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Biomedical subjects

P J Kelly

Publications and source records attributed to P J Kelly.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of immune complex components by dot blot analysis.

A method is described for the characterization of immune complex components by dot blot analysis. After isolation by chromatographic techniques and precipitation with polyethylene glycol, immune complexes were dissociated in 0.1 M phosphate (pH 2) and bound to a nitrocellulose membrane in a dot blot unit. Biotinylated probes were then used to identify the following immune complex components: specific antigens, biologically active antibodies, antibody isotypes, antibody subclasses, antibody idiotypes, and rheumatoid factors. This nonradioactive procedure takes less than 2 h to perform and has been used to analyze immune complexes isolated from sera (rabbit and human) and synovial fluid (human).

Acids↗
PubMed1992

Pathogens in dog bite wounds in dogs in Harare, Zimbabwe.

Over a year swabs were taken from 87 untreated bite wounds in dogs seen by veterinary practitioners in Harare, Zimbabwe. Swabs were also taken from normal skin adjacent to the wound site, and gingival swabs were collected from normal dogs coming to the same clinics. The swabs were cultured aerobically for pathogens, particularly Staphylococcus intermedius, and the antibiotic sensitivities of the pathogens were determined by disc diffusion assay. The most common pathogens isolated from the wounds were S intermedius (23 per cent), Escherichia coli (18 per cent) and non-lactose-fermenting coliforms (14 per cent). S intermedius was common on the normal skin of the dogs with infected wounds, and was associated with wounds on the abdomen, hindlimbs and tail and wounds that were more than three days old. This organism was, however, isolated only infrequently from the gums and there was little correlation in general between the prevalence of pathogens in the mouth and their prevalence in wounds. Of the S intermedius isolates from wounds, 30 per cent were resistant to penicillin and multiple antibiotic resistance was common among the enterobacterial isolates. The majority of the pathogens were sensitive to cotrimoxazole.

Animals↗
PubMed1992

Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin.

Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of bone turnover in normal and disease states. Its synthesis is induced by calcitriol, the active hormonal form of vitamin D, through the vitamin D receptor and a specific vitamin D-responsive element in the osteocalcin gene promoter. Serum concentrations of osteocalcin are under strong genetic influence. To ascertain whether variability in circulating osteocalcin levels may reflect allelic variation in the vitamin D receptor gene, we have analyzed the relationship between frequent restriction fragment length polymorphisms (RFLPs, detected by endonucleases Bsm I, EcoRV, and Apa I) that define human vitamin D receptor alleles and serum osteocalcin in a cohort of normal subjects. In 91 Caucasian subjects, RFLPs in the vitamin D receptor gene predicted circulating osteocalcin levels (P less than 0.0001) independent of age or menopause effects. Since the osteocalcin gene and the vitamin D receptor gene are encoded on different chromosomes, the interaction between these two genes occurs in trans. Thus, common alleles of this trans-acting factor, the vitamin D receptor, are functionally different and contribute to "normal" physiological variability in osteocalcin levels. Preliminary analysis in monozygotic and dizygotic twin pairs indicates that the greater diversity in lumbar spine density between the dizygotic pairs can be explained by divergence in vitamin D receptor alleles. Variations in this receptor and other transacting factor genes may confound physiological studies of regulation of target genes and will need to be considered in future human and animal studies. This approach to genetic analysis provides a paradigm for the study of functional variation in trans-acting factors and the role such variation may play in the generation and evolution of physiological diversity.

Alleles↗
PubMed1992

Anti-CD3-stimulated T cells induce the production of multiple Ig H chain isotypes by individual human peripheral B lymphocytes.

Polyclonal activation of human B cells is achieved by coculture with T cells stimulated by mAb to the CD3 molecular complex. By formal limiting dilution analysis, approximately 60% of human peripheral blood B cells were found to produce Ig in this system. When individual B cells were cultured in microtiter wells with anti-CD3-activated T cells, more than one-third of cultures producing Ig contained multiple Ig H chain isotypes. Similar results were observed when individual IgM-expressing B cells, selected and dispersed by FACS were cultured with anti-CD3-activated T cells. The clonality of the B cells producing multiple Ig isotypes was supported by L chain analysis of the secreted Ig. Of the wells containing more than one H chain isotype, nearly 85% contained only a single L chain type. Clonality was further examined by polymerase chain reaction amplification of cDNA harvested from cultures originally seeded with individual B cells. In general, only a single VH gene family could be amplified from cultures producing more than one Ig isotype. Three separate VH regions were cloned and sequenced. One, a VHIV-mu was nearly identical to a previously described VH gene VH71.4; as second, a VHIV-gamma was very similar to a previously described VH gene segment V-79, whereas a third, a VHIII-gamma differed by 14% in nucleotide sequence from its closest germline counterpart VH3005. These results indicate that anti-CD3-activated T cells not only stimulate the majority of B cells to secrete Ig, but also induce individual B cells to produce multiple Ig H chain isotypes. Additionally, the procedure described provides a reliable method to sample a large proportion of the human peripheral B cell repertoire.

