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Biomedical subjects

J L Roberts

Publications and source records attributed to J L Roberts.

At least 217 records · Page 12Linked to original sources
PubMed1983

Differential characteristics of immune-bound antibodies in diffuse proliferative and membranous forms of lupus glomerulonephritis.

Diffuse proliferative (PGN) and membranous (MGN) glomerulonephritis represent contrasting histologic lesions in systemic lupus erythematosus (SLE). Serum, cryoglobulins, and renal biopsies in 8 SLE patients with PGN and 8 with MGN were studied in order to determine whether variations in the properties of immune-bound antibodies correlate with the pattern of glomerular involvement. Several immunologic parameters suggested differences in complement activation between the two groups. PGN cryoglobulins demonstrated immunoglobulin G (IgG) anti-native DNA (nDNA) subclass heterogeneity with highest titers of IgG3. These findings contrasted with the observation that MGN was characterized by a predominance of IgG4 in cryoglobulins. The major glomerular IgG subclasses in PGN were IgG3 and IgG1, while MGN biopsies demonstrated IgG4 in largest amount. Serum C1q was lower in PGN than in MGN. Serum anti-nDNA antibodies, solid-phase C1q-binding IgG immune complexes, and cryoglobulin protein concentrations were higher in PGN sera. Cryoglobulin complement component and control protein concentrations were greater in PGN than in MGN, while cryoglobulin Ig and immune-bound anti-nDNA were not different. In vitro C3 fixation by cryoglobulin anti-nDNA was greater in PGN than in MGN. Glomerular C1q, C4-binding protein (C4bp), and C3c were present in comparable amounts to IgG deposits in PGN biopsies, while in MGN IgG was demonstrable in greater quantities than C1q, C4bp, and C3c. In contrast, glomerular C3d (alpha 2d), C5, C6, P, and H were comparable in the two groups. It was concluded that immune-bound antibodies in cryoglobulins and in glomerular immune deposits in SLE PGN appear to activate complement via the classical and alternative pathways, while complement activation in MGN appears to occur predominantly via the alternative pathway. These differences in IgG subclass composition may account for the differential complement activation and may explain the contrasting histologic expression of immune aggregate localization in glomerular capillaries in these variants of lupus nephritis.

Antibodies, Antinuclear↗
PubMed1983

Membranous and vascular choroidopathy: two patterns of immune deposits in systemic lupus erythematosus.

Two patterns of immune aggregate localization were demonstrated by immunofluorescence and electron microscopy in the choroid plexus of four young women with fatal systemic lupus erythematosus. The two patients with granular immune aggregates localized to the basement membrane of the choroid epithelium (membranous choroidopathy) had subepithelial and intramembranous electron-dense deposits and membranous glomerulopathy in their kidneys. The two patients with immune aggregates in the walls of choroidal blood vessels (vascular choroidopathy) had subendothelial electron-dense deposits and proliferative glomerulonephritis. Vascular deposits in the choroid plexus were associated with capillary thrombi and extravasation of fibrinoid material, while isolated membranous choroidopathy had no histopathologic evidence of inflammation. The clinical presentation and serological studies of blood and cerebrospinal fluid were compared in an effort to discriminate between patients with membranous and vascular choroidopathy. All patients had variable neuropsychiatric symptoms and major motor seizures. While those with vascular choroidopathy had more evidence of disease activity in their sera, both groups demonstrated elevated titers of immune-complexed antinuclear antibodies in cerebrospinal fluid. Although both patterns of choroidal localization of immune aggregates were associated with neuropsychiatric dysfunction, we were unable to identify discrete clinical-symptom complexes which differentiated patients with membranous and vascular choroidopathy. These contrasting patterns of choroid plexus immunopathology suggest that factors responsible for differential localization of immune aggregates are not restricted to the renal glomerulus.

Adult↗
PubMed1983

Necrotizing glomerulitis of systemic lupus erythematosus.

