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Biomedical subjects

C Rogers

Publications and source records attributed to C Rogers.

At least 145 records · Page 8Linked to original sources

Recommended protocols based on a survey of current practice in genotoxicity testing laboratories: III. Cell transformation in C3H/10T1/2 mouse embryo cell, BALB/c 3T3 mouse fibroblast and Syrian hamster embryo cell cultures.

A standardized protocol and guidelines for the performance of cell transformation testing in mouse embryo (C3H/10T1/2), mouse fibroblast (BALB/c 3T3) and Syrian hamster embryo (SHE) cells have been developed. The protocol is based primarily on current laboratory practices as determined by responses to a detailed questionnaire completed by North American and European governmental, university and contract laboratories involved with cell transformation experimentation. This report identifies those modifications to previously described methodologies which are being used on a regular basis and also serves to clarify confusing or inconsistent practices.

Animals↗

Role of the sigma receptor in the inhibition of [3H]-noradrenaline uptake in brain synaptosomes and adrenal chromaffin cells.

1. Rat brain synaptosomes and cultured bovine adrenal chromaffin cells were used to monitor the inhibitory effects of phencyclidine (PCP) and sigma (sigma)-receptor ligands on the uptake of [3H]-noradrenaline ([3H]-NA). 2. A Na(+)-dependent high affinity uptake was observed in synaptosomes (30 degrees C) and chromaffin cells (37 degrees C) with Km of 0.22 and 0.56 microM and Vmax of 2.5 pmol min-1 mg-1 protein and 0.7 pmol min-1 per 10(6) cells, respectively. 3. PCP and haloperidol inhibited the high affinity uptake with IC50 of 0.17 and 0.42 microM, respectively in synaptosomes and 0.24 and 0.47 microM, respectively in adrenal chromaffin cells. 4. A close correlation (r = 0.96) was established between the ability of various PCP and sigma-receptor ligands to inhibit [3H]-NA uptake in both systems: PCP greater than TCP greater than haloperidol greater than 3-(+)-PPP greater than MK-801 greater than or equal to (-)-butaclamol greater than (+)-SKF-10047 greater than DTG. Spiperone and opioid receptor ligands were ineffective at 20 microM. 5. These results indicate that the central and peripheral inhibitory effects of PCP and sigma-receptor ligands on [3H]-NA uptake involves a receptor (sigma 1-like) which is distinct from that (PCP2) recognized for the inhibition of [3H]-dopamine uptake by PCP.

Adrenal Glands↗

Findings in newborns of cocaine-abusing mothers.

Cocaine has recently been shown to affect the outcome of pregnancy when taken by pregnant women. The authors measured fetal concentrations of cocaine and benzoylecgonine and reviewed autopsy and historical data for 62 successive infants who died at less than two days of age and were seen at the Los Angeles County Office of the Chief Medical Examiner-Coroner. Of 43 infants without an obvious cause of death at autopsy, cocaine or benzoylecgonine or both were present in 40%. None of the parameters studied predicted which infants would show cocaine or benzoylecgonine. We conclude that cocaine and benzoylecgonine concentrations should be measured on all infants who die at less than two days of age when the cause of death is not evident at gross autopsy.

Autopsy↗

Effect of necrotizing enterocolitis on urinary epidermal growth factor levels.

The pattern of urinary epidermal growth factor/creatinine levels in necrotizing enterocolitis was examined in 75 infants (in 28 infants the diagnosis of necrotizing enterocolitis was considered; 47 infants were studied for effect of surgery or nutrition on epidermal growth factor levels). There was a consistent and significant increase in epidermal growth factor/creatinine values at the time of diagnosis of necrotizing enterocolitis compared with baseline values. Epidermal growth factor levels in infants without necrotizing enterocolitis and in early nutrition remained unchanged. These results suggested that urinary epidermal growth factor/creatinine levels may differentiate stage II and III necrotizing enterocolitis from stage I disease. The increased epidermal growth factor/creatinine levels may be related to the absorption into the circulation of preexisting gastrointestinal tract epidermal growth factor through damaged tissue or to increased synthesis by the gastrointestinal tract in response to the injury caused by necrotizing enterocolitis.

