Biomedical subjects

S E Ross

Publications and source records attributed to S E Ross.

At least 37 records · Page 2Linked to original sources

PubMed1998

Rapid sequence induction for intubation by an aeromedical transport team: a critical analysis.

Airway control is the initial priority in the management of the injured patient. The purpose of this investigation was to evaluate the experience of an aeromedical transport team in the utilization of rapid sequence induction (RSI) for endotracheal intubation in the prehospital setting. Records of a consecutive series of injured patients undergoing RSI between June 1988 and July 1992 by a university-based aeromedical transport team were reviewed for demographics, intubation mishaps, and pulmonary complications. The relationship between intubation mishaps and pulmonary complications was analyzed. Eighty-four patients were studied with a mean age of 30.8 +/- 15.3 years. The mean Revised Trauma Score was 11.3 +/- 2.4, and the mean Injury Severity Score (ISS) was 19.6 +/- 11.5. Intubation mishaps occurred in 15 patients (18%), and pulmonary complications developed in 22 (29%) of the 75 patients surviving longer than 24 hours. There was no relationship between intubation mishaps and pulmonary complications. Abbreviated Injury Scale (AIS) face score was significantly higher in patients with intubation mishaps, compared with patients without mishaps (1.1 +/- 1.2 and 0.5 +/- 0.9, respectively, P < .05, Wilcoxon rank-sum). ISS and AIS chest were higher in patients with pulmonary complications, compared with those without (25.7 +/- 12.6 and 17.4 +/- 10.3 and 2.2 +/- 1.8 and 1.0 +/- 1.5, ISS and AIS respectively; P < .05, Wilcoxon rank-sum). Eighty-one patients (96%) underwent successful RSI, 73 (87%) on the first attempt. Failure to intubate occurred in three patients (4%). Performed under strict protocol by appropriately trained aeromedical transport personnel, RSI is an effective means to facilitate endotracheal intubation in the injured patient requiring definitive airway control. Pulmonary complications were related to injury severity and not to intubation mishaps.

Adolescent↗

PubMed1998

Ureteral trauma: preoperative studies neither predict injury nor prevent missed injuries.

BACKGROUND: Ureteral injuries are uncommon, and the necessity, accuracy, and optimal use of perioperative testing remains unknown. Delays in diagnosis have also been associated with significant morbidity, including loss of renal function. STUDY DESIGN: The records of all patients (n = 20) admitted with ureteral injuries to two Level I trauma centers during a 5-year period were reviewed. Data collected included patient demographics, mechanism of injury, degree of associated injuries, and presence of gross or microscopic hematuria. The use of any pre- or intraoperative testing was specifically noted. The location of the ureteral injury was obtained from the operative notes. The morbidity and mortality associated with ureteral injuries in the primarily diagnosed and the delayed groups were assessed. Presenting signs and symptoms, diagnostic testing, and the urologic management of the patients in the delayed group were reviewed. RESULTS: All patients were men whose ages ranged from 15 to 72 years, with a mean age of 29. The mechanisms of injury were gunshot wounds in 15, stab wounds in 4, and blunt vehicular trauma in 1. Excluding other urologic injuries, the incidence of hematuria related to the ureteral injury alone was 53%. A total of 10 pre- and intraoperative studies were performed, only 2 demonstrated the ureteral injury. Seventeen patients had their injuries diagnosed primarily. In this group, the ureter was repaired by suturing and stenting in 12, suturing without a stent in 1 and ureterocystostomy in 4. Delayed diagnosis of their ureteral injuries occurred in three patients. All three missed injuries occurred in the upper portion of the left ureter. All ureters were successfully repaired. There were no mortalities in this group, nor did any patient require a nephrectomy. CONCLUSIONS: Direct visualization of the injury is the best and most accurate diagnostic modality in ureteral trauma. These results reinforce that a thorough exploration of all retroperitoneal hematomas after penetrating trauma remain an integral part of the total abdominal exploration for trauma.

