapk), mitogen-activated protein kinase kinase and p60c-src, respectively. To illustrate the effectiveness of adenosine-5'-(gamma-4-aminophenyl)triphosphate-Sepharose as an affinity column for protein kinases, we have used the resin to purify rabbit skeletal muscle mitogen-activated protein kinase kinase over 19000-fold to homogeneity.

Amino Acid Sequence↗