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M A Carroll

Publications and source records attributed to M A Carroll.

At least 55 records · Page 3Linked to original sources
PubMed1987

Cytochrome P-450-related arachidonic acid metabolites.

Arachidonic acid (AA) can be metabolized to diverse products that differ widely in their biologic activities. Depending on the cell type, AA can be metabolized by 3 pathways: cyclooxygenase, lipoxygenases, and cytochrome P-450 monooxygenases. Disease states, injury, and stress, will influence the enzymes that regulate the breakdown of AA and may favor the generation of products not usually associated with a tissue. Studies on renal eicosanoid mechanisms (all AA metabolites) can serve as a paradigm for other tissues and organs. Discrete stimulation of renal AA metabolism can occur-localized to specific cells within segments of the nephron; for example, cells of the medullary segment of the thick ascending limb of the loop of Henle (mTALH) have high cytochrome P-450 monooxygenase activity, through which novel AA metabolites are formed. These metabolites have characteristic biologic activities, inhibition of Na+-K+-ATPase activity and relaxation of blood vessels, and can be stimulated by peptide hormones. Cytochrome P-450-dependent monooxygenases are also present in the lung where, in their suggested capacity as oxygen sensors, they generate metabolites of AA that modify pulmonary vasomotion.

Animals↗
PubMed1987

Progress toward meeting the 1990 nutrition objectives for the nation: nutrition services and data collection in state/territorial health agencies.

Promoting Health, Preventing Disease, Objectives for the Nation, specifies nutrition as a priority area for improving the health of Americans by 1990. Eleven of the 15 nutrition objectives target adults or the public while four address pregnant and lactating women, infants, and children. To determine progress by states toward achieving the nutrition objectives, the Association of State and Territorial Public Health Nutrition Directors conducted a survey in 1985 to which 54 state and territorial nutrition directors responded. Three-fourths of the nutrition personnel focused efforts on maternal and child populations, and were supported largely by federal funds from the Special Supplemental Food Program for Women, Infants, and Children (WIC) and the Maternal and Child Health Block Grant. Only 15 per cent were funded by state and local sources. While most agencies reported using nutrition consultation in adult health programs, only 25 per cent paid for these personnel. Data to monitor progress were commonly available for only five of the 15 objectives. Achievement of the nutrition objectives by states will require a more comprehensive approach to nutrition programming with increased allocation of appropriate resources and expansion of health data systems.

Adolescent↗
PubMed1986

Regulation of arachidonic acid metabolism by cytochrome P-450 in rabbit kidney.

Renal microsomal cytochrome P-450-dependent arachidonic acid metabolism was correlated with the level of cytochrome P-450 in the rabbit kidney. Cobalt, an inducer of haem oxygenase, reduced cytochrome P-450 in both the cortex and medulla in association with a 2-fold decrease in aryl-hydrocarbon hydroxylase, an index of cytochrome P-450 activity, and a similar decrease in the formation of cytochrome P-450-dependent arachidonic acid metabolites by renal microsomes (microsomal fractions). Formation of the latter was absolutely dependent on NADPH addition and was prevented by SKF-525A, an inhibitor of cytochrome P-450-dependent enzymes. Arachidonate metabolites of cortical microsomes were identified by g.c.-m.s. as 20- and 19-hydroxyeicosatetraenoic acid, 11,12-epoxyeicosatrienoic acid and 11,12-dihydroxyeicosatrienoic acid. The profile of arachidonic acid metabolites was the same for the medullary microsomes. Induction of cytochrome P-450 by 3-methylcholanthrene and beta-naphthoflavone increased cytochrome P-450 content and aryl-hydrocarbon hydroxylase activity by 2-fold in the cortex and medulla, and this correlated with a 2-fold increase in arachidonic acid metabolites via the cytochrome P-450 pathway. These changes can also be demonstrated in cells isolated from the medullary segment of the thick ascending limb of the loop of Henle, which previously have been shown to metabolize arachidonic acid specifically via the cytochrome P-450-dependent pathway. The specific activity for the formation of arachidonic acid metabolites by this pathway is higher in the kidney than in the liver, the highest activity being in the outer medulla, namely 7.9 microgram as against 2.5 micrograms of arachidonic acid transformed/30 min per nmol of cytochrome P-450 for microsomes obtained from outer medulla and liver respectively. These findings are consistent with high levels of cytochrome P-450 isoenzyme(s), specific for arachidonic acid metabolism, primarily localized in the outer medulla.

Animals↗
PubMed1986

Survival of mice with NC carcinoma is unchanged by drugs that are thought to inhibit thromboxane synthesis or increase prostacyclin formation.

