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Biomedical subjects

J George

Publications and source records attributed to J George.

At least 19 recordsLinked to original sources

Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies: a model for T15-idiotype dominance.

Antibodies bearing the T15 idiotype dominate the murine primary immune response to phosphocholine (PC). Analysis of antigen binding of antibodies derived from V1:DFL16.1:JH1 (VH1) germline and N region-derived variant heavy (H) chains and kappa 22, kappa 24, and kappa 8 light (L) chains demonstrates that the T15H:kappa 22L (T15) antibody binds PC at least 20-40 times better than other antibodies derived from alternate germline forms of the VH1 H chain and kappa 22, kappa 24, or kappa 8 L chains. To achieve affinities in the same range as the T15 antibody, kappa 24 and kappa 8 L chain-containing antibodies must have H chains derived from variant N region or somatically mutated VH1 genes. Single amino acid differences at the VD junction of the various germline and N region variant VH1 H chains dictate the L chain that can associate with the H chain to produce a PC-specific antibody. Several H:L combinations give rise to T15 or M167 idiotype-positive antibodies that lack specificity for PC, and single amino acid substitutions or insertions at the VH1:D junction result in the loss of T15 or M167 idiotopes. Based on these observations, our data support a molecular model involving both preferential gene rearrangement and antigen-driven B cell selection to explain T15 idiotype dominance in the immune response to PC. In the absence of N region diversification, large numbers of neonatal B cells bearing the T15H:kappa 22L surface immunoglobulin M (sIgM) receptors would be selected and expanded by autologous or environmental PC antigen into the long-lived peripheral B cell pool.

Amino Acid Sequence

Prenatal diagnosis of tetrasomy 12p by in situ hybridization: varying levels of mosaicism in different fetal tissues.

Prenatal diagnosis of tetrasomy 12p is complicated by the discrimination of the 12p isochromosome from the duplication 21q as well as the level of mosaicism demonstrated in the particular tissue sampled. In this disease, a high percentage of chromosomally abnormal cells are generally found in fibroblastic cells, but lymphocyte karyotypes from the same individual may be normal. We report on the pregnancy of a 37-year-old female who presented to our centre at 16 weeks' gestation for genetic amniocentesis. Sonography of the fetus revealed dextrocardia and diaphragmatic hernia. Chromosome analysis of amniocytes demonstrated mosaicism of a 47,XY,+i(12p) line in 80 per cent of cells and a normal male line (20 per cent), consistent with the Pallister-Killian syndrome. Following termination, a 220 g male fetus of 18 weeks was examined. A flattened nose and low-set ears were noted. In situ hybridization with a chromosome 12 centromeric probe in lymphocytes and skin cells unequivocally confirmed the karyotype and showed the presence of a single centromere in the abnormal chromosome, suggesting a true isochromosome. Chromosome analysis of various fetal tissues was performed and the following percentages of abnormal cells were found: skin 100 per cent, chorion 50 per cent, placenta 30 per cent, and blood 80 per cent. The high frequency of tetrasomic cells in fetal blood at this early gestational age is noteworthy, since most reports of this syndrome show a very low percentage of abnormal cells postnatally.

Adult

Detection of feline immunodeficiency virus infection in bone marrow of cats.

Natural or experimental feline immunodeficiency virus (FIV) infection in cats is often associated with hematologic abnormalities which are similar to those observed in human immunodeficiency virus (HIV) infected patients. To determine if cells in bone marrow are infected with FIV and whether severity of hematopoietic disorder is correlated with the level of viral infection, bone marrow tissues from ten experimentally and two naturally FIV infected cats were examined by in situ hybridization for presence of FIV RNA. Seven of the 12 FIV infected cats were also naturally or experimentally coinfected with feline leukemia virus (FeLV). FIV RNA was detected mainly in megakaryocytes and unidentified mononuclear cells in the bone marrow of cats that were sick and had marrow hypercellularity and immaturity. These included all cats in the acute phase of FIV infection and two of seven long term FIV infected cats. One long term FIV infected cat with lymphosarcoma was also positive for FIV RNA in bone marrow cells. The other four long term FIV infected cats were relatively healthy, with normal bone marrow morphology, and were negative for FIV infected cells. Bone marrow from three non-infected and two cats infected with FeLV alone were also negative for FIV RNA by in situ hybridization. We concluded that megakaryocytes and mononuclear cells were targets of the viral infection and that the presence of FIV RNA in cells of the bone marrow correlated with marrow hypercellularity and immaturity, and severity of illness.

Animals

Delayed effects of acute oral and chronic inhalational exposure to methylparathion on learning and memory in rats.

Impairment of acquisition phase of the learning process was observed in rats even at 3 weeks after single oral exposure to the near-lethal dose of commercial grade methylparathion (MP) followed by atropine resuscitation. Though there was a trend towards memory impairment in this group of animals, memory retention was not significantly affected. Chronic inhalational exposure to MP (one exposure/day for 3 weeks) did not significantly alter learning or memory. No significant alteration in red blood cell or brain acetylcholinesterase levels were observed in either of the two groups. It appears that behavioural effects can persist even 3 weeks after exposure to acute near-lethal doses of the pesticide, as occurs in the clinical situation of suicidal attempts; while repeated exposure to no-observed-effect-level doses as occurs in farm and factory workers, may not be associated with behavioural changes.