Creatinine↗

What do hospices do? A survey of hospices in the United Kingdom and Republic of Ireland.

OBJECTIVE: To obtain baseline information about hospice clinical activity. DESIGN: Survey of hospices by postal questionnaire and telephone interview. SETTING: 98 Hospices in the United Kingdom and Republic of Ireland of 111 that had a named matron or senior nurse, including 17 funded by NHS and 81 independent units. PARTICIPANTS: Hospice matrons or nursing sisters in charge, to whom the questionnaire was addressed. RESULTS: Median age of hospices was 7 years, and those built during the past seven years had a median of 12 inpatient beds. All NHS hospices had some input from a medical consultant whereas 12 (15%) of independent units did not. 72 Hospices had home care teams and 12 of 20 of these randomly contacted by telephone provided 24 hour cover. The median number of whole time equivalent nurses was four, but 6 (30%) of teams did not include a doctor. Wide variations were found in discharge rates (range 1-76%) and throughput (1.7-31.8 patients/bed/year). In units with a full time consultant or medical director throughput was greater and more patients had palliative surgery and became organ donors than in units without (45/48 v 38/50 and 45/48 v 25/50, respectively). With the exception of pulmonary function tests and insertion of nasogastric tubes and indwelling epidural catheters, tests and procedures were used by over 90% of hospices, although sometimes the patient had to be transferred elsewhere. CONCLUSIONS: Respondents from units with a full time consultant or medical director were more likely to choose a "technical" description of their unit, such as "a pain relief centre" than those without, who favoured non-technical descriptions. These differences are likely to increase with the appointment of more fully trained consultants in palliative medicine.

Home Care Services↗

Crossbow injuries.

The crossbow is an uncommon source of fatal injury. In Los Angeles County, two crossbow homicides have occurred in the past 20 years. Following the second case, a crossbow was test-fired into a fresh pork thigh, resulting in distinctive wounds. Experimental studies also showed that the vanes of the bolt (arrow) may be a source of trace material found in the wound.

Adult↗

Presence of sigma and phencyclidine (PCP)-like receptors in membrane preparations of bovine adrenal medulla.

Receptor binding studies with [3H]-(+)SKF-10047 were carried out to characterize the putative sigma (sigma) and phencyclidine (PCP) receptors in membrane preparations of bovine adrenal medulla. Specific binding of the radiolabelled compound was observed after incubation with the membrane preparation at 37 degrees, the equilibrium being reached at 20 min and the maximal binding being observed with 0.6 mg/ml protein. Saturation binding studies were performed at equilibrium (30 min at 37 degrees with 0.5 mg/ml of membrane protein) in the presence of haloperidol (1 microM) or 1-[1-(2-thienyl) cyclohexyl] piperidine (TCP; 0.2 microM) to block sigma or PCP receptors, respectively. The binding of [3H]-(+)SKF-10047 was characterized by two distinct components. A high affinity binding site (haloperidol sensitive) had an apparent KD of 8.3 nM and a Bmax of 67 pmol/g protein. A lower affinity binding site (TCP sensitive) had an apparent KD of 32.7 nM and a Bmax of 83 pmol/g protein. The drug specificity of the high affinity binding site resembled that of the putative sigma receptor, being potently inhibited by haloperidol and pentazocine. The binding pharmacology of the low affinity site resembled that of the phencyclidine receptor, being potently displaced by TCP and PCP. The binding of [3H]-(+)SKF-10047 to both receptors showed marked stereoselectivity for the dextrorotatory (+) isomer of SKF-10047 and was insensitive to the receptor specific opioid ligands DAGO (mu), DSLET (delta) and U-69593 (kappa). These data indicate that bovine adrenal medulla contains sigma and PCP-like receptors.

Adrenal Medulla↗

Splenic vein thrombosis in patients with acute pancreatitis.