Abdominal Injuries↗

PubMed1998

Efficacy of the motor component of the Glasgow Coma Scale in trauma triage.

BACKGROUND: National guidelines recommend that patients with Glasgow Coma Scale (GCS) scores of less than 14 be triaged to trauma centers. We hypothesized that the motor component of the GCS (GCSM) would be equally sensitive as the total GCS in head injury triage. METHODS: A 2-year retrospective review of 3,235 injured adults transported directly to a Level I trauma center. RESULTS: One thousand four hundred ten patients (44%) had prehospital GCS scores recorded. GCSM was found to have a sensitivity of 0.90 for Abbreviated Injury Scale (AIS) score = 5 head injury and 0.61 for AIS score > 3 injury, whereas the GCS had sensitivities of 0.92 and 0.62, respectively (p = not significant). Specificities were equal at 0.85 for AIS score = 5 and 0.89 for AIS score > 3. CONCLUSION: GCSM is equivalent to GCS for prehospital triage, and in view of its simplicity it should replace the GCS in triage schemes.

Adolescent↗

PubMed1997

Suppression of TNF-alpha expression, inhibition of Th1 activity, and amelioration of collagen-induced arthritis by rolipram.

Rolipram is a type IV phosphodiesterase inhibitor that suppresses inflammation and TNF-alpha production. As anti-TNF-alpha therapy is effective in rheumatoid arthritis, we investigated the effect of rolipram on collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis. Rolipram was administered after the onset of clinical arthritis at doses of 0.5, 3, 5, or 10 mg/kg twice daily, with a dose-dependent therapeutic effect on clinical severity and joint erosion. Immunohistochemical analysis of joints of rolipram-treated mice revealed 67% reduction in TNF-alpha-expressing cells compared with control arthritic mice. In vitro studies using bone marrow-derived macrophages confirmed that rolipram directly suppressed TNF-alpha and IL-12 production following stimulation with IFN-gamma and LPS. The effect of rolipram on T cell activity was studied by measuring Th1/Th2 cytokine production by collagen-stimulated draining lymph node cells from arthritic mice treated in vivo with rolipram. Rolipram reduced IFN-gamma production and increased IL-10, indicating that rolipram down-regulated the ongoing Th1 response to type II collagen. Finally, the effect on CIA of combination therapy was studied using rolipram plus either anti-TNF-alpha or anti-CD4 mAbs. Rolipram plus anti-TNF-alpha was not therapeutically additive, whereas rolipram plus anti-CD4 mAb was clearly additive. This result indicates that the therapeutic effects of rolipram overlap with TNF-alpha blockade, but are complementary to anti-CD4 treatment. It is therefore proposed that a major mechanism of action of rolipram in CIA is suppression of TNF-alpha activity. These findings suggest that type IV phosphodiesterase inhibitors may be effective in pathologic conditions, such as RA, with overexpression of TNF-alpha.

Animals↗

PubMed1997

Signaling pathways through which insulin regulates CCAAT/enhancer binding protein alpha (C/EBPalpha) phosphorylation and gene expression in 3T3-L1 adipocytes. Correlation with GLUT4 gene expression.

