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Biomedical subjects

B Brooks

Publications and source records attributed to B Brooks.

At least 73 records · Page 4Linked to original sources
PubMed1989

Biologic contrasts between medullipin I and vasoactive glyceryl compounds.

Medullipin I causes a delayed onset depressor response when injected intravenously into rats. The glyceryl compounds selachyl alcohol (SA) and monoolein (MO) cause similar vasodepression. The neutral lipid 1-O-hexadecyl-2-acetyl-sn-glycerol (HAG) was suggested by Blank et al to be medullipin I (Med I, formerly ANRL). Biologic comparisons were made between Med I and various glyceryl compounds, including SA, MO, HAG, alkyl glyceryl ethers of phosphatidyl choline (termed APRL by us), diacylated SA, and the n-butyl boronic acid derivative of SA and MO. The n-butyl boronic acid derivative of Med I also was evaluated. The delay in onset of the depressor response to Med I was reduced by the injection of Med I into the portal vein; that of SA and MO was not. Med I, SA, and MO were activated by the liver, while APRL and HAG were not. Tween 20 inhibited Med I, SA, and MO, but not APRL and HAG. Proadifen (SKF 525A) inhibited Med I, but not SA and MO. The n-butyl boronic acid derivatives of SA, MO, and Med I were inactive. Med I, like SA and MO, appeared to have two hydroxyl groups in close proximity. It was concluded that Med I is neither HAG, APRL, SA, nor MO.

Animals↗
PubMed1989

The renal antihypertensive endocrine function: its relation to cytochrome P-450.

Unclipping the Goldblatt hypertensive rat lowers the blood pressure by cells in the renal papilla, the renomedullary interstitial cells (RIC), secreting a hormone that is part of a vasodilator system. A vasodilator, termed medullipin I, can be extracted from the renal papilla. Medullipin I and the renal venous effluent following unclipping have identical biologic properties. Medullipin I appears to be the agent secreted by the kidney following unclipping. Both medullipin I and the renal venous effluent must traverse the liver to be active. Medullipin I is converted in the liver to its active form, medullipin II. The blood pressure-lowering effect of both medullipin I and the renal venous effluent after unclipping are blocked by SKF 525A, the inhibitor of cytochrome P-450. The relation of the kidney to the liver was tested using the rate of decline of the blood pressure after unclipping as an index of the endocrine antihypertensive function of the kidney--acceleration of the decline being considered as increased function, decrease of the decline as decreased function. Five compounds: BW755C, phenobarbital, ketoconazole, eicosatetraynoic acid (ETYA) and butylated hydroxytoluene (BHT), and two manipulations: uretero-caval anastomosis (UCA) and removal of the liver from the circulation were used followed by unclipping. BW755C, inhibitor of both cyclo-oxygenase and lipoxygenase, potentiated the antihypertensive function to a maximum. It is reasoned that inhibition of the first two pathways of arachidonic acid metabolism potentiates the third pathway, the cytochrome P-450 pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1989

Low birthweight and impaired growth to 5 years in Australian aborigines.

Twelve per cent of Aboriginal infants born in the Kimberley region of Western Australia in 1980 were of low birthweight; this is more than twice the incidence in the non-Aboriginal population of Western Australia. There was widespread faltering of growth (weight and height) after 6 months of age in Aboriginal children whether they were of normal or low birthweight. Growth retardation was more marked in low birthweight babies who showed little evidence of 'catch-up' growth in the first 5 years of life.

Australia↗
PubMed1988

Valvular surgery in Western Australia: a 15-year review.

Between 1970 and 1984, 1138 patients underwent the insertion of 1300 prosthetic heart valves in Western Australia; 56% received an aortic-valve replacement; 34% received a mitral-valve replacement and 10% had more than one valve replaced. Mechanical valves were used in 93% of patients before 1977, in 20% of patients between 1978 and 1982 and in 70% of patients from 1983 onwards. The 30-day mortality was 18% before 1973 and has been below 6% since 1974. The over-all, 15-year actuarial survival rate was 67%; this was not affected by age, sex, race, valvular position or the type of prosthesis. Both the 30-day mortality and 15-year survival rates were significantly worse in patients who underwent multiple valvular replacements (13% and 54%, respectively) or reoperation (16% and 58%, respectively). The major causes of death were cardiac failure and myocardial infarction (65%); endocarditis (13%); cancer (6%); and thromboembolism and bleeding (6%). The hazard rate for reoperation was low and fairly constant in patients with mechanical valves, but increased markedly after four years in patients with tissue valves. Although our experience so far suggests that survival rates are not affected by the choice of prosthesis, this may not be so in the future, as more patients with tissue valves undergo reoperation and so become exposed to an increased risk of mortality.

