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Biomedical subjects

A M Walker

Publications and source records attributed to A M Walker.

At least 271 records · Page 15Linked to original sources
PubMed1984

An improved perfusion technique for fixation of sheep myocardium.

Although sheep have been widely used as models in the study of cardiac physiology, corresponding morphologic and morphometric data are scanty. For meaningful correlation of morphometric data with physiological information, it is desirable that fixation of the heart occur under controlled conditions. This paper describes a technique for in situ, retrograde aortic perfusion fixation of sheep myocardium under conditions of controlled pressure and minimal wastage of fixative. This is achieved by the application of snares around the brachiocephalic trunk and aortic arch, which are tightened at the start of the perfusion. These isolate the ascending aorta and the coronary vasculature from the remainder of the circulation and allow fixation of the whole heart at a controlled pressure. The method produces good fixation and contrast for transmission electron microscopy and is applicable to late-gestation fetuses, lambs, and adult sheep.

Animals↗
PubMed1984

Cluster microvilli in coronary endothelium.

Examination of cardiac vascular endothelium with scanning electron microscopy, and transmission electron microscopy of previously scanned tissue, revealed several regions of the coronary venous system that contained 'cluster' microvilli. These consisted of 2-15 microvillous projections that emanated radially from a common base or were grouped into a fan-like arrangement. Although rare, these clusters, when present, were widely distributed over the endothelial cell surface.

Animals↗
PubMed1984

Declining relative risks for lung cancer after cessation of asbestos exposure.

All studies that provide follow-up information for workers more than 35 years after initial exposure to asbestos show a declining ratio of observed to expected lung cancer deaths at the end of follow-up. The most parsimonious explanation of this finding is that relative risk for lung cancer begins to decline sometime after cessation of asbestos exposure.

Adolescent↗
PubMed1984

Physiological concentrations of L-leucine control the release of prolactin from cultured rat pituitary cells.

In an attempt to further define the optimum experimental conditions for the in vitro study of PRL endocrinology, the effect of extracellular leucine concentration on PRL secretion was assessed. Rat pituitary cells, maintained in short term monolayer culture, were washed free of serum and placed in Minimum Essential Medium (MEM; 0.39 mM leucine) supplemented with nonessential amino acids and 0.1% gelatin. After the establishment of a constant rate of basal PRL release, the MEM was replaced with leucine-free MEM (supplemented as above), and the rate of PRL release was followed. PRL release from the cells in the leucine-free medium fell within 15 min to a rate 30% of that seen in the controls. Return to the control rate was achieved by the addition of L-leucine only. The D-isomer, isoleucine, valine, proline, leucyl-leucine, and leucine-agarose were ineffective. In the short term, the rate of PRL synthesis was found to be independent of extracellular leucine and the inhibition of release seen upon removal of leucine, and the subsequent recovery upon replacement of leucine was also observed when this experiment was conducted in the presence of 50 micrograms/ml cycloheximide. The L-leucine recovery was found to be dose dependent, with an increase in leucine concentration from 20 to 40 mg/liter causing a tripling of the PRL release rate. The addition of 10(-7) M TRH showed that leucine can be limiting in the response to this stimulant and allowed a response to as little as 10 mg/liter leucine to be discerned. From these experiments, it is concluded that physiological concentrations of leucine specifically and profoundly affect the release of PRL by a mechanism independent of protein synthesis. This leucine requirement for release has not been previously reported.

Animals↗
PubMed1984

Chloroquine affects prolactin secretion and Golgi morphology in the mammotroph.