Mice transplanted with NC carcinoma were treated with the thromboxane synthetase inhibitor dazmegrel (UK38485) or with nafazatrom (BAY G 6575), a compound that is reported to increase prostacyclin formation. Some experiments included the cytotoxic drugs methotrexate and melphalan. The tumours were excised under anaesthesia on day 14 or day 21 after transplantation, and weighed; some were extracted for prostanoids which were measured by radioimmunoassay. Mouse survival time was determined up to day 121, and cancer spread was determined by postmortem examination. The survival was increased by methotrexate and melphalan but not by the other drugs. Nafazatrom-treated mice tended to have lighter tumours. Although dazmegrel reduced the formation of thromboxane B2 during clotting of blood from normal mice, it did not affect the tumour yields of prostanoids. Nafazatrom had no effect on serum or tumour prostanoids. There were no obvious effects of the treatments on the recurrence of tumour in the excision scar, lung metastasis or spread to lymph nodes.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Cytochrome P450-dependent arachidonate metabolism in renomedullary cells: formation of Na+K+-ATPase inhibitor.

The medullary portion of the thick ascending limb of the loop of Henle (mTALH) has one of the highest concentrations of Na+K+-ATPase found in mammalian tissues, reflecting the importance of this nephron segment in the regulation of extracellular fluid volume, as active sodium transport is driven by Na+K+-ATPase. We have isolated cells derived primarily from the mTALH of the outer medulla of rabbit kidney and have identified a cytochrome P450-dependent mono-oxygenase system which metabolizes arachidonic acid to two biologically active oxygenated peaks, each containing two or more products. One of the peaks potently inhibits cardiac Na+K+-ATPase and the other relaxes blood vessels. We report that formation of these oxygenated arachidonate metabolites is stimulated by arginine vasopressin (AVP) and salmon calcitonin (SCT). In mTALH cells obtained from rabbits made hypertensive by aortic constriction there was a selective increase in P1 and P2 formation compared to other renomedullary cells.

Animals↗
PubMed1986

Survey of nutritionists in state and local public health agencies.

A spring 1985 survey of 50 state and four territorial public health nutrition directors identified 2,931 budgeted positions for public health nutritionists--1,128 in state agencies and 1,803 in local health departments. To achieve the recommended staffing ratio of one public health nutritionist per 50,000 population, an estimated 1,827 more public health nutritionists are needed nationwide with more needed in some states than in others. About half of the state personnel systems require registration or registration eligibility to assure expertise of public health nutrition personnel; about one-third also require graduate training in public health for leadership, planning, and policymaking positions. Sixty-two percent of the funding for state and local health agency nutritionist positions is from the Special Supplemental Food Program for Women, Infants, and Children (WIC). When that is added to the 11% of funds from the Maternal and Child Health Block Grant, 73% of the public health nutritionist positions are federally supported to serve women of childbearing age, infants, and children. That leaves the remaining state and local funding sources and the federal Prevention Block Grant (2%) to pay salaries of nutritionists to serve the general public, including men, postmenopausal women, and the elderly.

Data Collection↗
PubMed1985

The topography of glycerophosphate acyltransferase in the transverse plane of the mitochondrial outer membrane.

In low ionic media, mitochondrial glycerophosphate acyltransferase was inhibited virtually completely within 15 min by the nonspecific proteases, proteinase K and subtilisin. In high ionic media, the mitochondrial enzyme was either not inhibited or was marginally inhibited by these proteases. Chymotrypsin and trypsin, regardless of the ionic strength of the medium, did not inhibit the acyltransferase. Substantial inhibition by proteinase K and subtilisin was observed in the high ionic media when the incubation was continued for 30 or 45 min. Adenylate kinase, an intermembrane enzyme, was not inhibited under any of the above conditions. These results demonstrate a cytosolic exposure of the mitochondrial acyltransferase. In a low ionic environment, when the outer membrane integrity was damaged either by gradually decreasing the tonicity of the medium or by stepwise addition of Triton X-100, either chymotrypsin or trypsin caused virtually parallel inhibition of glycerophosphate acyltransferase and adenylate kinase. A more direct approach in establishing the existence of protease-susceptible sites on the inner side of the outer membrane was taken by observing the inhibition of mitochondrial glycerophosphate acyltransferase and adenylate kinase in trypsinloaded right-side-out outer membrane vesicles incubated in the presence of externally located soybean trypsin inhibitor. The above results, taken together, suggest that mitochondrial glycerophosphate acyltransferase spans the transverse plane of the outer membrane.

Acyltransferases↗
PubMed1985

Enriched prostaglandin E-9 ketoreductase activity in outer medullary cells of the rabbit kidney.

