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Biomedical subjects

K Carr

Publications and source records attributed to K Carr.

At least 37 records · Page 2Linked to original sources
PubMed1994

Regional distribution of neuropeptide processing endopeptidases in adult rat brain.

Many peptide hormone and neuropeptide precursors undergo post-translational processing at mono- and/or dibasic residues. An enzymatic activity capable of processing prodynorphin at a monobasic processing site designated 'dynorphin converting enzyme' has been previously reported in rat rain and bovine pituitary. In this study the distribution of dynorphin converting enzyme activity in ten regions of rat brain has been compared with the distribution of subtilisin-like processing enzymes and with the immuno-reactive dynorphin peptides. The distribution of dynorphin converting enzyme activity generally matches the distribution of immuno-reactive dynorphin B-13 in most but not all brain regions. The regions that are known to have a relatively large number of immuno-reactive dynorphin-neurons also contain high levels of dynorphin converting enzyme activity. The distribution of dynorphin converting enzyme activity does not match the distribution of subtilisin-like processing enzyme or carboxypeptidase E activities. Taken together the data support the possibility that the dynorphin converting enzyme is involved in the maturation of dynorphin, as well as other neuropeptides, and peptide hormones.

Amino Acid Sequence↗
PubMed1992

Neutrophils are not necessary for ischemia-reperfusion lung injury.

The role of neutrophils (PMNs) in ischemia-reperfusion injury after lung transplantation is unclear. If PMNs are involved in ischemia-reperfusion injury in the intact rat, then PMNs should sequester in the injured lung and PMN-depleted rats should develop less injury. Group A rats were treated with a rabbit anti-rat PMN antibody causing profound neutropenia (less than 100 PMNs/microL) and group B with control serum (greater than 2,000 PMNs/microL). Rats were anesthetized and left lung ischemia was sustained for 90 or 180 minutes by clamping the bronchus and the pulmonary artery and vein. Lung injury was quantified by the accumulation of radiolabeled (125I) albumin in ischemic left and nonischemic right lungs (cpm per gram of lung/cpm per gram of blood). Ischemia caused significant lung injury (p less than 0.05) in both PMN-depleted (albumin leak index: 90 min, 0.208; 180 min, 0.218) and nondepleted (90 min, 0.222; 180 min, 0.241) animals compared with nonischemic controls (depleted: 90 min, 0.050; 180 min, 0.100; nondepleted: 90 min, 0.063; 180 min, 0.101); microscopy also demonstrated lung injury. The injury was not associated with PMN sequestration as shown by light microscopy. Thus, we conclude that PMNs are not necessary for ischemia-reperfusion injury and PMN-depletion does not attenuate ischemia-reperfusion injury.

Albumins↗
PubMed1991

Propofol and alfentanil infusions for sedation in intensive therapy.

Forty-four patients, with admission APACHE II scores between 5 and 24, undergoing mechanical ventilation in the intensive therapy unit, received a sedative regimen consisting of continuous infusions of propofol and alfentanil. Patients were randomly allocated to one of three groups to receive either alfentanil 0.25 microgram kg-1 min-1 (10 patients), 0.50 microgram kg-1 min-1 (15 patients) or 0.75 microgram kg-1 min-1 (18 patients) for analgesia. An infusion of propofol 20-200 mg h-1 ran concurrently to maintain a satisfactory level of sedation. Patients received the infusions for between 4 and 260 h and 38 patients spent more than 90% of this time at satisfactory sedation levels. After stopping the infusions all patients had short times to wakening (mean 3-18 min) and to establish spontaneous respiration (mean 8-28 min), suggesting no significant cumulation. Some depression of blood pressure was seen on starting the infusions, which was in general easily treated with fluids or small increases in inotropic agents. One patient, however, was withdrawn from the trial because of haemodynamic instability. This combination of drugs can be recommended for sedation of general intensive-therapy patients, provided the cost is not felt to be prohibitive.

