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Biomedical subjects

P Wong

Publications and source records attributed to P Wong.

At least 19 recordsLinked to original sources

Active cell death in hormone-dependent tissues.

Active cell death (ACD) in hormone-dependent tissues such as the prostate and mammary gland is readily induced by hormone ablation and by treatment with anti-androgens or anti-estrogens, calcium channel agonists and TGF beta. These agents induce a variety of genes within the hormone-dependent epithelial cells including TRPM-2, transglutaminase, poly(ADP-ribose) polymerase, Hsp27 and several other unidentified genes. Not all epithelial cells in the glands are equally sensitive to the induction of ACD. In the prostate, the secretory epithelial cells that are sensitive to hormone ablation are localized in the distal region of the prostatic ducts, and are in direct contact with the neighboring stroma. In contrast, the epithelial cells in the proximal regions of the ducts are more resistant to hormone ablation, probably because the permissive effects of the stroma are attenuated by the presence of the basal epithelial cells, which are intercalated between the epithelium and stroma. The underlying biology of ACD in prostate and mammary glands, and its relevance to hormone resistance, is discussed in this review.

Animals

The pharmacological activity of nitroxyl: a potent vasodilator with activity similar to nitric oxide and/or endothelium-derived relaxing factor.

Chemical oxidation of N-hydroxy-L-arginine (NOHA) and other N-hydroxyguanidines has been previously shown to generate either nitric oxide (NO) or nitroxyl (HNO), depending on the oxidative conditions. Because N-hydroxy-L-arginine has been demonstrated to be a biosynthetic intermediate in the oxidative conversion of arginine to endothelium-derived relaxing factor, the possible formation of HNO through a biological process was considered. This study, therefore, explores the biological activity of HNO as a possible effector molecule, and the results indicate that HNO is capable of eliciting vasorelaxation in both rabbit aorta and bovine intrapulmonary artery by a guanylate cyclase-dependent pathway. The pharmacological properties of HNO were very similar to those of endothelium-derived relaxing factor, and the possible relationship between HNO and endothelium-derived relaxing factor is discussed.

Animals

Cholesteryl ester storage disease: complex molecular effects of chronic lovastatin therapy.

To better characterize the in vivo effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition on human lipid metabolism, an adolescent male with cholesteryl ester storage disease (CESD) was treated chronically with lovastatin. Therapy was associated with decreased liver-spleen size, improved but not normal serum lipids, a 26% decrease in hepatic cholesteryl ester, a 12% decrease in unesterified hepatic cholesterol, and a fourfold increase in hepatic low density lipoprotein (LDL) receptor protein. Hepatic mRNA levels for the LDL receptor and apolipoprotein (apo) B standardized to levels of hepatic gamma actin mRNA were unchanged with therapy. Kinetic studies revealed no change in the LDL fractional catabolic rate and a decrease in the LDL production rate. Size exclusion chromatography showed striking reductions in plasma very low density lipoprotein (VLDL) cholesterol and intermediate density lipoprotein (LDL) cholesterol but not LDL cholesterol with therapy. Mean LDL particle size and the LDL particle size range were increased by treatment. However, there was no difference in the ability of pretreatment or treatment LDL to bind to the LDL receptor on cultured cells consistent with previous studies in animals, indicating that lovastatin may alter LDL particles to impair interaction with the LDL receptor in vivo but not in vitro. Lovastatin therapy in CESD appears to be clinically beneficial and has complex effects on lipid metabolism that may include a dominant inhibitory effect on hepatic lipoprotein production, posttranscriptionally mediated induction of the LDL receptor, and alterations of LDL particles that interfere with their clearance by the LDL receptor in vivo.

Actins

Person-to-person transmission of Brucella melitensis.

Human brucellosis is primarily an occupational hazard in the USA; in the Middle East and Africa ingestion of contaminated dairy products is an important route of infection. Whether human beings can become infected via person-to-person spread is uncertain. During an investigation of a commonsource, laboratory-associated outbreak due to Brucella melitensis, biotype 3, the wife of a microbiologist with serologically proven brucellosis became infected. Her blood isolate was indistinguishable from the epidemic strain. In the absence of other risk factors, we suggest that sexual intercourse is a possible means of transmission.

Brucella

Clinical investigations of halothane and isoflurane for induction and maintenance of foal anesthesia.

Fifty-eight foals were divided into two groups for study of aspects of the clinical anesthetic management of foals and to characterize effects of halothane (n = 30) and isoflurane (n = 28) in foals. There were no significant differences (P greater than 0.05) in the demographics of the two groups. Results of hemograms and biochemical analysis of venous blood samples before and after anesthesia were either not influenced or only mildly (clinically unimportant) affected by either agent. Like adult horses, foals have an increased PaCO2 when anesthetized with inhaled anesthetics. We could detect no difference in the magnitude of increase in PaCO2 with either anesthetic. Anesthetic induction and recovery was most rapid with isoflurane. The quality of induction and recovery was similarly acceptable with either agent. Heart rate during isoflurane was not significantly different from conscious conditions but during halothane, heart rate was significantly less than control except at 91-120 min when statistical significance was not detected. These results support the clinical impression that foals can be safely and reliably anesthetized with either agent.

Anesthesia, Inhalation

Isolation of an abnormally phosphorylated erythrocyte membrane band 3 glycoprotein from patients with myotonic muscular dystrophy.

