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Biomedical subjects

S Jackson

Publications and source records attributed to S Jackson.

At least 271 records · Page 15Linked to original sources

Characterization of a new G6PD variant: G6PD Titusville.

We describe a new glucose-6-phosphate dehydrogenase mutant, G-6-PD Titusville. The propositus is a 7-month-old black male infant with a transient hemolytic episode. The mutant enzyme is characterized by abnormal electrophoretic mobility, thermolability, Km for NADP, abnormal deamino NADP use and a decreased sensitivity to inhibition by NADPH. G-6-PD activity of hemolysate, as measured under optimal in vitro conditions, was not initially decreased, whereas fibroblasts, granulocytes, and platelets showed a markedly decreased level of enzyme activity. These properties identify G6PD Titusville as a unique variant of this X-linked, housekeeping enzyme. We conclude that although the propositus with G6PD Titusville had a transient hemolytic episode, we cannot be certain whether this association was a causative one.

Enzyme Stability↗

Identification of high molecular weight peptides in bovine adrenomedullary chromaffin granules using monoclonal antibodies to a preproenkephalin A fusion peptide.

Two mouse monoclonal antibodies (PE-1 and PE-2) raised to a beta-galactosidase-preproenkephalin A(69-207) fusion peptide recognize pro-enkephalin A (pro-enk-A) peptides of 33-5 kDa isolated from bovine adrenal chromaffin granules. The preliminary characterization of the high molecular weight adrenomedullary pro-enk-A peptides recognized by PE-1 and PE-2 is described. The high molecular weight peptides were resolved after Sephadex G-50 chromatography and high-performance liquid chromatography (HPLC) into three components (peaks I, II and III). Immunoblot analysis showed each HPLC peak to be heterogeneous. Peak I contained PE-1-and PE-2-immunoreactive peptides of 33, 29, 24 and 22 kDa; peak II contained a peptide of 22 kDa recognized by PE-2, and peptides of 24 and 22 kDa recognized by PE-1; peak III contained a PE-2-immunoreactive peptide of 15 kDa and PE-1-immunoreactive peptide of 18 kDa. Using polyclonal antibodies to peptide F and methionineenkephalin-Arg6-Gly7-Leu8 (MetEnk-RGL), the 22 kDa band cross-reacted with both MetEnk-RGL and peptide F antibodies, whilst the 24 kDa band was shown to possess predominantly MetEnk-RGL immunoreactivity. The 15 kDa (PE-2-immunoreactive) band was recognized by the peptide F but not the MetEnk-RGL antibody, whereas the polyclonal antibodies did not recognize the 18 kDa (PE-1-immunoreactive) band. We propose that the immunological and size characteristics of some of these peptides (29, 24/22, 15 kDa) suggest their similarity to the peptides of predicted molecular mass 23.3, 18.2 and 12.6 kDa previously found in bovine adrenal medulla. The results also indicate the existence of high molecular weight pro-enk-A peptides shortened at the N-terminus. The use of an immunoradiometric assay designed to measure the proenk-A-derived 18.2 kDa peptide using PE-2 and an affinity purified and radioiodinated MetEnk-RGL IgG has supported these findings.

Adrenal Medulla↗

Weight gain and breast yield of large white male turkeys fed diets varying in protein content.

Large White male turkeys were reared in floor pens to 20 wk of age. Diet changes were made every 4 wk, with dietary energy levels kept similar for diets within a period, and changes made in protein levels. Although significant differences in weight were noted at 4 and 8 wk, these diminished with age such that at 20 wk no significant differences were noted. Feed intakes paralleled weight gains. A sample of birds was taken every 4 wk for a measurement of breast meat (excluding skin) and composition. Although changes in dietary protein levels did not affect weight gains to 20 wk of age, breast protein yields were significantly reduced by lowered dietary protein levels. Breast meat varied from 15% of live weight at 4 wk of age to 23% at 20 wk. Protein composition of breast meat varied between 90 and 95% (DM basis), and was estimated to be in excess of 50% of edible carcass protein. With such a high level of edible carcass protein coming from breast meat, it is suggested that yield of breast protein be used as a parameter in determining optimum protein and amino acid requirements of heavy weight turkeys.