Chloroquine is widely used as a lysosomal enzyme inhibitor, and while effects on DNA repair and membrane recycling have also been reported, there has been no investigation of effects on the processing of secretory products. To determine whether chloroquine had any effect on secretion and secretory organelles, we monitored the effects of low concentrations (10(-6) M) of chloroquine on a cell population which normally secretes copious amounts of a simple polypeptide (PRL) in vitro and in which there exists a subpopulation of cells which releases PRL very rapidly after synthesis. Cultured anterior pituitary cells were exposed to 10(-6) M chloroquine for 6, 12, 24, or 48 h. At these times, the culture medium was used for determination of PRL content and beta-glucuronidase activity, and the cells were used for determination of DNA content and level of beta-glucuronidase activity or for electron microscopy. Treatment with 10(-6) M chloroquine resulted in 20-40% inhibition of PRL release (maximum inhibition at any dose), no change in the total amount of beta-glucuronidase activity, and a number of ultrastructural changes in the Golgi region consistent with an accumulation of chloroquine within the cisternae and immature granules. The effects of chloroquine on Golgi morphology were unaltered by cotreatment with 50 micrograms/ml cycloheximide, and chloroquine had no affect on PRL synthesis. These results are consistent with an adverse effect of chloroquine on packaging of PRL into immature granules in the Golgi apparatus, without any effect on the release of mature secretory granules.

Animals↗
PubMed1984

Mammotroph autoregulation: uptake of secreted prolactin and inhibition of secretion.

A dissociated preparation of normal adult rat pituitary cells has been used to study PRL autoregulation at the level of the mammotroph . Female rat pituitary cells previously cultured for 48 h on polylysine-coated petri dishes were washed to remove serum and accumulated PRL and then incubated in fresh medium in the absence or presence of increasing concentrations of rat PRL. Accurate balance sheets, allowing for degradation and nonspecific adsorption of PRL, showed exogenous PRL to regulate the amount of PRL released by the cells. That this regulation was partly produced by uptake of secreted PRL from the medium was demonstrated by supplementing the medium with [125I]iodo-rat PRL. Inhibition of secretion also played a role and was implied by experiments showing that ease of reversal of the inhibition was inversely proportional to the density of cell culture, which was itself proportional to the amount of PRL in the medium and the duration of autoregulation. These results indicate that normal adult rat pituitary cells in primary culture are capable of regulating the amount of PRL in their external milieu and that uptake of already secreted PRL is an important component of the regulatory mechanism.

Animals↗
PubMed1984

Cancer of the breast, colon, ovary, and testis in the United States: rates 1970-78 from a hospital reporting system.

We have explored the use of data from the Commission on Professional and Hospital Activities-Professional Activity Study ( CPHA -PAS) for ascertaining information on cancer incidence, with regional breakdowns. Extirpative surgical procedures were linked with discharge diagnoses to provide estimates of numbers of incident cases. We calculated incidence rates for four cancers: breast, colon, ovary, and testis. CPHA -PAS inferred rates corresponded closely to those of other reporting systems for breast cancer in most age groups, and for colonic and testicular cancer in some age groups. Ovarian cancer rates were consistently underestimated. We conclude that a cancer incidence reporting scheme based on hospital discharge data can work for certain cancers, and be very inexpensive and efficient. It must, however, be used with care.

Adult↗
PubMed1984

Oral contraceptive use and fibrocystic breast disease of different histologic classifications.

The relationship between oral contraceptive (OC) use and occurrence of fibrocystic breast disease (FBD) of different histologic classifications was evaluated with data from a cohort study. Biopsy specimens from 232 women with FBD were classified into different atypia categories. In 96 matched pairs of OC users and nonusers, atypia scores were lower in users than in nonusers. Women without breast diseases (500 OC users and 500 nonusers) were sampled from the original cohort to form a two-stage "anamorphic" study with the 232 cases of FBD. The previously shown inverse association between OC use and FBD occurrence was present and increased with increased length of OC use. However, the "protective effect" of OC use did not vary for different histologic classifications of FBD. The findings from both paired and anamorphic analyses of the data are not consistent with the hypothesis that the use of OC is associated with decreased frequency only of FBD with minimal epithelial atypia.

Adult↗
PubMed1984

Fetal oxygen consumption, umbilical circulation and electrocortical activity transitions in fetal lambs.