Treatment of 3T3-L1 adipocytes with insulin (IC50 approximately 200 pM insulin) or insulin-like growth factor-1 (IC50 approximately 200 pM IGF-1) stimulates dephosphorylation of CCAAT/enhancer binding protein alpha (C/EBPalpha), a transcription factor involved in preadipocyte differentiation. As assessed by immunoblot analysis of one- and two-dimensional PAGE, insulin appears to dephosphorylate one site within p30C/EBPalpha and an additional site within p42C/EBPalpha. Consistent with insulin causing dephosphorylation of C/EBPalpha through activation of phosphatidylinositol 3-kinase, addition of phosphatidylinositol 3-kinase inhibitors (e.g. wortmannin) blocks insulin-stimulated dephosphorylation of C/EBPalpha. In the absence of insulin, wortmannin or LY294002 enhance C/EBPalpha phosphorylation. Similarly, blocking the activity of FKBP-rapamycin-associated protein with rapamycin increases phosphorylation of C/EBPalpha in the absence of insulin. Dephosphorylation of C/EBPalpha by insulin is partially blocked by rapamycin, consistent with a model in which activation of FKBP-rapamycin-associated protein by phosphatidylinositol 3-kinase results in dephosphorylation of C/EBPalpha. The dephosphorylation of C/EBPalpha by insulin, in conjunction with the insulin-dependent decline in C/EBPalpha mRNA and protein, has been hypothesized to play a role in repression of GLUT4 transcription by insulin. Consistent with this hypothesis, the decline of GLUT4 mRNA following exposure of adipocytes to insulin correlates with dephosphorylation of C/EBPalpha. However, the repression of C/EBPalpha mRNA and protein levels by insulin is blocked with an inhibitor of the mitogen-activated protein kinase pathway without blocking the repression of GLUT4 mRNA, thus dissociating the regulation of C/EBPalpha and GLUT4 mRNAs by insulin. A decline in C/EBPalpha mRNA and protein may not be required to suppress GLUT4 transcription because insulin also induces expression of the dominant-negative form of C/EBPbeta (liver inhibitory protein), which blocks transactivation by C/EBP transcription factors.

3T3 Cells↗

PubMed1997

T cell receptor-induced phosphorylation of Sos requires activity of CD45, Lck, and protein kinase C, but not ERK.

Stimulation of the T cell antigen receptor (TCR) activates signaling pathways involving protein kinases, phospholipase Cgamma1, and Ras. How these second messengers interact to initiate distal activation events is an area of intense scrutiny. In this report, we confirm that TCR ligation results in phosphorylation of Sos, a guanine nucleotide exchange factor for Ras. This requires expression of both the CD45 tyrosine phosphatase and the Lck protein tyrosine kinase and depends upon signaling via protein kinase C. In contrast to previous studies examining requirements for Sos phosphorylation following insulin and epidermal growth factor receptor engagement, we show that TCR-induced phosphorylation of Sos does not require activation of the mitogen-activated protein kinase/extracellular-signal regulated kinase (MEK/ERK) pathway. However, the basal phosphorylation of Sos in T cells is affected by either MEK or MEK-dependent kinases. Although Sos phosphorylation results in its dissociation from Grb2 following insulin stimulation in Chinese hamster ovary cells, TCR engagement on the Jurkat T cell line fails to elicit a similar effect. These data demonstrate that the kinases responsible for Sos phosphorylation differ following ligation of various cell surface receptors and that the consequences of Sos phosphorylation relies, at least in part, on sites of its phosphorylation.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Three domains of SLP-76 are required for its optimal function in a T cell line.

We and others have shown that overexpression of SLP-76 augments TCR-stimulated IL-2 promoter activity in the Jurkat T cell line. In this report we investigate the signaling mechanisms through which SLP-76 mediates its effect on T cell activation. We show that overexpressed SLP-76 acts downstream of TCR-stimulated protein tyrosine kinases, but does not affect calcium signaling. Overexpression of SLP-76 does, however, augment TCR stimulation of both ERK (extracellular signal-regulated kinase) activity and a reporter construct driven by activating protein-1 binding sites. Structure/function analysis reveals that three distinct regions of SLP-76, each important for protein associations, are required for augmentation of TCR-induced nuclear factor-AT activity. These data suggest that SLP-76 functions as an adapter molecule that requires three unique domains to link proximal TCR signals in T cells.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Bradykinin antagonists in human systems: correlation between receptor binding, calcium signalling in isolated cells, and functional activity in isolated ileum.

