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Biomedical subjects

J B Jones

Publications and source records attributed to J B Jones.

At least 109 records · Page 6Linked to original sources

Bone marrow transplantation in canine mucopolysaccharidosis I. Effects within the central nervous system.

Five dogs with mucopolysaccharidosis I, a model of human Hurler/Scheie syndrome, were transplanted with marrow from phenotypically normal littermates at 5 mo of age. At 3 and 9 mo posttransplantation, biopsies of cerebral cortex, liver, and cerebrospinal fluid were obtained. The alpha-L-iduronidase levels in these tissues were 0.8-7.4, 26-45, and 6.3-14.9% of the paired donor tissues, respectively. Although iduronidase was present in relatively low levels in the recipients' brains and cerebrospinal fluid at both biopsy times, reduction in brain glycosaminoglycan (GAG) was comparable to that observed in liver. Ultrastructural studies of cells within the transplanted dogs' brains showed less lysosomal distension and storage product than in affected, nontransplanted, littermate controls. The most marked clearing of stored GAG was in cells surrounding blood vessels, but decreased lysosomal storage in neurons and glial cells was also observed. Urinary GAG excretion also decreased to near normal levels by 5 mo posttransplantation.

Animals↗

Cyclic hormonogenesis in gray collie dogs: interactions of hematopoietic and endocrine systems.

Cortisol, ACTH, T4, and T3 concentrations were determined in six cyclic hematopoietic (CH) dogs to determine if hormonal cycles were a feature of this hematopoietic disorder. It was determined that there were 12- to 14-day cycles of these hormones in CH dogs. Plasma cortisol and ACTH concentrations peaked 4-8 days after the onset of neutropenia and were concurrent with peak neutrophil counts. The peak ACTH concentration occurred 1-2 days before or concurrent with the cortisol peak concentration. T4 and T3 peak concentrations were opposite the cortisol cycles, and maximal concentrations were seen when cortisol levels were lowest. ACTH, GH-releasing factor and TRH response tests were performed in the CH dogs. No frank deficiencies in hormone production were seen with the ACTH, GH-releasing factor, and TRH responses in CH dogs relative to those in normal dogs. It was concluded that cyclic hormonogenesis is a central feature of CH disease. These findings are the first demonstration of extrahematopoietic system cyclicity in this rare disease and suggest the presence of common regulatory factors in the hematopoietic and endocrine systems.

Adrenocorticotropic Hormone↗

Long-term bone marrow culture systems: normal and cyclic hematopoietic dogs.

A continuous long-term liquid culture in both a micro and macro system that incorporates bone marrow cells from normal and cyclic hematopoietic dogs is described. An adherent layer composed of fibroblasts, endothelial cells, mononuclear phagocytic cells, and fat-containing cells is essential for continuous hematopoiesis. Hematopoiesis was measured by the recovery of the nonadherent cells and the generation of committed granulocyte-monocyte progenitor cells for a period of seven weeks. Optimum growth factors include the use of horse serum, fetal bovine serum, dog serum, hydrocortisone, a 33 degrees C incubation temperature and feeding twice a week. As is true for both human and murine marrow liquid cultures, horse serum and hydrocortisone are essential for development and maintenance of fat-containing cells in the described systems. Both factors are important in hematopoiesis but their respective roles have not been defined. Normal and cyclic hematopoietic dogs bone marrow cells are comparable in their ability to establish long-term cultures. The micro-method (Linbro-well culture) gave similar results in maintaining hematopoiesis as did a macromethod (flask culture).

Animals↗

An illustrative example of a synthetically useful enzyme: horse liver alcohol dehydrogenase.

The enzymes of most general and continuing value in organic synthesis are those that can operate stereospecifically on a wide range of structurally varied substrates. Horse liver alcohol dehydrogenase (HLADH, EC 1.1.1.1), a commercially available NAD(H)-dependent oxidoreductase that catalyses C = O in equilibrium CH(OH) interconversions, is such an enzyme. The scope of applications of enzymes endowed with this degree of versatility is illustrated by the preparative-scale use of HLADH to catalyse specific oxidoreductions of a broad spectrum of alcohol and ketone substrates. Examples are given of enantiomeric distinctions, of discrimination between enantiotopic groups in substrates possessing prochiral centres or in meso compounds, of regiospecific transformations and of combinations of various specificities. The value of the enzyme-derived products as chiral synthetic precursors of molecules of current interest is demonstrated.

Alcohol Dehydrogenase↗

Oxyhemoglobin saturation during sleep in subjects with and without the obesity-hypoventilation syndrome.