We performed a retrospective autopsy case-control study to identify clinical characteristics of acute pancreatitis associated with splenic vein thrombosis. Age, sex, spleen weight, presence or absence of gastrointestinal hemorrhage, and pancreatic pseudocyst were not associated with splenic vein thrombosis. Patients with peak serum amylase over 10,000 U/L were at high risk for splenic vein thrombosis. We conclude that, of the factors examined, only the peak serum amylase may be of value in diagnosing splenic vein thrombosis in patients with acute pancreatitis.

Acute Disease↗

Early identification of high-risk patients using the "estimated" injury severity score and age.

A prospective study was undertaken over a 2 1/2 year period (July 1, 1985-December 31, 1987) to determine the value of a prospective anatomical severity score ["Estimated" Injury Severity Score (EISS)], in combination with age, for early risk assessment. Five hundred ninety-two blunt trauma patients were used to develop a predictive model of mortality through a logistic regression. The model was validated using 216 patients; a high degree of agreement (Kappa 0.73) was found. When isolated head injuries were removed from the model and validation groups, the Kappa increased to 0.80. Prospective anatomical scoring in combination with age may help to identify high-risk trauma patients early during their care.

Adolescent↗

Duchenne muscular dystrophy in Wales: a 15 year study, 1971 to 1986.

A register of families with Duchenne muscular dystrophy (DMD) in Wales was set up in 1973 and has been regularly maintained ever since. All women at significant risk in these families were offered estimation of their carrier status by creatine kinase and pedigree analysis. A total of 225 of the 512 women tested was assigned a risk of carrying the DMD gene of less than 5%. One hundred and twenty live births from this group were notified to the register and only one was an affected male. This was the expected number and shows that the risks given were largely accurate. Women given a risk of 5% or greater were offered fetal sexing with termination of any male. Amniocentesis was of limited value and chorionic villus sampling, introduced in 1984, was acceptable to more women at risk. The incidence of DMD in Wales dropped from one in 3435 at the beginning of the study to one in 4046 by 1982, and the proportion of recurrent cases from 40% to 22%. Common reasons for recurrence were birth of a second affected boy before diagnosis of the first, and failure of families with affected dead members in previous generations to be notified to the register. Maintaining an accurate register of DMD families is an essential tool in their management.

Female↗

Effect of congenital renal disease and neonatal thyroid status on urinary human epidermal growth factor concentrations.

We have previously demonstrated that changes in urinary epidermal growth factor/creatinine ratios relate to gestational age and gender. It is unclear what controls this developmental pattern although chronic renal disease and thyroid aberrations have significant effects on epidermal growth factor and creatinine excretion in childhood and in adults. Therefore, we chose to explore the effects of these disease states on epidermal growth factor excretion during the perinatal time period. We collected urine samples from 8 infants with congenital renal disease and 45 infants with low T4 and normal TSH values who 'failed' the newborn screen. In addition, 2 infants with hypothyroidism and 2 infants with neonatal Grave's disease had urine samples examined. Values were compared with the epidermal growth factor and creatinine excretion from 190 infants. We demonstrated that epidermal growth factor excretion increased earlier in gestation than does creatinine excretion. In infants with renal disease or hypothyroidism, epidermal growth factor excretion was decreased while hyperthyroidism enhanced excretion. Epidermal growth factor excretion increased with relief of an obstruction but still remained low and creatinine excretion was unchanged. We confirm that in preterm infants as in childhood there are similar effects of thyroid and renal diseases on epidermal growth factor excretion.

Congenital Hypothyroidism↗

Spontaneous fusion between metastatic mammary tumor subpopulations.