The determination of the relationship between ligand affinity and bioactivity is important for the understanding of receptor function in biological systems and for drug development. Several physiological and pathophysiological functions of bradykinin (BK) are mediated via the B2 receptor. In this study, we have examined the relationship between B2 receptor (soluble and membrane-bound) binding of BK peptidic antagonists, inhibition of calcium signalling at a cellular level, and in vitro inhibition of ileum contraction. Only human systems were employed in the experiments. Good correlations between the studied activities of BK antagonists were observed for a variety of different peptidic structures. The correlation coefficients (r) were in the range of 0.905 to 0.955. In addition, we analyzed the effect of the C-terminal Arg9 removal from BK and its analogs on B2 receptor binding. The ratios of binding constants (Ki(+Arg)/Ki(-Arg)) for the Arg9 containing compounds and the corresponding des-Arg9 analogs varied from about 10 to 250,000. These ratios strongly depend on the chemical structures of the compounds. The highest ratios were observed for two natural agonist pairs, BK/des-Arg9-BK and Lys0-BK/des-Arg9-Lys0-BK.

Bradykinin↗

PubMed1997

Surface expression of hemopoietic cell phosphatase fails to complement CD45 deficiency and inhibits TCR-mediated signal transduction in a Jurkat T cell clone.

Previous studies have shown that the protein tyrosine phosphatase CD45 is required for initiation of signal transduction through several lymphoid receptors. In contrast, there is increasing evidence that another protein tyrosine phosphatase, hemopoietic cell phosphatase (known as HCP, SHP, PTP1C, SHPTP-1, or PTPN6), is a negative regulator of signaling in hemopoietic cells. To determine the effect of HCP on signal transduction through the TCR, HCP was expressed as a chimeric molecule with extracellular and transmembrane domains of the HLA-A2 molecule (A2/HCP) on wild-type Jurkat T cells and the CD45-deficient variant, J45.01. In this report, we show that expression of A2/HCP, unlike A2 chimeras containing the enzymatic regions of CD45, fails to rescue TCR-mediated signal transduction in J45.01. Furthermore, expression of A2/HCP on wild-type Jurkat T cells results in diminished inositol phosphate production following TCR ligation as well as markedly diminished nuclear factor of activated T cells promoter activity. Surprisingly, however, TCR-mediated tyrosine phosphorylation of phospholipase C gamma 1 remains intact in the Jurkat cells expressing the A2/HCP chimera. These experiments provide further evidence that HCP can serve a negative regulatory role in receptor-mediated signaling in immune cells. Additionally, our studies suggest that surface expression of HCP in T cells may provide a means to identify phosphotyrosine-containing proteins that are required for coupling signaling pathways initiated by ligation of the T cell Ag receptor.

Calcium↗

PubMed1997

Secondary emergency department triage (supertriage) and trauma team activation: effects on resource utilization and patient care.

BACKGROUND: Not all field triage patients need full trauma team activation. Secondary emergency department (ED) triage (supertriage), a clinical and anatomic screen, determines trauma team versus ED management. The purpose was to study the effects of supertriage on injury severity and disposition by patients managed with and without team activation. METHODS: Observational study of consecutive patients transported for alert consideration undergoing supertriage by a trauma nurse. Chart review was performed for disposition and Injury Severity Score. Contingency table or t test with p < or = 0.05 was used for data analysis. RESULTS: One hundred ninety patients were screened; 74% of the 54 with positive supertriage and team activation needed the operating room in 24 hours or the intensive care unit versus 46% of cases with negative supertriage managed in the ED and admitted (p = 0.015). Of the 35 admitted ED patients, 10 required the operating room and 6 required the intensive care unit. CONCLUSIONS: Supertriage identified a majority requiring team activation; however, resources must be available for the seriously injured not meeting field or hospital triage criteria.

Adolescent↗

PubMed1997

In vitro studies of a bradykinin B1/B2 antagonist linked to a human neutrophil elastase inhibitor; a heterodimer for the treatment of inflammatory disorders.