Acetylcholinesterase

Selection of B cell clones and memory B cells.

During a humoral immune response, a variety of histological, cellular, and molecular changes occur within the immune system. In this review, we would like to summarize and integrate these changes with a view toward gaining insight into the process of clonal selection. We describe here how antigen receptor number limits the sensitivity of a B cell to transduce a signal in response to antigen. We have also seen that this limitation can be compensated for by expressing a higher affinity receptor for antigen. These data suggest that the down regulation of antigen binding receptors in germinal center cells might be designed to exploit anticipated increases in affinity that result from somatic hypermutation in these tissues. This hypothesis is consistent with observed biological changes that occur during an immune response and has bearing on both the mechanism of affinity maturation and generation of immunologic memory.

Animals

Yolk polypeptide gene expression in cultured Drosophila cells.

The transfer of chimaeric plasmids to Drosophila melanogaster cell lines has been examined as a system for investigation of the hormonal regulation of the genes coding for D. melanogaster yolk polypeptide 1 (YP1) and Locusta migratoria vitellogenin B (VgB). Constructs containing promoters and putative 5'-regulatory sequences from these genes, ligated to bacterial chloramphenicol acetyltransferase (CAT) coding DNA, were transfected into Drosophila Kc (Kc-H) and S3 cells, and transient expression of CAT was assayed. Activity was expressed both from the homologous promoter of pYP1CAT and from the heterologous locust promoter of pVgCAT at comparable levels. In S3 cells, with calcium phosphate-mediated transfer of pYP1CAT there was a twofold induction of CAT activity after the addition of 10(-6) M ecdysterone, but no hormonal stimulation was noted when the polycation polybrene was used to achieve transfection. For Kc cells, calcium phosphate was ineffective for transfection, and after transfection with polybrene neither pYP1CAT nor pVgCAT was induced by the juvenile hormone (JH) analog methoprene. It is concluded that S3 cells may be useful for investigating the molecular basis of gene regulation by ecdysteroids, but conditions suitable for the analysis of JH action have not yet been established.

Animals

Molecular cytogenetics of alpha satellite DNA from chromosome 12: fluorescence in situ hybridization and description of DNA and array length polymorphisms.

A 340-bp EcoRI fragment of alpha satellite DNA from human chromosome 12 has been isolated and used in molecular cytogenetic and genetic studies. The clone, pSP12-1, detects tandemly repeated 1.4-kb repeat units at the centromeric region of chromosome 12. By fluorescence in situ hybridization, biotinylated pSP12-1 is highly specific for chromosome 12 and has been used to confirm an i(12p) in a case of Pallister-Killian syndrome, both in metaphase spreads and in interphase nuclei. A dominant DNA polymorphism for the centromeric D12Z3 locus is detected with the enzyme TaqI. In addition, a high frequency of D12Z3 array length polymorphisms can be detected using pulsed-field gel electrophoresis. The D12Z3 array has been measured by pulsed-field gel electrophoresis to span approximately 2,250-4,300 kb at the centromeric region of chromosome 12.

Centromere

Osmotic fragility of erythrocytes in Bolivian and Brazilian squirrel monkeys (Saimiri sciureus).

Median corpuscular fragility of erythrocytes does not differ significantly between fed and fasted Bolivian and Brazilian squirrel monkeys and are similar to values reported in humans and rhesus monkeys. This report further confirms that the fasting hyperbilirubinemia present only in Bolivian squirrel monkeys with a Gilbert-like syndrome is not due to an increased fragility of erythrocytes and should be classified as a nonhemolytic hyperbilirubinemia.

Animals

Serum zinc/copper ratio in subtypes of leprosy and effect of oral zinc therapy on reactional states.

Serum zinc and copper levels and zinc/copper ratios were studied in 86 healthy controls, 45 cases of borderline tuberculoid (BT), 31 cases of borderline lepromatous (BL), 117 cases of lepromatous (LL) leprosy patients, 16 cases with severe erythema nodosum leprosum (ENL) reaction, and 16 cases with ENL reaction receiving oral zinc therapy. A significant reduction in serum zinc levels was noticed in all types of leprosy, the maximum decrease being seen in cases with ENL reaction. Conversely, the copper levels were significantly increased from BT to LL cases with ENL reaction in a progressive manner. A very good negative correlation (r = -0.998) was noticed between mean serum zinc and copper levels from healthy controls to active LL cases with ENL reaction. After oral zinc therapy, the serum zinc levels were significantly increased in all of the 16 LL patients with ENL reaction. In contrast, the copper levels were not decreased, indicating that oral zinc therapy can restore normal zinc levels in leprosy patients but is unable to reduce the increased copper levels.

Administration, Oral

Percutaneous endoscopic gastrostomy: a two-year experience.

