Search PubMed⌕ Search

Biomedical subjects

D G Johnson

Publications and source records attributed to D G Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1988

Perifused precision-cut liver slice system for the study of hormone-regulated hepatic glucose metabolism.

A nonrecirculatory perfusion system for precision-cut rat liver slices has been developed and utilized for investigating hormone-regulated hepatic glucose metabolism. In this system, slices are cultured in a highly controlled environment and exhibit excellent retention of viability as judged by their maintenance of intracellular potassium and glycogen contents. Using this system, the complex physiological phenomenon of hormone-regulated glycogenolysis was investigated at both extra- and intracellular sites. Specifically, the sensitive responses of intracellular cyclic AMP (cAMP) production, activation of cyclic AMP-dependent protein kinase, and production of glucose upon glucagon stimulation have been measured. The maximal responses observed for these parameters were either equal to or greater than those previously reported for either isolated hepatocytes or perfused livers, demonstrating the sensitivity of this technique. Upon dose-response examination of glucagon challenge, it was observed that high doses of glucagon (greater than 16 nM) stimulate glucose production by activating the cAMP-second messenger cascade. In contrast, low doses (less than 4 nM) stimulate this process without production of intracellular cAMP or activation of cAMP-dependent protein kinase, suggesting the operation of cAMP-independent messenger. Since this system permits measurements of parameters common to many cellular processes, this methodology is suitable for addressing both pharmacological and toxicological questions.

Animals↗
PubMed1988

Inbreeding of and relationship among registered Holsteins.

Holstein-Friesian Herdbooks (Holstein-Friesian Association of America, Brattleboro, VT) were used to draw random samples of 600 registered females born during each of the yr 1970, 1976, and 1982. A two-line pedigree, one random line of ancestry tracing from the sire and another tracing from the dam to the beginning of the Holstein-Friesian Herdbook, was tabulated for each of these 1800 females. These were used to estimate inbreeding and inter se relationship for the Holstein breed. Estimates of inbreeding were 4.7, 3.8, and 4.3% for 1970, 1976, and 1982. These estimates were not different from one another or from 1928 and 1931 estimates. Estimates of inter se relationship were 5.2, 7.3, and 9.8% for 1970, 1976, and 1982. These estimates were different from one another and from an estimate of 3.4% for 1931. The increase in inter se relationship without corresponding increase in inbreeding indicates that a change in mating strategies has evolved over time. The majority of breeders now apparently mate animals that are less related than if mating was random, whereas in the past there was more of a tendency to mate within the same line. Despite these attempts to avoid inbreeding, it may be only a matter of time until increasing inter se relationship causes an increase in inbreeding. Because of detrimental effects associated with inbreeding, it is important that the Holstein breed be monitored on a regular basis for these parameters. Ancestors that occurred most frequently in the 1982 sample were identified and their direct relationships to the breed tabulated for the years studied.

Animals↗
PubMed1987

Atrial natriuretic peptide levels during development of chronic heart failure after myocardial infarction in rats.

Serum levels of atrial natriuretic peptide (ANP) are elevated in chronic heart failure presumably due to dilatation of the left atrium resulting from increases in intracardiac pressures. To define the time course of changes in serum ANP levels and to determine the relationship to left ventricular end-diastolic pressure, rats were subjected to coronary artery ligation to produce myocardial infarction and left ventricular failure. Atrial natriuretic peptide levels were measured weekly for four weeks thereafter. In rats with myocardial infarction and elevation of left ventricular end-diastolic pressure there was no change in ANP levels at 7 and 14 days. However, at day 21 and 28, ANP levels were elevated more than 3 fold. There was a correlation between ANP levels and left ventricular end-diastolic pressures. There was no correlation between ANP levels and right atrial pressures or serum sodium concentrations. We conclude that the chronic elevation of left ventricular end-diastolic pressure is required to produce an increase in ANP after myocardial infarction which results in chronic heart failure.