Actuarial Analysis↗
PubMed1988

Three-week beta-adrenergic blockade does not impair or improve general intellectual function in young healthy males.

The widespread use of beta blockers in treatment of both cardiovascular and nonvascular conditions has generated interest in changes in functions of the central nervous system during treatment. We studied the effect of 3 weeks of beta blockade on learning and memory ability, concentration, and verbal abstraction in 32 young normotensive healthy men. We chose healthy males to exclude the possible influence of changes related to a hypertensive state. Subjects were randomized into a 3-week treatment protocol with either atenolol 50 mg X 2 (cardioselective, hydrophilic), metoprolol 100 mg X 2 (cardioselective, lipophilic), propranolol 80 mg X 2 (noncardioselective, lipophilic), or placebo X 2. Each subject underwent two neuropsychological testing sessions. We found no significant enhancement or impairment of intellectual or psychomotor performances after the 3-week treatment with beta-adrenergic-blocking agents compared to a placebo-treated control group. Differences in pharmacokinetic profiles of the drugs (e.g., central nervous system penetrability, lipophilicity, or membrane-stabilizing effect) did not influence the test outcome. Antihypertensive treatment with beta blockers over a prolonged period does not affect young peoples' learning and memory abilities or reasoning powers, nor their ability to concentrate and perform psychometric tasks.

Adrenergic beta-Antagonists↗
PubMed1988

Structure and expression of the human L-myc gene reveal a complex pattern of alternative mRNA processing.

We analyzed in detail the structure of the L-myc gene isolated from human placental DNA and characterized its expression in several small-cell lung cancer cell lines. The gene is composed of three exons and two introns spanning 6.6 kilobases in human DNA. Several distinct mRNA species are produced in all small-cell lung cancer cell lines that express L-myc. These transcripts are generated from a single gene by alternative splicing of introns 1 and 2 and by use of alternative polyadenylation signals. In some mRNAs there is a long open reading frame with a predicted translated protein of 364 residues. Amino acid sequence comparison with c-myc and N-myc demonstrated multiple discrete regions with extensive homology. In contrast, other mRNA transcripts, generated by alternative processing, could encode a truncated protein with a novel carboxy-terminal end.

Amino Acid Sequence↗
PubMed1988

Human recombinant IL-4 suppresses the induction of human IL-2 induced lymphokine activated killer (LAK) activity.

The effect of recombinant human interleukin 4 (rhIL-4) on the induction in vitro of human lymphokine activated killer cell (LAK) activity was investigated. Peripheral blood mononuclear cells (PBMC) from normal healthy donors were incubated for 4 days with or without recombinant human interleukin-2 (rhIL-2) in the presence or absence of rhIL-4. LAK activity was measured against the NK-resistant colon adenocarcinoma cell line SW742, and NK mediated cytotoxicity was determined using NK sensitive K562 cells. Unlike previous reports using mouse effector cells, rhIL-4 neither induced LAK activity nor augmented the cytotoxic response induced by rhIL-2. In four out of six experiments there was a significant reduction of rhIL-2 induced LAK in the presence of rhIL-4, accompanied by a reduction of Tac antigen expression by rhIL-2 activated cells. Recombinant hIL-4 failed to influence the effector phase of the activated PBMC against SW742 or K562 targets.

Cytotoxicity, Immunologic↗
PubMed1987

Galanin-immunoreactive neurons in the guinea-pig small intestine: their projections and relationships to other enteric neurons.

Galanin immunoreactivity was observed in nerve cell bodies and nerve fibres, but not in enteroendocrine cells, in the small intestine of the guinea-pig. Nerve terminals were found in the myenteric plexus, in the circular muscle, in submucous ganglia, around submucous arterioles, and in the mucosa. Lesion studies showed that all terminals were intrinsic to the intestine; those in myenteric ganglia arose from cell bodies in more orally placed ganglia. Myenteric nerve cells were also the source of terminals in the circular muscle. Galanin (GAL) was located in a population of submucous nerve cell bodies that also showed immunoreactivity for vasoactive intestinal peptide (VIP) and in a separate population that was immunoreactive for neuropeptide Y (NPY). Processes of the GAL/VIP neurons supplied submucous arterioles and the mucosal epithelium. Processes of GAL/NPY neurons ran to the mucosa. It is concluded that galanin immunoreactivity occurs in several functionally distinct classes of enteric neurons, amongst which are neurons controlling (i) motility, (ii) intestinal blood flow, and (iii) mucosal water and electrolyte transport.

