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Biomedical subjects

M D Johnson

Publications and source records attributed to M D Johnson.

At least 181 records · Page 10Linked to original sources
PubMed1991

In vivo canine coronary artery laser irradiation: photodynamic therapy using dihematoporphyrin ether and 632 nm laser. A safety and dose-response relationship study.

This study examined the safety and dose-response relationships of 632-nm laser irradiation of photosensitized normal coronary arteries in 27 dogs. Fifteen received 2.5 mg/kg dihematoporphyrin ether (DHE), seven received no sensitizer, and five had coronary instrumentation but no laser (sham laser procedures) at nine coronary sites--four sensitized, five non-sensitized. Laser energy of 82 to 1,640 J/cm2 was delivered via a 584 microns diffusing-tip optical fiber, providing estimated tissue fluences of 20 to 410 J/cm2. Serial electrocardiograms and selective coronary arteriograms were performed up to 1 month post laser irradiation. Histologic examination was performed of all treated sites. Tissue fluences less than 200 J/cm2 produced no permanent electrocardiographic or angiographic changes; reversible spasm occurred in 2/8 photosensitized-lased, 0/2 non-photosensitized-lased. Minor medial damage occurred in 1/8 sensitized-lased, 1/2 non-sensitized-lased, and 0/9 sham-lased sites. At tissue fluences greater than 200 J/cm2 4/7 sensitized-lased animals died prematurely--one due to immediate and irreversible coronary spasm and Q wave infarction, one due to fibrillation during 48-hour follow-up coronary angiography (normal angiograms), two with normal electrocardiograms and angiograms within one day of undetermined death; 0/5 non-sensitized-lased animals expired or had coronary spasm; and 3/7 sensitized-lased and 0/5 non-sensitized/lased had significant medial to adventitial histologic damage. Coronary irradiation at less than 200 J/cm2 appears to be safe for photodynamic treatment of atherosclerotic lesions. Pretreatment for coronary spasm is appropriate.

Angioplasty, Balloon, Coronary↗
PubMed1991

Maternal and fetal plasma atrial natriuretic peptide concentrations during elective caesarean section.

Atrial natriuretic peptide (ANP) is stored in the atrial cardiocyte and is capable of exerting potent, selective, and transient effects on fluid and electrolyte balance and on blood pressure. Because fluid shifts and hemodynamic adjustments occur during parturition, ANP might play a homeostatic role in the parturient and fetoplacental unit. We measured maternal and fetal plasma ANP concentrations in 19 parturients during elective caesarean section. Plasma ANP levels were also measured in seven nonpregnant women of the same age group. The baseline ANP concentration in parturients was significantly higher (29.77 +/- 6.06 pg/ml vs 7.37 +/- 2.1 pg/ml; mean +/- s.e.mean) than in their nonpregnant counterparts. The umbilical artery (UA) ANP concentration was significantly higher than the umbilical vein concentration (91.91 +/- 14.91 pg/ml vs. 40.04 +/- 9.71 pg/ml). Factors under the anaesthesiologist's control may influence maternal and fetal plasma ANP levels. There was a significant correlation between the volume of maternal Ringer's lactate infusion received and maternal ANP concentration. A significant correlation was seen between the total dose of ephedrine administered acutely prior to delivery and the UA ANP concentration. These data suggest that: 1) increased blood volume during pregnancy is associated with increased maternal plasma ANP levels, and 2) the fetus can produce its own ANP, and is thereby capable of responding to ANP stimulating factors.

Anesthesia, Obstetrical↗
PubMed1991

Pressure-independent arteriolar rarefaction in hypertension.

To assess the role of pressure in the arteriolar rarefaction associated with hypertension, we studied microvascular density in a hindquarters muscle (cremaster) of rats, 8 wk after coarctation (n = 8) or sham-coarctation (n = 10) of the abdominal aorta. To document the level of arterial pressure in hindquarters vascular beds of similar rats 8-9 wk after initial surgery, we implanted femoral arterial catheters under anesthesia and, 2-5 days later, we measured conscious femoral arterial pressures in coarcted [93 +/- 4 (SE) mmHg; n = 7] and sham-coarcted (110 +/- 3 mmHg; n = 4) rats. The cremaster muscle microcirculation was examined after fixation and Microfil infusion at in vivo pressures. The density of distal third- to fourth-order arterioles was lower by 19% (P = 0.03) in coarcted (1.37 +/- 0.06 mm/mm2) than in sham-coarcted (1.69 +/- 0.11 mm/mm2) rats. We conclude that pressure-independent mechanisms are involved in the arteriolar rarefaction accompanying hypertension.