The authors report four cases of systemic lupus erythematosus (SLE) with severe, active glomerulonephritis. Associated with histologic evidence of glomerular inflammation were focal, predominantly mesangial immune reactants. This finding contrasts with reports that massive subendothelial electron-dense deposits are the ultrastructural feature that correlates best with the severity of glomerular inflammation. The patients studied had significantly fewer subendothelial electron-dense deposits than did other patients with SLE with comparable glomerular lesions (8 +/- 3 per cent versus 42 +/- 14 per cent of glomerular capillaries involved, respectively; P less than 0.05). In addition, serologic evidence of disease activity, assessed by measurement of serum levels of C3, C4, circulating immune complexes (cryoglobulins), and serum antinative DNA activity, was either normal or only mildly abnormal. The lack of correlation between the severity of glomerular lesions on the one hand and the paucity of glomerular immune reactants and mild serologic abnormalities on the other may be interpreted as questionable evidence that these cases of glomerulonephritis were mediated by immune complexes. In the light of recent clinical and experimental studies that support a possible role for cell-mediated immunity in the pathogenesis of glomerulonephritis, the authors propose that a role for cell-mediated hypersensitivity be considered.

Glomerulonephritis↗
PubMed1983

Regulation of the pro-opiomelanocortin mRNA levels in rat pituitary by dopaminergic compounds.

Dopamine-containing neurons directly innervate the intermediate lobe of the pituitary and dopaminergic compounds exert inhibitory effects on the secretion and the content of alpha-melanocyte-stimulating hormone and beta-endorphin in this tissue. In this study, we have investigated the effects of dopamine receptor agonists and antagonists on the level of pro-opiomelanocortin (POMC) mRNA in rat pituitary. RNAs isolated from neurointermediate pituitary (NIP) or anterior pituitary were spotted on nitrocellulose filters and the levels of POMC mRNA were quantified by hybridization to a POMC-specific complementary DNA probe coupled with autoradiography and densitometry. Administration of a dopamine receptor antagonist, haloperidol (2 mg/kg per day), to adult female rats resulted in a 3- to 5-fold increase in POMC mRNA level in the NIP. Treatment with the dopamine agonist 2-Br-alpha-ergocryptine (1 mg/kg per day) decreased significantly the content of POMC mRNA in the NIP. These drugs had no apparent effect on the POMC mRNA levels in the anterior pituitary. The effect of haloperidol and ergocryptine on POMC mRNA in the NIP is time- and dose-dependent. The elevation of POMC mRNA content in the NIP by haloperidol can be observed as early as 6 hr after treatment. These effects of dopaminergic compounds can also be demonstrated in adult male and ovariectomized female rats. The beta-endorphin content of the NIP, as measured by radioimmunoassay, and the de novo synthesis of POMC, as determined by radioactive amino acid labeling and two-dimensional gel electrophoresis analysis, also show negative regulation by dopaminergic compounds.

Animals↗
PubMed1983

Analysis of pro-opiomelancortin gene structure and function.

Pro-opiomelanocortin (POMC) is the protein precursor to several physiologically distinct peptide hormones. The POMC gene is expressed in several distinct cell types and appears to be under differential regulation depending upon the cell location. The structure of the POMC gene in human, bovine, rat, and mouse is very similar, suggesting that this particular structure has functional significance. The gene is broken by intervening sequences into a 5' noncoding region, a signal sequence-coding region, and a peptide hormone-coding region. Middle-repetitive DNA sequences are present in both introns of the genes as well as the 5'-flanking regions in all species studied; this too suggests that this structural element has functional significance. The peptide hormone-coding sequences are well conserved among species, whereas the nonhormonal "spacer" sequences are poorly conserved. Differential regulation of the POMC gene appears to occur by the differential recognition of effector molecules. Although the studies are not complete, all available evidence suggests that there is only a single POMC gene which is express in mammalian tissues.

Animals↗
PubMed1983

In situ hybridization histochemistry: a technique for the study of gene expression in single cells.

The patterns of growth hormone and proopiomelanocortin gene expression in the rat pituitary were used to detail the application of the in situ hybridization histochemistry technique in tissue sections. Parameters affecting the efficiency and resolution of hybridization have been optimized so that this technique can be used to identify sites of peptide synthesis and to study hormonal regulation of gene expression at the single cell level.

