Biomedical subjects

J H Johnson

Publications and source records attributed to J H Johnson.

At least 37 records · Page 2Linked to original sources

PubMed1997

Clinical outcome of pediatric gangliogliomas: ninety-nine cases over 20 years.

Gangliogliomas account for 1-4% of all pediatric CNS tumors. We reviewed the records of 123 patients treated at the Children's Hospital of Philadelphia between 1974 and 1995. Ninety-nine patients were eligible for review with complete medical records. The mean age was 9.5 years with 52% females. The mean follow-up was 3.7 years. The most common presenting symptom was seizures (49%). The mean length of symptoms to diagnosis was 24.4 months. Complex partial seizure was the most frequent seizure type (60%). Electroencephalograms were abnormal in 36%. The majority of gangliogliomas were in the temporal lobes (38%), with other sites in the parietal (30%) and frontal lobes (18%). All patients had abnormal nonspecific neuroimaging studies. Nine received chemotherapy, and 21 were treated with radiotherapy. Postoperatively, 78% were seizure free on no medication, 18% had improvement of seizure control, and 4% had stable seizure events. Nine died of disease. Gangliogliomas are benign tumors that frequently present with seizure disorders and nonspecific electroencephalographic and neuroimaging studies. Complete surgical extirpation of these tumors provides improved seizure control in most patients and a short course of antiepileptic medical therapy. Adjuvant therapy including radiotherapy and chemotherapy is limited to recurrent disease not amenable to reoperation.

Adolescent↗

PubMed1997

Post-1980 black population redistribution trends in the United States.

"Using data from the 1990 Public Use Microdata Samples (PUMS) and other U.S. census documents, this paper demonstrates how three rather dramatic shifts in the migration behavior of blacks, which took shape during the 1970s, continued to contribute to the geographical redistribution of the black population down the urban hierarchy during the 1980s. Analyses of black migration flows into six metropolitan areas suggest that liberal welfare benefits play, at best, a minor role in contemporary black population redistribution trends, kinship ties (i.e., location-specific capital), the search for affordable housing, and employment in the hospitality services industry appear to be the dominant forces influencing black migration into the case-study communities."

Black or African American↗

PubMed1997

Immigration reform and the browning of America: tensions, conflicts and community instability in metropolitan Los Angeles.

"Tensions, conflicts, and community instability associated with heightened immigration--especially of nonwhite immigrant groups--threaten to balkanize America. This article highlights the root causes of the growing opposition to both immigrants and U.S. immigration policy--the nativist backlash, presents a typology of the community-level conflicts that have arisen as a consequence of heightened immigration--legal and illegal--to the United States over the last 30 years, and outlines the conditions under which diversity can be brought to the forefront as one of society's strengths.... The 1992 Los Angeles County Social Survey (LACSS)...provides insights into the nature and magnitude of intergroup stereotyping and prejudice in a community in which large numbers of immigrants have settled."

Americas↗

PubMed1997

Heteropodatoxins: peptides isolated from spider venom that block Kv4.2 potassium channels.

Toxins isolated from scorpion, snake, and spider venoms are valuable tools to probe the physiologic function and structure of ion channels. In this study, we have isolated three new toxins (heteropodatoxins) from the venom of a spider, Heteropoda venatoria. These toxins are structurally similar peptides of 29 to 32 amino acids and share sequence homology with hanatoxins isolated from the venom of a Chilean tarantula. The heteropodatoxins prolonged the action-potential duration of isolated rat ventricular myocytes, suggesting that the peptides block K+ currents. The effect of toxins on cardiac K+ currents were studied using voltage clamp techniques. The toxins blocked the transient outward K+ current but not other K+ currents in isolated rat cardiac myocytes. The mechanism of block was studied further using Kv4.2, a cloned channel believed to underlie transient outward K+ current in rat myocytes. The toxins blocked Kv4.2 current expressed in Xenopus laevis oocytes in a voltage-dependent manner, with less block at more positive potentials. In addition, the toxins slowed the time course of current activation and inactivation and shifted the voltage dependence of current inactivation to more positive potentials. The heteropodatoxins represent new pharmacologic probes to study the role of Kv4.2 channels in cardiac and neural tissue.

Action Potentials↗

PubMed1997

Amikacin pharmacokinetics and the effects of ambient temperature on the dosage regimen in ball pythons (Python regius).