Animals↗
PubMed1987

Synthesis of two glucagon antagonists: receptor binding, adenylate cyclase, and effects on blood plasma glucose levels.

In diabetes mellitus, hyperglycemia is often associated with elevated levels of glucagon in the blood. This suggests that glucagon is a contributing factor in the metabolic abnormalities of diabetes mellitus. A glucagon-receptor antagonist would provide direct evidence for glucagon's role in diabetes mellitus. On the basis of careful consideration of conformational, amphiphilic, and structural factors, we have synthesized two new glucagon analogues with antagonist biological activities by using solid-phase methodology. These two new analogues, [Asp3,D-Phe4,Ser5,Lys17,18,Glu21]glucagon (2) and [D-Phe4,Tyr5,3,5-I2-Tyr10,Arg12,Lys17,18,G lu21]glucagon (3) had IC50 values 5.4% and 50% those of glucagon, respectively, and showed no measurable adenylate cyclase activity. When tested in normal rats, 2 lowered plasma glucose levels and suppressed glucagon-mediated hyperglycemia 105 +/- 8%, back to basal levels. Analogue 3, which lowered the basal adenylate cyclase activity in rat liver plasma membranes, increased plasma glucose levels at very high concentration in vivo and inhibited glucagon-mediated hyperglycemia in normal rats by 50%. However, neither of the new glucagon antagonists lowered the plasma glucose levels of diabetic animals. The data would suggest these new glucagon-receptor antagonists may have two actions: (a) in normal rats they can act as standard glucagon-receptor inhibitors of glucagon-mediated glycogenolysis; (b) in diabetic rats, however, because of the low levels of glycogen in the liver, the antagonists apparently have little or no antagonist effect or enhancement on glucagon-mediated glucose production.

Adenylyl Cyclase Inhibitors↗
PubMed1987

Antihypertensive effects of parenteral nicardipine alone and in combination with captopril.

We studied the safety and efficacy of intravenous nicardipine alone and in combination with oral captopril. Sixteen patients with essential hypertension received a single oral dose of captopril, 50 mg, to be certain that excessive hypotension would not occur. Nicardipine was given intravenously as a 2 mg bolus, followed by an infusion at a rate designed to lower the supine diastolic blood pressure at least 10 mm Hg; then oral captopril, 50 mg, or placebo was given. The next week, nicardipine was again infused, but the alternate oral treatment was given. Intravenous nicardipine reduced blood pressure from 156 +/- 15/101 +/- 5 mm Hg (mean arterial blood pressure 120 +/- 6 mm Hg) to 140 +/- 11/88 +/- 4 mm Hg (mean arterial blood pressure 105 +/- 5 mm Hg). When captopril was added to nicardipine, the mean arterial blood pressure fell an additional 8 mm Hg but the heart rate did not increase. The combination of angiotensin-converting enzyme inhibition and calcium channel blockage produces additive antihypertensive effects without additional reflex tachycardia.

Administration, Oral↗
PubMed1987

Comparison of sweet white lupin seeds with soybean meal as a protein supplement for lactating dairy cows.

Data were from 45 Holstein cows (23 multiparous, 22 primiparous) assigned by calving date and parity within groups to one of two isonitrogenous (16% crude protein) diets. The diets were 50% forages (corn silage, alfalfa silage) and 50% concentrate, dry basis. In diet A, soybean meal supplied 34.2% of total crude protein; in diet B, ground sweet white lupin seeds provided 37.9% of total crude protein. Cows were fed once daily during the experimental period (d 4 to 116 postpartum). Cows fed lupins consumed significantly less dry matter, produced 1.8 kg/d less milk (but not significantly different), and had lower milk protein percent. Milk fat and total solids percents were similar. Reasons for reduced intake of cows fed lupins were not evident. Traces of alkaloids (.005% dry basis) were present in diet B. Combined results of in vitro continuous culture fermentation and in situ degradation measurements indicated that crude protein from lupins was more degradable than that of soybean meal. Poor performances of cows fed lupins could be partly due to a reduced true protein supply to the small intestine.

