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Biomedical subjects

M D Johnson

Publications and source records attributed to M D Johnson.

At least 19 recordsLinked to original sources
PubMed1992

In vitro karyotypic and immunophenotypic characterisation of primitive neuroectodermal tumours: similarities to malignant gliomas.

Monoclonal antibody (Mab) mediated immunotherapy of brain tumours requires the identification of tumour-restricted cell surface antigens. We have characterised four primitive neuroectodermal tumours, which included pineoblastoma, medulloblastoma and ependymoblastoma cultures, that demonstrated in vitro evidence of malignant behaviour (anchorage-independent growth and nu/nu xenograft tumour formation). The cytogenetic findings ranged from normal G-banded and Q-banded karyotypes through mixed near-diploid/hyperdiploid. These cultures resembled the cell surface immunophenotypic spectrum of malignant gliomas. They were distinguished from normal glia in vitro by the expression of restricted fetal mesenchymal, neuronal, myoblastic, melanocytic, epidermal, chondrocytic, lymphoid and epithelial antigens. Certain antigens appeared sufficiently represented among central nervous system (CNS) neoplasms to afford potential targets for Mab-mediated immunotherapy.

Adolescent↗
PubMed1992

Growth factors in breast cancer: mitogenesis to transformation.

While endocrine steroid hormones have been known for many years to regulate normal and malignant mammary epithelium, recent studies have led to an appreciation of polypeptide growth factors as locally-acting autocrine and paracrine effectors. In the current article we summarize what is known about growth factor regulation and action in the normal mammary gland and about perturbations of the steroid-growth factor interplay as cancer progresses. A major theme is that oncogenic activation modulates both regulation of production and function of growth factors in the mammary gland.

Animals↗
PubMed1992

Effect of age on potassium- and tyramine-induced release of norepinephrine from cardiac synaptosomes in male F344 rats.

Potassium (K+)-induced norepinephrine (NE) release was examined in preparations of cardiac synaptosomes and sliced atria from 6-, 24-, and 26-mo-old male F344 rats. Cardiac synaptosomes were prepared from rat hearts by collagenase digestion followed by homogenization in 0.32 M sucrose and centrifugation. The synaptosome preparations and the sliced atria were labeled with 3H-NE and then placed in a superfusion system. K(+)-induced net fractional release of NE from synaptosomes prepared from 24- and 26-mo-old rats (4.3% and 3.0%, respectively) was significantly reduced when compared to NE release from synaptosomes from 6-mo-old rats (5.2%). K(+)-induced NE release from sliced atria from 24-mo-old rats (4.7%) was also significantly reduced when compared to NE release from atria from 6-mo-old rats (6.3%). Perfusion of cardiac synaptosomes with buffer prepared without calcium (CA++free, < 5 microM) reduced K(+)-induced release by 50% in all age groups studied. Perfusion with tyramine induced identical rates of NE release from cardiac synaptosomes prepared from 6- and 24-mo-old rats. These results confirm that depolarization-induced NE release from cardiac sympathetic nerves is reduced in the old male F344 rat.

Adrenergic Fibers↗
PubMed1992

Effects of an opiate receptor antagonist on renin release in dogs.

The present experiments were designed to determine whether blockade of endogenous opiate receptors with naloxone would suppress renin release induced by circulating epinephrine or by reductions of renal perfusion pressure. In the first series of experiments, anesthetized dogs were prepared with a flow probe around the left renal artery and a catheter in the left renal vein, permitting measurement of renin secretion before, during, and after 15-min infusions of epinephrine (50 ng.kg-1.min-1 iv). The epinephrine infusions were conducted either before or after blockade of opiate receptors with naloxone (1 mg/kg iv). Naloxone failed to alter the renin secretory response to intravenous epinephrine infusion. In a second series of experiments, anesthetized dogs were uninephrectomized and prepared with a constrictor cuff around the left renal artery and a renal arterial catheter distal to the cuff. After control measurements of renal perfusion pressure and plasma renin activity (PRA), the cuff was constricted at 15-min intervals to produce controlled stepwise reductions of renal perfusion pressure ranging from 15 to 90 mmHg. One-half of the animals was pretreated with naloxone (1 mg/kg iv). Naloxone pretreatment had no effect on the PRA response to reduced renal perfusion pressure at any pressure. The data fail to support the hypothesis that endogenous opioid peptides are modulators in the control of renin release.