This study describes a differential frequency of spontaneous fusion between metastatic and nonmetastatic subpopulations derived from a single mouse mammary tumor. Subpopulations 66, 66c14 (a variant of 66 which is resistant to both thioguanine and ouabain), 410.4, and 44FTO (a thioguanine-resistant, ouabain-resistant derivative of 410.4) spontaneously metastasize from subcutaneous and mammary fatpad sites. Subpopulations 168, 168FARO (a diaminopurine-resistant, ouabain-resistant derivative of 168), 67, 68H, and 410 do not. The ability of these subpopulation lines to fuse spontaneously in vitro was determined after coculturing a drug-resistant line with a wild-type line in nonselective media. After 16-20 h of coculture, cells were plated in the appropriate media to select for fusion products--either HAT (hypoxanthine, aminopterin, thymidine) plus ouabain or AA (alanosine, adenine) plus ouabain--to determine the number of colony-forming cells (fusion products) present per 10(4) cells plated. When both subpopulations of the pair in the fusion mixture were metastatic, a significantly greater number of fusion products was recovered than if one or both of the subpopulations in the fusion mixture was nonmetastatic, with one exception: line 410 readily fused with both 66c14 and 44FTO. Subline 410 was highly metastatic when originally isolated but lost its metastatic competence after a brief time in tissue culture.

Animals↗

Gastric mucosal protection by new aryl sulfhydryl drugs.

Alkyl sulfhydryl drugs protect against acute gastric hemorrhagic mucosal lesions. We tested the protective effect of cyclic drugs containing oxidized (KT1-32, KT1-39, KT1-94), or reduced (KT1-66, KT1-109, KT1-293, KT1-720, KT1-756) sulfhydryls. The most potent protective agents (KT1-32, KT1-109, KT1-720, KT1-756) were investigated in detail. Drugs were administered intragastrically to fasted rats 30 min before 100% ethanol (1 ml) or acidified aspirin (10 mg/100 g), and mucosal lesions were measured planimetrically 1 hr later. Control rats receiving only ethanol had lesions involving 14.5% of the glandular mucosa. KT1-32, KT1-109, KT1-720, or KT1-756 (10 mg/100 g) reduced lesions to 0.7, 2.7, 1.8, or 0.7% of glandular stomach respectively. Aspirin-induced lesions involved 1.52% of the glandular mucosa and 10 mg/100 g of KT1-32, KT1-109, or KT1-720, or 2 mg/100 g of KT1-756 diminished the damage to 0.13, 0.02, or 0.04, or 0.00%, respectively. Indomethacin interfered with protection against ethanol by KT1-109, while the sulfhydryl alkylator N-ethylmaleimide abolished protection by both KT1-32 and KT1-109. Among the drugs investigated in detail, KT1-756 increased gastric acid output, while KT1-720 and KT1-756 significantly enhanced pepsin secretion. All four compounds studied in detail (ie, KT1-32, KT1-109, KT1-720, KT1-756) decreased the extent of vascular lesions in the gastric mucosa as revealed by monastral blue 1 min after ethanol. Thus, the mechanism of gastric mucosal protection by these novel aryl sulfhydryl compounds cannot be ascribed to an antisecretory effect, but may be related to prevention of vascular injury.

Animals↗

Vascular injury in acute gastric mucosal damage. Mediatory role of leukotrienes.

Recent investigations indicate that microvascular injury, leading to increased vascular permeability and capillary stasis, precede the development of chemically induced hemorrhagic mucosal lesions in the stomach. The vascular damage is more amenable to protection by prostaglandins and sulfhydryls than the diffuse surface mucosal cell injury. The vascular and mucosal lesions may be the result of direct toxicity of damaging agents (eg, ethanol, HCl, NaOH) and the release of vasoactive amines and leukotrienes. We review here our recent studies performed in rats indicating that intraarterial infusion of LTC4 or LTD4 in the stomach caused vascular injury as revealed by monastral blue. Infusion of leukotrienes alone caused no hemorrhagic mucosal lesions but aggravated the damage caused by 25, 50, or 100% ethanol and 0.2 N HCl given intragastrically. The ethanol-induced mucosal lesions were slightly diminished by the lipoxygenase inhibitor L-651,392 and markedly decreased by eicosapentaenoic acid, which competes with arachiconic acid as a substrate for 5-lipoxygenase. These results are discussed and correlated with biochemical results from other laboratories demonstrating increased levels of leukotrienes in the gastric mucosa after administration of ethanol and decreased release following pretreatment with prostaglandins or sulfhydryl-related agents. New data thus support a mediatory role for leukotrienes in the pathogenesis of vascular injury and mucosal lesions in the stomach.

Animals↗