The results of percutaneous endoscopic gastrostomy in 25 patients who required enteral alimentation when feeding by mouth was not possible is reported. The procedure was successful on 30 occasions, with a low incidence of major complications. Endoscopic gastrostomy is a simple, less expensive alternative to surgical gastrostomy with a lower morbidity and mortality.

Adolescent

Haemostatic changes during hormone manipulation in advanced prostate cancer: a comparison of DES 3 mg/day and goserelin 3.6 mg/month.

Two hundred and fifty patients were entered into a randomized clinical study to compare the effectiveness of goserelin (Zoladex) in depot formulation with diethyl stilboestrol in locally advanced or metastatic prostate cancer. In 22 patients from the two arms of the study regular assessments were made of the effect of these hormone treatments on the haemostatic system. Selection of those patients with no recent surgical intervention and those on no drugs liable to interfere with the haemostatic mechanism was done at entry, in order to remove bias and achieve comparable groups. Baseline comparison of the two treatment groups showed no difference in clinical or biochemical measures of disease extent or activity, including serum prostate specific antigen (PSA) levels. There was a significant fall in plasma antithrombin-III (AT-III) activity in the DES treated group both from baseline and compared with the goserelin group. This effect commenced within 1 month and was maintained until monitoring ceased at 12 months. There was also a significant increase of fibrinolytic activity in the DES treated patients compared with those on goserelin. No divergence between the two treatment groups was seen in any other haematological parameters at baseline or on follow-up. A single AT-III estimation was also performed on a larger group of 74 patients at median follow-up time of 17 months (range 3-24). This confirmed the difference noted in the original study group. In the main study thrombotic episodes were noted in 13/126 patients treated with DES and 0/124 treated with goserelin (P less than 0.001). These findings suggest that lowered AT-III is the major factor through which DES affects the coagulation mechanism, and that no such effect is seen with goserelin treatment despite an equivalent therapeutic efficacy.

Aged

Frontal sinus osteoma with complicating intracranial aerocele.

An elderly man, who presented initially with clinical features of dementia, was found to have an intracranial tension aerocele due to an underlying osteoma of the frontal sinus. Plain skull roentgenograms and computerized tomography did not reveal the osteoma, although a communication between the frontal sinus and the aerocele was present. Surgical aspiration of the aerocele and excision of the osteoma produced an excellent clinical result.

Aged

Sex differences and the role of figural complexity in determining the rate of mental rotation.

Two experiments were conducted to investigate the effects of figural complexity on the rate of mental rotation of 3-dimensional figures and to compare the performance of men and women. Complexity was manipulated in three ways: by changing the number of blocks in the figure (7 or 10), by altering the number of turns (2 or 3), and by using outline or solid figures. In the first study, these factors were manipulated between groups of subjects. Women showed steeper slopes than men, but none of the complexity variables affected either slope or intercept for the mental rotation function. In the second study, number of turns and number of blocks were manipulated within-subjects, using only the solid figures. There were significant sex differences in both slope and intercept, and the number of blocks affected the slope of the rotation function. In both studies, a small percentage of the subjects showed nonlinear functions relating angular rotation to response time. Although the women consistently showed slower rotation functions, rate of rotation did not relate either to figural complexity or to nonlinearity. The results suggest that the rate of mental rotation is not affected by figural complexity, at least at the levels used in the present study, and that men and women employ essentially similar strategies.

Adult

Use of cervical Cytobrush samples for dot-blot detection and Southern blot typing of human papillomaviruses using subgenomic probes.

The use of Cytobrush samples for the detection and typing of cervical human papillomavirus (HPV) infections was analyzed. The average yield of squamous cells from Cytobrush samples was on the order of 10(6) cells when the sample was collected in a lytic collection buffer, which was approximately double the content of (1) samples collected in ethanol and (2) an average biopsy specimen. The material obtained could be used for sensitive detection and typing of HPV infections using, respectively, a nonradioactive dot-blot method and the Southern blot procedure performed with subgenomic probes, which permitted a simple interpretation even in cases of mixed infections. A sample containing at least 500,000 viral copies was required for the detection and typing. At this level of sensitivity, the frequencies of HPV obtained in different risk groups varied from 6% (in "healthy" young women) to 53% (in women with abnormal cytologic findings in simultaneous smears). The noninvasive nature of the sampling procedure and the relative simplicity of the test should allow this method to be applied in large-scale studies.

Blotting, Southern

Serosurvey of prevalence of human immunodeficiency virus amongst high risk groups in Port Sudan, Sudan.

During October, 1987, 593 sera were collected from risk groups in Sudan's only major deepwater port, Port Sudan. The risk groups included prostitutes, lorry drivers and prisoners. A large proportion of the study participants practised high risk behaviour which included sexual promiscuity, medical treatment by injection, scarification and tattooing. Despite high risk behaviour and evidence of a high prevalence of hepatitis B infection, a virus transmitted in a manner similar to HIV, no study participants were positive for HIV infection. This data suggests that the prevalence of HIV infection amongst high risk groups in Port Sudan is very low. These findings confirm a lack of clinical cases of AIDS in hospitalized patients in Port Sudan and the small number of reported cases in other areas of northern Sudan.

Acquired Immunodeficiency Syndrome