Amino Acid Sequence↗
PubMed1992

Prognostic value of cytogenetic analysis in human cerebral astrocytomas.

Cytogenetic analysis has become an important part of the diagnostic evaluation of most hematological neoplasms. However, there is limited information on the value of cytogenetic analysis in most solid tumors, including cerebral astrocytomas. This report summarizes a prospective cytogenetic study of 99 human cerebral astrocytomas, 16 mixed oligoastrocytomas, and 2 gliosarcomas. The cytogenetic procedure involved in situ culture and robotic harvesting techniques. Correlative clinical and survival data were available on all patients. We successfully cultured and obtained suitable metaphases in 107 of the 117 tumors. One or more chromosomally abnormal clones were observed in 72 tumors, and nonclonal or normal karyotypes were observed in 35 tumors. In a multivariate analysis, survival time was significantly better in patients whose tumors had normal or nonclonal karyotypes on cytogenetic analyses than in those whose tumors had clonal abnormalities (p = 0.0071). Our study demonstrates that cytogenetic analysis provides independent prognostic information in patients with cerebral astrocytomas.

Astrocytoma↗
PubMed1992

Cytogenetic and loss of heterozygosity studies in ependymomas, pilocytic astrocytomas, and oligodendrogliomas.

Cytogenetic and/or loss of heterozygosity studies were performed on 13 ependymomas, 11 pilocytic astrocytomas, and 18 oligodendrogliomas. Loss of chromosome 22 was the most frequent genetic abnormality among the ependymomas. We found no consistent genetic abnormality in pilocytic astrocytomas. The most common genetic abnormality in oligodendrogliomas was loss of a portion of chromosome 19. Each informative oligodendroglioma had loss of alleles mapped to the long arm (q) of chromosome 19. One oligodendroglioma had an apparent homozygous deletion of the D19S8 locus. Our results, when combined with those in the literature, indicate that chromosomes 9, 11, and 22 may harbor genes important for the pathogenesis of ependymomas and that 19q probably harbors a gene important for the pathogenesis of oligodendrogliomas.

Adolescent↗
PubMed1992

Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo-astrocytomas.

The aims of this study were to correlate cytogenetic studies and molecular genetic loss of heterozygosity (LOH) analyses in human astrocytomas and mixed oligo-astrocytomas, and to locate putative tumor suppressor genes on chromosome 10. Paired blood and tumor samples from 53 patients were analyzed. The tumors included 45 diffuse astrocytomas (39 grade 4, 4 grade 3, and 2 grade 2), 1 astroblastoma, and 7 mixed oligo-astrocytomas (2 grade 4, 4 grade 3, and 1 grade 2). By cytogenetic analyses the most common numeric chromosome abnormalities were +7, -10, -13, -14, -17, +19, -22, and -Y. The most common structural abnormalities involved chromosome arms 1p, 1q, 5p, and 9p. By LOH and dosage analysis the most common molecular genetic abnormalities were of chromosome arms 5p, 6p, 7q, 9p, 10p, 10q, 13q, 14q, 17p, and 19p. When the results of all methods were combined, the most commonly abnormal chromosomes were, in descending frequency, 10, Y, 17, 7, 13, and 9. In 80 percent of cases the cytogenetic and molecular genetic studies were concordant. LOH studies were more sensitive in detecting loss of genetic material than cytogenetic analyses and accounted for 60% of the discordant results. When there were structural abnormalities, such as translocations or inversions, cytogenetic analysis was more sensitive in detecting an abnormality than molecular genetic studies. In addition to the 24 tumors which appeared to lose an entire copy of chromosome 10, there were 10 tumors with molecular genetic or cytogenetic evidence of loss of only a portion of chromosome 10. The genetic analyses of these tumors suggest that there are 2 regions on chromosome 10 that may contain potential tumor suppressor genes. One lies distal to locus D10S22 from 10q22 to 10qter, and the other lies proximal to locus TST1 on the 10q arm near the centromere or on the 10p arm.

Adult↗
PubMed1992

Volumetric stereotactic resection of superficial and deep seated intraaxial brain lesions.

From 1984 to 1989 a total of 374 computer-assisted stereotactic resections based on computed tomography or magnetic resonance imaging were performed on 337 supratentorial and 37 infratentorial brain lesions. Computer-assisted stereotactic volumetric resection allows a more aggressive extirpation of tumours with less damaging of the adjacent brain tissue. This procedure is of most benefit in deep seated circumscribed lesions and of less benefit in infiltrating tumours such as high grade gliomas and in fibrillary astrocytomas located in essential brain areas.