Animal Feed↗
PubMed1986

Design and synthesis of glucagon partial agonists and antagonists.

The hyperglycemia and ketosis of diabetes mellitus are generally associated with elevated levels of glucagon in the blood. This suggests that glucagon is a contributing factor in the metabolic abnormalities of diabetes mellitus. A glucagon-receptor antagonist might provide important evidence for glucagons's role in this disease. In this work we describe how we combined structural modifications that led to glucagon analogues with partial agonist activity to give glucagon analogues that can act as competitive antagonists of glucagon-stimulated adenylate cyclase activity. Using solid-phase synthesis methodology and preparative reverse-phase high-performance liquid chromatography, we synthesized the following seven glucagon analogues and obtained them in high purity: [D-Phe4,Tyr5,Arg12]glucagon (2); [D-Phe4,Tyr5,Lys17,18]glucagon (3); [Phe1,Glu3,Lys17,18]glucagon (4); [Glu3,Val5,Lys17,18]glucagon (5); [Asp3,D-Phe4,Ser5,Lys17,18]glucagon (6); I4-[Asp3,D-Phe4,Ser5,Lys17,18]glucagon (7); [Pro3]glucagon (8). Purity was assessed by enzymatic total hydrolysis, by chymotryptic peptide mapping, and by reverse-phase high-performance liquid chromatography. The new analogues were tested for specific binding, for their effect on the adenylate cyclase activity in rat liver membranes, and for their effect on the blood glucose levels in normal rats relative to glucagon. Analogues showing no adenylate cyclase activity were examined for their ability to act as antagonists by displacing glucagon-stimulated adenylate cyclase dose-response curves to the right (higher concentrations). The binding potencies of the new analogues relative to glucagon (= 100) were respectively 1.0 (2), 1.3 (3), 3.8 (4), 0.4 (5), 1.3 (6), 5.3 (7), and 3 (8). Glucagon analogues 3-5 and 8 were all weak partial agonists with EC50 values of 500 (3), 250 (4), 1600 (5), and 395 nM (8), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1986

United States citizens studying medicine abroad. Their backgrounds and test performance.

To acquire information about the characteristics of U.S. citizens who had recently studied medicine abroad, the Educational Commission for Foreign Medical Graduates (ECFMG) and the Association of American Medical Colleges merged independently collected data on a study group of 10,460 U.S. citizens who attended 359 medical schools in 75 foreign countries and who took their first ECFMG examination between 1978 and 1982. The study group was markedly heterogeneous: 21 percent were not U.S. citizens at birth, 32 percent did not have English as a native language, and 12 percent had two or more years of undergraduate college education in Puerto Rico. Sixty-seven percent resided in New York, New Jersey, California, Florida, or Puerto Rico, and 74 percent studied medicine in Mexico or the Caribbean. Forty-six percent passed the ECFMG examination on their first attempt, and 22 percent passed a subsequent examination. Only 45 percent had applied to a U.S. medical school, and 65 percent had taken the Medical College Admission Test. The means of the college grade-point averages, known for 39 percent of the study group, and of the scores on the admission test, known for 65 percent, were lower than those of both accepted and unaccepted applicants to U.S. medical schools in the 1976 and 1978 entering classes. The finding that 55 percent of the study group did not apply to a U.S. medical school does not support the widely held belief that most, if not all, U.S. citizens who attend foreign medical schools do so only after several unsuccessful attempts to gain admission to a U.S. school.

Adult↗
PubMed1986

Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle.

Hind leg muscles of female rats (85-99 g) were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D-[U-14C]glucose, release of lactate and pyruvate, incorporation of D-[U-14C]glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-[1,2-3H]glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased by 50% the concentration of insulin receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin.

