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Biomedical subjects

D Read

Publications and source records attributed to D Read.

At least 37 records · Page 2Linked to original sources
PubMed1990

Factor XIII in scleroderma: in vitro studies.

The administration of Factor XIII (FXIII) produces a beneficial effect on the skin lesions in about 50% of the treated patients with progressive systemic sclerosis (PSS). The effect of FXIII on various skin fibroblast functions (proliferation, attachment, biosynthetic activity and mechanical properties) was investigated in vitro using normal and PSS strains. In cell culture, most of the PSS fibroblast strains synthesized excessive amounts of collagen. Other cell functions such as adhesion to collagen I or III, to fibronectin, retraction of collagen lattices, proliferation in low serum concentration and degradation of newly synthesized collagen were not significantly different. The addition of FXIII (I U/ml) inhibited the synthesis of collagen by normal fibroblasts and reduced it in PSS fibroblasts to a level similar to that of normal fibroblasts. This effect was observed for cells cultured on plastic or in a collagen lattice. In the latter, an increased amount of collagen degradation was observed. No significant effect of FXIII on the other cell functions was noted. Excessive collagen production by PSS fibroblasts can be repressed by FXIII in vitro by at least two distinct mechanisms: a reduction of collagen synthesis and an increased degradation of the newly synthesized collagen.

Adult↗
PubMed1990

The Drosophila even-skipped promoter is transcribed in a stage-specific manner in vitro and contains multiple, overlapping factor-binding sites.

To investigate the factors contributing to regulation of expression of the Drosophila segmentation gene even-skipped (eve), we have analyzed both the in vitro transcription and eve-promoter-binding proteins in embryo extracts. We show that the eve promoter is accurately and efficiently expressed in nuclear extracts derived from Drosophila embryos and that transcription is more efficient in extracts prepared from embryos at early stages of development than in those from older embryos, broadly reproducing the temporal pattern of expression observed in vivo. This stage-specific expression is dependent on sequences upstream of the eve transcription start site which contain multiple binding sites for at least two distinct proteins present in embryo nuclei. One of these proteins, the binding sites for which correspond to the sequences required for stage-specific expression, appears to be the previously described GAGA factor. Although the binding activity of the GAGA factor remains constant, the level of the binding activity of the other protein, which we have called the TCCT factor, changes during the course of embryogenesis. Activity is first detected 3 to 5 h after fertilization and decreases during later stages of embryogenesis. We discuss the possibility that the TCCT factor plays a role in the maintenance or refinement of the eve expression pattern.

Animals↗
PubMed1990

Expression of neurotensin in endocrine tumors.

Endocrine tumors are useful sources for determining the synthesis and metabolism of secreted regulatory peptides. The present study was performed to compare the synthesis and metabolism of neurotensin (NT) in normal subjects and four patients with NT-producing tumors. NT mRNA was measured and characterized using oligonucleotide probes and Northern blots, while NT-like peptides were quantitated by RIA with region-specific antisera and high pressure liquid chromatography. Northern blot analysis of mRNA isolated from normal human ileum revealed two species of mRNA hybridizing to a heterologous canine oligonucleotide probe; the apparent sizes of the mRNA were 1.4 and 1.0 kilobases. An identical pattern was found in a pancreatic endocrine tumor, a prostatic adenocarcinoma, and a fibrolamellar hepatoma. The ratio of mRNA to peptide varied between the different tissues. For instance, the hepatoma was the richest source of NT mRNA, but the prostatic tumor contained the highest peptide concentration. Measurements with region-specific antisera showed that N-terminal immunoreactive fragments were more abundant than C-terminal fragments in pancreatic, prostatic, and carcinoid tumors (N/C-teminal ratios, 4.0, 1.6, and 5.0) and in equal concentrations in normal ileum. Reverse phase high pressure liquid chromatography revealed the presence of intact NT in addition to a variable number of smaller N-terminal peptides, presumed to be metabolites. In contrast the hepatoma contained a 5-fold excess of C-terminal immunoreactivity. The excess C-terminal immunoreactivity was also present in the circulation of this patient. The chromatographic properties, immunoreactivity, and unusual stability of the C-terminal fragment found in the hepatoma patient suggest that it is a substance distinct from NT itself and is released specifically by the fibrolamellar hepatoma.

Animals↗
PubMed1989

Plasmodium falciparum: an abundant stage-specific protein expressed during early gametocyte development.

