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Biomedical subjects

P D Mehta

Publications and source records attributed to P D Mehta.

At least 19 recordsLinked to original sources
PubMed1992

Effect of treatment on oligoclonal IgG bands and intrathecal IgG synthesis in sequential cerebrospinal fluid and serum from patients with subacute sclerosing panencephalitis.

Oligoclonal IgG bands were analyzed in matching pairs of cerebrospinal fluid (CSF) and serum from 12 subacute sclerosing panencephalitis (SSPE) patients, using isoelectric focusing and immunofixation. Each patient was given isoprinosine, and four of the 12 patients were given alpha-interferon in addition. Two to 4 serial CSF and serum samples were collected from each SSPE patient during periods ranging from 1 to 16 months. In 3 SSPE patients a small number of new oligoclonal bands were seen in the follow-up CSF samples. In the other 9 SSPE patients there was no change in CSF band patterns between initial and follow-up specimens. Band patterns in serum remained unchanged between initial and follow-up samples. Although all 12 SSPE cases had higher IgG indices and increased rate of intra blood-brain barrier (BBB) IgG synthesis in comparison to patients with other neurological diseases, the values did not significantly differ between the first and follow-up specimens. We conclude that treatment of SSPE patients with isoprinosine or with isoprinosine and alpha-interferon had no significant effect on the CSF oligoclonal band profiles or IgG synthesis within the central nervous system.

Adolescent↗
PubMed1992

Increased levels of beta 2-microglobulin, soluble interleukin-2 receptor, and soluble CD8 in patients with subacute sclerosing panencephalitis.

We measured beta 2-microglobulin (beta 2-M), soluble interleukin-2 receptor (sIL-2R), and soluble CD8 (sCD8) antigen levels in paired cerebrospinal fluid (CSF) and sera from patients with subacute sclerosing panencephalitis (SSPE), multiple sclerosis (MS), and other neurological diseases (OND) using enzyme-linked immunosorbent assay. beta 2-M was significantly increased in CSF of the SSPE group compared to the MS or the OND group. Similarly, beta 2-M in the MS versus OND group was significantly increased in CSF. Although serum levels of beta 2-M were similar in the three groups, the CSF/serum ratios were higher in SSPE versus the MS group and in the MS versus the OND group. Levels of sIL-2R and sCD8 were higher in SSPE CSF than OND CSF; however, there were no differences between levels in SSPE and MS CSF. The levels of sIL-2R were increased in SSPE sera compared to those of MS or the OND group, whereas levels of sCD8 in serum from the three groups were similar. The findings of increased CSF/serum ratio of beta 2-M and higher levels of serum sIL-2R and CSF sCD8 in SSPE patients are consistent with those seen in patients with acute and chronic viral infections. When the levels between the initial and follow-up CSF and serum samples from SSPE patients were compared, the data showed that CSF levels of sCD8 elevated during periods of clinical worsening and decreased during clinical improvement. In contrast, serum beta 2-M decreased during periods of worsening and increased during improvement. The measurement of serum beta 2-M and CSF sCD8 may be useful in SSPE patients as markers to monitor disease activity.

Adolescent↗
PubMed1992

Intravenous gamma globulin in progressive MS.

In an attempt to prevent disease exacerbations, intravenous gamma globulin (500 mg to 2 g/kg) plus methylprednisolone was administered monthly to 14 patients with progressive multiple sclerosis, 11 of whom were steroid dependent. Seventeen exacerbations of disease activity were seen in 11 patients over a mean follow-up period of 7.8 months. Four exacerbations occurred in 3 patients within one month of receiving 1.6 to 2.0 g/kg of intravenous gamma globulin (IVGG). Most exacerbations occurred within 2 weeks of steroids being tapered; thus a steroid sparing effect of IVGG could not be demonstrated. We conclude that IVGG plus methylprednisolone can be given safely at monthly intervals for a prolonged period but in the dosage administered did not prevent exacerbations in 80% of patients with progressive multiple sclerosis.

Adult↗
PubMed1991

Immunolocalization of Alzheimer beta-amyloid peptide precursor to cellular membranes in baculovirus expression system.

