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S Hook

Publications and source records attributed to S Hook.

18 recordsLinked to original sources
PubMed2000

Th2-dependent airway eosinophilia is regulated by preproenkephalin.

We have used preproenkephalin (PPNK)-deficient mice to study the role of PPNK in the development of airway inflammation. Airway eosinophilia was established by either sensitization followed by airway challenge with OVA or by infection with Nippostrongylus brasiliensis. Both models induce a strong Th2 immune response, characterized by an IL-5-dependent airway eosinophilia. We observed that although the accumulation of lymphocytes in the airways of PPNK-deficient mice was similar to that induced in control mice, IL-5 production and eosinophil infiltration were reduced. We conclude from this work that PPNK has a role in enhancing Th2 cell function and that this molecule may be an important target in asthma immunotherapy.

Animals↗
PubMed2000

A comparative study of alternative conduits for lower extremity revascularization: all-autogenous conduit versus prosthetic grafts.

PURPOSE: In the absence of an adequate ipsilateral greater saphenous vein, various alternative conduits have been used for the performance of lower extremity revascularization. In this study we compared the effectiveness of all-autogenous arm vein bypass grafts with that of prosthetic grafts. METHODS: Seven hundred forty lower extremity revascularization procedures (506 arm vein, 234 prosthetic) performed between 1990 and 1999 were followed prospectively by means of a computerized vascular registry. RESULTS: Bypass graft configurations were femoro-above-knee-popliteal (26 arm vein, 100 prosthetic); femoro-below-knee-popliteal (38 arm vein, 29 prosthetic); femorotibial (174 arm vein, 55 prosthetic); femoropedal (23 arm vein, 2 prosthetic); popliteotibial/pedal (101 arm vein, 1 prosthetic); and extension "jump" grafts (144 arm vein, 47 prosthetic). The indications for surgery were limb salvage (98.0% arm vein, 89.7% prosthetic) and disabling claudication (2.0% arm vein, 10.3% prosthetic). The mean follow-up was 23.4 months (range, 1 month-7.4 years). Overall patient survival at 4 years was 54% (arm vein) and 69% (prosthetic). Cumulative patency varied with graft configuration. The 1-year primary patency rates for femorotibial grafts were 81.6% +/- 3.6% (arm vein) and 58.0% +/- 8.4% (prosthetic); the 3-year rates were 68.3% +/- 6.1% (arm vein) and 41.1% +/- 9.8% (prosthetic) (P<.01). The 1-year limb salvage rates for femorotibial grafts were 91.1% +/- 2.8% (arm vein) and 69.1% +/- 8. 8% (prosthetic); the 3-year rates were 81.4% +/- 5.6% (arm vein) and 63.2% +/- 10.3% (prosthetic) (P =.02). The 1-year primary patency rates for femoro-below-knee-popliteal grafts were 92.9% +/- 5.1% (arm vein) and 83.4% +/- 8.0% (prosthetic); the 3-year rates were 72.8% +/- 10.1% (arm vein) and 55.5% +/- 12.1% (prosthetic) (P=.05). The 1-year limb salvage rates for femoro-below-knee-popliteal grafts were 100% (arm vein) and 91.3% +/- 7.0% (prosthetic); the 3-year rates were 94.7% +/- 7.3% (arm vein) and 75.3% +/- 14.6% (prosthetic) (P = NS). CONCLUSION: In this study autogenous arm vein grafts demonstrated increased patency and limb salvage, compared with prosthetic grafts. These increases achieved statistical significance in the femoro-below-knee-popliteal and femorotibial configurations. An effort to use an all-autogenous vein conduit is justified on the basis of these results; however, if no autogenous vein is available, prosthetic grafts provide a reasonable alternative to primary amputation.

Aged↗
PubMed1999

Preproenkephalin is a Th2 cytokine but is not required for Th2 differentiation in vitro.

Preproenkephalin (PPNK) mRNA expression has been detected in many cells of the immune system, including monocytes and lymphocytes. In the present paper, the expression of PPNK mRNA in purified CD4+ Th1 and Th2 lymphocyte subpopulations is investigated and correlated with the presence of the opioid neuropeptides leu- and met-enkephalin. We found that PPNK mRNA and met-enkephalin were present at higher levels in the Th2 cultures compared with the Th1 cultures. Lymphocytes from PPNK-deficient mice were then used to look at the role of PPNK in Th2 lymphocyte differentiation. Lymphocytes from these mice could be driven into a Th2 phenotype, suggesting that cultures containing IL-4 do not require PPNK for Th2 differentiation.

