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Biomedical subjects

J Ohman

Publications and source records attributed to J Ohman.

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

Complement activation in the central nervous system following blood-brain barrier damage in man.

The central nervous system (CNS) is virtually isolated from circulating immunological factors such as complement (C), an important mediator of humoral immunity and inflammation. In circulation, C is constantly inhibited to prevent attack on host cells. Since a host of diseases produce an abnormal blood-brain/cerebrospinal fluid (blood-brain/CSF) permeability allowing C protein extravasation, we investigated if C activation occurs in CSF in vitro and in CNS in vivo during subarachnoid hemorrhage (SAH) or brain infarction. After SAH (n = 15), the terminal complement complex (TCC) concentration on days 0 to 2 was higher in the CSF, 210 +/- 61 ng/ml, than in the plasma, 63 +/- 17 ng/ml, but null in the CSF of controls (n = 8) or patients with an ischemic stroke (n = 7). TCC was eliminated from the CSF after SAH (24 +/- 10 ng/ml on days 7 to 10). Incubation of normal human CSF with serum in vitro also activated the terminal C pathway. In 10 fatal ischemic brain infarctions, immunohistochemical techniques demonstrated neuronal fragment-associated deposition of C9 accompanied by neutrophil infiltration. We conclude that the C system becomes activated intrathecally in SAH and focally in the brain parenchyma in ischemic stroke. By promoting chemotaxis and vascular perturbation, C activation may instigate nonimmune inflammation and aggravate CNS damage in diseases associated with plasma extravasation.

Adult↗
PubMed1996

Isolation and characterization of a trisulfide variant of recombinant human growth hormone formed during expression in Escherichia coli.

A new variant of human growth hormone was recently found [Pavlu, B. & Gellerfors, P. (1993) Bioseparation 3, 257-265]. We report here the identification and the structural determination of this variant. The variant, which is formed during the expression of human growth hormone in Escherichia coli, was found to be more hydrophobic than rhGH as judged by its prolonged elution time by hydrophobic interaction chromatography. The rhGH hydrophobic variant (rhGH-HV) was isolated and subjected to trypsin digestion and RP-HPLC analysis, resulting in an altered retention time of one single tryptic peptide as compared to the corresponding fragment of rhGH. This tryptic peptide constitutes the C-terminus (aa 179-191) of hGH and contains one of the two disulfide bridges in hGH, viz. Cys182-Cys189. Amino acid sequences and composition analyses of the tryptic peptide from rhGH-HV (Tv18-19) and the corresponding tryptic peptide from rhGH (T18+19) were identical. Electrospray mass spectrometry (ES MS) of Tv18+19 isolated from rhGH-HV revealed a monoisotopic mass increase of 32.7, as compared to T18+19 from rhGH. A synthetic Tv18+19 peptide having a trisulfide bridge between Cys182 and Cys189 showed identical fragment in ES/MS compared to Tv18+19 isolated from rhGH-HV, i.e. m/z 617.7 and 682.9. These fragments are formed through a unique cleavage in the trisulfide (Cys182-SSS-Cys189) bridge not found in the corresponding T18+19 disulfide peptide. Furthermore, the synthetic Tv18+19 co-eluted in RP-HPLC with Tv18+19 isolated from rhGH-HV. Two-dimensional NMR spectroscopy of the synthetic T18+19 and Tv18+19 peptides were performed. Using these data all protons were assigned. The major chemical shift changes (delta delta > 0.05 ppm) observed were for the beta-protons of Cys182 and Cys189 in Tv18+19 as compared to T18+19. CD spectroscopy data were also in agreement with the above results. Based on these physico-chemical data rhGH-HV has been structurally defined as a trisulfide variant of rhGH. The receptor binding properties of rhGH-HV was studied by a biosensor device, BIAcore. The binding capacity of rhGH-HV was similar to rhGH with a binding stoichiometry to the rhGHBP of 1:1.6 and 1:1.5, respectively, indicating that the trisulfide modification did not affect its receptor binding properties.

Amino Acid Sequence↗
PubMed1994

Prediction of psychosocial recovery after head injury with cognitive tests and neurobehavioral ratings.