Inflammatory disorders typically have a complex etiology and involve a multitude of inflammatory mediators, and hence, a polytherapeutic approach to these diseases would seem appropriate. In certain chronic inflammatory conditions, we believe that bradykinin (BK) and human neutrophil elastase (HNE) are cooperatively involved. We have previously synthesized compounds with inhibitory activity toward both the BK B2 receptor and HNE. The present study describes single compounds designed to incorporate HNE inhibitory activity and BK B1 and B2 antagonist activity. A proprietary HNE inhibitor (HNEI, CP-955) was directly linked via amide bond formation to a peptide-based combined BK B1/B2 antagonist (B-9430). Three compounds were made using different linking positions in the antagonist peptide. For all compounds, B1 and B2 receptor binding in human cloned receptors was at least 10-fold less than that of B-9430, whereas in the in vitro guinea pig ileum B2 receptor functional assay, the compounds had potencies equivalent to B-9430. Compound I was found to have a fourfold increase in HNEI activity compared with CP-955, whereas compounds II and III were inactive. These data clearly demonstrate that it is possible to retain BK B1/B2 receptor antagonist and HNE activity in a heterodimer.

Amino Acid Sequence↗

PubMed1996

Tyrosines 113, 128, and 145 of SLP-76 are required for optimal augmentation of NFAT promoter activity.

SLP-76 (SH2 domain leukocyte protein of 76 kDa) is a recently identified substrate of the TCR-stimulated protein tyrosine kinases that functions in the signal transduction cascade linking the TCR with IL-2 gene expression. In this report, we demonstrate that engagement of the TCR results in tyrosine phosphorylation of SLP-76 in its amino-terminal acidic region. Two tyrosines (Y113 and Y128) fall within an identical five amino-acid motif and are shown to be phosphorylated upon TCR ligation. Although mutation of either Y113 and Y128 has a minimal effect on SLP-76 function, mutation of both residues decreases significantly the ability of SLP-76 to promote T cell activation. A third tyrosine within the amino-terminal region (Y145) appears to be the most important for optimal SLP-76 function, as altering it alone to phenylalanine has a potent impact on SLP-76 augmentation of NFAT promoter activity.

Adaptor Proteins, Signal Transducing↗

PubMed1996

Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production.

Recently we described the molecular cloning of SLP-76, a hematopoietic cell-specific 76-kD protein that was first identified through its association with GST/Grb2 fusion proteins. The primary sequence of SLP-76 predicts a protein of 533 amino acids comprising an amino-terminal region with numerous potential tyrosine phosphorylation sites, a central region rich in proline residues, and a single carboxy-terminal SH2 domain. Here we demonstrate formally that Grb2 associates with unphosphorylated SLP-76 and map the Grb2 binding site on SLP-76 undergoes rapid tyrosine phosphorylation and associates with tyrosine phosphoproteins of 36, 62, and 130 kD. In vitro experiments show that the SH2 domain of SLP-76 associates with the 62- and 130-kD proteins and additionally with a serine/threonine kinase. Finally, we demonstrate that transient overexpression of SLP-76 results in dramatically enhanced TCR-mediated induction of nuclear factor of activated T cells (NFAT) and interleukin (IL) 2 promoter activity; and we provide evidence that a functional SLP-76 SH2 domain is required for this effect. Our data document the in vivo associations of SLP-76 with several proteins that potentially participate in T cell activation and implicate SLP-76 itself as an important molecule in TCR-mediated IL-2 production.

Adaptor Proteins, Signal Transducing↗

PubMed1996

Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity.