Amino Acids, Essential↗

Comparison of scintigraphic diagnostic criteria in suspected pulmonary embolism.

Various criteria have been proposed for the interpretation of ventilation and perfusion (V/Q) scintigrams in diagnosing pulmonary thromboembolism. The Biello criteria, with modifications, have been a standard for years but they differ from the criteria currently being used in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) trial. We carried out a retrospective study in an attempt to establish if one or the other set of criteria is better. Between February 1985 and September 1987, 38 patients had a V/Q scan for suspected pulmonary embolism and subsequently underwent pulmonary angiography. The V/Q scans were reviewed by two observers using the modified Biello and the PIOPED criteria. Receiver-operated characteristic curves were constructed separately for each set of criteria. Statistical analysis revealed that neither set of criteria was significantly better than the other, but the PIOPED criteria were felt to be better defined and easier to use. This may have implications for the practical application of the criteria.

Evaluation Studies as Topic↗

Monoclonal antibodies to a proenkephalin A fusion peptide synthesized in Escherichia coli recognize novel proenkephalin A precursor forms.

Monoclonal antibodies have been generated to a chimeric peptide comprised of Escherichia coli beta-galactosidase fused to the amino acid sequence 69-207 of human preproenkephalin A. Two monoclonal antibodies, PE-1 and PE-2, were identified by their ability to recognize the same segment of proenkephalin A fused to the cII gene product of the E. coli bacteriophage lambda. The binding domains of PE-1 and PE-2 have been broadly located, with respect to the primary translation product, within the amino acid sequences 152-207 and 84-131, respectively. Immunoblot analysis of total bovine adrenomedullary chromaffin granule lysate reveals PE-1 and PE-2 immunoreactive forms of observed molecular mass 35, 33, 29, 24, 22, and 15 kDa, and an 18-kDa PE-1 immunoreactive form. Separation of granule membranes from their contents reveals differential membrane association of these high molecular weight polypeptides. There is preliminary evidence that PE-1 may be detecting a subset of polypeptides where shortening from the NH2 terminus has occurred. We postulate that the 35-kDa form represents the intact bovine enkephalin precursor of predicted molecular mass 27.3 kDa. This experimental approach should be generally applicable to the generation of antibodies which will recognize intact peptide precursors together with their post-translational cleavage products.

Adrenal Medulla↗

IgA1 is the major immunoglobulin component of immune complexes in the acquired immune deficiency syndrome.

Compared to a panel of healthy controls, sera from 13 of 23 (57%) patients with the acquired immune deficiency syndrome (AIDS) were shown to have elevated levels of circulating immune complexes (CIC) containing IgA. Levels of IgG-containing CIC were increased in seven patients (30%); no patients had elevated levels of IgM-containing CIC. Additional experiments showed that in all instances in which IgG CIC were demonstrable, IgA was also present; however, IgA CIC could be found that did not contain IgG. The IgA in the CIC was restricted to the IgA1 subclass. These data suggest selective abnormalities of IgA regulation in AIDS and raise questions as to the role in this disease of the immunoglobulin isotype usually thought to possess different protective mechanisms from those attributed to other isotypes.

Acquired Immunodeficiency Syndrome↗

Occurrence of polymeric IgA1 rheumatoid factor in the acquired immune deficiency syndrome.

