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Biomedical subjects

S Baig

Publications and source records attributed to S Baig.

At least 37 records · Page 2Linked to original sources

Obstetric outcome in 232 ovum donation pregnancies.

OBJECTIVE: To study the obstetric outcome of ovum donation pregnancies. DESIGN: A retrospective analysis of 232 ovum donation pregnancies in the six years from 1988 to 1993. SETTING: Infertility clinic in a private hospital. PARTICIPANTS: All ovum donation recipients that achieved pregnancy in the clinic during the stated time period. MAIN OUTCOME MEASURES: Percentages of live birth and miscarriages and ectopic pregnancies; number of sacs identified in the uterus at early (four weeks after transfer) and later scans; incidence of antepartum and postpartum haemorrhage; incidence of pregnancy-induced hypertension; incidence of preterm, low birthweight and small-for-gestational age babies; and incidence of operative deliveries. RESULTS: Of 232 pregnancies, 151 babies were born (live birth rate of 20%); and 81 were lost (57 before eight weeks, 17 after eight weeks and seven ectopic pregnancies). In nine cases there were no intrauterine sacs at the early scan (two 'chemical pregnancies' and seven ectopic pregnancies). In 169 cases there was initially one intrauterine sac, ending with 102 singleton deliveries (60%); in 47 cases there were initially two intrauterine sacs, ending with 11 singleton deliveries (23%) and 32 twin deliveries (68%); in the seven cases where three sacs were identified initially, there were no singleton deliveries, three twin deliveries (one selective fetal reduction) and three triplet deliveries. Women with premature ovarian failures had a significantly higher pregnancy rate compared with those with functioning ovaries (P < 0.02). However, in the former group, the miscarriage rate was also significantly higher (P < 0.03) so that the number of term births was similar. The incidence of vaginal bleeding was 12% in the first trimester, 1.5% in the second trimester, and 2% in the third trimester. The incidence of postpartum haemorrhage was 12%. Thirty-two women had pregnancy-induced hypertension (23% of all deliveries). This occurred in 22/105 singletons (21%), 7/32 twins (22%) and in all three (100%) of the triplets. In the singleton group 13% of infants were preterm, 18% had a birthweight < 2.5 kg and 15% were < 3rd centile for birthweight at delivery (small-for-gestational age). Ovarian function was found to be the only factor that significantly influenced the incidence of small-for-gestational age babies (odds ratio 8.84; 95% confidence interval 1.1-70.0; P = 0.007). The overall operative delivery rate was 85% with the caesarean section rate being 69%. CONCLUSIONS: Women who become pregnant following oocyte donation should be considered obstetrically as high risk, especially those with ovarian failure because of the increased incidence of small-for-gestational age infants in these pregnancies. They are also at higher risk of pregnancy-induced hypertension and postpartum haemorrhage.

Abortion, Spontaneous↗

Characterization of a cysteine proteinase from Taenia crassiceps cysts.

Human neurocysticercosis, due to infestation of the central nervous system with Taenia cysts, is a common cause of neurologic disease in endemic areas and is being increasingly recognized in the United States. Previous studies have suggested that Taenia cysts bind host IgG via Fc-like receptors and that bound IgG is degraded by the parasite, perhaps as a source of nutrients or a means of immune evasion. We now demonstrate that IgG degradation is thiol dependent and is inhibited by the cysteine proteinase inhibitor, E-64. The cysteine proteinase activity from Taenia crassiceps cysts was purified 682-fold by acid extraction, gel filtration chromatography, and anion-exchange FPLC. The cysteine proteinase appeared as a 43 kDa band on silver-stained gels. Its isoelectric point was 5.27. The purified enzyme was inhibited by cysteine proteinase inhibitors and also by chloromethyl ketone inhibitors, but not significantly by other inhibitors of serine, aspartic, or metallo-proteinases. Substrate studies showed pronounced cleavage of Z-Phe-Arg-7-amino-4-trifluoromethylcoumarin (Z-Phe-Arg-AFC), but not of substrates with neutral or positively charged amino acids in the P2 position. Km for Z-Phe-Arg-AFC was 1.0 x 10(-7) M, Kcat 58 s-1, and Kcat/Km 5.8 x 10(8) mol-1s-1. Amino acid sequencing of the amino terminus revealed a single cysteine residue with surrounding residues suggestive suggestive of a cysteine proteinase active site. The sequence, however, did not contain the conserved active site associated with enzymes of known cysteine proteinase families. This cysteine proteinase may play an important role in the interaction of Taenia cysts and host immunoglobulin and is a potential target for antiparasitic chemotherapy.

