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Biomedical subjects

B Jackson

Publications and source records attributed to B Jackson.

At least 163 records · Page 9Linked to original sources
PubMed1990

Regional programs for surgical bone banking.

The findings of a survey of 12 regional programs engaged in collection, storage, and distribution of surgical bone grafts are described in this report. In approximately one year, 1944 grafts (mostly femoral heads) were collected. The overall discard rate for the grafts was 30%. An unacceptable medical history, and laboratory evidence of positive screening tests for hepatitis B surface antigen and human immunodeficiency virus (HIV) antibodies accounted for 34.0%, 3.4%, and 1.2% of the discard rate, respectively. Eighty-seven percent of the grafts were used for three surgical procedures, i.e., revision hip surgery, spinal fusions, and treatment of nonunited fractures. The practices and experiences of the regional program described in this report of surgical bone collection and transplantation appear to be similar to those previously described for the community-hospital-based institutional programs. Regional programs represent an alternative approach to institutional programs in surgical bone banking.

Bone Transplantation↗
PubMed1990

Pharmacologic nephrectomy with chronic angiotensin converting enzyme inhibitor treatment in renovascular hypertension in the rat.

Angiotensin converting enzyme (ACE) inhibitor treatment in renovascular hypertension is associated with acute compromise of renal function in patients with bilateral renal artery stenosis or with arterial stenosis to a single functioning kidney. Recent evidence has suggested that renal function is also compromised in the stenosed kidney of patients with unilateral renal artery stenosis. The long-term consequence of this reduction in renal function is not known. We have studied the effect of chronic ACE inhibition with enalapril on renal structure and function in rats with the two-kidney one-clip model of renovascular hypertension. Four weeks after placement of a clip on the left renal artery, hypertensive rats were randomized to treatment with enalapril, minoxidil, or to a no treatment group. Twelve months later split kidney function was determined by chromium 51-labeled ethylenediamine-tetraacetic acid clearance in surviving rats. Clearance of the clipped kidney was 0.0 ml/min (enalapril group), 0.26 +/- 0.23 ml/min (minoxidil group), and 0.74 +/- 0.13 ml/min (untreated group). The clipped kidney from the enalapril treated rats weighed much less than the minoxidil group or the untreated group (0.46 +/- 0.1 gm, 1.2 +/- 0.07 gm, and 1.14 +/- 0.10 gm, respectively). Enalapril treatment was stopped for 2 weeks in five rats. The clipped kidney remained small and nonfunctional. Histologic examination revealed marked interstitial fibrosis and tubular atrophy of the clipped kidneys from the enalapril treated group in contrast to minor changes in the minoxidil treated and untreated groups. After 12 months of treatment, survival in the enalapril group was 84%, 48% in the minoxidil group, and 15% in the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Inhibition of cholesterol 7 alpha-hydroxylase by an antibody to a male-specific form of cytochrome P-450 from subfamily P450IIC.

The absence of antibodies to cholesterol 7 alpha-hydroxylase (EC 1.14.13.17), the rate-determining enzyme for bile acid synthesis, has significantly compromised studies on this protein. Nine antibodies raised against proteins from the cytochrome P-450 gene families (P450I, P450IIA, P450IIB, P450IIC and P450III) were tested as inhibitors of 7 alpha-hydroxylase activity. An antibody raised against a male-predominant P-450 (PB2a, P450h) from the P450IIC gene subfamily was an effective inhibitor of activity in liver microsomal fractions from rat, mouse and hamster. The inhibition could be reversed by the addition of PB2a antigen, indicating structural similarity between cholesterol 7 alpha-hydroxylase and proteins within the P450IIC subfamily. Western blot analysis of hepatic microsomal fractions with the PB2a antibody gave three bands, two of which, like cholesterol 7 alpha-hydroxylase, did not inhibit sexual dimorphism. The intensity of one of the bands (apparent Mr 54,000) correlated with changes observed in activity due to diet [Spearman correlation of 0.800 (P less than 0.01)]. These findings suggest that cholesterol 7 alpha-hydroxylase is a form of P-450 which shares structural similarity with cytochromes P-450 in the P450IIC gene subfamily and that its feedback regulation by bile acid involves protein induction rather than simply post-translational modification.