The serum concentration of amikacin following intracardiac and i.m. administration of amikacin (3.48 mg/kg) in 12 ball pythons (Python regius) housed at 25 degrees C and 37 degrees C was studied. Blood samples were collected by cardiocentesis at intervals up to 144 hr after administration of amikacin. Drug concentration-versus-time curves following intracardiac administration at both temperatures best fit a two-compartment open model. For snakes housed at 37 degrees C, the extrapolated time 0 concentration (mean +/- SD) was 17.64 +/- 3.5 micrograms/ml with a median elimination half-life of 4.5 days. The maximum concentrations were 11.98 +/- 1.67 micrograms/ml and 13.87 +/- 2.61 micrograms/ml for snakes housed at 25 degrees C and 37 degrees C respectively. There were no significant pharmacokinetic differences among the snakes housed at 25 degrees C and 37 degrees C. Model-independent parameters were area under the curve, 69,900 +/- 0.011 micrograms.min/ml, apparent volume of distribution at steady state, 410 +/- 106 ml/kg, clearance, 0.036 +/- 0.009 ml/min/kg, and mean residence time, 3,530 +/- 273.7 minutes. Mean serum amikacin concentrations did not reach the recommended therapeutic peak concentrations for mammals (25 micrograms/ml). In addition, the amikacin serum concentration did not fall below the recommended therapeutic trough concentrations (2 micrograms/ml) by 6 days. The serum amikacin concentrations were efficacious based on the area under the curve. Therefore, amikacin (3.48 mg/kg) administered i.m. to ball pythons should produce maximum serum concentrations against most pathogenic bacteria. In this study, it would have taken another half-life, or 4.5 days, before trough concentrations of 2 micrograms/ml were achieved. To prevent accumulation, a one-time administration of amikacin may be appropriate.

Amikacin↗

PubMed1997

Duodenal perforation in a cheetah (Acinonyx jubilatus).

An 11-yr-old female cheetah (Acinonyx jubilatus) from a privately owned breeding center for endangered species was referred for evaluation with a history of vomiting and depression of 10 days' duration. After anesthetic induction with tiletamine and zolazepam and anesthetic maintenance with isoflurane, a complete diagnostic workup was performed, including hematology, serum chemistry, and radiography. The clinical diagnosis was septic suppurative inflammation and hemorrhage in the abdomen, consistent with perforation or rupture of the gastrointestinal tract. An exploratory laparotomy showed a perforated duodenal ulcer, which was resected. Subsequent endoscopy revealed no further evidence of ulceration in the upper gastrointestinal tract. Biopsy of the ulcerated tissue collected from the duodenum revealed Gastrospirillum-like organisms. Histologic examination revealed widespread infiltration of lymphocytes and plasma cells into the lamina propria and submucosa. Intraepithelial leukocytes were present along with attenuation, erosion, and ulceration of the superficial epithelium. Fourteen days after surgery, this cheetah was returned to its breeding compound, and no subsequent vomiting has been observed for 4 yr.

Acinonyx↗

PubMed1996

Defective fatty acid-mediated beta-cell compensation in Zucker diabetic fatty rats. Pathogenic implications for obesity-dependent diabetes.

Although obesity is associated with insulin resistance, most obese humans and rodents remain normoglycemic because of compensatory hyperinsulinemia. This has been attributed to beta-cell hyperplasia and increased low Km glucose metabolism of islets. Since free fatty acids (FFA) can induce these same beta-cell changes in normal islets of Wistar rats and since plasma FFA are increased in obesity, FFA could be the signal from adipocytes that elicits beta-cell compensation sufficient to prevent diabetes. To determine if FFA-induced compensation is impaired in islets of rats with a diabetogenic mutation, the Zucker diabetic fatty (ZDF) rat, we cultured islets from 6-week-old obese (fa/fa) rats that had compensated for obesity and apparently normal islets from lean ZDF rats (fa/+) in 0, 1, or 2 mM FFA. Low Km glucose usage rose 2.5-fold in FFA-cultured control islets from age-matched Wistar rats, but failed to rise in either the precompensated islets of ZDF rats or in islets of lean ZDF rats. Bromodeoxyuridine incorporation increased 3.2-fold in Wistar islets but not in islets from obese or lean ZDF rats. Insulin secretion doubled in normal islets cultured in 2 mM FFA (p < 0.01) but increased only slightly in islets from lean ZDF rats (not significant) and declined in islets from obese ZDF rats (p < 0.05). We conclude that, unlike the islets of age-matched Wistar rats, islets of 6-week-old heterozygous and homozygous ZDF rats lack the capacity for FFA-induced enhancement of beta-cell function.

Animals↗

PubMed1996

Activation of stimulus-secretion coupling in pancreatic beta-cells by specific products of glucose metabolism. Evidence for privileged signaling by glycolysis.

