Sprague-Dawley rats were subjected to a moderate level (2.2 atm) of traumatic brain injury (TBI) using fluid percussion. Injured animals were allowed to survive posttrauma for periods of 5 min, 3 h, and 24 h. The effect of TBI on binding to forebrain opiate receptors was assessed using quantitative receptor autoradiography, and compared to a sham control group. Binding of [3H]DAGO to mu receptors in neocortex and the CA1 pyramidal layer of the hippocampus was significantly decreased in the 24-h group (p less than 0.05). [3H]Bremazocine binding to kappa receptors was unchanged at 5 min and 24 h, but showed large decreases 3 h after TBI in the CA1 pyramidal layer (65%, p less than 0.05) and dentate gyrus (43%, p less than 0.05). Levels of delta binding (measured with [3H]DSLET) and lambda binding (measured with [3H]naloxone) were unaffected by TBI. These data support previous suggestions of a role for endogenous opioids in TBI, and provide further evidence that mu and kappa opioid receptor subtypes in neocortex and hippocampus may have different functions in TBI.

Amino Acid Sequence↗

PubMedDate not supplied

A rapid method to identify cytotoxic T-lymphocyte peptide epitopes from HLA-A2 (+) donors.

It would be useful to develop a method to rapidly identify peptide epitopes for vaccine development. We present an algorithm that can predict sequences that have a high binding activity for HLA-A2. These sequences were able to induce specific cytolytic cells from human peripheral blood lymphocytes (PBMC). A computer-assisted algorithm was constructed to predict binding activity for HLA-A2, according to anchoring amino acid combinations. The human papillomavirus (HPV) type 18 E7 oncoprotein was used to test the algorithm. Peptides predicted to bind were synthesized and binding activity was determined by using the T2 cell assay. T2 cells pulsed with HPV-18 peptides were incubated with PBMC. Cytotoxicity assays were performed. From 110 possible sequences, four peptides were found to have a high binding activity. One of these peptides was able to induce significant lysis. Using this selection process only 3.6% of the total number of possible sequences was synthesized to identify an immunogenic peptide. Our algorithm with the T2 binding assay allows a rapid method to detect peptide epitopes.

Algorithms↗

PubMedDate not supplied

Treatment of refractory recurrent malignant glioma with adoptive cellular immunotherapy: a case report.

We report the successful treatment of a patient with recurrent malignant glioma with adoptive cellular immunotherapy. The patient is a young adult with recurrent progressive disease refractory to aggressive multi-modality therapy including repetitive surgical resection, radiation, radiosurgery and chemotherapy. He received multiple courses of local administration of autologous lymphokine-activated killer (LAK) cells in combination with a low dose of interleukin-2 (IL-2) through an Ommaya reservoir-catheter system. The side-effects of this treatment were limited and manageable. The patient achieved a complete remission, as demonstrated by MRI and confirmed by glucose-positron emission tomography (PET) imaging 11 months after initiation of immune therapy. Twenty-six months later, the patient is still in remission with improving performance status. Adoptive cellular immunotherapy utilizing autologous LAK cells with low dose IL-2 appears to be a safe and effective therapy for a subset of patients with primary, recurrent or progressive malignant glioma following conventional therapy.

Adult↗

PubMedDate not supplied

Adoptive cellular immunotherapy for the treatment of malignant gliomas.

UNLABELLED: The median survival for adults with recurrent primary malignant gliomas is 56 weeks following surgery, radiation, and chemotherapy. Generally, reoperation can extend the median survival an additional 26-32 weeks. We have developed an aggressive treatment program that utilizes low doses of interleukin-2 (IL-2) combined with ex vivo activated killer cells (LAK) infused via an indwelling catheter placed into the surgical resection cavity. Autologous leukocytes were collected during a standard 3-4 h, outpatient leukapheresis procedure, then activated ex vivo for 4-5 days with high doses of IL-2. The treatment protocol consisted of two 2-week cycles of therapy over a 6-week period. Patients with stable disease or objective response on follow-up MRI scans were retreated at 3-month intervals. Acute and cumulative IL-2-related toxicities were observed, but limited, and included fever, headache and transient neurologic irritation. Corticosteroid levels and usage were strictly controlled during immunotherapy, although higher doses were used intermittently to mitigate toxicity. Biologic changes included lymphocytic infiltration, regional eosinophilia, tumor necrosis, and the localized production of IL-2, IFN-gamma and IL-12, demonstrated by in situ hybridization and immunohistochemistry. SUMMARY: IL-2 plus autogeneic LAK cells can be safely administered intracavitary to treat high grade primary brain tumors with limited toxicity within the central nervous system. Six out of 28 patients had long-term survival of greater than 2 years post-reoperation plus immunotherapy with 2 patients alive over 8 years. The presence of a marked regional eosinophilia appeared to correlate with increased survival and may be predictive of a biologic and therapeutic response. Regional adoptive immune therapy was well tolerated and should be considered an option for patients with high-grade tumors refractive to standard therapeutic approaches.