The sera of 34 acquired immune deficiency syndrome (AIDS) patients and 20 healthy male homosexuals were examined for the presence of elevated levels of IgA and IgM rheumatoid factor (RF) and compared with results obtained with sera from 23 healthy laboratory volunteers. IgA RF levels were elevated (greater than 3 standard deviation units) in 9 of 34 (26%) patients with AIDS as compared to the panel of laboratory controls. Levels of IgM RF did not differ significantly in the AIDS patients and in the controls. There were no differences in levels of either IgA RF or IgM RF when the homosexual controls were compared with the laboratory volunteers. Sucrose-gradient ultracentrifugation experiments and assays using monoclonal reagents specific for IgA subclasses indicated that the IgA RF was predominantly of the polymeric configuration and restricted to the IgA1 subclass, respectively. Polyethylene glycol (PEG) precipitates of serum enriched for circulating immune complexes (CIC) were also assayed for the presence of IgA RF and IgM RF. Although levels of IgA RF in serum and in PEG precipitates did not correlate with levels of IgA- or IgA/IgG-containing CIC in AIDS patients, levels of IgA RF in both serum and CIC-enriched material were significantly elevated in the AIDS population when compared with the control panel. In contrast, levels of IgM RF in both serum and CIC-enriched material were low and not significantly different from those in healthy controls. These results indicate that both IgA-containing CIC and IgA RF occur in many AIDS patients and raise the possibility that IgA RF may contribute significantly to the formation of immune complexes in this disease.

Acquired Immunodeficiency Syndrome↗

Use of fibre-optic endoscopes in studies of gastric digestion in carnivorous vertebrates.

1. Two methods of assessing gastric digestion rates of three prey types fed to Sooty albatrosses Phoebetria fusca were compared: removal of stomach contents, using a water-flushing stomach pump (a technique used commonly in diet studies), and inspection using a fibre-optic gastroscope (a previously unused technique). 2. The stomach pump yielded quantitative information, but proved stressful and resulted in incomplete recovery of meals ingested 3-6 hr before pumping. Gastric morphology of the animals studied and digestion state of their stomach contents may influence the effectiveness of this technique. 3. Inspection using the gastroscope yielded qualitative information only but permitted serial inspection of the same animal, and was less stressful than the stomach pump. Times for total evacuation of the stomach were 6-12 hr less when estimated using the gastroscope than when using the stomach pump. 4. The specifications of endoscopes relevant to their use by biologists are given. 5. Previous non-medical biological uses of endoscopes are given. Potential uses include underwater observations, sampling of digestive juices and stomach linings for enzyme analyses, observations of ingested prey, and assessment of parasite infestation.

Animals↗

Management of seminoma with bulky abdominal disease.

Thirty-three cases of seminoma with palpable abdominal disease were treated at the Cancer Control Agency of B.C. between 1948 and 1983. Twenty-three had disease confined to the abdomen (Stage IIB), eight had simultaneous involvement of mediastinal and supraclavicular nodes (Stage IIIB) and two had bone or pulmonary metastases (Stage IV). Five and 10-year disease-specific actuarial survivals for the whole group were 87% and 81%, respectively. Corresponding relapse-free survival was 64%. Of the twenty-three IIB cases, 15 had primary treatment with abdominal radiation only, and eight had prophylactic mediastinal/supraclavicular radiation. Although relapse in IIB was more common in the group receiving abdominal radiation only, survival was unchanged. For the entire IIB group, 5- and 10-year disease-specific actuarial survivals were 91% and 84%, respectively, and corresponding relapse-free survival was 74%. The eight IIIB patients were treated primarily with radiation. Four patients relapsed, all in extranodal sites. Two of these died of disease. Both Stage IV patients required radiation and chemotherapy for long-term disease control. Stage IIB disease can be treated primarily with abdominal radiation, but radiation alone is inadequate when bulky abdominal disease is associated with supradiaphragmatic lymphatic spread or hematogenous metastases.

Abdominal Neoplasms↗

Immunoglobulin-antiimmunoglobulin interactions and immune complexes in IgA nephropathy.

IgA nephropathy (IgAN) is characterized by mesangial co-deposition of IgA and C3. Elevated levels of circulating immune complexes containing these components in significant numbers of patients have been found in several studies; IgAN is therefore assumed by many investigators to be an immune complex-mediated disease. Our studies have shown that IgG is often co-complexed with IgA within circulating immune complexes, and we have begun to examine the potential mechanisms for these observations. In this regard, elevated levels of IgA rheumatoid factor and of IgG anti-IgA antibodies were found in some patients. Nevertheless, we were unable to correlate levels of circulating immune complexes with any clinical index of disease. Furthermore, many individuals with the acquired immune deficiency syndrome (AIDS) also have elevated levels of circulating immune complexes containing IgG and IgA, IgA rheumatoid factor, and IgG anti-IgA antibodies, although these patients apparently do not have mesangial IgA deposits. Therefore, the role of circulating IgA-containing immune complexes in the pathogenesis of IgAN requires further evaluation.