A series of 53 patients was studied using a battery of tests and a neurobehavioral rating scale on average 4 months after closed-head injury (CHI). Social outcome was assessed 1 year after injury by interviewing a family member. The results supported the hypothesis that tests of flexibility and programming rather than tests of cognitive skills predict psychosocial recovery after CHI. Spatial Learning with Self-Set Goals and Sorting were measures of flexibility and programming. Contrary to expectation, word fluency performance was unrelated to these measures, but was associated with conventional intelligence tests, which did not predict psychosocial recovery. Cognition/Energy deficit on the Neurobehavioral Rating Scale and increased age were useful predictors of poor psychosocial outcome, whereas computed tomography findings or the Glasgow Coma Score were weakly related to the outcome indices. Evidently, cognitive flexibility and mental programming are very important psychological prerequisites of social recovery after CHI.

Adolescent↗
PubMed1992

Cognitive test performances related to early and late computed tomography findings after closed-head injury.

Computed tomography (CT) findings from early (less than 24 hours) and late scan (6 months) after closed-head injury (CHI) were compared to cognitive test scores obtained on an average of 4 months after injury in a consecutive series of 53 patients. The presence of parenchymal lesion was associated with poor test results, indicating cognitive inflexibility and disinhibition of routine response tendencies in novel tasks. These deficits have previously been found to be related in particular to frontal-lobe dysfunction, but the present study did not support the hypothesis that frontal lesion is the principal cause of this impairment in CHI. Parenchymal lesions in the right and left hemisphere were associated with spatial and verbal deficits, respectively. Ventricular enlargement in the late CT was related to cognitive inefficiency, both being strongly associated with age. The results suggest that parenchymal lesion in the early CT is an indicator of diffuse axonal injury, which results in cognitive inflexibility during recovery.

Adolescent↗
PubMed1991

A trial of the effect of nimodipine on outcome after head injury.

We performed a randomised prospective double blind trial to study the effect of the calcium antagonist nimodipine on the outcome of head injured patients. The subjects were not obeying commands at the time of entry to the study, within 24 hours of injury. One hundred and seventy-five patients received nimodipine IV, 2 mg per hour for up to 7 days and 176 received placebo. The two groups were well matched for important prognostic features. Six months after injury 93 (53%) of the nimodipine group and 86 (49%) of the control group had a favourable outcome (moderate/good recovery). The relative increase in favourable outcomes (8%) was not significant but is compatible (95% C.I.) with an increase in favourable outcomes in treated patients by 33% or a decrease by 12%. Nimodipine was well tolerated and there were few adverse reactions; means of systolic and diastolic blood pressures and the intracranial pressure did not differ between the groups. It is unlikely that nimodipine has a marked effect on outcome (ie an increase in favourable outcome of greater than 15%) after head injury of this severity but the study does not exclude a modest but clinically useful benefit.

Adult↗
PubMed1991

Angiographic vasospasm and release of platelet thromboxane after subarachnoid hemorrhage.

We studied adenosine diphosphate-induced platelet aggregation and the associated release of thromboxane B2 in 49 patients with subarachnoid hemorrhage in relation to angiographic vasospasm. Postoperative cerebral angiography was performed less than or equal to 3 (median 1) days after surgery for an aneurysm 5-14 days after subarachnoid hemorrhage. Correspondingly, one sample from each patient was taken within 24 hours either before or after angiography. The occurrence of severe as well as diffuse, moderate, or severe angiographic vasospasm was associated with the presence of delayed cerebral ischemia (p less than 0.05). Patients with diffuse angiographic vasospasm had significantly higher (p less than 0.05) values for thromboxane B2 release than the others, even after adjustment by the clinical grades on admission and before surgery, the timing of surgery, the time from subarachnoid hemorrhage to angiography and blood sampling, and nimodipine therapy. Severe and diffuse angiographic vasospasm were also associated with poor outcome at 1 year (p less than 0.05). Our results suggest that augmented release of platelet thromboxane may be involved in the pathogenesis of vasospasm in large cerebral arteries.

Adenosine Diphosphate↗
PubMed1991

Recurrent parotitis and sialectasis in childhood. Clinical, radiologic, immunologic, bacteriologic, and histologic study.

Twenty children with juvenile recurrent parotitis, between 3 months and 16 years of age at onset, were followed up over a period of 7 to 22 years. Radiologic, histopathologic, cytologic, immunologic, and bacteriologic studies were performed to investigate the cause of sialectasis, commonly found in juvenile recurrent parotitis, and the pathogenesis of the disease. It was considered that a combination of a congenital malformation of portions of the salivary ducts and infections ascending from the mouth following dehydration of the children are contributory to the pathogenesis of the disease. The results of the investigations into the cause of the disease appear to exclude an auto-immunologic response or an allergic condition, an immature immune response, mumps, a sensitivity to upper respiratory tract infection, and familial factors.