Adolescent↗
PubMed1990

Role of chromatin structure in transcriptional regulation of MMTV LTR hormone-dependent promoter.

Studies of chromatin structure were performed in mouse fibroblast cell lines containing Bovine Papilloma Virus (BPV) based artificial minichromosomes containing Mouse Mammary Tumor Virus (MMTV) Long Terminal Repeat (LTR), a retroviral promoter regulated by glucocorticoids, driving the transcription of v-Ha-ras. These minichromosomes fractionate with the "active chromatin", indicating an association of the minichromosomes with components of the "nuclear matrix". Two regions of the minichromosomes upstream and downstream of v-Ha-ras are involved in this interaction. MMTV LTR promoter is associated with nucleosomes precisely positioned on the DNA sequences. Hormonal activation is accompanied by a structural change of the nucleosome associated with the hormone response elements (HREs). This structural change can be visualized by the appearance of a hormono-dependent DNaseI hypersensitive site. Anti-hormones, even when able to promote a strong binding of the receptor to the nucleus, are unable to induce the chromatin structural change. The strong association of the hormone-receptor complex with the nucleus is necessary to induce the DNaseI hypersensitive site and to maintain the transcription, but is not necessary for DNaseI hypersensitivity maintenance. This suggests a double role for the hormone-receptor complex: 1) induction of a chromatin rearrangement and 2) transcriptional transactivation.

Animals↗
PubMed1989

Effect of harvest medium composition on yield and chain nature of recombinant tissue-type plasminogen activator species.

The effect of harvest medium composition on yield and quality of two recombinant tissue type plasminogen activators (t-PA) has been examined. Protein hydrolysates increased the yield of native t-PA up to 3-fold compared to control cultures. In marked contrast, the yield of a growth-factor deleted t-PA mutant was adversely affected by the use of these additives. Partially purified t-PA that had been harvested in the presence of protein hydrolysates had higher fibrin plate activity: amidolytic activity ratios. In addition Western blotting showed these preparations contained less degraded material. These observations suggest that protein hydrolysates have opposite effects on two closely related recombinant cell lines and that they can affect quality as well as yield of secreted proteins.

Animals↗
PubMed1988

Normal blood lymphocytes from patients with adipose tissue tumors with rearrangements at 12q13-q14 do not express the fragile site fra(12)(q13.1).

An association between chromosomal fragile sites and cancer-specific breakpoints has been found to be statistically significant. Cancer patients have been shown to be carriers of fragile sites in chromosome regions involved in rearrangements in malignant cells. Based on these observations it has been hypothesized that fragile sites may be involved in the pathogenesis of human tumors. We have recently described a new recurrent cancer breakpoint at chromosomal region 12q13-q14 in adipose tissue tumors. The possible involvement in these tumors of the rare folate-sensitive fragile site 12q13.1 has been investigated in PHA-stimulated peripheral blood cells from three patients carrying the t(12;16)(q13;p11) in their liposarcoma cells and one patient with the t(3;12)(q28;q14) in his lipoma cells. No expression of the fragile site 12q13.1 could be detected in the blood lymphocytes of any of the patients. The involvement of the fragile site 12q13.1 in the pathogenesis of adipose tissue tumors with a 12q13-q14 breakpoint remains to be established.

Chromosome Banding↗
PubMed1988

Effects of daily administration of tetrahydrocannabinol on rat preovulatory follicles. A quantitative electron-microscopic analysis.

Using morphometric techniques, we analyzed the effects of delta 9-tetrahydrocannabinol (THC) on the ultrastructure of rat preovulatory follicles. Rats were injected intraperitonally once daily with vehicle alone, or with vehicle plus THC on diestrus (D), metestrus (M) and diestrus (D), or on estrus (E), M and D. All animals were killed on proestrus. Nuclear, mitochondrial, lipid droplet and lysosomal volume density in the membrana granulosa were analyzed. There was no change in nuclear volume, but there were significant THC-induced decreases in mitochondrial and lipid droplet volumes in the peripheral region of the granulosa. There were increases in dense-body volume in all regions of the granulosa from rats given THC either on D alone, or M and D. Dense-body volume returned to control levels in rats injected on E, M and D. It appears that THC can affect follicular ultrastructure and the effects change with the number of injections.