Amino Acid Sequence↗

Management of children with acute respiratory infections (ARI) by general practitioners in Multan - an observational study.

A knowledge, attitude and practices (K.A.P.) survey was conducted among doctors working as general practitioners (GP) in Multan, for diagnosis and management of acute respiratory infections (ARI) in children under five years of age. GPs in Multan were not familiar with national ARI control programme and rational drug use guidelines. They rarely asked about symptoms describing severity of disease while taking patient histories and did not look for signs of severe pneumonia during physical examinations. Most patients diagnosed as URTI (upper respiratory tract infection) received oral antibiotics and those with pneumonia received injectable antibiotics. Other drugs prescribed included cough syrups, antihistamines and antipyretics. The average number of drugs prescribed per patient was 3.4. The doctors were deficient in providing home care advice for sick children to the caretakers. Average time spent by doctors on each patient was two minutes and twenty-three seconds. A combination of biomedical and social factors help to perpetuate this irrational prescribing behaviour of the GPs. Continuing education programmes for doctors in general practice about ARI management in children and rational use of drugs and health education of the public may improve the current prescribing practices.

Acute Disease↗

Taenia saginata oncosphere excretory/secretory peptidases.

To identify oncosphere excretory/secretory peptidases, Taenia saginata adult worms were collected from 3 patients. Eggs were hatched and activated in vitro and oncospheres cultured in vitro. The culture medium from the oncospheres was assayed with peptide substrates coupled to 7-amino-4-trifluoromethyl coumarin (AFC), and free AFC was detected fluorometrically. The endopeptidase substrates Z-Phe-Arg-AFC and Z-Arg-AFC as well as the aminopeptidase substrate Arg-AFC were hydrolyzed when incubated with spent media from the oncospheres compared to control culture medium removed prior to incubation. Hydrolysis of Z-Phe-Arg-AFC was inhibited 78% by preincubation of the medium with the serine proteinase inhibitor Phenylmethylsulfonyl fluoride. Endopeptidase activity was partially enhanced in the presence of exogenous thiols and partially inhibited with the cysteine proteinase inhibitor E-64, suggesting the presence of both serine and cysteine endopeptidases. No significant inhibition was noted with pepstatin or phenanthroline. The peptidase activities detected with Z-Phe-Arg-AFC and Arg-AFC were separated by gel-filtration fast protein liquid chromatography and eluted at volumes corresponding to molecular weights of 18 and 30 kDa, respectively. These data demonstrate that T. saginata oncospheres produce excretory/secretory peptidases, including serine and cysteine endopeptidases and an aminopeptidase. These enzymes may play a role in invasion of the intestinal mucosa of the intermediate host.

Amino Acid Sequence↗

Increased cerebrospinal fluid concentration of nitrite in Parkinson's disease.

The concentration of nitrite, a metabolite of nitric oxide (NO), was increased in the cerebrospinal fluid (CSF) of untreated patients with Parkinson's disease and in patients treated with L-DOPA in comparison with a group of patients without dopaminergic dysfunction. There was no difference in the concentration of L-arginine (ARG), a precursor of NO, between the groups. There was a highly significant, linear relationship between the concentration of nitrite and ARG in the CSF suggesting that the production of NO is dependent on the availability of ARG. The results support the possibility that production of NO is increased in the brain in Parkinson's disease.