Adolescent↗
PubMed1991

Long-term effects of nimodipine on cerebral infarcts and outcome after aneurysmal subarachnoid hemorrhage and surgery.

A total of 213 patients with verified aneurysmal subarachnoid hemorrhage (SAH) of Grades I to III (Hunt and Hess classification) were enrolled in a double-blind placebo-controlled trial to determine the effect of intravenous nimodipine on delayed ischemic deterioration and computerized tomography (CT)-visualized infarcts after SAH and surgery. The administration of the drug or matching placebo was started immediately after the radiological diagnosis of a ruptured aneurysm had been made. Of the 213 patients enrolled in the study, 58 were operated on early (within 72 hours after the bleed: Days 0 to 3), 69 were operated on subacutely (between Days 4 and 7), and 74 had late surgery (on Day 8 or later). Eleven patients died before surgery was undertaken and one was not operated on. A follow-up examination with CT scanning, performed 1 to 3 years after the SAH (mean 1.4 years), revealed no significant differences in the overall outcome between the groups. However, nimodipine treatment was associated with a significantly lower incidence of deaths caused by delayed cerebral ischemia (p = 0.01) and significantly lower occurrence of cerebral infarcts visualized by CT scanning in the whole population (p = 0.05), especially in patients without an associated intracerebral hemorrhage on admission CT scan (p = 0.03).

Adolescent↗
PubMed1991

Risks factors for cerebral infarction in good-grade patients after aneurysmal subarachnoid hemorrhage and surgery: a prospective study.

A prospective series of 265 patients with aneurysmal subarachnoid hemorrhage (SAH) of Grades I to III (Hunt and Hess classification) upon admission were evaluated as to neurological outcome and computerized tomography (CT) findings 1 to 3 years (mean 1.4 years) after the SAH and surgery. A total of 73 patients underwent acute surgery (within 72 hours after the bleed: Days 0 to 3), 86 were operated on subacutely (between Days 4 and 7), and 91 had late surgery (on Day 8 or later). Fifteen patients died before surgery was undertaken and another 20 patients died during the follow-up period. A total of 104 patients received nimodipine and the rest of the patients received either placebo (109 patients) or no medication (52 patients). A logistical regression analysis revealed the following prognostic factors for cerebral infarction, in order of importance: the amount of blood on the primary CT scan; postoperative angiographic vasospasm; the timing of the operation; and a history of hypertension. The use of nimodipine was associated with a significant reduction of cerebral infarcts visualized by CT scanning in patients who received intermediate or late surgery. In patients who underwent acute surgery no significant difference between the incidence of cerebral infarcts was observed.

Adolescent↗
PubMed1991

Effect of intrathecal fibrinolytic therapy on clot lysis and vasospasm in patients with aneurysmal subarachnoid hemorrhage.

A prospective series of 30 patients with a single, angiographically verified aneurysmal subarachnoid hemorrhage (SAH) was studied for the effect of intrathecal thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) on outcome, angiographic vasospasm, and computerized tomography (CT) findings after surgery. The patients included fulfilled the following criteria: operation was performed by Day 3 after the hemorrhage, CT showed only blood in the basal cisterns, and the patient had a single aneurysm or multiple aneurysms that could be treated surgically at the same operation. The patients were divided into groups of 10, with patients receiving 3, 10, or 13 mg of rt-PA in a single intracisternal injection at the end of the operation. There were no differences between the treatment groups in overall outcome. One patient from the 3-mg rt-PA group developed a postoperative intracerebral hemorrhage, and one patient from the 10-mg rt-PA group had a postoperative epidural hematoma. There was one death in the 13-mg rt-PA group that was caused by inclusion of a segment of pericallosal artery in the clip. In all treatment groups a reduction was observed in the amount of blood seen on the postoperative CT scans compared to the preoperative CT scans. The reduction in SAH grade between the 10-mg and 13-mg rt-PA groups was significant (p less than 0.05). The difference in the severity of angiographic vasospasm between the 3-mg and 13-mg rt-PA groups was also significant (p less than 0.05).

Adolescent↗
PubMed1990

Social outcome related to cognitive performance and computed tomographic findings after surgery for a ruptured intracranial aneurysm.

