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Biomedical subjects

R R MacGregor

Publications and source records attributed to R R MacGregor.

At least 199 records · Page 11Linked to original sources
PubMed1977

Host defenses during prolonged alcohol consumption in a controlled environment.

To determine the pure effects of prolonged alcohol ingestion on host defenses, we studied six noncirrhotic alcoholic volunteers drinking in the Clinical Research Center. All had tests of granulocyte, humoral, and cell-mediated immune function before and at the end of eight to 28 days' intake of approximately 0.75 liter of 100-proof whiskey per day. Results of all tests were normal during the drinking period, except for the following: (1) granulocyte chemotaxis was depressed in three volunteers and improved on alcohol withdrawal; (2) antibody response to keyhole limpet hemocyanin (KLH) immunization was poor; and (3) delayed hypersensitivity could not be established to KLH. Although it is somewhat surprising that more abnormalities were not induced, the three defects noted may contribute to the alcoholic's poor resistance to infection.

Adult↗
PubMed1976

Conversion of proparathyroid hormone to parathyroid hormone by a particulate enzyme of the parathyroid gland.

The conversion of proparathyroid hormone (proparathormone) to parathyroid hormone (parathormone) by subcellular fractions of the bovine parathyroid has been investigated. The identification of the conversion product as parathormone was established by its elution postion during ion exchange chromatography and gel filtration, and by partial amino acid sequence analysis of its NH2-terminal region. Total homogenates and derived subcellular fractions (600 X g pellet, 5,000 X g pellet, 20,000 X g pellet, 190,000 X g pellet, and 190,000 X g supernatant) all catalyzed the conversion of exogenous [3H]- or [14C]prohormone. Over 60% of the converting activity was in the particulate fractions; the 190,000 X g particulate fraction contained the highest specific converting activity. The converting activity appeared to be an integral component of the membranes since it could only be partially removed by extraction with Triton X-100. The production of parathormone by the particulate converting enzyme increased with time and the concentration of enzyme protein. The optimum pH range was between 7 and 9, and the enzyme was inactive below pH 6. Conversion by the particulate enzyme was inhibited by benzamidine or chloroquine, but not by pancreatic trypsin inhibitor, indicating its dissimilarity to trypsin. When a mixture of [14C]proparathormone and [3H]parathormone was used as substrate, the particulate enzyme did not metabolize the hormone despite over 70% conversion of the prohormone to hormone and other peptides. There was a close correlation between the subcellular distribution of converting activity and that of newly formed parathormone found in the membrane fraction. These data suggest that the particulate converting activity is that concerned with the formation of parathormone in vivo.

Animals↗
PubMed1976

The effect of anti-inflammatory agents and inflammation on granulocyte adherence. Evidence for regulation by plasma factors.

Significant inhibition of granulocyte adherence to nylon fiber columns followed the administration of alcohol, aspirin, sodium salicylate, acetaminophen, indomethacin, phenylbutazone, colchicine or prednisone to normal subjects. The addition of salicylates and glucocorticoids to blood in vitro had no effect on adherence, but plasma from volunteer subjects treated with either drug contained a factor which inhibited the adherence of normal granulocytes. The factor is heat stable, nondialyzable and not present in serum; it produces a linear dose response in normal cells. When mixed with the adherence-increasing factor found in inflammatory diseases, it neutralizes the augmenting effect and normal granulocyte adherence results. The effect of anti-inflammatory therapy on inflammatory disease was studied in aspirin-treated patients with rheumatoid arthritis. Their granulocyte adherence fell into two categories based on the clinical control of their disease; patients in good control had only slightly increased granulocyte adherence, but those in poor control had an average adherence more than twice normal. Mean blood aspirin levels were equivalent for the two groups (11.0 mg/100 ml for the well controlled and 13.4 mg/100 ml for those poorly controlled). Thus, clinical response to anti-inflammatory therapy correlates well with granulocyte adherence, not with aspirin levels. The potential pathogenetic role of adherence-modifying factors in inflammatory diseases remains to be determined.

Adhesiveness↗
PubMed1976

Radiopharmaceuticals. 16. Halogenated dopamine analogs. Synthesis and radiolabeling of 6-iododopamine and tissue distribution studies in animals.