Aged↗

High performance liquid chromatography as a tool in the definition of abnormalities in monoamine and tryptophan metabolites in cerebrospinal fluid from patients with neurological disorders.

In this study we report the levels of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid, homovallinic acid, tryptophan, 5-hydroxyindole-3-acetic acid and serotonin in lumbar cerebrospinal fluid (CSF) from patients with multiple sclerosis, cerebrovascular disease and muscular tension headache the later, as healthy controls. The separation of these substances was performed on a reversed phase column by ion pair high performance liquid chromatography and detection was made by a glassy carbon electrode set at +900 mV vs Ag+/AgCl. The whole separation was achieved within 25 min. Concentrations of all substances (10-1000 pmole/L) were linearly proportional to areas obtained. The system is sensitive, stable and reproducible. The significance of CSF levels of these metabolites from patients groups compared with healthy controls are discussed.

Biogenic Amines↗

Use of high performance liquid chromatography in defining the abnormalities in the free amino acid patterns in the cerebrospinal fluid of patients with aseptic meningitis.

Free amino acids were quantitatively determined in cerebrospinal fluid (CSF) and plasma samples from patients with aseptic meningitis by a newly developed high performance liquid chromatographic (HPLC) method. The method of analysis was based on precolumn derivatization of orthophthaladehyde in the presence of 2-mercaptoethanol and detection was made at Eex = 340 nm and Eem = 450 nm. The method was sensitive and the limit for detection was less than 1 pmol for most of the amino acids. It took 45 min to separate 26 amino acids with highly reproducible results, giving a coefficient of variance for retention times and integrated areas less than 0.4% and 2%, respectively, after five replicate runs. The results accumulated in 10 patients were compared statistically with 11 age-matched healthy controls. Among the amino acids almost all the neurotransmitter candidates, such as aspartic acid, glutamic acid, glutamine, glycine, tyrosine, phenylalanine and gamma-aminobutyric acid (GABA), were significantly increased in the patients' CSF, whereas arginine and threonine were low. No change was observed in plasma amino acids in patients as compared to healthy controls. The higher levels of most of the neurotransmitters, especially GABA, aspartic acid and glutamic acid, could be used diagnostically in assessing the progression and remission in aseptic meningitis.

Adult↗

Cells secreting anti-MAG antibody occur in cerebrospinal fluid and bone marrow in patients with polyneuropathy associated with M component.

Occurrence and distribution of cells secreting antibodies against myelin associated glycoprotein (MAG) were studied in 9 patients with polyneuropathy associated with the monoclonal (M) component in serum. Utilizing an immunospot assay, we found that 4 of 7 patients with polyneuropathy associated with an IgM M component had cells secreting anti-MAG IgM antibody in cerebrospinal fluid (CSF) numbering between 1 per 212 and 1 per 3333 mononuclear cells. All 7 patients had cells secreting anti-MAG IgM antibody in bone marrow (median value 1 per 2000 cells). In contrast, peripheral blood from only 2 of these patients contained low numbers of such cells. One patient with polyneuropathy associated with an IgA M component had cells secreting anti-MAG IgA antibody in CSF, and 1 with an IgG M component had cells secreting anti-MAG IgG antibody in CSF; both patients also had anti-MAG IgM antibodies detectable in CSF only by ELISA. These 2 patients may thus have concurrent intrathecal production of antibodies of 2 different isotypes which are directed against the same or different epitopes of MAG. The production of antibodies directed against a component of myelin occurring in the immediate vicinity of the peripheral nervous system might be involved in the pathogenesis of the polyneuropathy.

Adult↗

Multiple sclerosis: cells secreting antibodies against myelin-associated glycoprotein are present in cerebrospinal fluid.

