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Biomedical subjects

D W Paty

Publications and source records attributed to D W Paty.

At least 127 records · Page 7Linked to original sources

Differentiation of glioblasts from adult brain.

Rat glial (RG) cells have established in continuous culture using sections of kainic acid-lesioned rat striata as the primary cell source. Such cultures consistently provided at least 2 morphologically distinguishable cell types. More than 95% of this population was composed of large, flat cells which possessed ill-defined junctions and lacked cellular processes. The second class of cells comprised less than 5% of the population, was smaller and had several processes per cell. Dibutyryl cyclic-AMP (dB-cAMP), which has been shown to promote a maturation-stimulating effect on embryonic glioblasts in vitro, appears to have a similar effect on RG cells. In the presence of 1 mM dB-cAMP virtually all RG cells undergo morphological transformation, becoming smaller and denser, in addition to forming several processes per cell. Furthermore, two cell-type-specific markers could be detected in dB-cAMP-treated cultures: the surface oligodendrocyte-specific galactocerebroside (GC) moiety was demonstrated to be present on less than 10% of the cells, whereas the intracellular astrocyte-specific glial fibrillary acidic (GFA) protein could be readily detected in 80% of the population. These data indicate that glia derived from the striata of injured adult rat brain exhibit fetal characteristics.

Animals↗

The effect of dibutyryl cyclic AMP on restricted replication of rubella virus in rat glial cells in culture.

Normal adult rat glial (RG) cells in culture have been shown to restrict rubella virus (RV) replication, permitting the synthesis of only five of the seven intracellular viral polypeptides associated with a normal, productive infection. Recently uninfected RG cells have been reported to differentiate into mature glia in the presence of dibutyryl cyclic AMP (dB-cAMP), suggesting that the RG cells may be a continuous cell line of undifferentiated glioblasts. This communication describes the effect of dB-cAMP on rubella-infected RG cells. Following exposure to dB-cAMP, RV antigens could be demonstrated in the cytoplasm of the differentiating glioblasts, all seven intracellular RV polypeptides could be detected following immune precipitation, slab gel electrophoresis, and autoradiography, and infectious progeny virions could be titered from the tissue culture medium. These data indicate that dB-cAMP promotes glioblast maturation and a concomitant activation of RV replication.

Animals↗

Suppressor T-lymphocytes in multiple sclerosis: analysis of patients with acute relapsing and chronic progressive disease.

T cell-specific antigens as identified by the anti-Leu 1, anti-Leu 2a, and anti-Leu 3a monoclonal antibodies were quantitated in 31 normal control subjects, 21 adults with spinal cord injury, 58 patients with stable multiple sclerosis, 31 patients with chronic progressive multiple sclerosis, and 15 patients with multiple sclerosis in acute relapse. The only significant deviations from normal values were a slightly low mean T cell (Leu 1-positive) value in patients in acute relapse and a low suppressor T cell (Leu 2a-positive) mean value in patients with chronic progressive multiple sclerosis. We were unable to confirm previous studies using the OK series of monoclonal antibodies that reported low suppressor T cell levels (OKT5 and OKT8 positive) in patients with acute relapses. We suggest that modulation (a spontaneous or induced variability in the expression) of individual cell surface antigens may explain the differences seen between our study and other reported series.

Adult↗

The predictive value of cerebrospinal fluid electrophoresis in 'possible' multiple sclerosis.

We undertook a prospective study of 183 patients with monosymptomatic demyelination to determine the predictive value of the finding of cerebrospinal oligoclonal banding (OB) for the subsequent development of clinically definite multiple sclerosis. The results of this study indicate that patients with monosymptomatic demyelination who are OB positive are at significantly higher risk than those who are OB negative to develop clinically disseminated disease over the period of follow-up in this study. Positive OB is associated with a higher frequency of electrophysiological abnormalities than negative OB, suggesting that OB development correlates with the degree of biological dissemination. The observation that some patients develop OB during the course of the disease has practical implications for the follow-up of patients with unifocal disease and negative banding.

Adult↗

Spinal cord swelling in multiple sclerosis.

Three cases of subacutely progressive spinal paraparesis had myelographic evidence of spinal cord swelling suggesting the diagnosis of intramedullary tumour. The diagnosis of multiple sclerosis (MS) was made in each case with the aid of CSF protein electrophoresis, evoked responses and CT scan. Because acute MS may produce cord swelling simulating tumor or syrinx, these additional investigations may be necessary to make a correct diagnosis.

Adult↗

Suppression of experimental allergic encephalomyelitis in guinea/pigs by liposome-associated human myelin basic protein.