Animals↗
PubMed1999

CTLA-4 blockade enhances the immune response induced by mycobacterial infection but does not lead to increased protection.

The murine immune response to a pulmonary mycobacterial infection is slow to develop, allowing bacterial numbers to increase in the lung for several weeks after infection. We sought to enhance the protective immune response induced during Mycobacterium bovis BCG infection by administering an antibody that blocks the interaction of CTLA-4 with its ligands, CD80 and CD86. We found that injection of anti-CTLA-4 monoclonal antibody (MAb) greatly enhanced and accelerated the immune response, as measured by increased cellularity of the draining mediastinal lymph nodes, and enhanced antigen-inducible proliferation and gamma interferon production by mediastinal lymphocytes in vitro. However, despite the apparently enhanced immune response in the mediastinal lymph node following treatment with anti-CTLA-4 MAb, there was no improvement in clearance of mycobacteria in the lungs, liver, or spleen. Examination of the primary site of infection, the lung, revealed that CTLA-4 blockade had no effect on the number or function of lymphocytes infiltrating the infected lung tissue. Taken together, these data suggest that in vivo CTLA-4 blockade enhances mycobacterial-infection-induced lymphocyte expansion and effector cell cytokine production in the draining lymph node but does not alter the number or function of lymphocytes at the primary site of infection and therefore does not lead to enhanced clearance of the infection.

Abatacept↗
PubMed1999

Analysis of two IL-4 promoter polymorphisms in a cohort of atopic and asthmatic subjects.

The Th2 cytokine interleukin 4 (IL-4) has been identified as having a central role in driving the inflammatory immune responses which are present in atopic airway disease. This study examined the distribution of two putative IL-4 promoter polymorphisms (-285 C-T and -81 A-G) in groups of patients with severe and moderate asthma, non-asthmatic atopy and control subjects. Neither polymorphism was identified in any of the samples tested. The data suggest that either the polymorphisms are present at very low frequencies or are artefacts of the B cell lines from which they were identified.

Adult↗
PubMed1999

The value of upper tract cytology after transurethral resection of bladder tumor in patients with bladder transitional cell cancer.

PURPOSE: Patients with transitional cell carcinoma of the bladder are at risk for concurrent or subsequent cancer of the upper tract. Traditionally disease is monitored by radiography (excretory or retrograde urography). Some elect to sample the upper tract by obtaining urine for cytology. Are the results meaningful when performed in a patient with bladder cancer? MATERIALS AND METHODS: We evaluated 27 consecutive patients with transitional cell cancer of the bladder (grade 1 to 3, Ta to T2) with bladder wash for cytology and cystoscopy as well as resection of visible tumor. A 5F ureteral catheter was positioned at each ureteral orifice, flushed with saline and passed into each renal pelvis. Urine was collected for cytology. RESULTS: Of 19 patients (68%) with high grade (grade 3) bladder cancer 13 had a positive bladder wash, including 6 (32%) with tumor cells detected in the urine from the upper tract. Of 8 patients (38%) with low grade (grade 1 to 2) transitional cell cancer 3 had a positive bladder wash and 2 (25%) had a positive upper tract cytology. All patients had a normal upper tract by excretory or retrograde urography. Ureteroscopy was not performed. CONCLUSIONS: Given the normal appearance of the upper urinary tract, it is highly unlikely that most, if any, of these patients with bladder cancer have tumor in the upper tract despite tumor cells in urine obtained by retrograde catheterization. Thus, upper tract sampling by a retrograde technique lacks specificity for localizing transitional cell cancer to the upper tract when performed in a patient with bladder cancer.

Aged↗
PubMed1997

To scale or not to scale: McCarthy and Wood revisited.

We dispute McCarthy and Wood's (1985) claim that some form of scaling should be applied routinely to ERP data before determining differences in scalp distributions between conditions (or groups). Their simulation study involved assumptions about the nature of the variability within each condition, most significantly that the standard deviations are identical at all electrodes, irrespective of the means. Alternative plausible assumptions may be proposed for which scaling is unnecessary. Furthermore, we show that the two main forms of scaling they proposed may distort or even completely eliminate real differences in scalp topography reflecting genuinely different underlying sources.