We evaluated the B-cell response in cerebrospinal fluid (CSF) and blood by enumerating cells secreting antibodies to myelin-associated glycoprotein (MAG) and, for reference, to myelin basic protein (MBP), two myelin components which may constitute targets for autoimmune attack in multiple sclerosis (MS). Among 25 untreated MS patients, 12 had cells in CSF secreting anti-MAG IgG antibodies (mean value 1 per 1429 CSF cells) and three also had cells secreting anti-MAG antibodies of the IgM isotype but at lower levels. In CSF from 2 out of 10 MS patients examined, anti-MAG and anti-MBP IgG antibody-secreting cells were present concurrently. Antibody-secreting cells were less frequent in blood and bone marrow, reflecting compartmentalization to CSF. Anti-MAG antibody-secreting cells were found in CSF from only 1 out of 27 control patients. The intrathecal production of anti-MAG and anti-MBP antibodies may be important in the pathogenesis of MS.

Adult↗

Anti-Borrelia burgdorferi antibody response over the course of Lyme neuroborreliosis.

Characteristic findings on examination of cerebrospinal fluid (CSF) in Lyme neuroborreliosis include mononuclear pleocytosis, oligoclonal immunoglobulin G (IgG) bands, and evidence for local production of specific antibodies. We utilized an immunospot assay to detect cells secreting anti-Borrelia burgdorferi antibodies of different isotypes over the course of disease. Such cells were detected in CSF from 13 consecutive patients with neuroborreliosis examined before treatment. IgG antibody-secreting cells were present in high numbers (mean, 32 cells per 10(4) CSF cells), whereas IgA and IgM antibody-secreting cells were found less frequently and at lower numbers (mean, 5 and 6 cells per 10(4) CSF cells, respectively). Clinical improvement after penicillin treatment was paralleled by a rapid decline of antibody-secreting cells in CSF, but they were still detected, although at lower numbers, in 5 of 10 patients examined more than 6 months after treatment. This specific B-cell response persisted despite clinical improvement. Whether it reflects persistence of antigen is unsettled.

Adult↗

Immunoglobulin producing cells in bone marrow and blood of patients with multiple sclerosis and controls.

Multiple sclerosis (MS) is characterised by intrathecal synthesis of IgG, less frequently of IgA and IgM. Local production of antibodies to myelin basic protein (MBP) and other myelin components has also been reported, and autoimmune pathogenesis has been postulated. Whether MS is accompanied by a systemic B cell response is less clear. To elucidate this question, we examined bone marrow and peripheral blood from patients with MS and controls for cells secreting IgG, IgA and IgM, as well as anti-MBP antibodies of these three isotypes. Patients with MS without any signs of concurrent infections had higher numbers of IgG + IgA + IgM secreting cells both in bone marrow and peripheral blood compared with healthy controls. The same abnormalities were observed in patients with other inflammatory neurological diseases (OIND). When analysing individual isotypes, patients with MS and OIND had higher numbers of IgA secreting cells both in bone marrow and blood compared with healthy controls. Only one of 13 MS patients examined had anti-MBP antibody secreting cells in bone marrow and blood. The systemic B cell response registered in MS is also present in other inflammatory neurological diseases and its specificity and possible role in the pathogenesis of MS remains unknown.

Adult↗

Cells secreting antibodies to myelin basic protein in cerebrospinal fluid of patients with Lyme neuroborreliosis.

An autoimmune response to myelin basic protein (MBP) has been proposed to participate in the development of the chronic neurologic manifestations that may accompany Borrelia burgdorferi-induced Lyme disease. Using an immunospot assay, we counted cells secreting antibodies to MBP. Anti-MBP IgG antibody-secreting cells were detected in CSF from eight of 13 consecutive patients with Lyme neuroborreliosis irrespective of stage of disease. The numbers were between 1/370 and 1/5,000 CSF cells (mean, 1/1,250 in the 13 patients). The highest numbers were encountered in two patients with severe signs of CNS involvement. The numbers decreased in parallel with clinical improvement after treatment. Anti-MBP IgG antibody-secreting cells were also observed in the CSF from patients with a variety of other inflammatory diseases of the nervous system, and their role in the development of tissue damage remains unsettled. Anti-MBP IgG antibody-secreting cells were not detected in the patients' blood, reflecting accumulation of this autoantibody response to CSF.