Chronically instrumented fetal lambs were employed to test the hypothesis that the high voltage electrocortical activity phase is a state of low fetal oxygen consumption compared with the low voltage electrocortical activity phase. Measurements of umbilical flow (electromagnetic flowmeter) together with oxygen saturations and haemoglobin concentration of umbilical venous and arterial blood were used to calculate oxygen consumption. Significant depression of umbilical flow occurred at the transition from low voltage electrocortical activity to high voltage electrocortical activity; the maximum change averaged 14% 2 min after the onset of the high voltage phase. Significant depressions of oxygen saturation in umbilical venous and arterial blood were found within 5 min of the onset of high voltage electrocortical activity, averaging 2.2% and 5.2% respectively. No depression of oxygen consumption was found during these transient changes in early high voltage electrocortical activity, as the venous-arterial oxygen content difference widened significantly as a consequence of a greater fall in umbilical arterial oxygen content (0.7 ml/dl) than in umbilical venous oxygen content (0.3 ml/dl). Overall, we detected no significant depression of oxygen consumption in high voltage electrocortical activity. However a small but significant depression of oxygen consumption (6%) was found late in the high voltage electrocortical activity phase when the level of oxygen consumption in low voltage electrocortical activity was greater than 7 ml/min per kg. We conclude that the high voltage electrocortical activity in fetal lambs is not associated with a marked depression of oxygen consumption, despite significant transient depressions of umbilical flow and oxygen levels in umbilical venous and arterial blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Assessment of local tumor control using censored tumor response data.

When animals die in the course of tumor control assays, the loss of information need not be absolute. Actuarial survival curves may be used to estimate local tumor control fractions, and these unbiased estimates may be weighted and used to estimate the parameters of dose/cure functions. The current standard procedure of discarding from analysis animals who do not complete a pre-assigned observation period is biased, and should not be used.

Actuarial Analysis↗
PubMed1983

Vasectomy and nonfatal myocardial infarction: continued observation indicates no elevation of risk.

The incidence of nonfatal myocardial infarction among 4,733 vasectomized men followed for 33,969 man-years was 1.3 cases per 1,000 man-years. This incidence was nearly identical in a 5-fold larger series of comparable nonvasectomized men. These data represent a substantially increased long-term followup over that reported previously for these groups and provide continued assurance of the lack of an association between vasectomy and myocardial infarction, particularly 10 or more years after vasectomy.

Adult↗
PubMed1983

Grouping occupations according to carcinogenic potential: occupation clusters from an exposure linkage system.

An occupational clustering scheme has been developed from an occupation and exposure linkage system. In this scheme, occupational titles are grouped together hierarchically according to the numbers and degrees of their shared exposures. The use of the clusters obtained from this hierarchy is demonstrated in the analysis of the data from a case-control study of bladder cancer.

Adult↗
PubMed1983

Hypotension in fetal and newborn lambs; different patterns of reflex heart rate control revealed by autonomic blockade.

Reflex heart rate (HR) responses to hypotension were studied in chronically instrumented fetal and newborn lambs. Studies spanned 106-141 days of gestation and 1-22 days after birth. Brief hypotensive stimuli (10 s) were produced by inflation of a cuff implanted around the inferior vena cava; HR and mean arterial pressure (MAP) were recorded from a carotid arterial catheter. Autonomic nervous control of HR was examined using selective sympathetic beta-adrenergic blockade (propranolol 1 mg/kg), cholinergic blockade (atropine 0.2-0.3 mg/kg), and total autonomic blockade (propranolol plus atropine). In newborn lambs (n = 4) HR increased progressively as MAP was reduced in the range 5-50%. Tachycardia during mild hypotension (less than 15% MAP fall) was due to sympathetic activation as it was abolished by propranolol. During severe hypotension (greater than 30% MAP fall) tachycardia was reduced by selective beta-adrenergic blockade and by cholinergic blockade, and totally abolished by total autonomic blockade; thus withdrawal of vagal tone plus augmentation of sympathetic activity contribute to the increase of HR in response to large MAP falls in the newborn. Fetal lambs (n = 4) responded with tachycardia in mild hypotension (less than 15% MAP fall) but this was reversed when hypotension was severe (greater than 30% MAP fall). The primary tachycardia was due to sympathetic activation and was indistinguishable from the newborn response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