Acquired Immunodeficiency Syndrome↗

Lipid storage myopathy associated with low acyl-CoA dehydrogenase activities.

A man with a painful proximal myopathy had excess lipid deposition in skeletal muscle, excretion of dicarboxylic acids in urine and low acyl-CoA dehydrogenase activities in skeletal muscle mitochondria. In addition he had little immunoreactive short-chain and medium-chain acyl-CoA dehydrogenase enzyme protein compared with normal controls. Following treatment with riboflavin there was considerable improvement in his clinical condition which was confirmed by further biochemical and morphological investigations.

Acyl-CoA Dehydrogenases↗

A multiple timepoint study of N-terminal pro-opiomelanocortin in depression using a two-site recognition immunoradiometric assay.

N-pro-opiomelanocortin (N-POMC) is secreted from the same precursor as ACTH and beta-endorphin. Elevated plasma ACTH and beta-endorphin/beta-lipotrophin concentrations have been reported in depression, however there have been no previous studies of N-POMC. Twenty-five patients with major depression and 18 control subjects were studied at five timepoints to examine diurnal rhythm and the effect of a dexamethasone suppression test. N-POMC was measured using a newly developed two-site recognition immunoradiometric assay (IRMA). This demonstrated advantages of sensitivity, specificity and simplicity compared with existing radioimmunoassays. N-POMC exhibited a pattern of diurnal rhythm and suppression in response to dexamethasone as described for other POMC derived peptides. Depressed subjects had higher levels of N-POMC at 0900 h post-dexamethasone than did control subjects. In conclusion, the results of this study are consistent with a hypothesis of cosecretion of POMC-derived peptides. N-POMC has a similar pattern of abnormal concentrations to ACTH and beta-endorphin/beta-lipotrophin in depression. This constitutes probable evidence of POMC-derived peptide resistance to glucocorticoid feedback in this condition.

Adult↗

Testicular lymphoma: improved outcome with early brief chemotherapy.

We investigated the impact of early brief chemotherapy on the natural history of primary testicular lymphoma. We compared the outcome for patients seen before 1980--a group primarily managed with orchiectomy and regional radiation--with those seen from 1980 to 1986--a prospectively and consecutively gathered group who were offered brief chemotherapy in addition to standard orchiectomy and irradiation. The historical and study groups were similar in clinical characteristics. However, the chemotherapy group had a better relapse-free survival, 93% v 50% (P less than .02), and overall survival, 93% v 50% (P less than .02). With a median follow-up of 44 months in the chemotherapy group, it is clear that the use of early, brief chemotherapy strongly alters the natural history of testicular lymphoma by preventing relapses, the large majority of which occur early after regional therapy. We conclude that a program incorporating orchiectomy, early brief chemotherapy, and involved-field radiation therapy confers the following benefits on patients with primary testicular lymphoma: (1) laparotomy is not needed for staging; (2) relapses, including those in the opposite testicle and CNS, are largely prevented; and (3) toxicity can be kept to a modest level acceptable in elderly patients.

Aged↗

Further evidence that N-terminal pro-opiomelanocortin peptides are involved in adrenal mitogenesis.