One characteristic of Alzheimer's disease (A beta disease) is the accumulation of amyloid deposits within the extracellular space of the brain and meninges. A 40 amino acid peptide called beta-peptide or A4 protein is the subunit of the amyloid fibrils found in these deposits. The sequence of beta-peptide is contained within those of a family of larger proteins called the Alzheimer beta-amyloid peptide precursor (APP). These APPs contain, in addition to a signal sequence, a hydrophobic sequence that is believed to span cell membranes. Although biochemical studies indicate that some APPs have properties of integral membrane proteins, morphological confirmation of this has not been reported. We recently described an expression system in which human APP751 cDNA was placed under the transcriptional regulation of the polyhedrin gene promoter in the baculovirus Autographica californica infecting a Spodoptera frugiperda cell line (Ramakrishna et al., Biochem Biophys Res Commun 174:983-989, 1991). As part of a larger biochemical and molecular biological study of APP, we have carried out an immunocytochemical study using antibodies directed against several epitopes within APP to reveal, at both the light and the electron microscopic levels, the cellular localization of APP in the baculovirus expression system. These studies demonstrate that APP751 is abundantly synthesized and inserted into certain of the membrane compartments of the cell. As early as 24 hr postinfection, APP751 is found associated with all membrane compartments excepting mitochondrial membranes. The patterns of immunolabeling are consistent with our biochemical findings that the protein is processed in these cells so as to release the extracellular domain and to retain a transmembrane and intracellular segment. These data provide the first morphological demonstration of the membrane location of APP751, its posttranslational processing to a secreted fragment, and its exclusion from the mitochondrial membranes. This system is especially valuable for identifying conditions under which antibodies raised against APP or appropriate synthetic peptides will react with native APP.

Amyloid beta-Protein Precursor↗
PubMed1991

Increased free light chains in the urine from patients with multiple sclerosis.

We quantitated free kappa (kappa) and lambda light (L) chains in coded urine specimens from subjects with clinically definite multiple sclerosis (MS) (N = 56), other neurologic diseases (OND) (N = 30), and age-matched normal controls (N = 28). Urine from MS patients showed statistically significant increases in free L chains compared with the other groups, although there was overlap between MS patients and OND patients. The ratio of kappa/creatinine was significantly greater in the relapsing-remitting MS group than in patients with clinically stable MS, OND, and normal controls. Elevated free L chains were usually independent of urinary albumin and beta 2-microglobulin levels. Serial studies showed that urinary free kappa/creatinine ratios were elevated during periods of clinical worsening in seven of eight MS patients and subsequently decreased during clinical recovery. The measurement of free L chains in urine obtained at intervals from MS patients may be useful as a marker to monitor disease activity.

Albuminuria↗
PubMed1991

Diagnostic usefulness of cerebrospinal fluid in multiple sclerosis.

Multiple sclerosis (MS) is one of the most common demyelinating diseases of the central nervous system affecting adults between the ages of 20 and 40 years. Clinically, it is characterized by episodes of exacerbations and remissions. Although the cause of MS is unknown, it is generally believed that one or more infectious agents triggers an autoimmune response that causes myelin destruction. There is no known cure for this disease; however, early diagnosis is helpful in the management of patients with MS. The diagnosis of MS is commonly made on the basis of established clinical criteria. No specific laboratory diagnostic test exists, but detection of abnormalities in cerebrospinal fluid (CSF) is a useful aid to support the clinical diagnosis of MS. This review describes the most common CSF abnormalities. These include (a) elevation of immunoglobulin G (IgG), IgG index and IgG synthesis rate; and (b) detection of oligoclonal IgG bands in the CSF by electrophoresis and isoelectric-focusing procedures.

Adult↗
PubMed1990

Immunologic consequences of taurine deficiency in cats.