Electrodes↗
PubMed1996

Activation of an interleukin-4 mRNA-producing population of peripheral blood mononuclear cells after infection with Mycobacterium bovis or vaccination with killed, but not live, BCG.

This study examines the expression of mRNA for the Th2 cytokine, interleukin-4 (IL-4). Peripheral blood mononuclear cells from deer infected with Mycobacterium bovis or vaccinated with live or killed M. bovis bacillus Calmette-Guérin (BCG) were cultured with mycobacterial antigens. IL-4 mRNA production was assayed using the polymerase chain reaction. Elevated levels of IL-4 mRNA were detected in response to at least one antigen preparation in all animals infected with M. bovis as compared with none of the non-infected control animals. After a primary immunization, elevated levels of IL-4 mRNA were detected in only a proportion of vaccinated animals and this did not correlate with whether the vaccine was live BCG or killed BCG in oil. After boosting, all the animals vaccinated with killed BCG in oil exhibited elevated IL-4 mRNA production whereas none of the animals vaccinated with live BCG showed elevated levels. The data suggest that IL-4 is turned off during the immune response to live BCG, that boosting of low-dose live BCG vaccine may be required to 'imprint' this signal and that this may be important in the development of protective immunity to tuberculosis. Killed BCG in adjuvant is not protective and as with experimental infection with virulent M. bovis it failed to switch off the IL-4 response. IL-4 may be useful as a diagnostic tool and as an in vitro marker of vaccine efficacy.

Animals↗
PubMed1995

Regional differentiation of cortical activity in schizophrenia: a complementary approach to conventional analysis of regional cerebral blood flow.

This study examines an alternative to a narrow locus-of-dysfunction cortical pathophysiology in schizophrenia, which in turn suggests a modified approach to the analysis of data from regional cerebral blood flow studies. The results provide qualified support for a model of impaired differentiation of cortical activity in schizophrenia. As an index of the differentiation of cortical fields, regional gradients of cortical blood flow were examined. Medicated patients (n = 15) failed to show the differentiation of networks in frontal areas during a verbal memory recognition task observed in normal comparison subjects (n = 15). Unmedicated patients (n = 15) at rest tended to lose normal lateralization and had increased gradients in the right frontal area compared with normal comparison subjects.

Adult↗
PubMed1995

Adjunctive selectin blockade successfully reduces infarct size beyond thrombolysis in the electrolytic canine coronary artery model.

BACKGROUND: An adjunctive pharmacological strategy to thrombolytic therapy that is tailored to limit reperfusion injury after thrombolysis could further maximize the unquestioned benefit of restoring flow to ischemic myocardium. Ischemia-reperfusion injury exhibits features characteristic of an acute inflammatory response, including the rapid activation and infiltration of neutrophils. The initial process of neutrophil migration from the circulation to injured tissue is modulated by a group of adhesion molecules called selectins. The purpose of the present study was to assess the efficacy of a selectin blocker (CY 1503) given as an adjunct to thrombolytic therapy to interfere with the inflammatory response after ischemia-reperfusion and subsequently reduce myocardial infarct size in the electrolytic canine model. METHODS AND RESULTS: A fully occlusive thrombus was formed in the left circumflex coronary artery by electrolytic injury in 20 anesthetized open-chest dogs. After occlusion, an infusion of 1 mg/kg recombinant tissue-type plasminogen activator (rTPA) was administered over 20 minutes with either a bolus of placebo or the selectin blocker CY 1503 (40 mg/kg). At the onset of reperfusion, 20 micrograms/kg per minute rTPA was administered for 1 hour to prevent reocclusion. After 1 hour of reperfusion, infarct size, myocardial myeloperoxidase activity, and reperfusion arrhythmias were measured. In CY 1503-treated dogs, there was a significant 69% reduction in infarct size when expressed as a percentage of the area at risk (6.7 +/- 8.4% versus 21.8 +/- 13.6%; P = .008) and a marked reduction in myeloperoxidase activity (0.014 +/- 0.009 versus 0.0370 +/- 0.025 U/min per gram; P = .02) compared with the placebo group. There was no difference between the groups in the occurrence of reperfusion arrhythmias. CONCLUSIONS: Selectin blockade as an adjunct to rTPA-mediated thrombolysis significantly reduces infarct size and myocardial neutrophil infiltration well beyond thrombolysis alone in the electrolytic canine model. These data suggest that selectin blockade is extremely effective at reducing ischemia-reperfusion injury and myocardial infarct size in this model and that the neutrophil is a potent mediator of ischemia-reperfusion injury.