Animals↗
PubMed1986

Receptor binding and adenylate cyclase activities of glucagon analogues modified in the N-terminal region.

In this study, we determined the ability of four N-terminally modified derivatives of glucagon, [3-Me-His1,Arg12]-, [Phe1,Arg12]-, [D-Ala4,Arg12]-, and [D-Phe4]glucagon, to compete with 125I-glucagon for binding sites specific for glucagon in hepatic plasma membranes and to activate the hepatic adenylate cyclase system, the second step involved in producing many of the physiological effects of glucagon. Relative to the native hormone, [3-Me-His1,Arg12]glucagon binds approximately twofold greater to hepatic plasma membranes but is fivefold less potent in the adenylate cyclase assay. [Phe1,Arg12]glucagon binds threefold weaker and is also approximately fivefold less potent in adenylate cyclase activity. In addition, both analogues are partial agonists with respect to adenylate cyclase. These results support the critical role of the N-terminal histidine residue in eliciting maximal transduction of the hormonal message. [D-Ala4,Arg12]glucagon and [D-Phe4]glucagon, analogues designed to examine the possible importance of a beta-bend conformation in the N-terminal region of glucagon for binding and biological activities, have binding potencies relative to glucagon of 31% and 69%, respectively. [D-Ala4,Arg12]glucagon is a partial agonist in the adenylate cyclase assay system having a fourfold reduction in potency, while the [D-Phe4] derivative is a full agonist essentially equipotent with the native hormone. These results do not necessarily support the role of an N-terminal beta-bend in glucagon receptor recognition. With respect to in vivo glycogenolysis activities, all of the analogues have previously been reported to be full agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1986

Maintenance of adult rat liver slices in dynamic organ culture.

Adult rat liver slices were maintained for 20 h in a novel organ culture system with minimal loss of viability and function. Potassium and adenosine triphosphate levels were maintained at in vivo levels, following an initial recovery period (2 to 4 h), for up to 20 h. Protein synthesis and secretion were linear for 20 and 16 h, respectively. In addition, the liver slices synthesized glycogen between 4 and 12 h in culture. Finally, the liver slices were hormonally responsive during the 20 h culture period as exemplified by glucagon-stimulated glucose production. This system provides a simple and effective method for the culture and biochemical maintenance of adult rat liver for 20 h with minimal loss of biochemical function.

Adenosine Triphosphate↗
PubMed1986

Multiple intestinal atresia and amyoplasia congenita in four unrelated infants: a new association.

Four unrelated infants with multiple segments of nonduodenal intestinal atresia and amyoplasia congenita are described. The extreme rarity of each of these conditions as a single entity indicates that their concurrent incidence in four separate unrelated patients is of significance with respect to pathogenesis. The nature of the relationship between the two conditions is unknown.

Arthrogryposis↗
PubMed1986

Predicting academic performance at a predominantly black medical school.

A study was conducted by the authors that examined the validity of the Medical College Admission Test (MCAT), undergraduate grade-point average (GPA), and "competitiveness" of undergraduate college in predicting the performance of students at a predominantly black college of medicine. The performance measures used in the analysis consisted of course grades in all four years of medical school and scores on both Part I and Part II of the National Board of Medical Examiners (NBME) examinations. The predictive validities of the MCAT scores and undergraduate GPAs were found to be similar to those revealed in earlier studies conducted at predominantly white schools. Two exceptions to these similarities were found. First, the MCAT scores at the black school had a somewhat lower validity in predicting NBME examination scores than was the case at the other schools. Second, of the six MCAT subtest scores, Skills Analysis: Reading had the highest correlation with first-year grades, in contrast to results at the other schools. No differences between men and women were found in the validity of MCAT scores and the GPA. The competitiveness of the undergraduate college attended was found to contribute significantly to the prediction of all measures of medical school performance.

Black or African American↗