Animals↗
PubMed1989

Effects of 6,6-difluorocholestanol and 7,7-difluorocholestanol on hepatic enzymes of cholesterol metabolism.

The effects of 6,6-difluorocholestanol and 7,7-difluorocholestanol on enzymes of hepatic liver cholesterol were examined. Neither compound affected the activity of 3-hydroxy-3-methylglutaryl-CoA reductase. 7,7-Diffluorocholestanol had no effect on the activity of acyl-CoA: cholesterol acyltransferase or cholesterol 7 alpha-hydroxylase. However, 6,6-difluorocholestanol was a competitive substrate for cholesterol in the esterification of cholesterol catalysed by the acyltransferase. 6,6-Difluorocholestanol also inhibited hydroxylation of cholesterol by cholesterol 7 alpha-hydroxylase but was not itself a substrate for this enzyme. These results show that substitutents in ring B of the sterol can have a significant effect on the binding of the sterol to enzymes and to the catalytic mechanism if the substituent is close to the groups in the molecule that participate.

Animals↗
PubMed1989

Genetic differences in a tail suspension test for evaluating antidepressant activity.

Tail suspension-induced immobility in rodents is specifically antagonized by antidepressants, and has been proposed as an animal model of depression. Marked differences in tail suspension-induced immobility were observed among nine inbred mouse strains, ranging from 1 +/- 0.3 to 96 +/- 8-s in a 300-s test period. Moreover, these nine strains could be ranked in four distinct groups based on their immobilities, in which Balb/cJ and DBA/2J mice displayed the highest and the lowest immobility times, respectively. While significant differences in open field activity were also observed among strains, these differences were unrelated to their immobility times in the tail suspension test. These findings strongly suggest that performance in this proposed animal model of depression is under specific genetic control, and may provide a useful tool to study neurochemical and neuroendocrine correlates of depression and antidepressant action.

Animals↗
PubMed1989

Anxiolytic properties of 1-aminocyclopropanecarboxylic acid, a ligand at strychnine-insensitive glycine receptors.

The effects of 1-aminocyclopropanecarboxylic acid were investigated on performance in an elevated plus-maze. This compound is a high-affinity, partial agonist ligand at strychnine-insensitive glycine receptors of the N-methyl-D-aspartate receptor complex. Like chlordiazepoxide, 1-aminocyclopropanecarboxylic acid increased in a dose-dependent manner both the percent entries into and the percent time spent in the open arms of the plus-maze. However, 1-aminocyclopropanecarboxylic acid was significantly less efficacious than chlordiazepoxide in these measures and increased, while chlordiazepoxide decreased, the time spent in the middle platform of the plus-maze. These findings indicate that ligands acting through strychnine-insensitive glycine receptors on the N-methyl-D-aspartate receptor complex may represent a new class of anxiolytic agents with a profile which differs from the benzodiazepines.

Amino Acids↗
PubMed1989

Angiotensin converting enzyme in the rat heart: studies of its inhibition in vitro and ex vivo.

1. The pharmacokinetics of angiotensin converting enzyme (ACE) inhibition in rat heart and lung was evaluated in vitro and ex vivo. 2. Radioinhibitor [125I]-351A binding displacement was used to assess the relative potency of six ACE-inhibitors (CI906, CGS14831, S9780, 351A, MK521, SQ27519) in rat heart and lung homogenates, and estimate equilibrium association constant (Ka). 3. Following oral administration of 0.3 mg/kg of Quinapril (CI928) specific binding of [125I]-351A to ACE was measured in rat heart. 4. Ka for binding to ACE of each inhibitor was significantly higher in right and left atrium than in lung (P less than 0.05) or the right and left ventricle (P less than 0.005). These differences did not affect the degree or time course of inhibition in vivo in the rat myocardial ACE following Quinapril treatment. 5. Rank order of potency of the ACE inhibitors tested was CI906 = CGS14831 greater than S9780 greater than 351A greater than MK521 greater than SQ27519

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Comparative studies of tissue inhibition by angiotensin converting enzyme inhibitors.