Animals↗
PubMed1992

Effect of naloxone on hypertension in Dahl salt-sensitive rats.

Experiments were conducted to test the hypothesis that chronic administration of an opioid receptor antagonist, naloxone, would affect the outcome of the developmental phase of hypertension in Dahl salt-sensitive (S/JR strain) rats. Accordingly, S/JR rats were maintained on either a low-salt (0.45% NaCl) or a high-salt (7% NaCl) diet for 4 wk. Half of the animals of each dietary group were treated with naloxone (100-130 micrograms/h) by osmotic minipump. Food and water intakes of the high-salt animals were measured for the first 25 days, and blood pressure was measured at the end of the 4 wk via an indwelling femoral arterial catheter. Naloxone treatment slightly but significantly reduced the level of hypertension attained in the high-salt animals (158 +/- 2 mmHg in naloxone-treated animals vs. 168 +/- 3 mmHg in control animals; P less than 0.05) and also attenuated food (and hence salt) and water intakes. Naloxone did not affect the blood pressure of the low-salt animals. To determine whether the slight attenuation of hypertension might be secondary to a reduction of salt intake, a group of control S/JR animals were fed a moderately high-salt diet (2% NaCl), and naloxone-treated S/JR animals were salt-intake matched to this group by daily adjustment of the dietary salt content. Blood pressures after 4 wk of treatment were not different between these two groups. Finally, acute administration of 1 and 30 mg/kg of naloxone failed to lower blood pressure of animals with established hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A PrP gene codon 178 base substitution and a 24-bp interstitial deletion in familial Creutzfeldt-Jakob disease.

Several mutations in the prion protein (PrP) gene are associated with familial Creutzfeldt-Jakob disease (FCJD). We describe a family in which five members in three generations have had FCJD. The proband and some descendants of the affected members carried an abnormal PrP gene allele. This allele contained a 24-bp deletion from the tandem repeat region of the open reading frame and a codon 178 missense substitution. Observations suggest that the codon 178 mutation is involved in the pathogenesis of FCJD in the family described here. The 24-bp deletion may be an uncommon polymorphism.

Adult↗
PubMed1992

Age-related decrease in omega conotoxin binding to rat cardiac synaptosomes.

A cardiac synaptosomal preparation developed by this laboratory was used to study neuronal calcium channels in aging rat heart. Ca2+ channels were quantified by measuring binding of iodinated omega conotoxin, which is reported to specifically block neuronal Ca2+ channels. We determined the binding of [125I]-omega conotoxin GVIA to a synaptosomal preparation from the hearts of 6- and 24-month-old male Fisher 344 rats. The maximum number of binding sites (Bmax +/- SD, fmol/mg protein) is lower in preparations from 24-month (2.2 +/- 0.6) than from 6-month (3.4 +/- 0.7)-old rats. This decrease in number of binding sites suggests an age-related reduction in the number of neuronal calcium channels. Since calcium is essential for exocytotic release of norepinephrine and is made available intracellularly through neuronal calcium channels, the reduction in neuronal calcium channel number may explain, in part, our previous observations of diminished release of norepinephrine in senescent hearts.

Age Factors↗
PubMed1992

Transforming growth factor-beta and transforming growth factor beta-receptor expression in human meningioma cells.

