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Biomedical subjects

R R MacGregor

Publications and source records attributed to R R MacGregor.

At least 163 records · Page 9Linked to original sources

A shielded synthesis system for production of 2-deoxy-2-[18F]fluoro-D-glucose.

A remotely operated, shielded synthesis system for the production of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) for clinical studies has been developed. Using this system, 25 mCi of 18FDG are produced a the end of a 60-min synthesis from approximately 300 mCi of F-18 (total F-18 recovered from the target at the end of bombardment). The fractional distribution of F-18 among various components of the synthesis system has been measured. This yield of 18FDG (25 mCi) is ample for two consecutive human studies in house or for shipment to collaborating institutions within a 3-hr (door to door) radius.

Deoxy Sugars↗

Significance of bacteriuria with presumed non-pathogenic organisms.

The results of 2,793 clean catch midstream specimens submitted to the microbiology laboratory were examined to determine if the isolation of reputed non-pathogens such as Lactobacillus, Staphylococcus epidermidis. Micrococcus and diphtheroids represented poor collection technique, contaminant growth by failure to plate or refrigerate quickly or actual urinary tract infection. Eight per cent of the inpatient cultures and 18 per cent of the outpatient cultures had more than 10(5) colony-forming units per ml. of these non-pathogens. Of the outpatient cultures with more than 10(5) colony-forming units per ml. of non-pathogens 44 per cent had symptoms of urinary tract infection and more than 10 white blood cells per high power field in the urinary sediment, compared to 3 per cent of inpatients. In a prospective analysis of an outpatient population a second clean catch midstream specimen was collected within 2 hours of the first specimen with careful attention to sterile collection technique. Of 15 cases of significant bacteriuria with non-pathogens in the first specimen only 1 had significant bacteriuria with the same organism in the second specimen. In contrast, in the inpatient population 7 of 11 cases with pathogen significant bacteriuria in the first specimen had significant bacteriuria in the second specimen. These findings suggest that most episodes involving isolation of non-pathogens in greater than 10(5) colony-forming units per ml. from urine represent poor techniques of specimen collection rather than urinary tract infection.

Bacteria↗

Granulocyte function in recipients of renal transplant from live related donors and from cadavers.

Granulocyte adherence, chemotaxis, phagocytosis, and bactericidal activity were studied in patients receiving renal transplants to determine whether defects in granulocyte function can explain increased susceptibility to infection. Five points were studied: preoperatively; immediately after transplantation; at the time of any rejection crises (when the patient was receiving large doses of prednisone and azathioprine); at discharge; and six months postoperatively with stable renal function. The major defect was depressed granulocyte adherence early postoperatively and at the time of rejection crises, when prednisone dosage was maximal. Chemotactic activity improved progressively after transplantation despite large doses of prednisone and azathioprine and was supranormal at the time of rejection crises. Phagocytosis was enhanced early postoperatively and at the time of rejection crises. Bactericidal activity was unaffected by renal transplantation and immunosuppressive therapy in recipients of transplants from live related donors, but was depressed in recipients of cadaveric kidneys.

Azathioprine↗

Virus infection of endothelial cells increases granulocyte adherence.

Adherence of human granulocytes was measured on endothelial monolayers of human and bovine origin, grown in 35-mm Diam petri dishes and in cluster wells. Adherence to human endothelium in petri dishes using 1.0 ml of whole blood averaged 17.9+/-3.7%, and to bovine endothelium was 20.3+/-3.7%. Cluster wells required only 1/5 the endothelial cells needed for petri dishes, and 0.25 ml of whole blood yielded average adherence of 26.2+/-3.4 to human cells and 28.0+/-3.7 to bovine in the wells. The impact of infection of the endothelium by different viruses on subsequent granulocyte adherence was measured. Polio virus produced an acute lytic infection of human endothelial cells, with associated increased adherence to 185.4% of control 24 h after inoculation. Significantly increased adherence was noted at 6 h, before detectable cytopathic effect. Herpes simplex type I caused a similar rapidly lytic infection of bovine endothelium associated with increased adherence to 213.7% of control 6 h after inoculation. This augmented adherence could be demonstrated when granulocytes were suspended in physiologic saline solution, showing that antibody and complement need not be present. Trypsin treatment of infected monolayers did not prevent the augmentation, and supernate from infected monolayers increased the adherence of polymorphonuclear leukocytes to normal, uninfected monolayers. Chronic, slowly lytic infections, lasting 7 d or more, were induced with adenovirus in human endothelium and with measles virus in bovine cells. Adherence increased as virus was noted in the cell cultures on day 4, several days before cytotoxicity was seen. Thus, chronic viral infection of the endothelium appears possible, and results in increased granulocyte adherence. In naturally occurring disease, such an infection may act synergistically with adherent granulocytes to damage the endothelium, and may represent an in vitro model of vasculitis.