Our results show that a lack of taurine in the diet of cats results in a significant leukopenia, a shift in the percentage of polymorphonuclear and mononuclear leukocytes, an increase in the absolute count of mononuclear leukocytes, and a change in the sedimentation characteristics of white cells. Functional studies of polymorphonuclear cells isolated from cats fed taurine-free diets show a significant decrease in the respiratory burst as measured by chemiluminescence as well as a decrease in phagocytosis of Staphylococcus epidermis compared to cats fed the same diet containing taurine. In addition, serum gamma globulin in cats fed taurine-free diets was significantly increased compared to taurine-supplemented cats, indicating that other immune cells may be affected by taurine deficiency. Histological examination of lymph nodes and spleen revealed regression of follicular centers with depletion of reticular cells, mature and immature lymphocytes (B cell areas), as well as mild extravascular hemolysis. These results indicate that there are profound immunologic consequences in cats with prolonged taurine deficiency.

Animals↗
PubMed1990

Detection of myelin basic protein-like material in cerebrospinal fluid of multiple sclerosis patients by immunoblot assay.

Myelin basic protein (MBP)-like material in 15 cerebrospinal fluid (CSF) samples from patients with multiple sclerosis (MS) was analyzed by isoelectric focusing (IEF) followed by immunoblot assay using rabbit antiserum against human MBP- peptide 69-89, which contains the dominant epitope for MBP-like material. Samples from seven of 10 MS patients with disease in the exacerbation stage showed one band and in three other samples, a number of faint bands also appeared in the alkaline pH region in addition to the one band. CSF from five MS patients whose disease was in remission showed no detectable bands. Our results are consistent with those obtained by quantitative assay, reported in the literature.

Amino Acid Sequence↗
PubMed1990

Measles virus-specific immunoglobulin D antibody in cerebrospinal fluid and serum from patients with subacute sclerosing panencephalitis and multiple sclerosis.

Quantitation of measles-specific immunoglobulin D (IgD) antibody was carried out in cerebrospinal fluid (CSF) and serum samples from 18 patients with subacute sclerosing panencephalitis (SSPE), 12 patients with multiple sclerosis (MS) and seven normal controls with high measles antibody titers in serum, using polyclonal and monoclonal antibodies specific for human IgD and enzyme-linked immunosorbent assay. Measles-specific IgD activity was significantly higher in CSF and serum from SSPE patients compared to that found in patients with MS or normal controls. The IgD antibody to measles virus was not due to high levels of measles-specific IgG since significant measles IgD activity was found after eluting IgG from SSPE serum. The increased level of measles-specific IgD found in SSPE sera is consistent with the levels observed in patients with acute and chronic viral infections.

Enzyme-Linked Immunosorbent Assay↗
PubMed1990

Identification of IgG subclasses' oligoclonal bands in multiple sclerosis CSF.

IgG subclasses' oligoclonal bands in unconcentrated CSF from MS patients were detected by isoelectric focusing in agarose gel with subsequent immunoblotting using mouse monoclonal antibodies to human IgG subclasses and double-antibody avidin-biotin-alkaline phosphatase system. All MS CSF showed presence of oligoclonal bands specific to the IgG1 subclass; in addition, several of these samples also had oligoclonal bands specific to IgG3, IgG2, or IgG4, in order of decreasing frequency. Since the CSF of a greater number of MS patients showed oligoclonal bands specific to the IgG1 and IgG3 subclasses, the findings are consistent with those reported in patients with chronic viral infections and autoimmune diseases.

Humans↗
PubMed1989

Distribution of IgG subclasses in human colostrum and milk.

Immunoglobulin G (IgG) subclasses in human colostrum and milk were quantitated using mouse monoclonal antibodies specific for human IgG subclasses and an enzyme-linked immunosorbent assay (ELISA). The percentage of IgG1 was significantly increased and that of IgG2 was decreased in both colostrum and milk relative to the percentage distribution reported in healthy adult and maternal sera. Percentages of IgG3 and IgG4 in colostrum, milk and sera were similar. All IgG subclass concentrations decreased by 90% during the first week of lactation and remained constant thereafter. The possible antiviral role of high levels of IgG1 in colostrum and milk is discussed.

Age Factors↗
PubMed1989

Immunoglobulin G subclass antibodies to measles virus in patients with subacute sclerosing panencephalitis or multiple sclerosis.