Animals↗
PubMed1991

Expression of transforming growth factor-beta 1, -beta 2, and -beta 3 mRNA and protein in the murine lung.

Evidence has accumulated suggesting that the various isoforms of beta-type transforming growth factors (TGF-beta s) regulate important functions in the lung; however, the cellular source of these proteins is not well defined. Northern blot analysis of murine lung tissue demonstrates that mRNA transcripts for all three TGF-beta isoforms are found from birth through adulthood. Although the level of expression for each TGF-beta is variable during the first 2 wk post partum, all three isoforms are equal in the adult lung. Using in situ hybridization and immunohistochemical analysis, we have localized both mRNA and protein expression for all three isoforms of TGF-beta in the adult murine lung. At low magnification, immunohistochemical localization of TGF-beta proteins appears coincident in their pattern of expression with TGF-beta mRNAs in the large proximal conducting airways of the lung. However, on closer analysis, protein expression of all three TGF-beta isoforms is confined to the bronchiolar epithelium, while TGF-beta mRNA transcripts for each of the TGF-beta genes are found in smooth muscle cells and connective tissue fibroblasts lying subjacent to the epithelium. Although the levels of both TGF-beta mRNA and protein expression are high in the proximal bronchiolar tree, their signal intensities completely disappear as the terminal bronchioles progress to respiratory bronchioles. Additionally, in the lung vasculature, there is very high expression of all three TGF-beta mRNA transcripts in the smooth muscle cells of the large vessels. TGF-beta2 and TGF-beta but not TGF-beta1 proteins are expressed in these same smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Responsible alcohol service: a study of server, manager, and environmental impact.

A responsible alcohol-service training program was evaluated for its impact on changing beliefs, knowledge, and behavior in 97 servers and 43 managers and on changing establishment policies that encourage safer drinking environments. The training program had a significant impact on changing the beliefs and knowledge of both servers and managers. Observation 4 to 6 weeks after training showed no effects on server behavior, but there was a tendency toward more establishment policies compared with controls.

Accidents, Traffic↗
PubMed1991

Alterations in cardiovascular responsiveness and adrenoceptor binding during catecholamine infusion hypertension in rats.

Chronic continuous infusion of norepinephrine in rats causes alterations in biochemical and physiologic responses of the cardiovascular system and in cardiovascular adrenoceptor number. The response of cardiac and aortic ornithine decarboxylase (ODC) activity to stimulation by norepinephrine was decreased in rats receiving norepinephrine infusion. These responses are due to stimulation of beta- and alpha-adrenergic receptors, respectively. Additionally, there was reduced stimulation of aortic ODC activity by angiotensin II and vasopressin. The cardiac ODC response to angiotensin II was decreased, but the response to vasopressin was not affected. The decreased ODC response is accompanied by decreased pressor responses to the alpha-adrenergic agonist phenylephrine. Decreased numbers of alpha- and beta-adrenoceptor binding sites (as measured by the binding of [3H]prazosin and [125I]pindolol) might mediate, in part, the altered responses to adrenergic agonists. The decreased cardiovascular responsiveness measured in these animals after several days of norepinephrine infusion hypertension contrasts with the increased responses found in most other forms of hypertension. This provides a useful model in which to examine the consequences of prolonged adrenergic receptor stimulation.

Angiotensin II↗
PubMed1991

Reduced G protein function in desensitized rat aorta.