Adult↗

Antimyelin basic protein and antimyelin antibody-producing cells in multiple sclerosis.

The B-cell response to myelin and myelin basic protein was studied in patients with multiple sclerosis and in patients with acute aseptic meningoencephalitis by using a nitrocellulose immunospot assay. This method allows detection of single cells producing antibodies. Twenty-seven (79%) of 34 patients with multiple sclerosis had cells producing IgG antibodies against myelin, and 11 (57%) of 19 had cells producing IgG antibodies against myelin basic protein in cerebrospinal fluid (CSF), with mean values of 30 and 14 per 10(4) mononuclear cells, respectively. Total numbers of IgG-producing cells occurred at a mean number of 75 per 10(4) CSF cells. Cells producing antimyelin or anti-myelin basic protein antibodies of IgA or IgM isotypes were rarely found in CSF. Patients with acute aseptic meningoencephalitis less frequently showed CSF cells producing IgG antibodies against myelin and myelin basic protein. No cells producing antibodies against myelin or myelin basic protein were detected in peripheral blood of patients with multiple sclerosis or meningoencephalitis. Thus, a majority of patients with multiple sclerosis had CSF cells that produced IgG antibodies against myelin and myelin basic protein. These cells comprised a large proportion of the total IgG-producing cells. A pronounced B-cell response against autoantigens produced at the target for immune attack might be important in the pathogenesis of multiple sclerosis.

Adult↗

Persistent anti-myelin basic protein IgG antibody response in multiple sclerosis cerebrospinal fluid.

Antibodies to myelin components, such as myelin basic protein (MBP), may play a role in pathogenesis of multiple sclerosis (MS) but results from determinations of anti-MBP antibodies are inconsistent. Enumeration of cells secreting antibodies represents a new approach to evaluate a specific antibody response regarding extent and localization, and reduces effects of e.g. antibody binding to target. Anti-MBP IgG antibody secreting cells were present in MS patients' cerebrospinal fluid (CSF) at a mean value of 1 per 833 cells, and they amounted to a mean value of about 2454 in the whole CSF compartment. Similar numbers were encountered in patients with other inflammatory neurological diseases (OIND). During follow-up, anti-MBP IgG antibody secreting cells persisted regarding frequency and numbers in MS, but decreased in OIND. Such cells were rarely detected in patients with tension headache. No correlations to clinical exacerbation of MS, disability or duration were discernable. In blood from MS and OIND patients, anti-MBP IgG antibody secreting cells were detected infrequently and at low numbers. The anti-MBP antibody response is strongly restricted to the IgG isotype. The anti-MBP IgG antibody response which is persistent and compartmentalized to the diseased organ, may be important for the development of MS.

Adult↗

B cells expressing CD5 are increased in cerebrospinal fluid of patients with multiple sclerosis.

By two-colour flow cytometric analysis, we found increased numbers of B cells co-expressing the pan-T cell marker CD5 and the B cell marker CD19 in cerebrospinal fluid (CSF) of 21 patients with multiple sclerosis (MS), compared with 17 control subjects with muscular tension headache. Only one patient with MS, but nine controls lacked CD5+ B cells in CSF. This difference was not observed in peripheral blood. Numbers of CD5+19+ B cells were increased in CSF compared with blood in MS, but not in the controls. In both groups, CD5+19+ B cells were not restricted to small resting lymphocytes, but were also found among larger-sized lymphocytes. The relative density of CD5 molecules and of CD19 molecules was lower in CD5+19+ than in CD5-19+ B cells and CD5+19- T cells. CD5+ B cells are assumed to be responsible for autoantibody production, and our results suggest a pathogenetic role of such cells, predominantly within the central nervous system, in MS.