Animals↗

The effect of target-gas purity on the chemical form of F-18 during 18F-F2 production using the neon/fluorine target.

Irradiation of gas mixtures of F2/Ne (20Ne leads to d,alpha 18F) which contained percent levels ( > 0.1%) of N2, CO2, CO2, or CF4 resulted in the production of unacceptable levels of F-18-labeled NF3 and CF4 at the expense of 18F-F2. Analycical gas chromatographic methods have been devised to determine contaminant levels in the target gas as well as in the products arising from them. Commercial mixtures of 1T F2/Ne, pur F2, and neon have been analyzed for contaminants (N2, O2, CO, CO2, and CF4) and found to vary widely in the levels of these impurities from batch to batch. The N2 levels in the 1% F2/Ne mixtures varied from 0.039 to 0.49%, and the CO2 levels from 0o.018 to 0.13%. No detectable impurities were found in the neon (Research Purity), but F2 was found to contain approximately 11% CF4. Reproducibly high yields of 18F-F2 are obtained if the levels of N2, CO2, and CF4 in the final target gas mixture are < 0.01% and carrier F2 is approximately 0.1%. Hydrocarbons and CO were not detected in our gas mixtures, but would also be expected to decrease yields of 18F-F2.

Carbon Dioxide↗

Nosocomial infection control problems in neonates and infants.

Nosocomial infection rates of 4-6% are standard in most general hospitals. Wound and urinary tract infections are most common on the Surgical Services. Respiratory tract infections cluster on the Medical Service. Programs of infection control should be Service-directed. Among pediatric patients, particular emphasis should be placed on monitoring colonization by S. aureus and antibiotic-resistant gram-negative rods. Control measures include maintenance of low colonization rates, development of an infection control team, and institution of restrictive practices when an outbreak occurs.

Cross Infection↗

A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection.

Rapid uptake of F-18 FDG was observed in a variety of transplanted and spontaneous tumors in animals. The tumor uptake reached a peak by 30 min and remained relatively constant up to 60 min, with a very slow wash-out of F-18 activity from the tumor thereafter. Tumor-to-normal tissue and tumor-to-blood ratios ranged from 2.10-9.15 and 2.61-17.82, respectively, depending on the type of tumor. A scintiscan of a seminoma in a dog showed very high uptake in the viable part and lack of uptake in the necrotic mass. Toxicological studies in mice using 1000 times human tracer dose (HTD) per wk for 3 wk and in dogs using 50 times HTD per wk for 3 wk did not show any evidence of acute or chronic toxicity.

Abscess↗

Anhydrous F-18 labeled eslemental flurine for radiopharmaceutical preparation.

Interest in fluorine- 18 as a label in radiopharmaceutical studies has led to the development of a method for the production of decicuries of anhydrous 18F-F2 using the 20Ne(d, alpha) 18F reaction. The amount of anhydrous 18F-F2 that can be removed from the target is a function of target pressure and carrier cokncentration increasing with rising target pressure and decreasing with decreasing carrier concentration. At a target pressure of 24 atmospheres and a carrier concentration of 0.1% F2, nearly 95% of the theoretical yield of fluorine- 18 produced can be removed and up to 85% delivered through a 10o-m stainless steel tube to the reaction chamber. Other functions affecting yield--including target design, target-gas handling and purity--have been addressed. Thick target yields for 14.0- and 9.4-MeV deuterons on target were measured to be 82 and 67 mCl/microA at saturation. With the BNL 60-in. cyclotron, production okf 600-800 mCl of 18F-F2 with a specific activity of approximately 10 mCi/mumole has been in effect since 1976.

Fluorine↗

Isolation and characterization of porcine parathyroid cathepsin B.

Cathepsin B was isolated from porcine parathyroid tissue and from liver by a procedure involving acetone precipitation, gel filtration, and carboxymethylcellulose chromatography. The final preparations of each migrated as single bands upon sodium dodecyl sulfate polyacrylamide gels but exhibited several minor active variants upon isoelectric focusing. The parathyroid and liver enzymes were similar to each other and also resembled cathepsin B from other sources. The molecular weights for the porcine enzymes were estimated as 25,000, and the isoelectric point was at pH 4.8. The parathyroid enzyme cleaved benzyloxycarbonyl-Val-Lys-Lys-Arg-(4-methoxy)-2-naphthylamide at pH 5.8 and 37 degrees C with a Km of 0.14 mM and a kcat of 68 s-1. The pH optimum for this reaction was pH 6 to 7. The enzyme was unstable above pH 7.5 and below pH 4.5. It was strongly inhibited by HgCl2, ZnSO4, iodoacetate, iodoacetamide, and N-ethylmaleimide which indicated that it is a thiol protease, and by leupeptin, a strong inhibitor of cathepsin B from other sources. Antibodies to the parathyroid enzyme were elicited in rabbits. The antisera formed single precipitin bands upon double diffusion in agar gels against both the parathyroid and liver enzymes. Precipitin bands were formed at both pH 6 and pH 8.5 which indicated that the antisera recognized both native and denatured forms of the enzymes.