A simple halogenated derivative of dopamine, 6-iododopamine (1), has been synthesized using two different methods. These synthetic sequences have been applied to the radiolabeling of 1 with carbon-11, iodine-131, and iodine-123. The tissue distribution of 1 in mice, dogs, and rats was determined. The ratio of radioactivity (%/g) in the adrenal medulla-kidney in dogs increases from 3.45 at 2 h postinjection to 33.3 at 24 h postinjection. Thyroid uptakes in mice, dogs, and rats show that in vivo deiodination of 1 is not significant.

Adrenal Glands↗
PubMed1976

The induction of augmented granulocyte adherence by inflammation. Mediation by a plasma factor.

The adherence of granylocytes to surfaces, measured in vitro in nylon fiber columns, is inhibited by in vivo administration of anti-inflammatory agents. Therefore, the effect of inflammation itself was assessed in blood from patients with acute inflammatory diseases. Mean adherence in these patients was twice normal (56.4 +/- 5.6% vs. 29.4 +/- 5.2%); their plasma contained a factor that augmented adherence of normal cells to 47.5 +/- 5.6% whereas the patient's cells showed a normal level of adherence (34.0 +/- 6.8%) when resuspended in normal plasma. Although exudate fluid from exprimental inflammation also contained the augmenting factor, cells from the exudate maintained their high level of adherence after washing and suspension in normal plasma. The augmenting factor detected in plasma from patients with inflammation was not present in serum and was inactivated by heating plasma to 56 degrees C for 30 min; restoration of augmenting activity was accomplished by addition of 20% guinea pig serum to the heat-treated plasma. Because the guinea pig serum itself did not increase adherence when added to normal plasma, it appears that the augmenting factor is heat-stable, but requires a heat-labile cofactor like complement. Sephadex G-200 fractionation of inflammatory plasma showed adherence-augmenting activity in the majority of fractions, with peak activity in the fractions corresponding to approximate molecular wts of 30,000, 160,000 and 400,000.

Adrenal Cortex Hormones↗
PubMed1976

Carbon-11 labeled aliphatic amines in lung uptake and metabolism studies: potential for dynamic measurements in vivo.

In order to assess the potential utility of amines labeled with short-lived nuclides as agents for lung imaging and function studies in humans, a series of aliphatic amines (C4-C10 and C13) labeled with carbon-11 (T 1/2 = 20.4 minutes), which decays by the emission of body-penetrating radiation, has been used as a model for studying some basic parameters affecting amine uptake and metabolism by the lung and other tissues in mice. The lung uptake (percentage of dose per organ) of aliphatic amines at 1 minute increased from 2.18 +/- 0.13% for butylamine to 13.33 +/- 0.84% for tridecylamine. Partition coefficients (between n-octanol and pH = 7 buffer) were measured for the C4 through C10 amines and for octanoic acid and octanenitrile. Within the amine series, the partition coefficient correlated with lung uptake. A comparison of a series of compounds all having a carbon chain length of eight but with different functional groups (--NH2, --C=N, --CO2H, --OH) showed that the amino group as well as the relatively lipophilic alkyl group were required for lung specificity. The 11C-aliphatic amines were rapidly metabolized via monoamine oxidase (ultimately to 11CO2). Non-amine metabolites in blood and lungs at 5 minutes postinjection were 95 and 50%, respectively. Pretreatment of mice with iproniazid and with pargyline decreased 11CO2 excretion, and iproniazid significantly increased the radioactivity retained by the brain, lungs and liver at 15 minutes. The rate of 11CO2 excretion depended on carbon chain length (C4 less than C5 less than C6 greater than C7 greater than C8 greater than C9 greater than C10 greater than C13).

Amines↗
PubMed1975

Puerperal endometritis: a prospective microbiologic study.

This study was undertaken to determine the flora in the endometrial cavity of two groups of puerperal patients: 47 afebrile control subjects and 27 with endometritis. A transcervical culturing technique designed to avoid cervical contamination and to preserve aerobes, anaerobes, and mycoplasma was employed, and bacterial colony counts were reported semiquantitatively. No difference was found in the flora of these two groups. Furthermore, the most common pathogenic organisms (in decreasing order of frequency) were peptostreptococci, peptococci, Bacteroides sp., gamma-streptococci, enterococci, beta-streptococci, alpha-streptococci, and E. coli.

Adult↗
PubMed1975

A year's experience with tuberculosis in a private urban teaching hospital in the postsanatorium era.