A series of 83 patients was examined with a battery of cognitive tests, a clinical interview, and computed tomography 1 year after surgery for a ruptured intracranial aneurysm. Disability on the Glasgow Outcome Scale (33%), failure to return to work (25%), impaired social relations (25%), and subjective or clinical mental impairment (56%) were found to be related to each other and to poor performance on cognitive tests, especially to verbal impairments in patients with left lateral infarctions and to memory deficits and cognitive inflexibility in patients with frontal medial infarctions. Furthermore, cognitive deficits and poor outcome were associated with diffuse brain damage. Depression and anxiety were unrelated to test performances, but were frequently reported by patients with right lateral infarctions.

Adult↗
PubMed1990

Hypertension as a risk factor for epilepsy after aneurysmal subarachnoid hemorrhage and surgery.

A prospective, consecutive series of 307 patients with aneurysmal subarachnoid hemorrhage ranging from Grades 1 to V according to the classification of Hunt and Hess on admission were evaluated to determine the incidence of epilepsy 1 to 3 years (mean, 1.4 years) after aneurysmal subarachnoid hemorrhage (SAH) and surgery. Sixty-three patients had died and one patient was lost to follow-up. Twenty-nine patients developed epileptic seizures after the SAH and surgery. The mean time from the SAH to epileptic seizure varied from 0 days (day of the SAH) to 2 years (mean, 6.7 months). The seizures were classified as focal in 9 patients (31%) and as generalized in 20 patients (69%). All patients received anticonvulsant medication after more than one seizure. The risk factors for development of posthemorrhagic/postoperative epilepsy were, in order of importance: a history of hypertension; an infarct on late computed tomographic scan; and the duration of coma after the ictus. Of the 85 patients with histories of hypertension, 17 (20.0%) developed epilepsy. Only 12 (5.4%) of the 222 nonhypertensive patients developed epileptic seizures. The difference between the groups was significant (P = 0.0001). Computed tomographic scans were undertaken in 237 patients 1 to 3 years (mean, 1.4 years) after the SAH and surgery. Postoperative epilepsy was significantly associated with infarcts visualized on computed tomographic scan (P = 0.0005).

Adolescent↗
PubMed1989

Allergen-specific human T cell clones: derivation, specificity, and activation requirements.

The interaction between allergen and immune cells plays a pivotal role in the development of human allergy. In an attempt to understand this interaction, we have studied allergen-specific T cells in vitro. These T cells are derived from rodent-allergic individuals and are specific for a major allergen found in mouse urine (MA-1). Antigen-specific, major histocompatibility complex-restricted, human T cell clones have been generated by limiting dilution from lines derived from the peripheral blood T cells of allergic individuals. Antigen (Ag)-presenting cells are necessary for this response, and they can be modulated by appropriate agents. These clones can be propagated in vitro under conditions of restimulation with Ag in the presence of Ag-presenting cells without the continuous use of exogenous interleukin-2. Most clones are CD3+ or CD4+, but one clone is CD3+ CD8+ by fluorescence-activated cell sorter and monoclonal antibody-killing data. Ag stimulation of these clones induces them to produce interleukin-2 and proliferate. These T cell clones can provide a basis for studying the structure of allergenic epitopes and the potential role of altered Ag in the induction of T cell tolerance. If the determinants of T cell allergen recognition and tolerance are solved, it might provide a basis for a new approach to the immunotherapy of allergic disease.

Antibodies, Monoclonal↗
PubMed1989

Cognitive deficits related to computed tomographic findings after surgery for a ruptured intracranial aneurysm.

A consecutive series of 118 patients operated on for ruptured intracranial arterial aneurysms was studied. Ninety-six of them could be adequately examined with a battery of psychological tests and computed tomographic scans 1 year after a subarachnoid hemorrhage. Seventeen orthopedic control patients with no history of brain damage were also tested. The pattern of cognitive deficits was strongly related to the findings on the computed tomographic scans. Patients with left lateral infarctions had deficits on performances requiring verbal efficiency, including memory and classification tasks, whereas patients who had right lateral infarctions were poor on a visuoconstructional task (the copying of Rey's Figure). These deficits were pronounced when lateral infarction was associated with diffuse brain damage. Patients with frontal medial infarctions had low scores on memory tests; the inefficiency in verbal fluency, categorical reasoning, and memory was related to diffuse brain damage. The patients who had no infarctions did not differ significantly from the control group. Cognitive impairments after left lateral and frontal medial infarctions, as well as diffuse brain damage, correlated with the Glasgow Outcome Scale.

Brain↗