The energy requirements of most cells supplied with glucose are fulfilled by glycolytic and oxidative metabolism, yielding ATP. In pancreatic beta-cells, a rise in cytosolic ATP is also a critical signaling event, coupling closure of ATP-sensitive K+ channels (KATP) to insulin secretion via depolarization-driven increases in intracellular Ca2+ ([Ca2+]i). We report that glycolytic but not Krebs cycle metabolism of glucose is critically involved in this signaling process. While inhibitors of glycolysis suppressed glucose-stimulated insulin secretion, blockers of pyruvate transport or Krebs cycle enzymes were without effect. While pyruvate was metabolized in islets to the same extent as glucose, it produced no stimulation of insulin secretion and did not block KATP. A membrane-permeant analog, methyl pyruvate, however, produced a block of KATP, a sustained rise in [Ca2+]i, and an increase in insulin secretion 6-fold the magnitude of that induced by glucose. These results indicate that ATP derived from mitochondrial pyruvate metabolism does not substantially contribute to the regulation of KATP responses to a glucose challenge, supporting the notion of subcompartmentation of ATP within the beta-cell. Supranormal stimulation of the Krebs cycle by methyl pyruvate can, however, overwhelm intracellular partitioning of ATP and thereby drive insulin secretion.

Animals↗

PubMed1996

Islet fructose 6-phosphate, 2-kinase:fructose 2,6-bisphosphatase: isozymic form, expression, and characterization.

Polymerase chain reaction analysis of the mRNA isolated from rat islets demonstrated that the major isozyme of Fructose 6-P,2-kinase:Fructose 2,6-bisphosphatase was the heart type enzyme, and that the liver type enzyme was not detectable. The islet enzyme was expressed in Escherichia coli and purified to homogeneity. The islet enzyme showed the highest Fructose 6-P,2-kinase activity (478 milliunits/mg) compared to the other isozymes and Fructose 2,6-Pase activity (39 milliunits/mg). Fructose 6-P,2-kinase showed KmF6P = 17 microM, which is within the range of in vivo Fru 6-P concentrations in islets. 6-P-Gluconate was a potent inhibitor of Fructose 2,6-Pase. The data suggest that Fructose 6-P,2-kinase activity of the bifunctional enzyme was high and Fructose 2,6-Pase activity was inhibited under physiological variations of blood glucose concentration.

Animals↗

PubMed1996

Differential effects of overexpressed glucokinase and hexokinase I in isolated islets. Evidence for functional segregation of the high and low Km enzymes.

Glucose-stimulated insulin secretion is believed to require metabolism of the sugar via a high Km pathway in which glucokinase (hexokinase IV) is rate-limiting. In this study, we have used recombinant adenoviruses to overexpress the liver and islet isoforms of glucokinase as well as low Km hexokinase I in isolated rat islets of Langerhans. Glucose phosphorylating activity increased by up to 20-fold in extracts from islets treated with adenoviruses containing the cDNAs encoding either tissue isoform of glucokinase, but such cells exhibited no increase in 2- or 5-[3H]glucose usage, lactate production, glycogen content, or glucose oxidation. Furthermore, glucokinase overexpression enhanced insulin secretion in response to stimulatory glucose or glucose plus arginine by only 36-53% relative to control islets. In contrast to the minimal effects of overexpressed glucokinases, overexpression of hexokinase I caused a 2.5-4-fold enhancement in all metabolic parameters except glycogen content when measured at a basal glucose concentration (3 mM). Based on measurement of glucose phosphorylation in intact cells, overexpressed glucokinase is clearly active in a non-islet cell line (CV-1) but not within islet cells. That this result cannot be ascribed to the levels of glucokinase regulatory protein in islets is shown by direct measurement of its activity and mRNA. These data provide evidence for functional partitioning of glucokinase and hexokinase and suggest that overexpressed glucokinase must interact with factors found in limiting concentration in the islet cell in order to become activated and engage in productive metabolic signaling.

Animals↗

PubMed1996

Response of human artery, vein, and cultured smooth muscle cells to atrial and C-type natriuretic peptides.