Animals↗
PubMed1987

The reno-hepatic axis of blood pressure control: further studies.

A reno-hepatic axis of blood pressure (BP) control has been proposed primarily by two developments: the lag period between the injection of the antihypertensive neutral renomedullary lipid (ANRL) into the vena cava and the beginning of the drop of the BP is significantly reduced by injection of this lipid into the portal vein; and a reno-portal shunt (RPS) accelerates markedly the drop of the BP following unclipping the Goldblatt hypertensive rat. In the present studies, three maneuvers were performed: perfusion of the isolated, blood-drained rat liver with plasma containing ANRL and delivery of the plasma into the jugular vein of a hypertensive rat; injection of captopril, establishment of a RPS of a hypertensive rat (one-kidney, one-clip) followed by unclipping; and establishment of a RPS in a normal rat. The blood-drained liver was capable of decreasing significantly the lag period of ANRL. Captopril did not potentiate the antihypertensive action of the kidney when RPS was coupled with unclipping. Following the RPS, the BP of the normal rat dropped modestly over a 3-hour period. These results further support the concept of reno-hepatic axis of BP control.

Animals↗
PubMed1987

Selachyl alcohol as an oral antihypertensive agent: a preliminary note.

Selachyl alcohol (SA) is a mono-oleyl glyceryl ether. It has certain biologic activities similar to those of the antihypertensive neutral renomedullary lipid (ANRL) derived from the renal papilla and its renomedullary interstitial cells (RIC). These include a vaso-depressor effect following bolus injection and a requirement for hepatic activation for the development of biological activity. In view of this similarity to ANRL, it appeared worthwhile to test the antihypertensive action of SA when given via the GI tract. Accordingly, pure SA was given either by gavage or by tube into the stomach or duodenum of one-kidney, one-clip hypertensive rats (5-10 mg per dose). The role of hepatic activation was demonstrated by comparing the BP response to bolus injection of SA and ANRL with and without the presence of an intact circulation to the liver. Administration of SA via the GI tract resulted in a significant decline in BP without tachycardia or weight loss. In the absence of a circulation to the liver, neither SA nor ANRL was active. SA appears to be an effective antihypertensive agent when given via the GI tract.

Animals↗
PubMed1986

The activity and properties of an acidic triacylglycerol lipase from adult and fetal rat lung.

Triacylglycerol lipase with maximal activity at pH 5 was present in adult and fetal lung. The activity was inhibited by serum concentrations used to measure lipoprotein lipase and by 0.5 M NaCl. The activity in homogenates from fetal lung was about 40% of the activity in adult lung homogenates. The activity increased to 80% of the adult levels during the first 24-48 h following birth. Acidic triacylglycerol lipase was present in all subcellular fractions from adult lung. However, the major amount of activity appeared to be associated with lysosomes. Fetal lung contained significantly more activity in the cytosolic fraction compared to the adult. The reaction produced free fatty acids (65%), 1,2(2,3)-diacylglycerol (22%) and 2-monoacylglycerol (12%). Minimal amounts of 1,3-diacylglycerol and 1(3)-monoacylglycerol were formed. Diacylglycerol lipase and monoacylglycerol hydrolase activities at pH 5 were independently determined and both were higher than the triacylglycerol lipase activity. The subcellular distribution of diacylglycerol lipase and monoacylglycerol hydrolase differed from that of triacylglycerol lipase. Overall, the results indicated that the lung has considerable intracellular lipase activity and therefore could readily hydrolyze intracellular triacylglycerol to free fatty acids. The reaction also produced significant amounts of 1,2-diacylglycerol which suggests that triacylglycerol could be a direct source of diacylglycerol for phospholipid synthesis.

Aging↗
PubMed1986

Evaluation of prostatic cancer histology and grade distribution: experience with the Colorado Central Cancer Registry.