Amino Acids↗

The degradation of proparathormone and parathormone by parathyroid and liver cathepsin B.

Purified cathepsin B from porcine parathyroid glands was allowed to act upon radioactive bovine parathormone and proparathormone at various ratios of enzyme to substrate and for different times. The reaction products were isolated by ion exchange chromatography and analyzed by gel electrophoresis, amino acid composition, sequence analysis, and bioassay. The enzyme cleaved parathormone between residues 36 and 37 yielding a major carboxyl and amino fragment and appeared to cleave proparathormone at the same locus. The amino fragments were degraded further by removal of small peptides (possibly, di- or tripeptides) from their COOH termini. In contrast there was little if any degradation of the carboxyl fragment (residues 37 to 84). Despite the ease with which the enzyme cleaved the arginyl bond in the synthetic substrate benzyloxycarbonyl-Val-Lys-Lys-Arg-(4-methoxy)-2-naphthylamide, it did not remove the near homologous NH2-terminal hexapeptide extension of proparathormone (Lys-Ser-Val-Lys-Lys-Arg-R)--a reaction that would lead to the formation of parathormone from proparathormone. Purified liver cathepsin B cleaved the hormonal substrates in a fashion identical with that of the parathyroid enzyme.

Amino Acid Sequence↗

Comparative penetration of various cephalosporins into inflammatory exudate.

A rabbit sterile peritonitis model was used to determine the relative penetration of four cephalosporin antibiotics into exudate fluid. Male New Zealand white rabbits were given 120 ml of sterile saline intraperitoneally, and peritonitis developed over the following 8 h, with exudate fluid containing a mean of 17,188 granulocytes per mm(3) at 8 h. Each antibiotic was administered intramuscularly at a dose of 30 mg/kg 3 h after peritonitis was initiated, and serum and peritoneal concentrations were measured 0.5, 1, 2, and 4 h later. Cefamandole gave the highest mean peak serum level (26.8 mug/ml), and cephalothin, cephacetrile, and cephradine all gave peak serum levels between 13 and 15 mug/ml. When peak peritoneal exudate concentration was expressed as a percentage of peak serum concentration, cephradine developed 28.5% of the peak serum level, cephacetrile 27.7%, cephalothin 14.0%, and cefamandole 12.5%. These percentages of exudate penetration were inversely proportional to the degree of serum protein binding: cephradine 26.6%, cephacetrile 36.3%, cephalothin 50%, and cefamandole 88%.

Animals↗

Inadvertent administration of intravenous fluids contaminated with fungus.

We present here the case of a patient inadvertently infused with intravenous fluid containing a "fungus ball." Because little is known about such cases, we surveyed 113 infectious diseases specialists for their experiences and ideas on management. Seventy-six responded, of whom 18 had seen a total of 24 cases. Intravenous-fluid containers were often defective, and the fungi involved were usually "contaminants." One patient developed significant fungal infection, and six others had transient symptoms temporally related to the infusion. Most specialists would administer antifungal therapy if symptoms developed, the patient was immunocompromised, or the fungus was pathogenic for humans.

Antifungal Agents↗

The mode of conversion of proparathormone to parathormone by a particulate converting enzymic activity of the parathyroid gland.

The cleavage products from the conversion of proparathormone to parathormone by a bovine and porcine parathyroid microsomal converting activity have been analyzed. In the conversion reaction, the first 6 amino acid residues of the prohormone (Lys-Ser-Val-Lys-Lys-Arg-) are released as an intact hexapeptide. This is rapidly converted to a pentapeptide by removal of the NH2-terminal lysine and then to a tetrapeptide by removal of the COOH-terminal arginine. In order to test for the presence of a postulated COOH-terminal extension of the parathormone sequence in proparathormone, mixtures of 14C-proparathormone and 3H-parathormone were subjected to digestion by trypsin or Staphylococcus aureus protease. The resulting radioactive peptides from the hormone and its precursor were compared. There was no evidence that any fragments different from those from the hormone were released from the prohormone except those accounted for by the NH2-terminal hexapeptide adduct on proparathormone. Thus, the conversion of the prohormone to the hormone catalyzed by the microsomal membrane activity requires only the cleavage of this hexapeptide.

Amino Acid Sequence↗