Human myelin basic protein (MBP) was inserted into phosphatidyl-serine liposomes and Hartley guinea pigs were treated with 1 or 2 injections of MBP-liposomes mixture by the intracardial route before an encephalitogenic challenge with MBP in CFA. Other groups of guinea pigs were pretreated with equivalent amounts of MBP in saline or of MBP in IFA. Of 24 untreated animals, 22 developed EAE and died or had to be sacrificed within 15 days after challenge. Only 4 of 29 guinea pigs treated with either 75 microgram or 112 microgram MBP-liposomes developed clinical signs of the disease. In the group pretreated with MBP in saline, 11 of 15 animals died, whereas in the MBP-IFA group, only 4 out of 10 died. Histologic modifications were also decreased in the MBP-liposomes and MBP-IFA groups, but in many instances, clinical normal guinea pigs showed disseminated perivascular infiltrates in the brain and spinal cord. Delayed hypersensitivity reactions to MBP were positive in all but 1 animal tested. Early T-rosette levels followed essentially the clinical course of the disease: they were drastically decreased 7 days after challenge in the untreated and MBP-saline-treated groups, but remained essentially normal in the MBP-liposomes group throughout the experiment. Lymphocyte transformation tests carried out in parallel with soluble MBP and with MBP-liposomes indicated that animals in certain groups responded preferentially to 1 form or the other of the antigen. Compared with prevailing procedures, the single i.v. injection of a relatively small amount of liposome-associated MBP appears to represent a promising approach for the antigen-specific suppression of EAE.

Animals↗

CSF electrophoresis in one thousand patients.

Agarose and/or cellulose acetate electrophoresis was performed on the CSF of one thousand patients. In patients with clinically definite multiple sclerosis (MS) (N = 267) 92.8% had oligoclonal banding (O.B.). In patients with possible MS (N = 283) O.B. was present in 31.1%. In patients with other neurological diseases (N = 450) O.B. was present in 8% (N = 36). Nineteen non-MS patients with positive O.B. had serum bands or disorders known to be associated with local immune response. The remaining 17 patients had no explanation for the oligoclonal banding. In the majority of these MS had not been a diagnostic consideration. CSF electrophoresis is the single most reliable laboratory test in multiple sclerosis and deserves incorporation into the diagnostic criteria for the disease.

Electrophoresis, Agar Gel↗

Spongiform encephalopathy of long duration: a family study.

Seven members of a family succumbed to prolonged dementing illnesses. In two, those dementia lasted 10 years, spongiform encephalopathy was found at autopsy. This duration of illness has not been a feature in other instances of familial Creutzfeldt-Jakob disease.

Adult↗

Chronic progressive myelopathy: investigation with CSF electrophoresis, evoked potentials, and CT scan.

Chronic progressive myelopathy (CPM) is a difficult clinical problem. Many patients who present with CPM turn out to have a spinal form of multiple sclerosis (MS), but until there is clear lesion dissemination, a definite clinical diagnosis cannot be made. We have looked for MS-related abnormalities in 72 patients with CPM. The mean age of onset was 42 years, mean duration was ten years, and mean Kurtzke disability rating was 4.5. Studies performed were cerebrospinal fluid electrophoresis for oligoclonal banding, pattern-reversal visual evoked responses, blink reflex latencies, and computerized axial tomography. Oligoclonal banding was found in 32 patients (44%), patterned visual evoked responses were abnormal in 32 (44%), and blink latencies were abnormal in 40 (56%). A least one of these studies was abnormal in 61 patients (85%) and at least two in 48 (66%). The CT scan was abnormal in 38 )53%), 36 with atrophy and 3 with low-density or enhancing lesions. These results suggest that at least 44% of patients with CPM may have MS that could be diagnosed by oligoclonal bands. Other physiological tests suggesting diffuse or disseminated disease bring the total to 85%. Only autopsy follow-up will tell us the exact diagnostic accuracy of these studies in this complex syndrome.

Adult↗

The use of baclofen in treatment of spasticity in multiple sclerosis.

Baclofen was used in a double-blind crossover placebo-controlled trial to treat spasticity in patients with multiple sclerosis (MS). While on Baclofen, patients obtained a significant (p less than 0.001) reduction in spasticity compared to controls. The drug was particularly effective in alleviating flexor and extensors spasms, as well as their associated pain. Side effects were common in this study, but were usually well tolerated by the patients. The commonest side effects were sedation, nausea and vomiting. There were no changes in hepatic, renal, or hematological function in any patients. Increase weakness due to loss of spasticity for support was also a fairly common complaint. The drug seems best indicated in patients in whom spasticity is not required for support or other activities of daily living. Careful monitoring of the patient is essential for effective use of this drug.

Adult↗

CSF electrophoresis: an adaptation using cellulose acetate for the identification of oligoclonal banding.

An adaptation of cellulose acetate electrophoresis for studying concentrated cerebrospinal fluid is described. Two hundred and twenty-one patients have been studied, and the specificity for multiple sclerosis and sub-acute sclerosing panencephalitis is discussed. This has been positive for oligoclonal banding (OB) in 79% of patients with clinically definite multiple sclerosis.

Cerebrospinal Fluid Proteins↗