There is increasing evidence that inhibition of tissue angiotensin converting enzyme (ACE) is important for the pharmacokinetics and pharmacodynamic effects of ACE inhibitors. Radioligand inhibitor binding methods using 125I-351A and either tissue homogenates or in vitro autoradiography have allowed in vitro and ex vivo quantitation of tissue ACE inhibition by a variety of ACE inhibitors. The rank order of potency against plasma as well as lung, kidney, and cardiac homogenates was quinaprilat = benazeprilat greater than perindoprilat greater than lisinopril greater than enalaprilat greater than fosinoprilat. The highest concentration of ACE in the heart was found in the cardiac valves followed by the right and left atria, then the right and left ventricles. Ex vivo studies showed that after oral administration of quinapril, ACE was inhibited dose-dependently in the lung, kidney, aorta and heart for more than 24h. Tissue bioavailability of the inhibitor is also an important determinant of tissue ACE inhibition. Perindopril crossed the blood-brain barrier and inhibited brain ACE at high doses, but after equivalent doses of quinapril no brain ACE inhibition could be demonstrated. These results suggest that it may be possible to design ACE inhibitors to have specific effects on ACE in different tissues.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Angiotensin-converting enzyme inhibition in renal disease; contrasting effects on renal function in renal artery stenosis and progressive renal injury.

Renal failure is progressive irrespective of the underlying primary renal disease or continued disease activity. Intrarenal haemodynamic changes may contribute to progressive loss of renal function, and may be modified by pharmacological therapies. Angiotensin-converting enzyme (ACE) inhibitors may have a specific therapeutic advantage in the treatment of hypertension associated with progressive renal disease. We have studied the effects of an ACE inhibitor and a calcium channel blocker on systemic BP, glomerular filtration, proteinuria and histological injury in animal models of progressive renal disease (the remnant kidney and diabetes). Systemic BP was lowered similarly by each treatment in both models. Beneficial effects on renal structure, proteinuria, and glomerular filtration only occurred in the ACE inhibitor-treated animals. Intrarenal haemodynamic effects of ACE inhibitors may therefore offer an advantage over other antihypertensive agents in progressive renal disease. Where there is reduced renal perfusion, intrarenal haemodynamic effects of ACE inhibitors may lead to compromised renal function. Acute renal failure is a common consequence of ACE inhibitor therapy in patients with bilateral renal artery stenosis, or renal artery stenosis to a single functioning kidney. Acute studies have suggested that these effects are reversible; function returns following withdrawal of ACE inhibitor therapy. We examined the long-term effects of ACE inhibitor therapy in rats with the two-kidney, one-clip (Goldblatt) model of hypertension. Rats were treated for 12 months with an ACE inhibitor or a vasodilator. After 1 year of treatment the clipped kidney from the ACE inhibitor-treated rats was small, fibrotic, and had no glomerular filtration. No functional improvement of the clipped kidney occurred following ACE inhibitor withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Thrombotic thrombocytopenic purpura and pancreatitis.

Abdominal pain is frequently encountered in patients with thrombotic thrombocytopenic purpura (TTP). Often the pain is secondary to inflammation of the pancreas. A case is presented in which the usual signs of TTP developed well after the clinical and laboratory demonstration of pancreatitis, raising the possibility that the pancreatic inflammation triggered the onset of TTP. Treatment with plasmapheresis resulted in prompt improvement. TTP should be considered in patients with abdominal pain or pancreatitis in whom thrombocytopenia, microangiopathic hemolytic anemia, neurologic changes, fever, and renal disease are present.

Female↗
PubMed1988

Smooth-muscle differentiation in stromal cells of malignant and non-malignant breast tissues.