Astrocytoma↗
PubMed1992

Distribution of transforming growth factor-beta 1 in human astrocytomas.

We used immunohistochemical techniques to study the distribution of transforming growth factor-beta 1 (TGF-beta 1) and infiltrating lymphocytes and macrophages in human astrocytomas. Thirteen of 15 grade 4 astrocytomas (glioblastomas) showed staining with anti-TGF-beta 1 antibody, predominantly in proliferating endothelial complexes and surrounding small and medium-sized blood vessels. Brain tissue microscopically free of tumor cells (n = 8) and more differentiated astrocytomas of varying grade (1 to 3; n = 6) devoid of endothelial proliferation did not stain with anti-TGF-beta 1. Normal brain contained only rare lymphoreticular cells. The majority of astrocytomas studied, however, contained T lymphocytes and macrophages with smaller numbers of B lymphocytes. The lymphoreticular infiltrates were concentrated primarily in close proximity to blood vessels. Within an individual tumor perivascular regions staining for TGF-beta 1 never contained more than occasional T lymphocytes. Perivascular regions not staining for TGF-beta 1 frequently contained low to high numbers of T lymphocytes. The inverse relationship in the distribution of TGF-beta 1 and lymphocyte infiltrates is compatible with a functional relationship between this cytokine and an immune effector cell response to glioblastomas.

Astrocytoma↗
PubMed1992

MRI in the presurgical evaluation of patients with frontal lobe epilepsy and children with temporal lobe epilepsy: pathologic correlation and prognostic importance.

We performed magnetic resonance imaging (MRI) using a high-field strength magnet (1.5 T) in two series of 53 patients with intractable partial epilepsy of frontal lobe or temporal lobe origin who subsequently received ablative surgery for their seizure disorder. In the first series of patients the pathologic correlation and prognostic importance of an MRI-identified lesion in the frontal lobe were assessed. Twenty-five percent of the patients with negative MRI studies and 67% of patients with neuroimaging abnormalities restricted to the frontal lobe, were seizure-free at a minimum duration of follow-up of 1 year. None of the patients with a multilobar MRI-detected abnormality was seizure-free postoperatively. In the second study the sensitivity and specificity of MRI-based hippocampal volumetry was determined in pediatric patients with partial epilepsy of temporal lobe origin unrelated to foreign-tissue pathology. Hippocampal formation atrophy in the epileptic temporal lobe was identified in 63% of patients. The sensitivity and specificity of hippocampal volumetry was 100% in patients with mesial temporal sclerosis. The presence of an MRI-detected epileptogenic lesion in the frontal lobe and hippocampal formation atrophy in the temporal lobe may correlate with the underlying pathology and affect the identification of potential candidates for epilepsy surgery.

Adolescent↗
PubMed1992

Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours.

The expression of p53 protein, epidermal growth factor receptor (EGFR), and Ki-67 nuclear antigen was examined by immunohistochemistry in biopsies of 16 types of human brain tumours, including 43 astrocytomas. P53 protein, almost certainly its mutant form, was expressed in seven of the 16, and EGFR in 11 of the 16 types of tumours. In astrocytomas both the proportion of tumours which expressed p53 or EGFR increased with grade of malignancy as did the mean Ki-67 labelling index (LI): p53-0% in grade 1, 17% in grade 2, 38% in grade 3, 65% in grade 4; EGFR-0% in grade 1, 33% in grade 2, 85% in grade 3, 95% in grade 4; mean Ki-67 L1-1.1% in grades 1 and 2, 8.3% in grade 3, and 13.4% in grade 4. Astrocytomas which expressed p53 or EGFR had a significantly higher Ki-67 LI at P less than 0.05 (11.8% and 10.7%, resp.) than those that did not (6.2% or 4.1%, resp.). Patients with astrocytomas expressing p53 or EGFR had a significantly reduced survival (P = 0.035 and P = 0.007, resp.): only 11% of the p53 + ve and 13% of the EGFR + ve patients were alive at 100 weeks following diagnosis compared to 36% of p53-ve or 60% of EGFR-ve patients. Patients with Ki-67 LI greater than 5% had a reduced survival (P less than 0.0001)--none survived beyond 86 weeks following diagnosis, whilst 63% of patients with less than 5% positive cells were still alive at 100 weeks. The univariate analysis showed that in astrocytomas expression of p53 mutants, EGFR protein, and Ki-67 greater than 5% are associated with malignant progression and poor prognosis. The multivariate analysis revealed that only tumour grade and Ki-67LI were independent prognostic factors for survival.

Adolescent↗
PubMed1992

Bacterial contamination of the small bowel in elderly people: is it necessarily pathological?