Animals↗
PubMed1990

Alpha Cradles in breast cancer treatment: easy immobilization for the potentially difficult breast set up.

Due to the preference of the present multimodality treatment of breast cancer, we have found the need for a more customized approach to our patient set-up position. Using Smithers Medical Alpha Cradle Kits (AC 325) we have been able to achieve individual casts for our physically challenging patients. The results are a comfortable, easily reproducible position for a technically involved isocentric set-up which requires little additional simulation time and allows the majority of the allotted time for physics measurements and patient interaction. Examples of patient set-ups and consistent treatment field verification are discussed in the following pages.

Breast Neoplasms↗
PubMed1983

Efficacy and tolerance of intranasally applied recombinant leukocyte A interferon in normal volunteers.

The prophylactic effect of recombinant leukocyte A interferon (rIFN-alpha A) (dosage, 10 X 10(6) units per day for four days) against illness and infection in 26 volunteers challenged with rhinovirus type 13 was measured in a double-blind, placebo-controlled study. Significant reductions in illness frequency (7.1% vs 66.7%, P less than 0.003), mean symptom scores, nasal secretion weights, and frequency of virus isolation were observed. However, there was no significant difference in infection rates between rIFN-alpha A- and placebo-treated volunteers. Late posttreatment virus shedding, which was unassociated with late illness, was observed in the rIFN-alpha A-treated group. In two double-blind, placebo-controlled tolerance studies of rIFN-alpha A, five (26%) of the 19 volunteers treated with rIFN-alpha A reported bleeding mixed with mucous nasal discharge and had documented superficial erosions of the nasal mucosa. Future studies will be necessary to evaluate lower doses and/or alternative treatment schedules for improved tolerance and continued efficacy.

Administration, Intranasal↗
PubMedDate not supplied

Isolated noncompaction of the ventricular myocardium.

Isolated noncompaction of the ventricular myocardium is a recently described anomaly. We report the first case of this anomaly presenting as a restrictive cardiomyopathy, and the first association of this entity with endocardial fibrosis.

Cardiomyopathy, Restrictive↗
PubMedDate not supplied

Comparison of myocardial cell injury in acute cellular rejection versus acute vascular rejection in cyclosporine-treated heart transplants.

BACKGROUND: Myocyte necrosis has been cited as a key feature in the diagnosis and classification of both moderate and severe acute cellular rejection (International Society for Heart and Lung Transplantation grades 3A to 4). However, our previous work suggests that myocyte necrosis is not a typical feature of cellular rejection. METHODS: To clarify this point and to elucidate differences between cellular rejection and acute vascular rejection, we compared the light and electron microscopic features of 35 consecutive endomyocardial biopsy specimens from six patients with acute vascular rejection diagnosed with positive immunofluorescence, 12 consecutive endomyocardial biopsy specimens from three patients with mixed acute vascular rejection and cellular rejection, and 435 endomyocardial biopsy specimens of International Society for Heart and Lung Transplantation grades 2 to 4 cellular rejection. RESULTS: Endomyocardial biopsy specimens from eight of nine patients with acute vascular rejection and mixed acute vascular rejection/cellular rejection exhibited classic myocyte necrosis as the typical form of myocardial cell injury. Myocyte necrosis was characterized by lysis of the sarcolemma, marked swelling of mitochondria, and intramitochondrial flocculent densities. In contrast, the typical form of myocardial cell injury in cellular rejection was reversible. Reversible cellular rejection was characterized by extensive loss of myosin filaments and Z-lines with subsarcolemmal and intracytoplasmic accumulation of Z-band material. Cell swelling, mitochondrial swelling, intramitochondrial densities, and lysis of sarcolemma were not observed. CONCLUSIONS: We conclude that myocyte necrosis is a characteristic feature of acute vascular rejection, whereas reversible myocardial cell injury is characteristic of cellular rejection, including grade 4. Myocyte necrosis is not a feature of cellular rejection. The presence of true myocyte necrosis in endomyocardial biopsy specimens from cyclosporine-treated heart transplants implicates some process other than cellular rejection. Processes producing myocyte necrosis include acute vascular rejection, peritransplantation ischemia, and accelerated atherosclerosis.

Acute Disease↗