Heat shock proteins as targets for gamma-delta T cells in multiple sclerosis.
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Artifacts↗
Biomedical subjects
M Salvetti
Publications and source records attributed to M Salvetti.
Experimental allergic encephalomyelitis and multiple sclerosis: immunoregulatory mechanisms and T cell repertoires.
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Antibody Formation↗
T-lymphocyte reactivity to the recombinant mycobacterial 65- and 70-kDa heat shock proteins in multiple sclerosis.
Owing to their conservation and immunogenicity, heat shock proteins (hsps) represent a class of potential autoantigens. Moreover, they could be targets for gamma delta T lymphocytes, which are prominent in various immune disorders. We studied the T cell proliferative primary responses to recombinant M. bovis 65 kDa hsp (hsp65) and M. tuberculosis 70 kDa hsp (hsp70) in 31 patients with multiple sclerosis (MS), 19 patients with other neurological diseases (OND) and 19 healthy individuals. Positive responses to hsp70, but not to hsp65 were significantly more frequent in patients with MS than in patients with OND or in healthy individuals. In order to verify and refine these results and to characterize the hsp reactive T lymphocytes, we screened 147 PPD-specific long-term T cell lines (76 from 10 patients with MS and 71 from 12 healthy donors) for their proliferative response to hsp65 and hsp70. hsp70-reactive T lines were significantly more common in patients with MS than in healthy controls. The number of T lines responding to hsp65 increased in the MS group only slightly. In 19 T lymphocyte lines from patients with MS and healthy donors, a cytofluorometric analysis was performed with special attention paid to distinct T cell receptor gamma delta determinants. With one exception, in each line the population of gamma delta T cells remained a minority. We conclude that an increased T cell response to mycobacterial hsp70 may be present in patients with multiple sclerosis.
Adolescent↗
Structural brain correlates of neurologic abnormalities in multiple sclerosis.
We examined the relationship between cerebral magnetic resonance imaging (MRI) findings and urinary dysfunction in 70 consecutive patients with definite multiple sclerosis. MRI-weighted lesion scores for seven different brain regions were recorded according to the number and size of cerebral lesions. Thirty-two subjects (46%) had urinary symptoms and 38 (54%) were asymptomatic. Subjects with urinary symptoms exhibited greater overall functional disability and a higher midbrain MRI-weighted lesion score than asymptomatic patients. No statistically significant group differences were found for the other brain regions.
Adolescent↗
Embolization and chemoembolization for hepatocellular carcinoma.
A check on the rationale for embolization and chemoembolization for hepatocellular carcinoma and a revisit to the background of the anatomy of blood supply to the liver is discussed. The technique of the embolization is different and mostly in the range of home made configuration. There is no data concerning the stability of different choices such as the popular mixture of cytotoxic agents and lipiodol. Therefore the authors have preferred the use of microencapsulated Mitomycin believing that this special formulation of the drug can attain the present best reproducibility. The survival of 32 treated patients was longer than the control group. Twelve, 36 and 60 month survival was 70%, 45% and 15% vs 37%, 0%, and 0% respectively.
Capsules↗
Tumour necrosis factor-alpha synthesis by cerebrospinal-fluid-derived T cell clones from patients with multiple sclerosis.
T-cell clones derived from the CSF (cerebrospinal fluid) of MS (multiple sclerosis) patients have been analysed for the production of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interleukin-4 (IL-4). Each CSF-T clone (both CD4+ and CD8+) produced substantial amounts of IFN-gamma and especially TNF-alpha compared with autologous peripheral T clones and liver-infiltrating T clones from patients with chronic active hepatitis. The large quantities of TNF produced by CSF-T cell clones suggest an important role for this cytokine in MS immunopathogenesis.
Adult↗
Hemianopic ataxic hemiparesis. A case report.
Ataxic hemiparesis and homonimous hemianopia developed in a hypertensive 60-year-old woman. Magnetic resonance imaging detected multiple lesions in the territory of distribution of the posterior cerebral artery and in the inferior region of the left cerebellar hemisphere. At computed tomography only a right hypodense area involving the posterior right thalamus, the postero-medial region of the temporal lobe and the occipital lobe was evident.
Ataxia↗
[Combined use of real-time digital subtraction radioscopy and computerized tomography: potential advantages in diagnostic and interventional radiology].
The idea of combining fluoroscopy and CT arose from the daily practice in diagnostic and interventional radiology. A Diasonics OEC high-performance image intensifier complete with a digital subtraction system was connected to a Siemens Somatom-DRH CT scanner to work in tandem. CT is used for a localization in-depth and fluoroscopy for the subsequent maneuvers within an organ or body compartment. With this combination, complex procedures such as transarterial portography, percutaneous embolizations, pain treatment and manipulation for catheterization of the bile ducts and urinary tract could be performed in one place and in one session. CTF is especially useful when patients should not be moved about from room to room or undergo an examination in several sessions, as it happens with children or critically ill or contagious patients.