A stage-specific protein has been identified in gametocytes of Plasmodium falciparum. The protein is represented on two-dimensional electrophoresis by peptides of two apparent Mr of 27,000 and 25,000, each of which has at least four different isoelectric points between pH 6.0 and 5.0. The protein is designated Pfg 27/25 (P. falciparum gametocyte-specific antigen of 27 and 25 kDa). By indirect immunofluorescence with a monoclonal antibody 1H12 specific for Pfg 27/25, this protein is present in gametocytes within 30 to 40 hr after invasion of a red blood cell by a merozoite and is present throughout subsequent maturation of the gametocyte; Pfg 27/25 is not detectable on the surface of extracellular gametes by immunofluorescence with Mab 1H12. Pfg 27/25 is absent from asexual stages of P. falciparum at any stage in their development. Pfg 27/25 is an abundant protein in gametocytes and represents between 5 and 10% of total protein of these stages. Pfg 27/25 is also a major immunogen in man during P. falciparum infection. Antibodies to this protein were readily detected in human sera from an area of holoendemic P. falciparum and also from an individual following a primary attack of P. falciparum.

Animals↗
PubMed1988

[Treatment of the acute graft versus host skin reaction with cyclosporin and PUVA].

Acute graft-versus-host reaction is usually managed by immunosuppressive therapy, and cyclosporin is one drug of choice. In some patients, cyclosporin alone cannot always control the evolution. The use of other immunosuppressive drugs could be considered but their toxicity and side-effects are such that a vital risk is introduced for the patient. Conversely, when the disease primarily affects the skin, photochemotherapy (PUVA) associated with cyclosporin appears to be effective and safe.

Adult↗
PubMed1987

Cell- and promoter-specific activation of transcription by DNA replication.

To study the effects that DNA replication can exert on transcription in mammalian cells, we have analyzed transient expression from the adenovirus major late promoter contained on replicating and nonreplicating plasmids in several cell types. When a 100-bp fragment containing the late promoter was used to direct expression of the simian virus 40 (SV40) early region, efficient transcription could be detected that was only slightly enhanced when a functional origin of replication was included in the plasmid. In contrast with this, and with similar findings using related late promoter-containing plasmids, expression from this promoter was absolutely dependent on DNA replication when it was inserted in the region of SV40 DNA encoding the late mRNA 5' ends and expression was assayed in human HeLa cells and BSC-1 and COS-7 monkey cells. In contrast, transcription was totally independent of replication in human 293 cells. These results, which were not due to differences in template copy number, suggest that both cis- and trans-acting factors can influence a promoter's response to DNA replication and point to possible functional similarities between replication origins and transcriptional enhancers.

Adenoviruses, Human↗
PubMed1987

Treatment of gram-positive peritonitis with two intraperitoneal doses of vancomycin in continuous ambulatory peritoneal dialysis patients.

Eight patients with end-stage renal failure on continuous ambulatory peritoneal dialysis (CAPD), who developed peritonitis, received an intraperitoneal dose of vancomycin (30 mg/kg body weight) with 6 h of peritoneal dwell and then resumed their routine CAPD schedule. Vancomycin concentration in serum, peritoneal dialysate (PD) from an overnight dwell and 1, 2 and 3 h after a new exchange was measured at 48 h (in 5 patients) and 7 days (in 6 patients). Except for an occasional 1-hour peritoneal fluid sample on the 7th day, all samples had satisfactory vancomycin levels. Five of the 8 patients who had gram-positive peritonitis and 1 with 'sterile' peritonitis received another similar intraperitoneal dose of vancomycin at the 7th day. All of these patients had good therapeutic response with a negative PD culture 3 weeks after the cessation of therapy and no relapse of infection in at least 1 month of follow-up. We conclude that 2 intraperitoneal doses of vancomycin (30 mg/kg body weight) given 1 week apart with 6 h of intraperitoneal dwell is an effective and adequate treatment for gram-positive and 'sterile' peritonitis in CAPD patients.

Bacterial Infections↗
PubMed1986

Very short patch mismatch repair in phage lambda: repair sites and length of repair tracts.

Five amber mutations in the repressor (cI) gene of bacteriophage lambda recombine anomalously with nearby cI mutations. When any of these markers is used in four-factor crosses, cI+ recombinants that are expected to require three cross-overs occur at high frequencies. These recombinants are attributable to very-short-patch (VSP) repair of specific mismatches in DNA heteroduplexes formed during recombination between the markers flanking cI. The sites of the repair-prone mutations and the lengths of repair tracts have now been determined. Amber mutations subject to VSP repair are C to T transitions in 5'CCATGG, the sequence methylated by the product of gene dcm, and also in the related 5'CAGG or 5'CCAG sequences. Ambers arising in CAG sequences found in other contexts, or in codons other than CAG, were not subject to VSP repair. Repair tracts rarely, if ever, exceed ten nucleotides in length, and can be as short as two nucleotides. A repair-prone mutation does not stimulate recombination between flanking cI markers.

