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Biomedical subjects

J A Anderson

Publications and source records attributed to J A Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae.

We report the isolation of a cDNA (KAT1) from Arabidopsis thaliana that encodes a probable K+ channel. KAT1 was cloned by its ability to suppress a K+ transport-defective phenotype in mutant Saccharomyces cerevisiae cells. This suppression is sensitive to known K+ channel blockers, including tetraethylammonium and Ba2+ ions. The KAT1 cDNA contains an open reading frame capable of encoding a 78-kDa protein that shares structural features found in the Shaker superfamily of K+ channels. These include a cluster of six putative membrane-spanning helices (S1-S6) at the amino terminus of the protein, a presumed voltage-sensing region containing Arg/Lys-Xaa-Xaa-Arg/Lys repeats within S4, and the highly conserved pore-forming region (known as H5 or SS1-SS2). Our results suggest that the structural motif for K+ channels has been conserved between plants and animals.

Amino Acid Sequence↗
PubMed1992

Purification and properties of versiconal cyclase from Aspergillus parasiticus.

Versiconal cyclase catalyzes the dehydration of versiconal to versicolorin B or versicolorin C [versicolorin B(C)]. The enzyme was purified from mycelia of Aspergillus parasiticus by DEAE-cellulose, hydroxylapatite, and Mono Q column chromatography. The protein contains two identical subunits of molecular weight 72,000 per molecule of native protein. The pI of the enzyme is 3.95. The pH activity curve had a broad maximum with a peak at 5.5. The Km and Vmax for versiconal at 30 degrees C and pH 6.0 are 3.1 microM and 0.15 mumol min-1mg-1, respectively. Most of the formation of versicolorin B(C) in the cell is attributed to the action of versiconal cyclase.

Aflatoxins↗
PubMed1992

Developmental toxicity of CI-921, an anilinoacridine antitumor agent.

CI-921, an anilinoacridine compound active against leukemic and solid tumors, was evaluated for potential developmental toxicity. Intravenous injections of CI-921 in dextrose were given to female Sprague-Dawley rats (0.1, 0.5, and 1.0 mg/kg) on Gestation Days (GD) 6-15 and to female New Zealand White rabbits (0.1, 1.0 and 2.0 mg/kg) on GD 6-18. Appropriate vehicle and untreated controls were included. Maternal and fetal parameters, including external, visceral, and skeletal malformations and variations, were assessed. Treatment of rats with 1.0 mg/kg resulted in maternal toxicity, manifested as reduced body weight gain and food consumption during and after treatment. Reduced fetal body weight, an increased incidence of stunted fetuses, malformations of the axial and appendicular skeleton, microphthalmia, and an increased number of anatomical variations (including anomalies of the axial skeleton and apparent hydronephrosis) also occurred in rats at 1.0 mg/kg. Treatment of rabbits resulted in no apparent maternal toxicity. However, reduced fetal body weight, agenesis of the azygous lobe of the lung, and an increased incidence of variations of the axial skeleton occurred at 2.0 mg/kg in rabbits. These results indicate that CI-921, at the highest dose tested in each species, produced developmental toxicity in the presence of maternal toxicity in rats, but in the absence of maternal toxicity in rabbits.

Abnormalities, Drug-Induced↗
PubMed1992

Cutaneous xanthogranulomatous inflammation: a potential indicator of internal disease.

Cutaneous xanthogranulomatous inflammation is usually regarded as a primary disease process. We describe two patients with xanthogranulomatous pyelonephritis and nephro-cutaneous fistulae, one patient with xanthogranulomatous cholecystitis and a chole-cutaneous fistula and one patient with xanthogranulomatous appendicitis and appendiceal-cutaneous fistula. After the first case, awareness that cutaneous xanthogranulomatous inflammation can be secondary to related internal disease played a vital diagnostic role in the subsequent cases.

Aged↗
PubMed1992

Esmolol is more effective than sodium nitroprusside in reducing blood loss during orthognathic surgery.