Adrenalectomy↗
PubMed1982

The regulation of hepatic stearoyl-coenzyme A desaturase in obese-hyperglycaemic (ob/ob) mice by food intake and the fatty acid composition of the diet.

1. The effects of food intake and the fatty acid composition of the diet on the hepatic stearoyl-CoA desaturase activity of obese-hyperglycaemic (ob/ob) mice were investigated. 2. Obese mice fed on a commercial mouse diet, ad libitum, had 6.5-fold more activity per liver cell than had lean mice. 3. On a diet containing 14% corn oil the activity was 65% less in obese mice and 62% less in lean mice compared with animals fed on the commercial diet. 4. Feeding with 14% saturated fat in the diet doubled the activity in lean mice compared with those on the commercial diet, but had no effect on the activity in obese mice. 5. Obese mice fed on the corn-oil diet contained a higher proportion of linoleic acid in the liver lipids than did lean mice fed on the commercial diet, but the acyl-CoA desaturase activity was 125% higher than in the lean mice. 6. Limiting the food intake of obese mice by pair-feeding with lean mice decreased their acyl-CoA desaturase activity when the animals were fed on the saturated-fat diet, but the activity remained 75% higher than in lean mice, whereas in obese mice pair-fed on the corn-oil diet the activity was the same as in lean mice. 7. During starvation the acyl-CoA desaturase activity in livers from obese mice decreased more slowly and proportionately less than in livers from lean mice. 8. It is concluded that increased substrate supply as a result of hyperphagia and not low concentration of linoleic acid is the main factor causing high acyl-CoA desaturase activity in obese mice.

Animals↗
PubMed1982

Auditory brainstem responses in preterm neonates: maturation and follow-up.

Seventy-five neonatal intensive care unit patients with given auditory brainstem response screening tests at 40 db and 70 db above the normal adult hearing threshold. The presence of wave V, the criterion for pass, was strongly related to postconceptual age: It appeared at 70 db in 50% of the infants tested at 32 weeks' PCA and at 40 db in 50% of the infants tested at 40 weeks' PCA. Forty-four infants failed the last test before NICU discharge (15 at 70 db and 29 at 40 db), but most infants were discharged at a PCA of less than 40 weeks. No significant correlation appeared between ABR test failure and intraventricular hemorrhage, hyaline membrane disease, perinatal asphyxia, hyperbilirubinemia, or aminoglycoside therapy. Follow-up information was obtained in 23 of the 36 "failing" infants who survived (8 died). This consisted of definitive hearing tests in ten patients and historical information supporting normal auditory function in 13 patients. One case of severe hearing loss was confirmed. Thus, most failures of the ABR screen apparently resulted from immaturity. These data raise doubts regarding the effectiveness of ABR screening in the NICU.

Age Factors↗
PubMed1982

Pharyngeal airway obstruction in preterm infants during mixed and obstructive apnea.

The site of upper airway obstruction during mixed and obstructive apnea was investigated in nine preterm infants with clinical apnea. The level of obstruction was determined using a saline-filled pharyngeal catheter that detects respiratory pressure changes. High pharyngeal obstruction was found in 87 of 94 spells. These data suggest that the mechanism of upper airway obstruction in infants with apnea may be similar to that seen in older children and adults with obstructive sleep apnea.

Airway Obstruction↗
PubMed1982

The prevalence and economic significance of liver disorders and contamination in grain-fed and grass-fed cattle.

Livers were examined from 5,647 grain-fed and 621 grass-fed cattle of similar breed, age and weight, killed at a Queensland abattoir in 1980-81. The prevalences of disorders found in grain-fed cattle were liver abscesses 5.6% and 11.1% (after 80 and 120 days in the feedlot), telangiectasis 8.4%, Echinococcus granulosis 3.3%, Fasciola hepatica 0.4%, unclassified lesions 7.4%, and contamination 3.2%. In grass-fed cattle liver abscesses were 0.2%, telangiectasis 1.0%, E. granulosis 18.9%, F. hepatica 5.4%, unclassified lesions 6.5%, and contamination 1.0%. Liver abscess disease was the main cause of loss in grain-fed cattle and the mean carcase weight of affected steers was 298kg +/- 42kg, compared with 308kg +/- 40kg in non-affected (p less than 0.01). Liver weights of grain-fed and grass-fed cattle were highly significantly correlated with carcase weights (r = 0.78 and 0.49 respectively). Total losses were $2.25 per head in grain-fed steers and $0.90 in grass-fed steers.