Bacteriophage lambda↗
PubMed1984

Laboratory basis for the medical management of necrotizing enterocolitis (NEC).

Necrotizing enterocolitis (NEC) is a serious condition affecting the neonate that may be responsive to medical management. This study evaluates the efficacy of supplemental oxygen (FiO2 40% and 50%), systemic antibiotics (ampicillin and gentamicin, cephamandole) and oral antibiotics (trimethoprim-sulfamethoxazole, neomycin and gentamicin) in a weanling rat bowel ischemia model induced by a transient (one minute) occlusion of the superior mesenteric artery. Animals were evaluated for overall survival, duration of survival, presence of bowel necrosis or perforation at seven days. Mortality in ischemic controls was 83.8%. This was reduced to 52% by FiO2 of 50%, and 40% with systemic ampicillin and gentamicin (with or without FiO2 50%) (P less than .001). Length of survival was 3.4 days in controls and increased from 5.4 to 5.9 days in rats given FiO2 50% and/or ampicillin and gentamicin (P less than .001). The incidence of bowel necrosis in controls was 60% and was reduced to 25% in rats given systemic ampicillin and gentamicin and 23.3% with 50% FiO2 and the same antibiotics (P less than .001). Systemic cephamandole and oral antibiotics had no beneficial effects.

Animals↗
PubMed1983

Stridor and parkinsonism.

A patient is described with idiopathic Parkinson's disease and severe laryngeal stridor. Other than urinary frequency and urgency, not uncommon in this condition, and postoperative levodopa-sensitive postural hypotension, there were no features of generalized autonomic failure. The laryngeal stridor responded to levodopa therapy, and we are not aware that this has been reported previously.

Aged↗
PubMed1982

A study of measles virus and canine distemper virus antibodies, and of childhood infections in multiple sclerosis patients and controls.

We investigated the levels of neutralizing antibodies to measles virus and canine distemper virus (CDV) in 72 multiple sclerosis patients (MS) and matched controls and also examined the frequency and age of onset of a number of childhood illnesses, including measles. The frequency of each childhood illness was not significantly different between cases and controls, but cases did report a later age at measles infection. Our data suggest that the risk of MS is increased by a factor of 1.9 if measles infection occurs between 5 and 9 years of age. A validity survey, based on a questionnaire to general practitioners, suggested substantial inaccuracy in the patients' reports of when they had measles, but the direction and degree of inaccuracy did not appear to be different between cases and controls. We also found higher titres of neutralizing antibodies in cases than controls to both measles virus and CDV, although the CDV difference was not statistically significant. In the light of a significant correlation between measles and CDV titres in both cases and controls, we used paired logistic regression to determine if the case-control difference in titres for each virus could be explained by a confounding effect on one by the other. The numbers were too small, however, to enable us to separate out any independent association of either virus with MS.

Age Factors↗
PubMed1982

Multiple sclerosis and dog ownership. A case-control investigation.

In 1977 and 1978 Cook and his associates demonstrated a positive association between ownership of small dogs and both familial and sporadic cases of multiple sclerosis in New Jersey. Because of the far reaching implications of this work, a similar study was carried out and 72 patients with clinically definite multiple sclerosis (MS) who were resident in the area covered by the Oxford Regional Health Authority, were interviewed to ascertain their past exposure to housepets and other animals. Two hospital controls were chosen for each patient matched for age and sex and area of residence, and these were interviewed in the same manner as the MS cases by the same interviewer, usually in the patients' homes. Similar proportions of cases and controls had resided in a household with a dog at some time prior to the onset of their disease and there was no evidence that cases had lived with more dogs or had lived with them for longer periods than had controls. There was no indication that cases had greater exposure than controls to dogs or any other housepet in the early years of their life or in the period immediately prior to disease onset. Our data suggest that exposure to housepets and other domestic animals is unlikely to be an aetiological factor in MS.

Animals↗
PubMed1979

Fusiform basilar artery aneurysm in a child.

A giant fisuform basilar artery aneurysm ruptured, causing the death of an 11-year-old girl who had presented with a 5-month history of headaches and a 1-month history of progressive brainstem features with choreiform movements. This case, unlike other reported cases, demonstrated no evidence of a generalized arteriopathy, and draws attention to the occurrence of this rare cause in the differential diagnosis of progressive brainstem syndrome in children.

Basilar Artery↗