The goal of this study was to compare the efficacy of esmolol and sodium nitroprusside (SNP) as primary drugs for producing controlled hypotension and limiting blood loss during orthognathic surgery. Thirty ASA physical status I and II patients (mean age 22 yr) undergoing LeFort I maxillary osteotomies were randomly assigned to receive either esmolol (n = 15) or SNP (n = 15) as the primary drug to induce hypotension. All patients received a balanced anesthetic technique including isoflurane, with controlled hypotension during the downfracture of the maxilla. Patients assigned to the esmolol treatment group received boluses of 500 micrograms/kg of esmolol, followed by a continuous infusion of 100-300 micrograms.kg-1.min-1, and the SNP treatment group received a continuous infusion of SNP at 0.25-4.00 micrograms.kg-1.min-1; both infusions were titrated to obtain a mean arterial blood pressure within the target range of 55-65 mm Hg. The mean arterial blood pressure during the hypotensive period was 58.7 +/- 0.7 (mean +/- SEM) and 61.8 +/- 0.4 mm Hg for esmolol and SNP, respectively (P less than 0.001). In addition, 40% +/- 4% of the observed values in the esmolol group and 53% +/- 3% in the SNP group were outside the target range for mean arterial blood pressure (difference significant at P less than 0.05), and a greater proportion of the deviations were above 65 mm Hg in the SNP group than in the esmolol group (0.64 vs 0.46, respectively, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Prevalence of RAS oncogene mutation in head and neck carcinomas.

RAS genes encode for a protein (p21) known to play an important role in the regulation of normal signal transduction and cell growth. Activation of RAS genes have been strongly implicated in the pathogenesis of cancer in cell line studies, animal models and in human tumors. RAS genes have been shown to be mutated in 10 to 15% of human solid tumors but the frequency of mutation varies widely depending on the tumor type. The prevalence of RAS mutation has not been well-established in head and neck squamous cell carcinomas (SCC). The purpose of our study was to screen a relatively large number (50) SCC tumors using a gene amplification technique, the polymerase chain reaction (PCR). H-RAS gene mutation is identified by diagnostic restriction length polymorphism, created by introducing specific mismatched primers in the PCR. The first 20 tumors were also amplified and directly sequenced for K-RAS codon 12 and 13. Four of the 50 screened tumors were positive for H-RAS codon 12 mutation. All tumor DNA screened normal at codon 61 and the first 20 tumors were also normal at K-RAS codon 12 and 13. The prevalence of RAS mutations appears to be low in head and neck squamous cell carcinomas. Tumors positive for point mutation in the H-RAS gene revealed some unusual clinical characteristics.

Adult↗
PubMed1992

Evaluation of tear protein deposits on contact lenses from patients with and without giant papillary conjunctivitis.

Giant papillary conjunctivitis (GPC) associated with contact lens wear is believed to result from an irritative or allergic response to accumulated lens surface deposits. In a masked study, contact lenses worn short-term (2 weeks or less) or long-term (2-12 months), and obtained from patients with and without active GPC, were examined for deposited proteins: IgA, IgE, IgG, IgM, lactoferrin, and lysozyme. Using immunohistochemical methods lenses were separately graded on a 4+ scale for extent of protein coverage. All lenses showed substantial deposits (averaging 50-75% lens coverage) of the normal tear proteins, with the exception of IgE which averaged less than 25% lens coverage; maximum protein deposition was apparent on lenses worn for only 3 days. Both symptomatic and asymptomatic persons deposited similar amounts of the common tear proteins on their contact lenses, with the exception of IgM. A statistically significant increase in IgM deposition was found when the short-term GPC lenses were compared to short-term asymptomatic lenses. Our data suggest that the development of GPC does not depend on amount of deposition of the normal tear proteins IgA, IgG, IgE, lactoferrin or lysozyme. Differences observed in IgM deposition may reflect an immune response in GPC.