In order to demonstrate the mitogenic effects of N-terminal pro-opiomelanocortin (N-POMC) peptides on the adrenal glands further, female rats with bilateral adrenal enucleation (hereafter referred to as enucleation) were hypophysectomized 11 days after enucleation and injected twice daily with 5 micrograms purified human N-POMC(1-28), ACTH(1-24) or 0.9% (w/v) NaCl. On day 14 after enucleation, rats were injected with colchicine and, after killing, their adrenal glands weighed, fixed and mitotic counts in histological sections assessed. Plasma corticosterone was measured fluorometrically. In other experiments, rats 7 days after enucleation were hypophysectomized and implanted with osmotic minipumps delivering 5 micrograms purified N-POMC(1-28) per day. On day 14 after enucleation, animals were treated as above. Collagenase-dispersed adrenal cells were incubated with purified or synthetic N-POMC(1-28) or synthetic N-POMC (1-36) (1-300 nmol/l) and [3H]thymidine incorporation into DNA was determined. Intact female rats were implanted with osmotic minipumps delivering 8 micrograms purified or synthetic N-POMC(1-28)/day, 8 micrograms synthetic N-POMC(1-36)/day or saline alone. Mitotic counts were performed on histological sections. Both s.c. injection or continuous delivery from minipumps of purified N-POMC(1-28) partially prevented the atrophy of regenerating adrenal glands after hypophysectomy (s.c. injection of N-POMC: 2.29 +/- 0.92 mitoses/section compared with 0.52 +/- 0.39 for controls; minipump delivery: 5.02 +/- 0.97 compared with 0.13 +/- 0.05; P less than 0.01 for both experiments). ACTH did not augment mitotic activity in enucleated-hypophysectomized rats but significantly increased plasma concentrations of corticosterone in s.c. injection experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

Adrenal regeneration in the rat is mediated by mitogenic N-terminal pro-opiomelanocortin peptides generated by changes in precursor processing in the anterior pituitary.

In order to investigate the role of N-terminal proopiomelanocortin (N-POMC) in adrenal regeneration after bilateral adrenal enucleation (hereafter referred to as enucleation) rats 13 days after enucleation were injected (200 microliters s.c. plus 200 microliters i.p.) at 08.00 and 20.00 h with normal rabbit serum (NRS), an ACTH antiserum or an N-POMC antiserum. On the next day the animals were injected with colchicine, killed and mitotic figures in adrenal histological sections counted. The same treatment was given to rats 20 days after enucleation. Only the N-POMC antiserum significantly diminished adrenal mitotic activity 14 and 21 days after enucleation (P less than 0.01 and 0.05 respectively) when compared with NRS-treated enucleated rats, whereas plasma corticosterone levels in rats 14 days after enucleation were significantly (P less than 0.005) decreased only by treatment with ACTH antiserum. To determine whether the mitogenic N-POMC peptides involved in adrenal regeneration originated from the pituitary intermediate lobe, 0.9% (w/v) NaCl or ergocryptine (10 mg/kg body weight) was administered s.c. twice daily to rats between 7 and 13 days after enucleation. On day 14, adrenal mitotic activity and plasma levels of ACTH and N-POMC were not significantly different between ergocryptine and saline-treated enucleated rats, whereas alpha-MSH levels in ergocryptine-treated enucleated rats were significantly (P less than 0.02) decreased. Increases in N-POMC content of the pituitary lobe accompanied those of ACTH in animals 7, 10, 14 and 21 days after enucleation (P less than 0.01 compared with sham-treatment). Anterior lobes from rats 10 days after enucleation or from adrenalectomized rats showed raised ACTH and N-POMC levels compared with sham-treated animals, whereas alpha-MSH content in the anterior lobe of enucleated rats was significantly (P less than 0.005) decreased. Adrenalectomized animals had raised (P less than 0.005) amounts of alpha-MSH compared with sham-treated animals. Plasma levels of ACTH and N-POMC were significantly (P less than 0.01) raised in rats 10 days after enucleation or in adrenalectomized rats compared with those in sham-treated animals, whereas alpha-MSH levels were raised (P less than 0.005) only in adrenalectomized rats. Sephadex G-75 chromatography of anterior lobe extracts obtained 10 days after surgery from sham-treated, enucleated and adrenalectomized rats was performed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗

Anesthesia and postanesthetic considerations.

The anesthesiologist is to be considered a consultant for the anesthetic and perioperative management of the podiatric patient. Each rheumatologic disease offers unique clinical features. The anesthesiologist focuses on the following: pharmacology of therapeutic drugs, control and management of the airway, interaction between the disease and anesthesia, and the available anesthetic regimens. This article addresses each of these subjects, and adds disease-specific information when applicable.

Adrenal Cortex Hormones↗