Adult↗
Flexibility and efficacy of automatic continuous fluorodeoxyuridine infusion in metastases from a renal cell carcinoma.
Complete and lasting control of diffuse metastases from a renal cell carcinoma has been achieved by automatic continuous infusion of a single cytotoxic agent, fluorodeoxyuridine (FUDR). A patient with a single brain metastasis from renal cell carcinoma developed pulmonary, mediastinal, and retroperitoneal metastases after radical nephrectomy. A Medtronic Synchromed pump (Medtronic Inc., Minneapolis, MN) was implanted for the circadian systemic infusion of FUDR in 14-day courses with 14-day drug-free intervals. A complete response (CR) at all sites, was obtained in 3 months, and maintained for 22 months. After a second brain metastasis, treated by radiation therapy and cisplatin as radiosensitizer, a CR was obtained again and is now of 31 months' duration, which is four times the record to date. The overall hospitalization was 2 days. Acceptance of the pump is excellent and it functions precisely and reliably. This case should stimulate greater interest in techniques of automatic continuous infusion of cytostatics, given its greater efficacy and lower toxicity.
Brain Neoplasms↗
Acetylcholine receptor-specific T-lymphocyte clones in the normal human immune repertoire: target epitopes, HLA restriction, and membrane phenotypes.
Potentially autoimmune T-lymphocyte lines specific for the nicotinic acetylcholine receptor of the neuromuscular junction have been isolated previously from patients with myasthenia gravis. We report on the isolation and expansion of T cells specific for the acetylcholine receptor of Torpedo californica or for a recombinant mammalian acetylcholine receptor alpha chain peptide (X4), from the peripheral blood of 11 healthy donors. Two major T-cell epitopes, located between amino acid positions 44-104 and 141-172, were identified using a panel of overlapping mammalian alpha chain fusion proteins. Most T lines recognized the acetylcholine receptor epitopes in the molecular context of HLA-DR molecules. Unexpectedly, all the T. californica acetylcholine receptor-specific T lines obtained from one DR4 (DRw53), DQw3 donor and two DR4, w8 (DRw53), DQw3 donors were restricted by DRw53 product(s). Using DR gene-transfected L cells as antigen presenters, in 4 lines, a close relationship between the recognized epitope and the restricting DR element was revealed. The membrane phenotype of the T. californica acetylcholine receptor-and X4-specific T lines was predominantly CD4+CD8-, with some CD4+CD8+ components. It did not significantly differ from that of control, tuberculin purified protein derivate-specific T lines raised from the same donors. These findings are in harmony with previous ones demonstrating the presence of potentially autoimmune T-lymphocyte clones within normal immune repertoires.
Antigens, CD↗
Staging of hepatocellular carcinoma by ultrasonography, computed tomography, and angiography: the role of CT combined with arterial portography.
A series of 60 patients with hepatocellular carcinoma (HCC) were evaluated over a 2-year period of ultrasonography (US), computed tomography (CT), and angiography. The angiographic studies carried out with intraarterial digital technology were compared to both US and CT of the liver. In 16 of 60 patients, we observed discordance of the findings obtained with angiography, CT, and US. We therefore compared these three methodologies in those cases where diagnostic discordance was noted. In our experience, US had a sensitivity of 73.4%, 76.7% for CT, and 95% for angiography. In 13 of 60 patients, we performed CT with arterial portography (CTAP) which demonstrated a better resolution than conventional CT. In view of the sensitivity of US - comparable to that of CT - and for the even greater sensitivity of intraarterial digital angiography, we performed an US study of patients at risk of HCC. CT was found to play a diagnostic/staging role after angiographic study has been performed, especially when enhanced by arterial portography.
Adult↗
Circadian continuous chemotherapy of renal cell carcinoma with an implantable, programmable infusion pump.
The authors treated 42 metastatic renal cell carcinoma (RCC) patients who had received no previous chemotherapy or radiation therapy with circadian venous continuous infusion of 5-fluoro-2-deoxyuridine (FUDR). The drug was delivered by Medtronic Synchromed implantable pump (Medtronic, Inc., Minneapolis, MN) in 14-day cycles alternating with 14-day intervals of heparinized physiologic saline infusion. In the course of 24 months 444 cycles of therapy have been given for a total of 12449 days of pump function. Of the patients observed for at least 3 months (range, 3 to 23 months; median, 7 months) three showed complete response (7%; 95% confidence interval, 0% to 15%), three partial response (7%; confidence interval, 0% to 15%), 18 stable disease, and 18 showed progression. Eighteen patients, all with advanced disease at the time of implantation, were living 6 months after treatment started. Circadian continuous central venous infusion of FUDR is minimally toxic. The FUDR can be delivered safely and conveniently in this way for long spans. This therapy is as active as any currently available treatment, is administered in an entirely outpatient setting, and is associated with a normal quality of life.