These studies investigated the role of G proteins in vascular desensitization. Rats were infused with norepinephrine (NE) subcutaneously (0.1 mg/kg/hr) for 6 days using osmotic minipumps and aortas were obtained. NE-stimulated contraction was blunted in aortas obtained from NE infused rats compared to aortas from vehicle infused controls. Contractile responses to KCl and serotonin (5-HT) were not affected by NE infusion indicating desensitization was specific to certain receptors. Dose response curves for NaF-stimulated contraction were right-shifted in aortas from NE infused rats suggesting reduced G protein function in these vessels. G protein function was studied further by assessing G protein activation in response to receptor stimulation. This was done by measuring agonist-stimulated increases in 35S-GTP gamma S binding to G protein alpha subunits in aortic membranes. The alpha 1 adrenergic agonist phenylephrine stimulated GTP tau S binding to Gs and Gi in aortic membranes and the degree of stimulation was reduced in desensitized vessels. 5-HT stimulated binding to Gi and Go in aortic membranes and the response was not altered in desensitized vessels. Thus, vascular desensitization produced by NE infusion involves selective reductions in the ability of alpha 1 receptors to activate Gs and Gi.

Animals↗
PubMed1990

A polygenic model for the evolution and maintenance of conditional strategies.

We develop a genetic model for conditional strategies which places such strategies in the context of phenotypic plasticity. The model, which treats conditional strategies as polygenic threshold traits, indicates that, given requisite genetic variation in reaction norms, conditional strategies will evolve to their optimum level and be maintained by stabilizing selection, provided environmental variation results in a fitness trade-off for the alternative conditional phenotypes. The precise value for the evolutionary optimum is found to depend primarily on the probability density function of the environmental variation that influences the production of the conditional phenotypes and the magnitude of the fitness trade-offs of the conditional phenotypes across such environmental variation. The model is tested by application to three well-studied conditional strategies. In each case the predictions of the model are in good agreement with the results of these studies.

Animals↗
PubMed1990

Protein kinase C activity and contractile responsiveness in senescent blood vessels.

To examine Ca2(+)-signaling receptor function in the aging vasculature, the status of the diacylglycerol/protein kinase C (DAG/PKC) arm of the signal transduction pathway was assessed. contractile responsiveness to the PKC activator, phorbol 12-myristate 13-acetate (PMA), is substantially reduced in aortae from 24-month-old Fischer 344 rats compared to 6-month-old rats. PKC activity is reduced in all senescent vessels yet studied including aorta, renal artery, iliac artery and vena cava. This may account for the reduced contractile responsiveness. Additionally, PMA-stimulated PKC translocation is substantially reduced in senescent aorta and this may also contribute to reduced contraction.

Aging↗
PubMed1990

Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells.

Estrogen sensitizes the MCF-7 estrogen-responsive breast cancer cell line to the mitogenic effect of insulin and the insulin-like growth factors (IGFs). This sensitization is specific for estrogen and occurs at physiological concentrations of estradiol. Dose-response experiments with insulin, IGF-I, and IGF-II suggested that the sensitization is mediated through the type I IGF receptor. Binding experiments with 125I-IGF-I and hybridization of a type I IGF receptor probe to RNA showed that the levels of the type I IGF receptor and its mRNA are increased 7- and 6.5-fold, respectively, by estradiol. IGF-I and estradiol had similar synergistic effects on other estrogen-responsive breast cancer cell lines, but IGF-I alone increased the proliferation of the MDA MB-231 cell line which is not responsive to estrogens. These experiments suggest that an important mechanism by which estrogens stimulate the proliferation of hormone-dependent breast cancer cells involves sensitization to the proliferative effects of IGFs and that this may involve regulation of the type I IGF receptor.

Breast Neoplasms↗
PubMed1990

Thermal laser probe angioplasty: influence of constant tip temperature, plaque composition, and probe/vessel diameter ratio.