Conjunctivitis, Allergic↗
PubMed1992

Clonidine therapy for Shapiro's syndrome.

Shapiro's syndrome comprises agenesis of the corpus callosum in association with episodic hyperhidrosis and hypothermia. We describe a 25-year-old man who is the twentieth case to be reported. There was no evidence of epilepsy, sympathetic nervous system dysfunction or inappropriate vasopressin release. However, investigation demonstrated a central defect in temperature regulation with an abnormally low hypothalamic set-point and normal homeothermic reflexes. Therapy with clonidine, an alpha 2-adrenoceptor agonist, was associated with remission of symptoms: these recurred on four occasions when clonidine was withdrawn. Clonidine therapy was also associated with a return to normal central temperature regulation. We suggest that the efficacy of clonidine reflects an action on hypothalamic thermoregulation rather than on peripheral catecholamine release. These findings have implications for the use of clonidine in other patients with Shapiro's syndrome and in more common disorders of temperature control, including perimenopausal flushing.

Adult↗
PubMed1991

Structural and functional conservation between the high-affinity K+ transporters of Saccharomyces uvarum and Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, high-affinity K+ uptake is dependent upon a 180-kDa plasma membrane protein encoded by TRK1 (c-TRK1) [Gaber et al., Mol. Cell. Biol. 8 (1988) 2848-2859)]. Although hybridization with a c-TRK1 probe revealed highly homologous sequences in the genomes of most Saccharomyces species, the TRK1 sequence in S. uvarum (u-TRK1) was detected only under low-stringency conditions. We cloned u-TRK1 and found it to confer high-affinity K+ uptake in S. cerevisiae. A comparison of the inferred amino acid sequences reveals 78% identity and 86% similarity between the two high-affinity transporters. The most highly conserved regions are the putative membrane-spanning domains (95% identical), suggesting that the structure of the transmembrane domains is important for high-affinity K+ transport.

Amino Acid Sequence↗
PubMed1991

Measurement of mechanical properties of bone material in vitro by ultrasound reflection: methodology and comparison with ultrasound transmission.

An ultrasound reflection technique was designed and implemented to study the mechanical properties of bone material. The technique uses the fact that an ultrasound beam produced in water undergoes total internal reflection off a bone sample at a critical angle formally related to the velocity of a pressure wave in bone. When the plane of scattering is rotated around the normal to the sample surface, the critical angle varies with a periodic dependence dictated by the intrinsic symmetry of the bone structure at the point being examined. Most current measurements of sound velocity are made using transmission techniques. A double-blind intercomparison between this technique and a transmission technique, which was previously validated against tensile mechanical testing, was performed for samples of isotropic materials and of human cortical bone. Strong correlations were found for both sets of samples. For the isotropic materials the velocities were approximately equal, but for bone they were on average 11% higher in reflection than in transmission. This was the result both of the higher frequency employed in reflection (3.5 rather than 2.25 MHz) and of the different effects of sample imperfections on the two measurements. In particular, the reflection technique used in this work studied the surface of the sample, but the ultrasound beam in the transmission method propagated through its interior. In assessing the mechanical properties of bone specimens by ultrasound, the reflection technique samples a discrete bone surface element and the transmission method analyzes the entire volume of the specimen. Thus the reflection technique may yield a measure of the mechanical property of bone trabeculae that is largely unaffected by the mass of the entire specimen, but mass and the structural density of the specimen affect the transmission method.

Biomechanical Phenomena↗
PubMed1991

Developmental toxicity of pentostatin (2'-deoxycoformycin) in rats and rabbits.