Adult↗
Multiple sclerosis and HTLV retroviruses.
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Adult↗
Susceptibility and resistance of human autoimmune T cell activation to the immunoregulatory effects of transforming growth factor (TGF) beta 1, beta 2, and beta 1.2.
The transforming growth factors type beta (TGF-beta) regulate immune responses by suppressing a variety of leukocyte functions. Using a panel of human autoimmune T cell lines specific for the acetylcholine receptor (AchR) we investigated the immunoregulatory effects of TGF-beta 1, TGF-beta 2, and TGF-beta 1.2. The cytokines have identical effects inhibiting activation of most T line cells and the activation-dependent changes in interleukin-2 (IL-2) receptor and T cell receptor expression. IL-2-dependent growth was not modulated by TGF-beta. However, autoimmune T cell lines specific for AchR differ in their susceptibility to TGF-beta and some are completely refractory. Resistance of autoimmune T cell activation to immunosuppressive cytokines might be an element in the development of chronic autoimmune disease.
Antigens, Surface↗
[Rare vascular complications of Behçet's disease (so-called angiobehçet)].
Vascular involvement in Behçet's disease is rare and may cause life-threatening complications. We report on 3 patients who presented with vascular problems in the course of the illness. (1) A 37-year-old woman suffered multiple pulmonary artery aneurysms (PAA) 3 years after the first symptoms of Behçet's disease (BD) had been noted. They completely regressed under three-month high-dose corticosteroid therapy and remission has lasted now for 2 years. (2) The second patient, a 22-year-old man, developed 2 vascular complications of BD: first (1986-1987), he was shown to have a sinus venous thrombosis which resolved under prednisone and oral anticoagulation therapy. Then (1988) he presented with multiple large PAA and high fever. Despite marked radiological regression of the multiple PAA under high-dose prednisone treatment, he remained symptomatic. Repeated hemoptysis in September 1988 prompted us to add cyclosporine A in a dosage providing whole blood levels of 250-350 ng/ml. Four months later pulmonary radiological studies had normalized, but manifestations of BD on the skin and mucosa remained unchanged. 7 months after starting Cy A therapy the patient died suddenly of massive hemoptysis. (3) The third patient, a 23-year-old Spanish immigrant, had a diagnosis of BD when presenting with sinus thrombosis. Later he underwent surgery 3 times for false aneurysms of the common femoral artery which developed at the site where he had been punctured for angiography.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Systemic hypertension as a treatable risk factor for cerebrovascular disease.
It has long been established that hypertension is the major risk factor for stroke. Three Italian studies have been reviewed in order to examine different aspects of the problem. In the first study, the role played by the systolic, diastolic and systodiastolic components of hypertension in causing atherosclerotic damage of extracerebral and intracerebral arteries was examined. At the extracranial level, a significant correlation between systolic hypertension and atherosclerotic lesions was evident. The second study evaluated the risk of major stroke, myocardial infarction and death in patients with transient ischemic attacks and reversible ischemic neurologic deficits. Possible prognostic predictors of these events were thoroughly considered: Cumulative survival with the multivariate Kaplan-Meier analysis was significantly lower in hypertensive than in normotensive subjects, particularly for cerebral deaths and for all deaths. The third study was aimed at assessing the risk factors for transient ischemic attacks and stroke in young adults. Again, hypertension emerged as a fundamental risk factor, significantly more frequent in the subgroup of older patients than in the younger subgroup.
Age Factors↗
[Percutaneous biopsy of paracardiac masses].
Computed tomography was used to guide 55 biopsies on paracardiac masses. The authors' experience, gained with over 800 thoracic biopsies, points to CT as the method of choice for paracardiac masses, especially in those cases where the masses are located close to mediastinal and cardiovascular structures, which are not easily evaluated with fluoroscopy and, therefore, imply a greater bioptic risk. Furthermore, CT allows a more accurate needle trajectory to be selected than fluoroscopic guidance does. A diagnosis was reached in 47 of 55 cases, with 85% diagnostic accuracy. No complications such as hemoptysis, hemothorax, pericarditis and hemopericardium were observed. Only one patient required drainage after pneumothorax.
Biopsy, Needle↗
Changing prognosis of primary intracerebral hemorrhage: results of a clinical and computed tomographic follow-up study of 104 patients.
One hundred four consecutive cases of primary intracerebral hemorrhage hospitalized at the time of stroke were followed until death or for 1 year. All were treated nonsurgically. The 30-day mortality rate was 30%. Good clinical outcome and complete resolution of the lesion on computed tomography were observed in 49 and 13% of patients, respectively. Age, state of consciousness, and size of the hemorrhage on computed tomography scan were reliable prognostic indicators. The long-term survival rate, 66%, was higher than that previously reported and should be considered in future trials evaluating medical and surgical treatment of intracerebral hemorrhage.
Adult↗