Thermal laser angioplasty uses constant laser power, producing widely variable tip temperatures in vivo. Results have been suboptimal. We studied the effect of 50-400 degrees C tip temperatures on depth of ablation at 192 sites on plaqued and normal human aorta in vitro, and the angiographic and histologic response in vivo of 300-400 degrees C at probe/vessel ratios of 0.5-1.0, in 40 normal canine femoral artery segments. In vitro, there was a direct relationship between tip temperature and depth of ablation, r = 0.71 (all segments), r = 0.74 for fibrous plaque, but a poor correlation in fatty plaque r = 0.35. In fibrous plaque, there was proportionately more ablation at tip temperatures greater than 300 degrees C, mean depth 0.62 mm, than at 150-300 degrees C, mean 0.37 mm, (P less than .001). Ablation was similar in plaqued and normal aorta. In vivo, 300 degrees C, 350 degrees C, and 400 degrees C produced similar effects. At probe/vessel ratios less than 0.8, only disruption of internal elastic lamina was observed. At ratios greater than or equal to 0.8, spasm occurred in 39% (7/18), transmural damage in 28% (5/18), and perforation in one of 18. Ablation is not selective for plaque and is highly variable in fatty plaque. Tip temperatures above 300 degrees C produce greater ablation than at lower temperatures. In clinical applications, probe/vessel rations less than or equal to 0.7 may be most appropriate, and it appears that thermal remodeling may contribute more to outcome than plaque ablation.

Angioplasty, Laser↗
PubMed1990

Increased levels of phorbin, c-myc, and ornithine decarboxylase RNAs in human colon cancer.

Our previous work on protein kinase C (PKC) and colon cancer has shown altered levels of PKC activity in human colon tumors, as well as activation of PKC by colon tumor promoters such as bile acids. To understand further the role of PKC in colon carcinogenesis, we analyzed the expression of phorbin, a gene induced by PKC activation, in a series of different stages of human colon tumors. As shown by northern blot analyses of poly (A)+ RNA, higher levels of phorbin RNA were seen in 26 colon tumor samples than in their adjacent normal colonic mucosa. There also appeared to be a correlation between the abundance of phorbin RNA in the tumors and the extent of invasion (tumor-to-normal tissue phorbin RNA ratio = 4.2, 8.0, and 11.9 for Dukes' A, B, and C, respectively). Phorbin RNA was also abundant in a human colon cancer line (HT29). We also examined the expression of other mitogen-responsive genes (c-myc, ODC, and beta-actin) in a set of 19 colon tumor samples. All tumors displayed significant (mean 3.8-fold) increases in the level of c-myc RNA compared with their adjacent normal colonic mucosa. About 47% and 16% of these tumor samples also showed increased levels of ODC (mean 3.1-fold) and beta-actin (mean 1.6-fold) RNA, respectively. The increased levels of c-myc, ODC, and beta-actin RNA did not correlate with the extent of tumor invasion. Taken together, these results demonstrate that human colon tumors usually display increased levels of both phorbin and c-myc RNAs. The marked increases in phorbin RNA suggest that this could serve as a useful biomarker in studies on human colon cancer.

Actins↗
PubMed1990

Alpha 1 adrenergic receptor function in senescent Fischer 344 rat aorta.

There have been numerous conflicting reports concerning alpha 1 adrenergic receptor-mediated blood vessel contraction during aging and possible changes in alpha 1 receptor transduction mechanisms have not been investigated. These studies assess capacity of the aging vascular alpha 1 receptor to stimulate production of inositol phosphates, which are its intracellular second messengers, and to elicit a contractile response via this pathway. Aortic ring segments from mature adult (6 month old) and senescent (24 month old) Fischer 344 rats were incubated with [3H]myo-inositol and then stimulated with the alpha 1 agonist norepinephrine (NE, 10(-7)M-3 x 10(-5)M) in the presence of LiCl (10mM), an inhibitor of inositol phosphate metabolism. There was a substantial increase in inositol phosphate accumulation throughout the dose range in aortic rings from 24 month old rats compared to 6 month old rats. This is an alpha 1 receptor response since it is blocked by the alpha 1 antagonist prazosin but not by the alpha 2 antagonist yohimbine. Aortic inositol phosphate accumulation in response to serotonin did not change with age. To assess second messenger stimulated contraction, aortic ring segments were placed in Ca++ free buffer and then stimulated with NE. Under these conditions Ca++ influx is eliminated and contraction depends on the actions of intracellular second messengers. There is an age-related reduction in aortic contraction in Ca++ free buffer. These results suggest that aortic alpha 1 receptor-mediated formation of inositol phosphate intracellular second messengers is enhanced during aging. Despite this, the capacity of senescent arteries to elicit contraction utilizing second messenger pathways seems to be deficient.