Although well-defined grading schemes for prostatic adenocarcinoma have been developed, they are not yet universally accepted by practicing surgical pathologists. The complexity of these schemes often leads surgical pathologists to develop their own modified Broders scheme. This study compared the grade distribution as obtained by a community of surgical pathologists with that obtained using the National Prostatic Cancer Project (NPCP) and Gleason grading schemes. In 1978, 308 cases of prostate cancer were reported to the Colorado Central Cancer Registry (CCCR) from the Denver Standard Metropolitan Statistical Area. Two hundred eighteen of these cases were regraded. The grade distribution as reported by the CCCR revealed a predominance of low-grade tumors (grade I-41%, grade II-28%, grade III-17%, grade IV-3%). Regrading of these same cases revealed a shift to higher grades (NPCP: grade I-14%, grade II-11%, grade III-37%, grade IV-29%; Gleason: pattern scores less than 6-30%, score 6-24%, score 7-12%, score 8-11%, score 9-10%, score 10-4%). Twenty-one cases of histologic variants which were not originally diagnosed were also noted (six mucinous, 12 ductal, two endometroioid, one squamous). There were 18 cases in which no evidence of carcinoma was confirmed. These results suggest that there is a tendency to underestimate grade and potentially malignant behavior when well-defined prostatic cancer grading schemes are not applied.

Adenocarcinoma↗
PubMed1986

Thoracoabdominal aortic aneurysms: preoperative and intraoperative factors determining immediate and long-term results of operations in 605 patients.

Graft inclusion and vessel reattachment to openings made in the graft were employed in the treatment of 605 patients with thoracoabdominal aortic aneurysms. These patients were divided into four groups on the basis of the extent of aneurysm. Group I consisted of those patients with involvement of most of the descending thoracic and upper abdominal aorta; group II involved most of the descending thoracic aorta and most or all of the abdominal aorta; group III involved the distal descending thoracic aorta and varying segments of abdominal aorta; and group IV involved most or all of the abdominal aorta including the segment from which the visceral vessels arose. The cause of aneurysm formation was medial degenerative disease in 80%, and dissection in 17%; other causes were responsible in the remaining 3%. The median age was 65 years and associated diseases including aneurysms involving other segments, atherosclerotic occlusive disease, heart disease, chronic obstructive pulmonary disease (COPD), hypertension, and renal insufficiency were frequent. The aneurysm was symptomatic in 70% of cases and rupture had occurred in 4% of cases. There were 54 (8.9%) early (30-day) deaths and 151 late deaths; 400 (66%) patients were still alive 3 months to 20 years after operation, including 60% at 5 years. Statistically significant pre- and intraoperative variables by univariate analysis that were predictive of increased risk of early death were advancing age, associated diseases that included COPD, renal artery occlusive disease, atherosclerotic heart disease, renal insufficiency, and long aortic clamp time. Three of these (age, clamp time, and the presence of COPD) retained significance by multivariate analysis. Variables predictive of risk of late death were age, dissection, extent of aneurysm, rupture, heart disease, cerebrovascular disease, COPD, hypertension, and poor renal function. Age, rupture, renal dysfunction, extent of aneurysm, and dissection retained their significance by multivariate analysis. Variables predictive of neurologic disturbances of the lower extremities included rupture, reattachment of intercostal and lumbar arteries, clamp time, dissection, extent and age. Rupture, reattachment of vessels, dissection, and extent of aneurysm retained significance by multivariate analysis. Thus, the risk of this complication was greatest in patients with extensive lesions (group II) with aortic dissection. The greatest risk of renal failure after operation that required dialysis was in patients who had impaired renal function before operation. Methods employed did not prevent these complications.

Adolescent↗
PubMed1986

The liver converts the antihypertensive hormone of the kidney. The renohepatic axis.

The antihypertensive neutral renomedullary lipid, derived from the renal papilla, causes a vasodepressor effect when injected into a peripheral vein, such as the inferior vena cava, after a lag period of 1 to 2 minutes. The blood pressure tracing is skewed (cuplike effect). The lag period is significantly reduced after injection of the antihypertensive lipid into the portal vein. The vasodepressor configuration (cuplike) is the same whether the lipid is injected into the vena cava or portal vein. Removal of the liver from the circulation prevents the depressor effect. Thus, passage through the liver is essential for antihypertensive lipid activity. Renoportal shunting of blood potentiates the antihypertensive function of the kidney after unclipping in the one-kidney, one clip hypertensive rat. Lack of a hepatic circulation prevents the antihypertensive function of the kidney after unclipping. Antihypertensive neutral renomedullary lipid and the renal venous effluent after unclipping have the same biological behavior. We conclude that antihypertensive neutral renomedullary lipid is a promolecule, the putative prohormone of the renal papilla and its renomedullary interstitial cells. The liver converts the antihypertensive prohormone of the kidney to an active antihypertensive substance. A renohepatic axis of blood pressure control appears to exist.

Animals↗