Mouse monoclonal antibodies specific for human immunoglobulin G (IgG) subclasses and a sensitive immunoassay were used to evaluate the IgG subclass antibody response to measles virus antigens in cerebrospinal fluid and serum samples from 20 patients with subacute sclerosing panencephalitis (SSPE), 12 patients with multiple sclerosis (MS), and 11 controls with high measles virus antibody titers in serum. In patients with SSPE, measles virus-specific antibodies were found mainly in the IgG1 subclass and the IgG subclass distribution remained unchanged, irrespective of the clinical stage or duration of the disease. In patients with MS and in controls, measles virus activity was also associated mainly with IgG1. However, the activity was significantly lower than that found in patients with SSPE. The results suggest that there is no primary abnormality in humoral immune response to measles virus in patients with MS. The disproportionately high levels of the measles virus-specific IgG1 subclass found in patients with SSPE may be due to persistent antigenic stimulation or reflect a defect in immunoregulatory mechanisms in response to viral infection.

Adolescent↗
PubMed1988

Comparison of oligoclonal immunoglobulin G bands in multiple sclerosis cerebrospinal fluid by immunoblotting and immunofixation.

We previously analyzed unconcentrated cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and other neurologic diseases by isoelectric focusing in agarose gel. We have now developed an immunoblot method for detection of oligoclonal IgG bands in unconcentrated MS CSF. The oligoclonal IgG band patterns seen after immunoblotting were compared with those of conventional immunofixation. Although immunoblotting was found to be rapid the resolution and intensity of oligoclonal IgG bands were somewhat better after immunofixation. Since immunofixation is simpler than immunoblotting, we recommend that clinical laboratories use immunofixation after isoelectric focusing to detect oligoclonal IgG bands in CSF.

Humans↗
PubMed1987

Specificity of oligoclonal IgG bands against myelin proteins in chronic relapsing EAE in guinea pigs.

We showed previously by using imprint electroimmunofixation that the oligoclonal IgG in sera and CSF from chronic relapsing EAE in guinea pigs were specific to spinal cord and Mycobacterium tuberculosis. We now show that most oligoclonal IgG bands are directed predominantly against isolated myelin basic protein (MBP). Activity to the latter could be removed from sera or CSF by absorption with MBP but not with histone or lysozyme. The oligoclonal IgG reacted weakly with isolated proteolipid apoprotein, and lacked reactivity to myelin-associated glycoprotein. When the oligoclonal IgG activity to myelin proteins was removed from the sera by absorption with a preparation of delipidated myelin before imprint electroimmunofixation, a few bands in some sera still reacted with whole spinal cord homogenate. These results indicate that, in some sera, a part of the oligoclonal IgG was directed against non-myelin proteins or lipids. In contrast to chronic relapsing EAE, CSF oligoclonal IgG from patients with multiple sclerosis showed no reactivity against human brain homogenate, whole myelin, delipidated myelin, and MBP in imprint electroimmunofixation.

Animals↗
PubMed1987

Quantitation of IgG and albumin in CSF and serum from multiple sclerosis patients by enzyme-linked immunosorbent assay.

Immunoglobulin G (IgG) and albumin from unconcentrated cerebrospinal fluid (CSF) and serum of patients with multiple sclerosis (MS) and non-MS controls were quantitated using enzyme-linked immunosorbent assay (ELISA). The IgG levels, IgG/albumin ratios and IgG indexes were significantly increased in CSF of MS patients compared to those of non-MS controls. The method is sensitive, rapid and reproducible and can be applied to routine laboratory use for quantitation of IgG and albumin in unconcentrated CSF from humans as well as in experimental animals used as models for demyelinating diseases.

Albumins↗
PubMed1986

Oligoclonal immunoglobulin bands in cerebrospinal fluid of a patient with lymphocytic choriomeningitis.

We describe a patient with meningitis caused by lymphocytic choriomeningitis virus. Oligoclonal IgG bands were found in the patient's cerebrospinal fluid during acute and convalescent stages of the illness, and results of liver function tests were abnormal. Acute attacks of lymphocytic choriomeningitis virus infection in humans can be added to the list of diseases associated with cerebrospinal fluid oligoclonal IgG.

Adult↗