Aging↗
PubMed1990

Ontogeny of epidermal growth factor receptor and lipocortin-1 in fetal and neonatal human lungs.

The ontogeny and distribution of the epidermal growth factor (EGF) receptor and lipocortin-1, a major cellular substrate of the EGF receptor, were evaluated in a developmental series of fetal and neonatal human lungs (8 to 41 weeks' gestation and stillborn to 16 days' postnatal age). The peroxidase anti-peroxidase technique with two polyclonal antibodies recognizing the EGF receptor and one polyclonal antibody recognizing lipocortin-1 were used for immunohistochemical localization. Extensive or scattered bronchiolar EGF receptor immunoreactivity appeared in the entire series of frozen lung specimens from 15 to 32 weeks' gestation. Bronchial glands exhibited EGF receptor immunostaining from 19 weeks onward, and immunoreactivity in bronchial epithelium was detected from 23 weeks onward. Most tracheas showed extensive lipocortin-1 immunoreactivity in the epithelium beginning at 10 weeks' gestation. Immunostaining was also seen in cells lining the ducts of submucosal glands after 15 weeks' gestation and in nonmucous acinar cells of tracheal glands after their appearance at 18 weeks' gestation. Bronchial epithelium exhibited lipocortin-1 immunoreactivity from 12 weeks' gestation onward. Bronchial gland necks became immunostained from 16 weeks' gestation onward, followed by acinar immunostaining as they subsequently developed. Bronchiolar epithelium was immunostained as early as 12 weeks, beginning with the largest airways, and by 24 weeks extending distally to the bronchioloalveolar portals. Lipocortin-1 immunostaining of larger conducting airway epithelium was primarily confined to ciliated cells. Neither EGF receptor nor lipocortin-1 immunoreactivity was detected in alveolar type I or type II cells, fibrocytes, chondrocytes, or smooth muscle cells at any gestational age. These developmental patterns suggest that the EGF receptor and lipocortin-1 may participate in normal growth factor-induced proliferation of the conducting airways and their glands in the human fetal lung and trachea.

Annexins↗
PubMed1990

Spinal opioids in the management of obstetric pain.

Spinal opioids have become increasingly popular agents for providing analgesia during labor, augmenting anesthesia during cesarean section, and providing pain relief after operative delivery. The development of spinal opioids in the management of obstetric pain is reviewed.

Analgesia, Epidural↗
PubMed1990

Bupivacaine with and without epinephrine for intercostal nerve block.

In a double-blinded study, 15 American Society of Anesthesiologists class I or II patients, following lateral thoracotomy with general anesthesia, were randomized into two groups for intercostal nerve block with either bupivacaine, 0.5%, and epinephrine, 1:200,000, or plain bupivacaine, 0.5%. Blood concentrations of bupivacaine, epinephrine, and norepinephrine were serially measured. Blood pressure, heart rate, respiratory rate, temperature, and electrocardiogram were monitored. Peak blood bupivacaine concentrations were significantly lower in patients receiving bupivacaine with epinephrine. Peak epinephrine concentrations were significantly greater in patients receiving bupivacaine with epinephrine, but still within a safe range. No significant differences were seen in heart rate, blood pressure, respiratory rate, or temperature between the two groups, and/no dysrhythmias occurred. Peak norepinephrine concentrations were not significantly different between the two groups. The potential risk of toxic bupivacaine blood concentrations associated with intercostal nerve blocks can be reduced by the addition of epinephrine at a concentration of 1:200,000.

Absorption↗
PubMed1990

Anabolic steroid use in adolescent athletes.

Anabolic steroids are being used by adolescents largely to improve athletic performance but also to improve their appearance and to obtain peer approval. With the appropriate knowledge about the effects and side effects of anabolic steroids, primary care physicians can adequately educate teenagers, parents, teachers, and coaches about them and can screen for steroid use, if necessary.

Adolescent↗