We report a systematic probing of the structural requirements of the bradykinin (BK) type 2 (B(2)) receptor for antagonist activity by incorporating N-alkyl-amino acid residues at positions 7 and 8 of a potent antagonist sequence. Compound 1 (D-Arg(0)-Arg(1)-Pro(2)-Hyp(3)-Gly(4)-Thi(5)-Ser(6)-D-Tic(7)-N-Chg (8)-Arg(9), CP-0597)(1,2) is a potent (pA(2) = 9.3, rat uterus; pK(i) = 9.62, binding, human receptor clone) B(2) receptor antagonist devoid of in vitro B(1) antagonist activity (rabbit aorta). Compound 1 exhibits high potency (ED(50) = 29.2 pmol/kg/min, iv, rabbit) and duration of action when tested in models for in vivo B(2) antagonist activity. Although devoid of activity in a classic B(1) isolated tissue assay, B(1) antagonist activity for 1 was demonstrated in vivo, in a LPS-treated, inducible BK(1) receptor rabbit blood pressure model (ED(50) = 1.7 nmol/kg/min). D-Arg(0) of 1 can be formally replaced by an achiral arginine surrogate, without significant loss in antagonist potency on rat uterus (compound 11, B(2) pA(2) = 9.1). Antagonist 13 (Hyp(2), Nchg(8)), pK(i) = 10.2, and agonist 4 (N-methylcyclohexyl-Gly(8)), pK(i) = 10.1, also exhibited substantial binding to guinea pig ileum membrane receptors as well as a human B(2) receptor clone. Very minor structural changes in the N-alkyl amino acid residues in positions 7 and 8 can modify the activity of this class of compounds from being extremely potent antagonists to tight binding partial or full agonists. These studies have resulted in a series of compounds containing inexpensive amino acid residues but which produce broad spectrum BK receptor blocking potency and exceptional in vivo duration of action.

Amino Acid Sequence↗

PubMed1996

Infant survival after cesarean section for trauma.

HYPOTHESIS: Emergency cesarean sections in trauma patients are not justified and should be abandoned. SETTING AND DESIGN: A multi-institutional, retrospective cohort study was conducted of level 1 trauma centers. METHODS: Trauma admissions from nine level 1 trauma centers from January 1986 through December 1994 were reviewed. Pregnant women who underwent emergency cesarean sections were identified. Demographic and clinical data were obtained on all patients undergoing a cesarean section. Fetal distress was defined by bradycardia, deceleration, or lack of fetal heart tones (FHTs). Maternal distress was defined by shock (systolic blood pressure < 90) or acute decompensation. Statistical analyses were performed. RESULTS: Of the 114,952 consecutive trauma admissions, more than 441 pregnant women required 32 emergency cesarean sections. All were performed for fetal distress, maternal distress, or both. Overall, 15 (45%) of the fetuses and 23 (72%) of the mothers survived. Of 33 fetuses delivered, 13 had no FHTs and none survived. Twenty infants (potential survivors) had FHTs and an estimated gestational age (EGA) of greater than or equal to 26 weeks, and 75% survived. Infant survival was independent of maternal distress or maternal Injury Severity Score. The five infant deaths in the group of potential survivors resulted from delayed recognition of fetal distress, and 60% of these deaths were in mothers with mild to moderate injuries (Injury Severity Score < 16). CONCLUSIONS: In pregnant trauma patients, infant viability is defined by the presence of FHTs, estimated gestational age greater than or equal to 26 weeks. In viable infants, survival after emergency cesarean section is acceptable (75%). Infant survival is independent of maternal distress or Injury Severity Score. Sixty percent of infant deaths resulted from delay in recognition of fetal distress and cesarean section. These were potentially preventable. Given the definition of fetal viability, our initial hypothesis is invalid.

Adolescent↗

PubMed1996

Lorazepam and midazolam in the intensive care unit: a randomized, prospective, multicenter study of hemodynamics, oxygen transport, efficacy, and cost.