The developmental toxicity of the potent adenosine deaminase (ADA) inhibitor, pentostatin (2'-deoxycoformycin), was investigated in pregnant rats and rabbits administered daily iv doses during organogenesis. Rats received 0, 0.01, 0.10, or 0.75 mg/kg on gestation days 6-15 and rabbits received 0, 0.005, 0.01, or 0.02 mg/kg on gestation days 6-18 and maternal and fetal parameters were evaluated on gestation day 21 (rats) or 30 (rabbits). Live fetuses were examined for external, visceral, and skeletal malformations and variations. In rats, maternal body weight gain and food consumption were significantly suppressed at doses of 0.10 and 0.75 mg/kg during the treatment period but returned to control levels during posttreatment. Increased postimplantation loss and decreased numbers of live fetuses, litter size, and fetal body weight were observed at 0.75 mg/kg. A statistically significant increase in the incidence of vertebral malformations occurred at 0.75 mg/kg. The incidence of certain skeletal variations (extra presacral vertebrae, extra ribs, hypoplastic vertebrae) was also increased at 0.75 mg/kg. Ossification of cervical centra was reduced at 0.75 mg/kg compared with controls. In rabbits, marked maternal toxicity (death, body weight loss, and decreased food consumption) and reproductive toxicity (abortion and premature delivery) occurred in all pentostatin-treated groups. However, there were no significant effects on number of live fetuses, pre- or postimplantation loss, litter size, or fetal body weights in the animals with live litters. There was also no apparent increase in the incidence of malformations or variations in the live fetuses of pentostatin-treated rabbits. Thus, these studies demonstrate developmental toxicity of pentostatin in rats and rabbits, and teratogenicity in rats, at maternally toxic doses.

Abnormalities, Drug-Induced↗
PubMed1991

Fertility and perinatal/postnatal studies in rats with the angiotensin-converting enzyme inhibitor, quinapril.

Quinapril, an inhibitor of angiotensin-converting enzyme (ACE) and an antihypertensive agent, was evaluated in rats for effects on fertility, reproduction, and perinatal and postnatal development. In a fertility study, male rats were treated by gavage for 60 days prior to and during mating and female rats were treated by gavage for 14 days prior to mating, during mating and gestation, and during lactation with doses of 0, 10, 50, or 100 mg quinapril/kg body wt. There were no significant effects on body weight, food consumption, fertility indices, fetal development, or neonatal growth, survival, development, behavior, or reproduction. In a perinatal/postnatal study, administration of quinapril to females at doses of 25, 75, or 150 mg/kg during late gestation and lactation had no effects on parturition, lactation, or postnatal development, but a significant decrease in neonatal body weight during the suckling period was observed at all doses. In a subsequent study, female rats were given 150 mg/kg during late gestation, lactation, or late gestation and lactation. No adverse effects were seen in the dams or the offspring, and no reduction in neonatal body weight was observed. Kidneys from pups whose mothers received quinapril during gestation and/or lactation had minimal juxtaglomerular cell hypertrophy, characteristic of treatment with ACE inhibitors. Low levels of quinaprilat (the major and pharmacologically active metabolite of quinapril) were detected in fetal blood and in neonatal blood, indicating offspring exposure to quinapril. Milk quinaprilat concentrations were 3-5% of the plasma concentrations 3-5 hr after dosing. These studies demonstrate no adverse effects of quinapril on fertility, reproduction, or perinatal and postnatal development.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

A double-blind comparison of low-dose intravenous ketamine and methohexital in adults.

Two ultralight general anesthetic techniques, one using low-dose ketamine and the other using methohexital as the primary anesthetic agent, were compared for efficacy, safety, and psychomotor recovery in a double-blind fashion for use during third molar surgery. Low-dose intravenous ketamine as the primary anesthetic following premedication with fentanyl and midazolam, and in conjunction with nitrous oxide, appeared to produce less hypoxia, hypercarbia, and apnea than when methohexital was used. No significant differences were noted in heart rate or blood pressure between the techniques. The ketamine technique was universally preferred by the surgeons and anesthesiologists because of superior patient cooperation and airway management. No unpleasant psychomimetic side effects of significance were noted with the use of ketamine. Postoperative recovery took slightly longer in the ketamine group, with patients being judged fit for discharge approximately 10 to 15 minutes later than the patients who received methohexital.

Adolescent↗