Adult↗

Predominance of Borrelia burgdorferi specific B cells in cerebrospinal fluid in neuroborreliosis.

A nitrocellulose immunospot assay that allows the counting of cells secreting IgG, IgA, or IgM antibodies to Borrelia burgdorferi was used to compare B cell response to B burgdorferi at the cellular level in cerebrospinal fluid (CSF) and blood from patients with neuroborreliosis with that in patients with aseptic meningoencephalitis (AM) or non-inflammatory neurological diseases. 13 of the 14 patients with untreated neuroborreliosis had CSF cells secreting IgG antibodies to B burgdorferi (mean 17 cells per 10(4) CSF cells), whereas 8 of 12 patients examined had cells secreting IgA antibodies (mean 6 cells) and 10 of 12 had cells secreting IgM antibodies (mean 6 cells) per 10(4) CSF cells. IgG antibody producing cells predominated except in 2 patients with mainly or only IgM secreting cells. Cells secreting antibodies to B burgdorferi were rarely found in the blood and then at very low numbers, which reflects preferential compartmentalisation of the specific B cell response to the CSF. The cells were not detectable in CSF or blood from the two control groups. Evaluation of humoral immunity at the cellular level is a novel approach to the detection and localisation of immune events in neuroinflammatory disorders.

Adolescent↗

Distribution of plasma cells secreting antibodies against nervous tissue antigens during experimental allergic encephalomyelitis enumerated by a nitrocellulose immunospot assay.

The B cell response to central nervous system (CNS) myelin and myelin basic protein, as well as total numbers of IgG secreting cells, was studied in acute experimental allergic encephalomyelitis using a nitrocellulose immunospot assay. The method was able to detect single plasma cells secreting antibodies. Cells secreting antibodies against myelin antigens were detected in regional lymph node cell suspension by day 5 post-immunization (p.i.). At that time no anti-myelin antibodies were detected free in serum. Later, at day 15 p.i., specific antibody secreting cells were found in bone marrow and spleen indicating a generalization of the immune response. The B cell response became partly sequestered to the target of immune attack since an increased number of IgG secreting cells was detected among mononuclear cells recovered from the CNS. Studies of cellular secretion of antibodies rather than free levels in body fluids may be a more accurate reflection of the in vivo B cell response. These findings may be generally considered in studies of B cell mediated immunity in neuroinflammatory diseases.

Animals↗

Immunoglobulin-secreting cells in the cerebrospinal fluid from patients with muscular tension headache.

Intrathecal B cell function in healthy subjects has been poorly elucidated. Although there are measurable quantities of immunoglobulins (Ig) in the cerebrospinal fluid (CSF) of 'normal' individuals, it is not clear whether this reflects transudation from serum or is due to some production within the central nervous system. We have therefore isolated cells from CSF to assess the frequency of Ig-secreting cells, utilizing a nitrocellulose immunospot assay for enumeration of the IgG-, IgA- and IgM-producing cells per 10(4) mononuclear cells (MNC) isolated from CSF and blood. Contrary to previous belief, the CSF obtained from 22 of 23 'normal' subjects (95%) with muscular tension headache but no evidence of organic neurological disease contained 2-50 (mean 20) IgG-secreting cells per 10(4) MNC. The corresponding peripheral blood specimens contained 0-6 (mean 3) IgG-secreting cells per 10(4) MNC. The proportion of IgG-secreting cells among MNC is thus about 7-fold higher in CSF than in blood of healthy individuals. IgA- and IgM-producing cells were also found in normal CSF, but less frequently than cells secreting IgG and at proportions similar to those in peripheral blood. We suggest that there is continuous production of Ig of different isotypes in CSF, even in subjects without any signs of neurological disease.

Adult↗