The transforming growth factor-beta (TGF beta) family in mammals includes three closely related peptides that influence proliferation and numerous physiologic processes in most mesenchymal cells. In this study, Northern blots, immunohistochemistry, TGF beta radioreceptor assays, TGF beta receptor affinity labeling and [3H] thymidine incorporation were used to evaluate whether primary cell cultures of human meningiomas synthesize the three TGF beta isoforms, bear TGF beta receptors, and respond to TGF beta. Transcripts for TGF beta 1 and 2 were detected in the three cases analyzed. Transforming growth factor-beta 1 immunoreactivity was detected in three of six cases, and TGF beta 2 and 3 immunoreactivity were detected in each case analyzed. Media conditioned by cells cultured from six meningiomas also contained latent TGF beta-like activity. Transforming growth factor-beta receptor cross-linking studies identified TGF beta binding sites corresponding to the type 1, type 2, and type 3 receptors on meningioma cells. Treatment with active TGF beta 1 produced a statistically significant reduction in [3H] thymidine incorporation after stimulation with 10% fetal calf serum and epidermal growth factor in all six cases studied.

Blotting, Northern↗
PubMed1992

Evidence for transforming growth factor-beta expression in human leptomeningeal cells and transforming growth factor-beta-like activity in human cerebrospinal fluid.

BACKGROUND: Little is known about the factors regulating growth and maintenance of human leptomeningeal cells. The influence of cerebrospinal fluid on these functions is also unknown. Possible mediators include the transforming growth factor-beta (TGF beta) family, three closely related peptides that regulate proliferation and numerous other physiologic processes in most mesenchymal cells. EXPERIMENTAL DESIGN: Expression of both mRNA and protein for TGF beta isoforms TGF beta 1, TGF beta 2, and TGF beta 3 as well as TGF beta-competing activity were evaluated in primary human leptomeningeal cultures by Northern blot analysis, immunohistochemistry, and a radioreceptor assay, respectively. TGF beta 1, TGF beta 2, and TGF beta 3 immunoreactivity was also evaluated in brain sections containing leptomeninges from which these cell cultures were established. An additional study analyzed human cerebrospinal fluid for TGF beta-like activity. RESULTS: Transcripts for TGF beta 1, TGF beta 2 and TGF beta 3 were detected in RNA from each of the eight leptomeningeal cultures. Significant TGF beta 1 immunoreactivity was detected in leptomeningeal tissue from five of eight cases. TGF beta 2 and TGF beta 3 immunostaining was seen in eight and seven of the cases, respectively. Similarly, cells cultured from these meninges exhibited variable TGF beta 1 and extensive TGF beta 2 and TGF beta 3 immunoreactivity. Radioreceptor assays of conditioned media from four cultures demonstrated significant latent TGF beta-like activity. TGF beta radioreceptor competing activity was also detected by radioreceptor assay in normal blood-free cerebrospinal fluid from 32 patients without neurological disease. In addition, pooled cerebrospinal fluid (from six additional patients) exhibited dose dependent TGF beta-like activity in the radioreceptor assay, stimulation of AKR-2B cell growth in soft agar and inhibition of growth in CCL-64 cell assays suggesting that cerebrospinal fluid contains TG beta-like activity. CONCLUSIONS: These findings suggest that the human leptomeninges synthesize TGF beta 1, TGF beta 2 and TGF beta 3 and secrete latent TGF beta s at least in vitro. Human cerebrospinal fluid may also contain TGF beta isoforms. Collectively, these observations raise the possibility that members of the TGF beta family contribute to biologic processes of the leptomeninges.

Agar↗
PubMed1991

Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas.

Phospholipase C-gamma 1 (PLC-gamma 1) is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. However, the biological significance of this molecule in normal or malignant human epithelial cell proliferation is unknown. We determined the relative content of PLC-gamma 1 in primary human mammary carcinomas and in nonmalignant mammary tissues. By Western blot and immunohistochemistry, considerably higher levels of PLC-gamma 1 protein were detectable in the majority of carcinomas and in one of two benign fibroadenomas compared to normal breast tissues. In 18 of 21 carcinomas that contained high levels of PLC-gamma 1, the presence of phosphotyrosine on PLC-gamma 1 could also be detected. All carcinomas in which tyrosine phosphorylated PLC-gamma 1 was present also expressed detectable levels of the epidermal growth factor receptor or erbB-2, two tyrosine kinases known to phosphorylate this enzyme. Thus, a high percentage of mammary carcinomas concomitantly display increased levels of receptor tyrosine kinases and a direct tyrosine phosphorylation substrate, thereby potentially amplifying two successive steps in a signal transduction pathway.