Animals↗
PubMed1988

The synthetic human growth hormone fragment (32-38) increases glucose uptake in the conscious dog.

hGH32-38 was tested to determine if the peptide could affect hepatic glucose production in the conscious dog under basal conditions (euglycemia) or if it could enhance glucose uptake when hyperglycemia was induced. hGH32-38 (1.6 nmol.kg-1.min-1) or vehicle was infused in a cross-over design study into each of 4 conscious 16 h-fasted dogs for 3 h (0-180 min) following a 40 min control period. At 90 min, plasma glucose was raised to and maintained at 9.4 mmol/l by glucose infusion for 3 h (until 270 min). Neither hGH32-38 nor vehicle infusion had a significant effect on insulin and glucagon levels or on tracer determined [( 3-3H]glucose) glucose production. As a result, neither treatment changed plasma glucose (5.72 +/- 0.17 to 5.78 +/- 0.17 mmol/l with hGH32-38; 5.50 +/- 0.22 to 5.50 +/- 0.17 mmol/l with vehicle). Induction of hyperglycemia (9.4 mmol/l) caused glucagon concentrations to fall similarly to about 50 ng/l with and without hGH32-38. Insulin rose to similar levels in both protocols, yet more glucose was required to maintain the same hyperglycemia with hGH32-38 (135-180 min) (74.9 +/- 12.7 vs 43.7 +/- 7.1 mumol.kg-1.min-1, P less than 0.05). In summary, hGH32-38 significantly increased glucose disposition during hyperglycemia and this effect may be attributed to enhanced insulin action or to an insulin independent action of the peptide.

Animals↗
PubMed1987

Dietary manipulation during experimental colorectal carcinogenesis: a morphological study in the rat.

The effect of the dietary manipulation of fat and fibre on the gross pathological, histopathological and scanning electron microscopic appearances of colonic mucosa was studied before and during experimental carcinogenesis in 232 male Albino Swiss rats. Carcinogen treated animals were given 12 consecutive weekly injections of Azoxymethane in a dose of 10 mg/kg per week. The animals were divided between four dietary groups (1: high fat high fibre, 2: low fat high fibre, 3: high fat low fibre and 4: low fat low fibre). The colorectal morphology was assessed at autopsy using standard histopathological techniques. In addition, scanning electron microscopic studies on selected samples were performed. A scoring system was introduced to allow a more accurate comparison of the surface architectural appearances. The high fat low fibre diet was associated with the greatest risk for macroscopic tumour production and the low fat high fibre diet with the lowest risk. Statistically significant differences between each of the dietary groups were noted with the exception of the comparison for tumour induction between the high fat high fibre and low fat high fibre dietary groups. Histopathological analysis confirmed the inter dietary relationships with respect to the extent of neoplastic change. The scanning electron microscopic study revealed that both dietary manipulation and carcinogen treatment influenced the surface characteristics. Control animals fed diet 2 (low fat high fibre) but not treated with carcinogen, showed the greatest deviation from the normal appearances. Animals treated with carcinogen and fed diet 3 (high fat low fibre) consistently showed the greatest surface abnormalities.

Animals↗
PubMed1987

Morphological and cell kinetic effects of dietary manipulation during colorectal carcinogenesis.