Abattoirs↗
PubMed1982

Differential regulation by glucocorticoids of proopiomelanocortin mRNA levels in the anterior and intermediate lobes of the rat pituitary.

Glucocorticoids negatively regulate de novo synthesis of proopiomelanocortin (POMC) and the steady state POMC mRNA levels in the rat pituitary anterior lobe. The POMC system of the intermediate lobe is far less sensitive to alterations in circulating glucocorticoid levels. Possible mechanisms for this differential regulation of POMC gene expression in the two tissues are discussed.

Adrenalectomy↗
PubMed1982

Quantitative studies of ovine haemonchosis. 2. Relationship between total worm counts of Haemonchus contortus, haemoglobin values and bodyweight.

The relationships between Haemonchus contortus burdens, haemoglobin levels and bodyweight, were examined in 50 commercial Merino sheep, 9-18 months of age, in south-east Queensland where haemonchosis was endemic. Worm counts and haemoglobin levels were predictable (P less than 0.001, r = 0.68) from the equations log worm count = B.wt. X 0.06942 + log worm count X (-2.18896) + 12.51557. Bodyweight was not predictable from either worm counts or haemoglobin levels. Although bodyweight was represented in both equations, it was only a small and insignificant contributor. When haemoglobin levels became moderately depressed (less than 10.5 g%) or severely depressed (less than 8.0 g%), then the number of worms associated with these haemoglobin levels varied with the bodyweight of the sheep. For sheep up to 20 kg, 10.5 g% Hb was associated with 112 worms and 8 g% with 355 worms. However, 355 worms caused only moderate depression of Hb levels in sheep over 50 kg, and 1259 worms were required to cause severe depression (less than 8.0 g%) in sheep over 50 kg. Three sheep were found to be severely anaemic in the presence of less than 100 worms. It was postulated that additional factors of time and nutrition may have affected these sheep. The sheep were of low bodyweight, in poor condition (low fat score) and were subject to high stocking rates on long grass pastures and high rainfall in autumn. Other internal parasite species present were Nematodirus spp. and Trichostrongylus spp. However, their numbers were low (57 and 218 worms, respectively) and did not contribute to anaemia. The correlation between H. contortus and Nematodirus spp. was found to be negative but non-significant (r = -0.26, P less than 0.01), while the correlation between H. contortus and Trichostrongylus spp. was positive and significant (r = 0.38, P less than 0.01).

Abomasum↗
PubMed1982

Quantitative studies of ovine haemonchosis. 3. The interpretation and diagnostic significance of the changes in serial egg counts of Haemonchus contortus in a sheep flock.

An examination of the level and distribution of egg counts of H. contortus within an extensively managed flock of Merino sheep in south-east Queensland was carried out on three occasions over a ten week period. During this time the geometric mean egg count increased from 527 to 1331 eggs per gram, and although 26.3% of the flock were responsible for this increase, clinical evidence of haemonchosis was not observed. Examination of the distribution of counts supported the hypothesis that counts followed a negative binomial distribution. The values obtained for "k" (the index of over-dispersion), ranged from 0.5 to 1.4. However, on the two latter examinations, counts showed a divergence from the expected pattern (P = 0.015; P = 0.014). Further examinations of flocks at higher mean levels of count are required to establish if the trend towards a more normal distribution were maintained. The evidence from the present study and from outbreaks previously reported, suggested that in extensively managed sheep, the level of variance remained high as the mean egg count increased. It therefore appeared likely that in outbreaks of acute haemonchosis under grazing conditions, only a small proportion of the flock may become seriously affected.

Animals↗