Bacterial contamination of the small bowel is probably the commonest cause of occult malabsorption in the elderly. It may occur in patients without a 'blind loop' or suggestive symptoms of diarrhoea and weight loss. We have prospectively studied the apparent prevalence of presumed bacterial contamination of the small bowel and its effect on nutritional state. Subjects were divided into three groups: (A) 54 young fit subjects; (B) 103 fit community elderly subjects; (C) 73 elderly long-stay hospital patients. All subjects had simultaneous lactulose hydrogen breath test and 14C-glycocholic acid breath test. Nutritional state was assessed by anthropometry, haematology and biochemistry. There were significantly fewer positive 14C-glycocholic acid breath tests in the young than in the elderly subjects (3% vs. 20% and 17%, p less than 0.0001) but no difference in the number of positive hydrogen breath tests between groups. There was no association between positive breath tests and anthropometry, haematology and biochemistry except for a lower albumin in group B and a lower red blood cell folate in group C with positive breath tests. These abnormal breath tests indicate that bacterial contamination of the small bowel may be common in normal fit elderly people and in elderly long-stay hospital patients and may be a concomitant of 'normal' ageing, not necessarily leading to ill-health.

Adult↗
PubMed1992

Ageing and duodenal morphometry.

Small bowel morphometry was studied in 25 subjects under the age of 70 years and 22 over the age of 70. There was no evidence of malabsorption or malnutrition in either group. Two distal duodenal endoscopic biopsy specimens were examined morphometrically. There were no significant correlations between age and areas of duodenal surface epithelium, crypts and lamina propria, heights of villi and surface epithelium, depth of crypts, crypt to villus ratio, number of intraepithelial lymphocytes, duodenal architecture, enterocytes, brush border and Brunner glands. Contrary to previous reports there was no evidence for a significant effect of age on proximal small bowel morphometry.

Aged↗
PubMed1992

Comparison of the neurochemistry of the endogenous opioid systems in two brainstem pain-processing centers.

SCH-32615 is a new enkephalinase inhibitor whose analgesic effects were examined following its stereotactic microinjection into the periaqueductal gray (PAG) and the ventromedial medulla (VMM) regions of the brainstem of the rat. SCH-32615 produced a strong, dose-dependent, naloxone-reversible analgesia to thermal noxious stimuli as measured by the hot plate test (HP; supraspinal analgesia) and the tail flick test (TF; spinal analgesia). The peak analgesic effect was seen within 10 min and remained for 45-60 min. ED50 were for PAG, HP = 10.7 micrograms and TF = 17.3 micrograms, and for VMM, HP = 5.7 micrograms and TF = 7.2 micrograms. Using the irreversible mu receptor antagonist, beta-funaltrexamine, it was found that the endogenous enkephalins in the PAG produce their analgesic effects by acting at only one receptor subtype (the mu receptor) while in the VMM both mu and delta opioid receptors are involved (not through the delta alone as previously believed).

Animals↗
PubMed1992

Stereotactic resection and its limitations in glial neoplasms.

With imaging-based volumetric stereotactic techniques, it is possible to selectively and accurately remove any CT- or MRI-defined part or all of any intra-axial neoplasm. However, glial neoplasms are composed of two elements: tumor tissue and isolated tumor cells which infiltrate brain parenchyma. In high-grade gliomas and pilocytic astrocytomas, the tumor tissue component is most accurately defined by the volume of contrast enhancement. Tumor tissue in low-grade nonpilocytic gliomas is indistinguishable on imaging from infiltrated parenchyma. Stereotactic biopsy is presently the only method by which CT hypodense tumor tissue can be differentiated from infiltrated parenchyma, which is also hypodense. In eloquent brain areas, stereotactic resection is appropriate for the tumor tissue component only in patients harboring glial tumors.

Brain Neoplasms↗
PubMed1992

Computer-assisted stereotactic biopsy and volumetric resection of thalamic pilocytic astrocytomas. Report of 23 cases.

Twenty-three cases of pathologically verified thalamic pilocytic astrocytomas diagnosed at computer-assisted stereotactic biopsy and/or volumetric resection at the Mayo Clinic between January 1985 and October 1990 were reviewed. Computer-assisted stereotactic volumetric resection was performed in 19 patients. Postoperative imaging demonstrated no residual contrast-enhancing tumor in 14 patients and a small amount of contrast-enhancing tumor (less than 5% of the original tumor volume) in 5 patients. Biopsy only was performed in 4 patients: 2 with primarily cystic tumors successfully treated with stereotactic instillation of 32P, and 2 patients with stable (nonprogressive) deficits. There was 1 operative death; a patient with tumor extending into the midbrain became comatose and died 10 days after surgery. The remaining 22 patients are alive and well. Computer-assisted stereotactic volumetric resection of thalamic pilocytic astrocytomas can be performed with low morbidity and a favorable long-term prognosis.

Adolescent↗