Eosinophils↗

PubMedDate not supplied

Identification and preliminary validation of novel biomarkers of acute hepatic ischaemia/reperfusion injury using dual-platform proteomic/degradomic approaches.

Hepatic ischaemia/reperfusion (I/R), a major cause of liver damage associated with multiple trauma, haemorrhagic and septic shock, and liver transplantation, contributes significantly to multiple organ failure. Development of novel sensitive biomarkers that detect early stages of liver damage is vital for effective management and treatment of ischaemic liver injury. By using high-throughput immunoblotting and cation-anion exchange chromatography/reversed-phase liquid chromatography-tandem mass-spectrometry, we identified several hepatic proteins, including argininosuccinate synthase (ASS) and estrogen sulfotransferase (EST-1), which were degraded in the liver and rapidly released into circulation during I/R injury. ASS accumulated in serum within 10 min, reached a steady state at 30 min, and persisted up until 3 h after reperfusion following 30 min of total hepatic ischaemia. EST-1 appeared rapidly in blood and attained maximum within 1 hour followed by a decline at 3 h of reperfusion. No ASS or EST-1 protein was detected in serum of control or sham operated rats. ASS and EST-1 exhibited greater sensitivity and specificity toward I/R liver injury as compared with alanine aminotransferase (ALT), an established marker of hepatocellular necrosis. In contrast, serum ASS and EST-1 were undetectable in rats with chronic alcoholic liver disease, while the levels of ALT protein were significantly increased. In addition, ASS, but not EST-1 or ALT accumulated in blood only 6 h after treatment with hepatotoxic combination of lipopolysaccharide and D-galactosamine. These data demonstrate the utility of ASS and EST-1 as novel sensitive and specific biomarkers of acute liver ischaemic injury for prospective clinical studies.

Animals↗

PubMedDate not supplied

Histological study of the dentition of Tautoga onitis.

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

Pharmacological treatment of head injury--a new challenge.

Explore the source record for details and available documents.

Brain Injuries↗

PubMedDate not supplied

A new model of concussive brain injury in the cat produced by extradural fluid volume loading: I. Biomechanical properties.

This study presents a new device for producing experimental, concussive head injury together with a detailed description of biomechanical features of fluid percussion brain injury in the cat. Anaesthetized cats were subjected to multiple (N = 3) or single injuries (N = 87). The variables studied in repeated injury experiments included the volume of fluid injected intracranially, rate of fluid flow, and the associated pressure transients recorded extracranially in the injury device and intracranially at supratentorial and infratentorial sites. Peak fluid flow increased with increasing volumes of fluid loaded intracranially. Extracranial pressure peaks and durations increased when volume loading was increased. Extracranial and intracranial pressure transients were similar at all recording sites. The form of pressure transients recorded in single injury experiments was similar to that recorded in multiple injury experiments. In single injury experiments, the extracranial pressure peaks and durations also increased with increased intracranial fluid volume loading. The slopes describing the relationships between intracranial volume loading and extracranial pressure transients were significantly different in single and multiple injury experiments. Details of the design and use of the head injury device are also discussed.

Animals↗

PubMedDate not supplied

A new model of concussive brain injury in the cat produced by extradural fluid volume loading: II. Physiological and neuropathological observations.

This study examined physiological and histopathological changes in the cat produced by a new experimental fluid injury device. Spontaneously breathing (N = 14) and artificially ventilated (N = 45) cats were subjected to systemically varied magnitudes of fluid percussion brain injury. Within certain injury ranges, increasing magnitudes of fluid percussion injury produced increasing durations of apnea, as well as greater transient increases in mean arterial blood pressure, intracranial pressure and cerebral perfusion pressure. Acute increases in intracranial pressure may have been related to cerebral vasodilatation produced by the systemic hypertension following brain injury. Injuries associated with pressure transients greater than 10 atm ms produced concussive responses, including irreversible apnea in spontaneously breathing cats and temporary pupillary dilatation, increases in heart rate and mean arterial blood pressure in artificially ventilated cats. Injuries greater than 39 atm ms frequently produced histopathological and physiological indices of significant irreversible brain damage, including fixed and dilated pupils, systemic cardiovascular hypotension and deteriorating blood gases. Injury magnitudes less than 20 atm ms did not produce macroscopic evidence of histopathology, intermediate injury ranges produced increasing evidence of subarachnoid and petechial hemorrhage while injury levels greater than 40 atm ms frequently produced significant histopathology including massive hematomas. Injury greater than 10 atm ms resulted in opening of the blood-brain barrier, as assessed by extravasation of horseradish peroxidase. Injury greater than 19 atm ms produced suppression of EEG amplitudes which did not recover for up to 40 minutes after injury. These data provide detailed information on the physiological and histopathological consequences of fluid percussion injury in the cat and indicate that this modified fluid percussion apparatus can produce graded levels of brain injury similar to those previously reported for fluid percussion injury.

Animals↗