OBJECTIVES: We determined the response of intracellular cyclic GMP in human arteries and veins and in smooth muscle cells cultured from these vessels to C-type natriuretic peptide in comparison with atrial natriuretic peptide. DESIGN: Repeated-measures analysis of concentration-response curves. SETTING: Anesthesia research laboratory. SUBJECTS: Vascular smooth muscle cells from human blood vessels obtained with Institutional Review Board approval and patient consent. MEASUREMENTS AND MAIN RESULTS: Segments of internal mammary artery and saphenous vein were obtained from patients undergoing coronary artery bypass surgery. Smooth muscle cells were cultured from these vessels. Concentration-response curves of intracellular cyclic GMP were determined and analyzed by two-way analysis of variance with repeated measures. In segments of intact saphenous vein, C-type natriuretic peptide was significantly more effective than atrial natriuretic peptide (16-fold increase in cyclic GMP in response to 1 microM of C-type natriuretic peptide vs. six-fold increase in cyclic GMP in response to 1 microM of atrial natriuretic peptide, p < .05). In rings of intact internal mammary artery, 1 microM of atrial natriuretic peptide (26-fold increase in cyclic GMP over basal value) was more effective than 1 microM of c-type natriuretic peptide (three-fold increase in cyclic GMP over basal value, p < .05). In cultured cells from these vessels, the pattern of response to C-type natriuretic peptide and atrial natriuretic peptide was the same as in the intact vessels. CONCLUSIONS: These results indicated that human smooth muscle cells in arteries and veins express both forms of natriuretic peptide receptors but that atrial natriuretic peptide acts primarily on the artery and C-type natriuretic peptide acts predominantly on the vein. Increased concentrations of C-type natriuretic peptide could contribute to venous pooling in septic shock.

Analysis of Variance↗

PubMed1996

Function and expression of a human idiotypic network in Schistosomiasis japonica.

The cross-reactive idiotype (Hu-SJ-CRIM) is defined by polyclonal human anti-idiotypic antibodies derived from chronically S. japonicum infected patients. The present study shows that serum levels of Hu-SJ-CRIM expressed by antibodies to S. japonicum soluble egg antigen (SEA) are associated with acute infection and hepatosplenic disease. Xenogeneic anti-idiotypic antisera (anti-Hu-SJ-CRIM) suppressed human lymphocyte blastogenesis to SEA in vitro by 47-82% (P < 0.05). These anti-idiotypic antibodies also suppressed in vitro granuloma formation induced by SEA coated heads in a dose dependent manner. This immunosuppression was antigen specific in that mitogen (PHA) or non-related antigen (PPD) induced blastogenic responses were not suppressed. Surprisingly, anti-idiotypic antibodies (anti-SJ-CRIM), which describe the mouse correlate CRIM were not suppressive in the human blastogenesis or in vitro granuloma formation assays. These data indicate a dichotomy in the function and specificity of the idiotype/anti-idiotype human and murine immune networks in S. japonicum infection. Thus, only the patient derived molecules and serology form the basis for an immunoregulatory network in Schistosomiasis japonica.

Adult↗

PubMed1996

Malignant gliomas in children.

Childhood supratentorial malignant gliomas, though less common than those in adults, are responsible for disproportionately high morbidity and mortality rates. Important advances have been made in our ability to diagnose these tumors by noninvasive neuroimaging techniques. In addition, progress has been made in our ability to correlate pathology and biological features with clinical outcomes to provide prognostic information. Neuroimaging and tissue prognostic factors now have important roles which directly affect clinical management. While surgery and radiation therapy are critical components of the treatment of childhood supratentorial gliomas, the role of chemotherapy is less clear. Significant responses have been demonstrated for chemotherapy regimens in infants with malignant gliomas and high-dose chemotherapy and ABMR regimens also produce encouraging response rates. The results of current clinical trials will help us determine if these response rates will translate into prolonged patient survival and allow us to identify subgroups of childhood malignant glioma patients that may benefit from adjuvant chemotherapy.

Astrocytoma↗

PubMed1996

Laboratory reference values for a group of captive Ball Pythons (Python regius)

OBJECTIVE: Laboratory reference values, including hematologic and serum biochemical variables, and oropharyngeal bacteria flora, were determined in a group of captive Ball Pythons (Python regius). ANIMALS: 20 adult Ball Pythons, weighing between 700 and 1,510 g, were allowed to acclimate at the recommended temperature range for the species (25 C night-time, up to 30 C daytime), then were evaluated for internal parasites and treated with appropriate medication prior to the start of the study. PROCEDURE: Hematologic values determined included WBC, hemoglobin, hematocrit, plasma protein, and differential cell count. Clinical biochemical analysis included determination of glucose, uric acid, calcium, phosphorus, total protein, alanine transaminase, alkaline phosphatase, and aspartate transaminase values. In addition to blood values, oropharyngeal swab specimens of the mouth were submitted for culture to determine the species of bacteria found in this population. Descriptive statistics were calculated for each hematologic and clinical biochemical value. Mean, SEM, and ranges were calculated. RESULTS: Hematologic values were similar to those reported in other snake species, except the hematocrit, which was lower. Clinical biochemical values different from those of other species were alkaline phosphatase activity, which was lower, and calcium and phosphorus concentrations, which were lower than values in other species. Bacteria isolated from the oropharynx were principally gram-negative organisms. CONCLUSION: Reference intervals reported in this study are important for establishing a database for comparative studies of Ball Pythons in other locations and under different husbandry conditions. CLINICAL RELEVANCE: Accumulated laboratory reference values will assist veterinarians in assessing the health status of Ball Pythons.