Because brief general hospital admission and extended ambulatory management have replaced sanatorium care for tuberculosis, we reviewed 41 cases admitted to a private urban hospital during 1971-1972 to assess the spectrum of disease and the problems created by the closing of sanatoriums. Almost half the cases were misdiagnosed, exposing an average of 35 hospital personnel to unisolated patients with positive smears. Clinical manifestations often were subtle. Of those with pulmonary involvement, 14 per cent denied having symptoms and less than half had positive sputum smears. Transfer to ambulatory care for half the patients was complicated by having different physicians manage their hospital and outpatient care, with poor communication between the two. Outpatient physicians were sent discharge summaries for fewer than two thirds of their patients, and then only after an average 2 1/2 month delay. Similarly, slowness in case reporting impaired contact investigation. Only three contacts were identified per patient, and only 71 per cent of these were investigated. Improved diagnostic ability, better communication with public health workers, and attention to details of transfer to ambulatory care are necessary for effectively integrating the present components of tuberculosis management.

Adult↗
PubMed1975

The by-pass of tissue hormone stores during the secretion of newly synthesized parathyroid hormone.

Bovine parathyroid gland slices were incubated in Krebs' buffer with [3-H] leucine in order to assess the biosynthesis and secretion of parathyroid hormone (PTH). After incubation the particulate structures of the tissue were extracted with sodium deoxycholate to yield primarily newly synthesized (radioactive) PTH in the extract and preexisting granule PTH in the residue. In pulse-chase experiments radioactive PTH entered the granule fraction at a time when total tissue radioactive hormone was declining, which indicates that some newly-synthesized PTH was packaged into these granules. The specific radioactivity of the PTH in the incubation medium was from 20-fold to more than 80-fold greater than that of the granule PTH of the tissue, but was similar in magnitude to that of the tissue's newly synthesized hormone. Secretion of newly synthesized PTH was greater during incubation in buffer with 1.25 mM Ca than it was at 2.5 mM Ca which indicated that the hormone release was subject to physiological control. The PTH content of the tissue granule fraction was lower following incubation at 1.25 mM Ca than at 2.5 mM Ca. The possibility was excluded that the higher specific radioactivity of PT1 of incubation medium compared to that of the secretory granule fraction resulted from a diffusion gradient of [3-H] leucine into the tissue slices. These data indicate that a major portion of the newly synthesized PTH was secreted without prior equilibration with the hormone in the pool of secretory granules.

Amino Acids↗
PubMed1975

The significance of isolating low numbers of mycobacterium tuberculosis in culture of sputum specimens.

Because fewer than five Mycobacterium tuberculosis colonies were isolated from single sputum specimens from several patients with little clinical evidence of pulmonary tuberculosis, we reviewed all of our low colony isolates (LCIs) from an 18-month period. Thirty-one patients had 35 LCIs and were separated easily into groups that either appeared to have tuberculosis by clinical criteria or appeared to be uninfected. Patients in the "tuberculosis likely" group reasons such as concurrent antituberculosis therapy or an interstitial location of their pulmonary lesion to account for their LCIs. In contrast, patients in the "tuberculosis unlikely" group were all culture-negative when reevaluated two to four months after their first culture, and they had no evidence of tuberculosis on chest x-ray film despite having received no antituberculosis therapy. Half had negative tuberculin reactions, without generalized anergy. Epidemiologic study showed that most had been cultured the same day as patients with smear-positive tuberculosis, and the possibility of cross-contamination was investigated.

Humans↗
PubMed1975

Acute thanol effect on chemotaxis and other components of host defense.

The effect of alcohol on granulocyte chemotaxis was studies with a radioactive assaysystem. Chemotaxis was inhibited in vitro by concentrations of alcohol above 400 mg. per cent when present during all steps in the assay, but levels above 800 mg. per cent required for inhibition when alcohol was present only during the granulocyte incubation. No inhibition of chemotactic factor generation was found with alcohol concentration up to 1,500 mg. per cent. Cells and serum exposed to alcohol in vivo by acute intxication of donors demonstrated normal in vitro chemotactic performance, even when the assay itself was carried out in medium containing 200 mg. of alcohol. Thestudies do not exclude alcohol's in vivo induction of an inhibitor which must remain present during chemotaxis for inhibition; nor would they have detected an impairment of chemotaxis occurring after the peak blood alcohol concentration. The intoxicated volunteer subjects were also evaluated for changes in delayed hypersensitivity, serum complement concentration, granulocyte hexose monophosphate shunt activity, and circulating whiteblood cell counts; no consistent changes were seen.

Adult↗