Amino Acid Sequence↗
PubMed1991

Phorbol diester-induced alterations in the expression of protein kinase C isozymes and their mRNAs. Analysis in wild-type and phorbol diester-resistant HL-60 cell clones.

In an HL-60 cell subline (PR-17) which was greater than 100-fold resistant to the differentiating and cytostatic activities of phorbol 12-myristate 13-acetate (PMA), the protein kinase C phenotype was found to be nearly identical to that of wild-type HL-60 cells. A measurable decrease (30%) in the specific activities of crude preparations of PR-17 cell protein kinase C was observed when the enzyme was measured with histone as the phosphate acceptor substrate, but other aspects of the protein kinase C phenotype (intracellular concentrations and binding affinities of phorbol diester receptors, translocation of activated enzyme from cytosolic to particulate subcellular fractions, relative expression of the alpha and beta isozyme proteins) were equivalent in both PMA-resistant PR-17 cells and in wild-type HL-60 cells. Direct analysis of the behavior of the alpha and beta isozymes after the exposure of each cell type to 100 nM PMA for 12 h revealed that the activities and intracellular concentrations of both isozymes were downregulated to an equivalent extent in both wild-type and PMA-resistant cells. These results suggest that the cellular basis for the resistance to the effects of PMA was present "down-stream" from the activation and down-regulation of protein kinase C and was perhaps a nuclear component. Among the genes which were likely to be differentially regulated when each of the two cell lines were treated with PMA were those for the protein kinase C isozymes themselves. In wild-type HL-60 cells, the intracellular concentrations of type HL-60 cells, the intracellular concentrations of mRNA for each of the beta isozymes were increased (up to 5-fold) 48 h after the initiation of PMA treatment; further studies indicate that an activator of protein kinase C could influence the expression of HL-60 cell protein kinase C genes in an isozyme-specific manner. Comparable PMA-induced alterations in mRNA levels were not observed in PMA-resistant cells, even under conditions of significant activation and subsequent down-regulation of protein kinase C protein. Taken together, these data suggest that activation and down-regulation of the isozymes of protein kinase C may not represent absolute determinants of the PMA-induced differentiation of HL-60 cells, but that specific alterations in the levels of the mRNA for the beta isozymes of protein kinase C, or of other genes which may be regulated by the activated kinase isozymes, are important to the induction of leukemia cell differentiation by PMA.

Animals↗
PubMed1991

Effect of age on presynaptic beta2 receptor mediated responses in the rat heart.

Presynaptic alpha2 adrenergic receptor inhibition of norepinephrine (NE) release is diminished in older animals [1]. To determine whether presynaptic beta2 adrenergic receptor facilitation of NE release is also affected by age, the effect of propranolol on neurally-induced NE release was examined in perfused heart preparations isolated from 6- and 24-month-old rats. The heart was isolated with the right cardiac sympathetic nerve and then was stimulated electrically in the absence and presence of propranolol (10(-8)-10(-6) M). NE content in the effluent was measured by an HPLC/EC methodology. The data indicate that there is a greater suppression of NE release by propranolol in preparation isolated from younger animals. For example, in nerve-heart preparations of 6-month-old animals stimulated at 12 Hz, propranolol (10(-6) M) reduced the amount of NE released by 34% whereas in preparations from 24-month-old animals at 12 Hz there was no significant change in the NE overflow. Like the alpha2 receptor mechanism, autoregulation of NE release by presynaptic beta2 receptors is diminished in older animals. Lack of presynaptic autoregulation may explain in part, the reduced capacity of adrenergic influences to control and regulate cardiac function in older animals.

Aging↗
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↗