Alanine Transaminase↗

PubMed1996

Characterization of fuel and aftertreatment device effects on diesel emissions.

Heavy-duty diesel engines operated with a low-sulfur (LS)* fuel and either a particle trap or an oxidation catalytic converter (OCC) have been studied during steady-state operation (and during regeneration of the particle trap) to determine the effects of these devices on regulated and unregulated emissions, including the chemical and biological character of the exhaust. This study consisted of two phases, both of which were designed to determine the effects of fuel, particle control system, and engine type on (1) levels of regulated emissions such as oxides of nitrogen (NOx), total hydrocarbons (HC), and total particulate matter (TPM); (2) levels of unregulated emissions such as particle-associated soluble organic fraction (SOF), sulfate (SO4), solids (SOL), and the vapor-phase organic fraction collected on XAD-2 resin (XOC); (3) levels of selected mutagenic and carcinogenic polynuclear aromatic hydrocarbons (PAHs) in the particle-associated and vapor-phase organic fractions; (4) mutagenic activity associated with the same organic fractions; and (5) exhaust particle size distributions. Phase I involved a 1988 Cummins Engine Co. LTA 10-300 (L10) engine equipped with a ceramic particle trap having built-in regeneration controls. Phase II involved a 1991 prototype Cummings Engine Co. LTA 10-310 (LTA) engine equipped with an OCC. The 1991 LTA engine also contained a higher pressure fuel-injection system than the 1988 L10 engine and used an intake charge air-to-air aftercooling system, instead of the intake air-intercooler system on the 1988 engine.

Analysis of Variance↗

PubMed1995

Automated sample preparation for cholesterol determination in foods.

An automated sample preparation system has been developed for the determination of cholesterol in a wide range of matrices. Isolation of cholesterol is performed with a robotic arm coupled with a series of modular stations. Samples are introduced into the system which adds the appropriate reagents, carries out the saponification, pH adjustment, solid-phase extraction and drying steps. This system was evaluated using 15 different food matrices. The average recovery for NIST standards exceeded 97%. A solution of n-hexane-2-propanol was substituted for the traditional methanol-chloroform extraction. Manual pH adjustment was replaced with a buffer. Manual and automated methods were compared and no difference was observed at the 95% confidence level.

Automation↗

PubMed1995

Surgical repair of traumatically induced collapsing trachea in an ostrich.

A region of tracheal collapse was identified by endoscopy after surgical repair of a traumatic injury to the neck in an ostrich. During periods of excitation, the ostrich would become dyspneic and collapse. A tracheal split-ring prosthesis was placed surgically to support the collapsing trachea. This technique, which is frequently used in dogs, is applicable for use in birds with collapsing trachea.

Animals↗

PubMed1995

Pancreatic beta-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids.

To elucidate the mechanism of the basal hyperinsulinemia of obesity, we perfused pancreata from obese Zucker and lean Wistar rats with substimulatory concentrations of glucose. Insulin secretion at 4.2 and 5.6 mM glucose was approximately 10 times that of controls, whereas beta-cell volume fraction was increased only 4-fold and DNA per islet 3.5-fold. We therefore compared glucose usage at 1.4, 2.8, and 5.6 mM. Usage was 8-11.4 times greater in Zucker islets at 1.4 and 2.8 mM and 4 times greater at 5.6 mM; glucose oxidation at 2.8 and 5.6 mM glucose was > 12 times lean controls. To determine if the high free fatty acid (FFA) levels of obesity induce these abnormalities, normal Wistar islets were cultured with 0, 1, or 2 mM long chain FFA for 7 days. Compared to islets cultured without FFA insulin secretion by FFA-cultured islets (2 mM) perifused with 1.4, 3, or 5.6 mM glucose was increased more than 2-fold, bromodeoxyuridine incorporation was increased 3-fold, and glucose usage at 2.8 and 5.6 mM glucose was increased approximately 2-fold (1 mM FFA) and 3-fold (2 mM FFA). We conclude that hypersecretion of insulin by islets of obese Zucker fatty rats is associated with, and probably caused by, enhanced low Km glucose metabolism and beta-cell hyperplasia, abnormalities that can be induced in normal islets by increased FFA.

Animals↗