OBJECTIVES: To evaluate and compare the clinical efficacy, impact on hemodynamic and oxygen transport variables, safety profiles, and cost efficiency of sedation and anxiolysis with lorazepam vs. continuous infusion of midazolam in critically ill, intensive care unit patients. DESIGN: Multicenter, prospective, randomized, open-label study. SETTING: Teaching hospitals. PATIENTS: Ninety-five critically ill, mechanically ventilated patients with fiberoptic pulmonary artery catheters in place were randomly assigned to receive short-term (8 hrs) sedation with either intermittent intravenous injection lorazepam (group A, n = 50) or continuous intravenous infusion midazolam (group B, n = 45) titrated to clinical response. MEASUREMENTS AND MAIN RESULTS: The severity of illness, demographic characteristics, levels of anxiety and agitation, hemodynamic parameters, oxygen transport variables, quality of sedation, nursing acceptance, and laboratory chemistries reflecting drug safety were recorded. There were no significant differences with regard to demographic data, hemodynamic and oxygen transport variables, or levels of anxiety/agitation between the two groups at baseline, 5 mins, 30 mins, and 4 and 8 hrs after administration of sedation. There were no significant differences in the quality of sedation or anxiolysis. Midazolam-treated patients used significantly larger amounts of drug for similar levels of sedation and anxiolysis (14.4 +/- 1.2 mg/8 hrs vs. 1.6 +/- 0.1 mg/8 hrs, p = .001). Both drugs were safely administered and patient and nurse satisfaction was similar. CONCLUSIONS: Sedation and anxiolysis with lorazepam and midazolam in critically ill patients is safe and clinically effective. Hemodynamic and oxygen transport variables are similarly affected by both drugs. The dose of midazolam required for sedation is much larger than the dose of lorazepam required for sedation, and midazolam is therefore less cost-efficient.

Adolescent↗

PubMed1996

Patterns of injury and disability caused by forklift trucks.

Over a 7-year period, 34 patients were treated at the Southern New Jersey Regional Trauma Center for forklift-related injuries, ranging from minor contusions to multiple organ-system trauma. Hospital and rehabilitation courses were prospectively evaluated, documenting long term impairment of function and disability. Patients injured by falling from forklifts generally had less severe injuries, requiring fewer surgical procedures, shorter hospital stays, and less overall disability, than patients who received crush-type (object-oriented) injuries. The more serious injuries were most frequently caused by a forklift striking or running over the patient. There were strong correlations between the Injury Severity Score assessed upon initial evaluation and subsequent length of hospitalization, degree of disability, and extent of functional impairment after recovery. These findings support the enforcement of existing safety precautions for the operation of forklift trucks.

Accidents, Occupational↗

PubMed1996

Tyrosine phosphorylation of Grb2-associated proteins correlates with phospholipase C gamma 1 activation in T cells.

Ligation of the T-cell antigen receptor (TCR) results in the rapid activation of several protein tyrosine kinases, with the subsequent phosphorylation of numerous cellular proteins. We investigated the requirement for tyrosine phosphorylation of proteins which bind the Grb2 SH2 domain in TCR-mediated signal transduction by transfecting the Jurkat T-cell line with a cDNA encoding a chimeric protein designed to dephosphorylate these molecules. Stimulation of the TCR on cells expressing this engineered enzyme fails to result in sustained tyrosine phosphorylation of a 36-kDa protein likely to be the recently cloned pp36/Lnk. Interestingly, TCR ligation of the transfected cells also fails to induce soluble inositol phosphate production and intracellular calcium mobilization, although receptor-mediated tyrosine phosphorylation of phospholipase C gamma 1 still occurs. TCR-mediated Ras and mitogen-activated protein kinase activation remain intact in cells expressing the engineered phosphatase. These data demonstrate that tyrosine phosphorylation of a protein(s) which binds the SH2 domain of Grb2 correlates with phospholipase C gamma 1 activation and suggest that such a phosphoprotein(s) plays a critical role in coupling the TCR with the phosphatidylinositol second-messenger pathway.

Adaptor Proteins, Signal Transducing↗