PGE2 metabolism was examined in rabbit renal slices and cell suspensions from the outer medulla, enriched (TALH) and depleted (OMC) for the thick ascending limb of Henle's loop. Metabolism was negligible in intact cells, either OMC or TALH fractions. However, in OMC and TALH homogenates, transformation of PGE2 to PGF2 alpha by NADPH-dependent prostaglandin E-9 ketoreductase (PGE-9KR) was observed at a PGE2 concentration of 4 X 10(-9) M. This activity was not reversible and was enriched ten-fold in the TALH with 41% of PGE2 transformed to PGF2 alpha after 30 min incubation. PGF2 alpha formation from PGE2 could not be detected in homogenates of cortex, medulla or papilla. PGE-9KR activity, particularly in the thick ascending limb, may be a source of PGF2 alpha in urine.

Animals↗
PubMed1985

Treatment of mouse carcinoma in vivo with a prostaglandin E2 analogue and indomethacin.

WHT/Ht mice transplanted s.c. with NC carcinoma were treated with 16,16-dimethyl prostaglandin E2 methyl ester (di-me-PGE2) and/or indomethacin. Each primary tumour was excised under anaesthesia 3 weeks after transplantation, weighed and extracted for prostaglandins. Mouse survival time and tumour recurrence were measured. Di-me-PGE2 10 micrograms, injected at the tumour site on alternate days from day 1 to 19, indomethacin 2.5 mg kg-1 daily by mouth, or both drugs together resulted in lighter tumours (respectively 45, 45 and 52% less, n = 18 to 20 per group, P less than 0.02) compared with vehicle-treated controls. Indomethacin reduced the tumour prostaglandin yield, but the biological activity in extracts of tumours from mice given di-me-PGE2 was high. The median survival time was longer in mice receiving indomethacin alone (61 days from tumour transplantation compared with 50 days in controls P less than 0.02). Di-me-PGE2 alone had little or no effect on survival (median 48 days) but counteracted the increase with indomethacin (di-me-PGE2 + indomethacin, 49 days median survival). There were no obvious effects of the treatments on tumour recurrence at the excision site, but there was a higher incidence of involved lymph nodes in mice given di-me-PGE2.

16,16-Dimethylprostaglandin E2↗
PubMed1982

Increased survival of cancer-bearing mice treated with inhibitors of prostaglandin synthesis alone or with chemotherapy.

In mice with a transplantable mammary carcinoma, treatment with the prostaglandin-synthesis inhibitors flurbiprofen or indomethacin produced various beneficial effects. Survival time after excision of the transplanted tumour was increase, particularly when the drugs were given with the chemotherapeutic agents methrotrexate and melphalan, and there were more disease-free survivors. The combined treatment with flurbiprofen also gave less tumour recurrence at the excision site. Flurbiprofen did not seem to alter the bioavailability of the chemotherapeutic agents.

Adenocarcinoma↗
PubMed1982

Prostaglandins and human lung carcinomas.

Lung primary carcinomas and normal tissue from 136 patients have been extracted for prostaglandins, and the findings examined in relation to histology. In most cases, tumours yielded more prostaglandin-like material (PG-lm), as judged by bioassay, than did normal tissue from the same lungs. Amounts varied with tumour types, in the following ascending order: small-cell carcinomas, large-cell undifferentiated carcinomas, well-differentiated squamous carcinomas, poorly-differentiated adenocarcinomas, poorly differentiated squamous carcinomas, and well-differentiated adenocarcinomas. Tumour PG-lm was highest when necrosis or the neutrophil content of the tumours were moderate, whereas PG-lm from normal lung tissue correlated with the number of macrophages. Chromatography indicated the presence of various prostaglandins, in agreement with our recent findings using gas chromatography--mass spectrometry.

Adenocarcinoma↗
PubMed1982

Quantitative analysis of effect of neodymium-YAG laser on transplanted mouse carcinomas.

Intradermally transplanted non-immunogenic murine carcinomas measuring 3-6 mm in diameter were exposed to a neodymium-YAG laser beam (1060 nm) over a range of exposure times (0.5-6 seconds) and energy densities (expressed as watts/mm2 exposure field). Subsequent growth of the irradiated tumours was compared with that of untreated tumours. A clear dose-response relationship dependent only on power delivered per unit area was found. Below a given dose threshold (about 2 joules/mm2) the tumours continued to grow at the same rate as the control tumours although an effect of irradiation could be seen histologically. Above this threshold the tumours completely disappeared but by 10-14 days started to regrow at a rate slightly greater than in the control mice; the reason for this increased rate remains to be determined. At the highest doses (above about 5.5 joules/mm2) there was complete regression and skin healing, with no evidence of local recurrence in seven animals and with no evidence of distant metastases in six out of seven up to 12 months later, a result not previously achieved by surgical excision. The laser provides a controlled and simply applied method of tumour eradication. This animal model gives a quantitative basis for further studies of the effects of laser irradiation on tumour growth.

Adenocarcinoma↗