A fraction of erythrocyte Band 3 (Mr, 93,000) glycoprotein that demonstrates decreased autophosphorylation in membranes from myotonic muscular dystrophy patients is demonstrated. Sequential affinity chromatography of Triton X-100 solubilized erythrocyte membrane proteins separated three specifically retained glycoprotein fractions on a Ricin Communis I-Sepharose 4B column. One fraction contains a portion of the major sialoglycoprotein (apparent Mr, 78,000) and is specifically eluted from the column by 10 mM NaCl and 100 mM D-galactose (10/100). The two other glycoprotein fractions are eluted by 100 mM NaCl, 10 mM D-galactose (100/10) and 100 mM NaCl, 100 mM D-galactose (100/100). The composition of both fractions contains greater than 95% Band 3 (apparent Mr, 93,000 glycoprotein. The quantities of glycoprotein in each fraction obtained from erythrocytes of myotonic dystrophy patients did not differ from the quantities obtained from control erythrocytes. Following endogenous protein kinase incubations of ghosts with [gamma-32P]ATP, the specific [32P] phosphorylation of the 10/100 and 100/10 fractions are identical. The 100/100 fraction, which makes up approximately 3% of the total erythrocyte membrane protein, demonstrates a different pattern for myotonic dystrophy patients; specific phosphorylation was reduced by 50% relative to activity in control experiments. These findings are consistent with previous experiments that demonstrated decreased autophosphorylation of the glycoprotein portion of Band 3 (Roses & Appel, 1975, J. Membrane Biol 20:51) and are consistent with the autosomal dominant mode of inheritance in this disease.

Chromatography, Affinity

Real-time high resolution ultrasound in the detection of biliary calculi.

A high-resolution real-time ultrasound sector scanner was used in the evaluation of patients with suspected gallbladder disease. This technique is noninvasive, requires minimal preparation, and takes less than five minutes for a thorough examination of the gallbladder and related anatomy. In 17 months, 959 patients were examined for suspected gallbladder disease and the gallbladder was adequately visualized in all but 5 patients. Follow-up information was obtained from surgery in 153 cases. There were 132 true-positive studies, 15 true-negative, 5 false-negative and one-false positive study. In a correlative study with oral cholecystography, calculi were detected ultrasonically in 5 cases that had been missed on the oral cholecystogram.

Cholecystography

Combined immunotherapy of malignant melanoma. Unusual survival following cerebral metastasis.

An 18-year-old woman was found to have solitary cerebral, choroidal, and pulmonary metastases of malignant melanoma three years after excision of a primary malignant melanoma. The cerebral metastasis was excised, and the patient's condition was treated with CNS irradiation followed by combined immunotherapy with transfer factor and Bacille bilié de Calmette-Guérin. The transfer factor donor was her father, who showed cellular immunity to melanoma extracts on in vitro testing. Histologic examination of the pulmonary nodule, which was excised after the initiation of immunotherapy, revealed a dense lymphocytic infiltrate associated with the metastatic melanoma. The patient is currently free of detectable melanoma more than three years after the cerebral metastasis. Studies in a second patient also demonstrated the appearance of inflammatory infiltrate in metastatic melanoma following transfer factor therapy.

Adolescent

Group B streptococcal colonization in a newborn nursery: effects of iodophor and triple dye cord care.

Control of nosocomial group B streptococcal (GBS) colonization of newborn infants was attempted in a four-cycle study alternately employing single applications of povidone-iodine (iodophor) and triple dye to the umbilical cord stump and periumbilical area. GBS colonization rates were 49% and 34% following iodophor cord care (cycles II and III) and 11% and 50% following triple dye cord care (cycles II and IV). The apparent significant reduction of GBS colonization during triple dye cycle II could not be reproduced in a subsequent follow-up culture survey and remains unexplained.

Coloring Agents

Variable expression in flecked (speckled) dystrophy of the cornea.

Five members of a three-generation pedigree had flecked corneal dystrophy. The number of flecks varied from patient to patient, and one individual was affected in only one eye. Visual acuity was normal in all family members. Homocystinuria also occurred in this family, but appeared to be coincidental. Central cloudy dystrophy of the cornea appears to be genotypically identical to flecked dystrophy of the cornea but is phenotypically distinct.

Adult

Nosocomial transmission of group B Streptococci in a newborn nursery.

Group B streptococcal colonization of normal newborn infants increased from 22.5% within 20 hours of birth to 65.4% at the time of hospital discharge (P less than .001). In contrast, colonization in mothers did not change significantly between the time of admission to labor and delivery (27.7%) and the time of discharge (31.1%). Epidemiologic data suggested but did not prove that the mode of nosocomial transmission of group B streptococci among infants was cross colonization via personnel contact.

Cross Infection

Failure of penicillin to eradicate the carrier state of group B Streptococcus in infants.

Serial cultures were obtained from 12 patients being treated with a form of penicillin for group B streptococcal disease or asymptomatic colonization. These cultures were collected prior to initiation of therapy, during therapy, and at the end of the treatment period. Pencillin eradicated GBS from the involved system (blood, CSF, bone, and joint). Cultures remained positive from at least one of three carrier sites (throat, umbilicus, and rectum) in 70% of patients cultured between days one and eight of treatment and 66% between days 10 and 21. These data demonstrate the failure of penicillin to eradicate GBS from mucous surfaces of young infants.

Arthritis

Evaluation of four methods for detection of group B streptococcal colonization.

Four methods (streak plate, pour plate, selective broth, and direct fluorescent-antibody staining) were evaluated for their ability to detect group B streptococcal colonization in parturient women and their offspring. When colonization was defined as a positive culture by any method from any site, selective broth was the most sensitive method, detecting 100% of colonized mothers and infants at birth and 48 h of age. This method failed to detect only one colonized individual (infant at 24 h of age). The other three methods detected from 20 to 56% of colonized individuals.

Adult

[Snake bites].

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Humans