A mouse monoclonal antibody (MAb) recognizing alpha-smooth-muscle actin has been used to study smooth-muscle differentiation features in the stromal cells of desmoplastic reactions accompanying mammary tumors. We have studied, by the same immunohistochemical technique, a series of malignant and non-malignant human breast tissues. Cells composing the desmoplastic reaction were found to express alpha-smooth-muscle actin in all the 11 breast carcinomas examined, whereas no immunostain was demonstrated in the stromal cells of 7 breast tissue samples histologically defined as normal. Three of 9 cases of fibrocystic disease showed a minority of positively stained stromal cells, generally in association with epithelial hyperplasia. All the 7 cases of sclerosing adenosis, 3 of 4 cases of diffuse papillomatosis and all 3 intraductal papillomas exhibited a majority of immunoreactive stromal cells. Numerous stromal cells in 3 of 11 circumscribed fibroadenomas analyzed expressed low amounts of alpha-smooth-muscle actin. The factor(s) responsible for smooth-muscle differentiation in stromal cells are presently unknown, but the detection of this previously unsuspected stromal cell phenotype in nonmalignant mammary tissues might help in characterizing the variant morphological aspects designated under the label "fibrocystic disease" and in understanding the biology of premalignant or early malignant lesions of the breast.

Actins↗
PubMed1988

The effect of inhibition of cholesterol esterification on the fate of cholesterol derived from HDL in rat hepatocyte monolayers.

Rat HDL2 is known to stimulate bile acid synthesis in rat hepatocyte monolayers. The intracellular fate of the cholesterol derived from the HDL2 was studied using the inhibitor of cholesterol esterification, Sandoz compound 58-035. Rat HDL2 added to rat hepatocyte monolayers caused a stimulation of cholesterol esterification of 32%. This stimulation could be inhibited by 58-035. A small significant increase in bile acid synthesis was also observed in cells in the presence of HDL2, confirming our earlier observations. 58-035 prevented this increase. These observations imply that cholesterol entering the cell from HDL2 is first esterified and can only enter the substrate pool for bile acid synthesis after subsequent intracellular hydrolysis.

Amides↗
PubMed1988

3-Ethoxy-beta-carboline: a high affinity benzodiazepine receptor ligand with partial inverse agonist properties.

3-Ethoxy-beta-carboline binds with high affinity to benzodiazepine receptors in the central nervous system (Ki approximately equal to 10.1, 15.3, and 25.3 nM in rat cerebellum, cerebral cortex, and hippocampus, respectively). This compound has pharmacological actions reminiscent of benzodiazepine receptor partial inverse agonists such as FG 7142 and 3-carboethoxy-beta-carboline. Thus, while not a convulsant, 3-ethoxy-beta-carboline potentiated the convulsant actions of pentylenetetrazole in mice. Furthermore, this compound reduced both the time spent and the total entries in the open arms of an elevated plus maze and also inhibited stress-induced ulcer formation, effects that are also observed with benzodiazepine receptor inverse agonists. These findings suggest that 3-ethoxy-beta-carboline is a partial inverse agonist at benzodiazepine receptors which may prove useful for in vivo studies since it has a higher affinity for benzodiazepine receptors and better solubility than the commonly used partial inverse agonist FG 7142. Furthermore, 3-ethoxy-beta-carboline appears to be less vulnerable to metabolic degradation than ester analogs with a similar pharmacological profile such as 3-carboethoxy-beta-carboline.

Animals↗
PubMed1988

Recovery of human immunodeficiency virus from ocular tissues in patients with acquired immune deficiency syndrome.

Human immunodeficiency virus (HIV) was recovered from multiple ocular tissues in three patients with acquired immune deficiency syndrome (AIDS). Consistently found in the retina, HIV was also detected in the conjunctiva, cornea, and iris. In two cases, HIV was detectable despite treatment with oral zidovudine. All three patients had bilateral cytomegalovirus (CMV) retinitis managed by intravitreal injection of ganciclovir. Culture of the retina for CMV was negative in all three cases. The finding of HIV in multiple ocular tissues is consistent with the neurotropic nature of the virus, and may explain some of the common ocular manifestations of AIDS such as AIDS retinopathy. Infection with HIV may predispose the retina to other opportunistic infections and may explain the high incidence of CMV retinitis in AIDS patients. This is the first report of HIV isolation from tissue within the eye.

Acquired Immunodeficiency Syndrome↗