The effect of dietary manipulation of fat and fibre on the structural and cell kinetic characteristics of colonic mucosa was studied before and during experimental carcinogenesis in 232 male Albino Swiss rats. Carcinogen treated animals were given 12 weekly injections of azoxymethane (10 mg/kg/week). The animals were divided between four dietary groups (1) high fat, high fibre, (2) low fat, high fibre, (3) high fat, low fibre and (4) low fat, low fibre. Pathological and cell kinetic information together with details of certain faecal characteristics was collected when the animals were killed 4, 20, and 28 weeks after starting their experimental diet. Tumour induction was significantly influenced by diet. The highest risk of colorectal tumour development was found in groups fed diet 3: high fat, low fibre (p less than 0.03). In contrast, diet 2: low fat, high fibre was associated with the lowest risk. The proportion of histologically proven colonic tumours occurring in each dietary group was: diet 1-10.9%, diet 2-3.6%, diet 3-63.7%, diet 4-21.8%. Scanning electron microscopic (SEM) studies done on selected samples indicated both dietary and azoxymethane related alterations in crypt unit integrity. The most marked surface architectural changes were seen in carcinogen treated animals maintained on diet 3 (high fat, low fibre). Stathmokinetic analysis revealed considerable intergroup variability. Both fat and fibre produced significant effects, principally during the preneoplastic phase of carcinogenesis. Faster proliferative activity tended to be found in animals at low risk of tumour induction (diet 2), slower proliferation being more characteristic of animals at high risk (p less than 0.05). The findings suggest that both topographical and cell kinetic parameters have an important relationship with promoting and protecting dietary factors during the development of colorectal cancer.

Animals↗
PubMed1987

Quantitative electron-microscopic analysis of the in vivo effects of tetrahydrocannabinol on rat preovulatory follicles.

The ultrastructural composition of 4 regions of rat preovulatory follicles was examined using stereological techniques following an intraperitoneal injection of tetrahydrocannabinol (THC), once each day, for 3 days prior to sacrifice on proestrus. Control rats were injected with solvent alone. Changes in nuclear, mitochondrial, lipid droplet and dense-body volume density were measured. No differences in volume density were noted in the theca or antral region of the membrana granulosa. Compared to controls, the mitochondrial volume density decreased in the peripheral region and the corona radiata. The volume density of lipid droplets decreased in the peripheral region. These changes, and their relationship to the roles of these regions in follicular steroidogenesis, are discussed.

Animals↗
PubMed1984

Apolipoprotein A and B (Sf 100-400) metabolism during bezafibrate therapy in hypertriglyceridemic subjects.

This study describes the effects of bezafibrate, an analogue of clofibrate, on the plasma lipid and lipoprotein profiles of 11 hypertriglyceridemic subjects and on their metabolism of apolipoproteins A-I, A-II, and B. The major action of the drug was to lower plasma triglyceride (by 58%; P less than 0.01). This was accompanied by a reduction in the level of very low density lipoprotein apoprotein B (Svedberg units of flotation [Sf] 60-400), whose mean residence time in the plasma fell threefold (from 3.4 to 1.0 h). Synthesis of the B protein in this fraction was not significantly altered, so the drug acts to accelerate the transit of very low density lipoprotein particles down the delipidation cascade. The metabolism of very low density lipoprotein remnant apoprotein B (Sf 12-100) changed little in response to treatment, although we detected a 30% increment (P less than 0.05) in the plasma concentration of this fraction. The mean residence time of these remnant particles in the plasma did not correlate with that of Sf 100-400 very low density lipoprotein apoprotein B, nor was this parameter altered by the drug. The most consistent and significant perturbation seen in the Sf 0-12 fraction (low density lipoprotein) was a reduction in the fractional catabolism of its apoprotein B moiety (26%; P less than 0.05). In those subjects who were grossly hypertriglyceridemic and who responded well to treatment, the level of this protein rose substantially owing to a combined increase in its synthesis and a reduction in its catabolism. In the group as a whole, high density lipoprotein cholesterol rose 13% (P less than 0.02), and detailed examination showed that this was associated with a small but significant increment in the plasma concentration of the high density lipoprotein subfraction 2. High density lipoprotein subfraction 3 also rose on the average, but this was not a consistent feature in all patients. The plasma concentrations and turnovers of the A proteins (A-I and A-II) were not significantly altered by bezafibrate therapy.

Apolipoproteins A↗