The etiology of the obesity-hypoventilation syndrome (OHS) is unknown. Recent reports that treatment of obstructive sleep apnea with nasal continuous positive-airway pressure eliminates the manifestations of OHS suggests that obstructive sleep apnea may contribute to OHS. The purpose of this study was to determine whether hypoxemia during sleep was more severe in patients with OHS than in those without OHS. In our sleep laboratory, we studied 32 subjects with a ratio of the forced expiratory volume in one second over the forced vital capacity (FEV1/FVC) greater than 0.73 and no neuromuscular disease. Seven subjects had OHS characterized by obesity and daytime hypercapnia, and 25 subjects did not. The seven patients with OHS all had sleep apnea. Of the 25 without OHS, 23 had sleep apnea. Subjects with OHS had significantly greater oxyhemoglobin desaturation during sleep than subjects without OHS, even when subjects with and without OHS were matched for sex and weight. These findings are consistent with the hypothesis that severe sleep apnea is a contributing cause of OHS.

Adult↗

Viability and growth of clinical isolates of Haemophilus influenzae.

Studies were done on clinical isolates of Haemophilus influenzae to investigate viability and determine the effects of disc-agar diffusion (DAD) medium modification on antimicrobial susceptibility results. Most isolates were viable for two days in distilled water, up to a week on chocolate agar and months when frozen in skim milk at -70 degrees C. Differences in viability were not related to biotype, serotype, beta-lactamase production or site of isolation of isolates. Several medium modifications resulted in better growth of isolates for antimicrobial susceptibility testing by DAD, but the zone sizes of inhibition differed from those of the recommended medium.

Culture Media↗

Abnormal function and thromboxane release from platelets of dogs with cyclic hematopoiesis.

Investigation of platelet function in dogs with cyclic hematopoiesis (CH) revealed a platelet aggregation disorder. Collagen-induced aggregation of CH dog platelets was significantly abnormal, although normal aggregation in response to ADP was observed. Aggregation was particularly defective on days 2-4 and 14 of the 14-day neutrophil cycle that is typical of CH dogs. The lack of response to collagen suggested a defect in the arachidonic acid pathway of platelet metabolism, since platelet-generated thromboxane-B2 levels were about 30% (p less than 0.0005) of control values. Platelets from dogs heterozygous for CH demonstrated moderately depressed responses to collagen that were intermediate between the values found for platelets from CH dogs and platelets from normal, mixed-breed dogs. Not only does this work indicate a platelet defect in CH dogs, but this phenomenon may be useful as a genetic marker for identification of dogs heterozygous for the CH gene.

Adenosine Diphosphate↗

Tritiated thymidine incorporation into canine cyclic hematopoietic bone marrow in vitro.

To investigate changes in the proliferative activity of bone marrow cells in canine cyclic hematopoiesis, nonadherent cells were incubated for 1 h with tritiated thymidine either immediately after the cultures were established or following an 18-h preincubation period. The data suggest that changes in thymidine incorporation show a 12- to 14-day cycle that consists of two distinct phases. During the first six days of the cycle (from peripheral neutropenia to relative neutrophilia), two peaks of incorporation were observed. During the second phase (corresponding to the neutrophilia and oncoming neutropenia), thymidine incorporation was uniformly lower than control values. The change from an apparently cyclical process to a low stable value occurred after the wave of marrow myelopoiesis and close to a time point (days 8-10 of the cycle) at which we have recently suggested significant changes in cell release and/or proliferation take place. The data can be interpreted in the context of a periphery-to-stem-cell feedback loop through an intermediate cell population, probably of myeloid precursors.

Animals↗

Nucleotide and prostaglandin cycling in canine cyclic hematopoiesis.

Bone marrow cells were collected from normal dogs, normal dogs made neutropenic with cyclophosphamide, and 11 dogs affected with cyclic hematopoiesis (CH) on 3 consecutive days of separate 12- to 14-day cycles. The mononuclear marrow cells from both groups of control dogs and from the CH dogs on each of 12-cycle days were cultured for 2.5 hr in serum-free media. The amounts of prostaglandins (PGF2 alpha and PGE) and cyclic GMP (cGMP) measured in the media were found to vary with the cycle in the CH dog. PGF2 alpha was highest as the dogs recovered from the neutropenia and lowest 4 days before the onset of the next neutropenic episode. Cyclic GMP was lowest 4-5 days before the onset of neutropenia, then dramatically increased as the neutropenic period approached. Cyclic GMP was highest when PGF2 alpha was lowest. Normal dogs, made neutropenic with a single dose of cyclophosphamide, had elevations of PGF2 alpha but not PGE or cGMP during the recovery period of active granulopoiesis.

Agranulocytosis↗

A calorimetric investigation of the binding of indole and phenylethane boronic acid to chymotrypsin.

The heat of formation of the chymotrypsin-phenylethane boronic acid complex has been observed calorimetrically from pH 4 to 8 at 25 degrees C and is found to be pH-dependent, changing from near -6 kcal/mol at pH 4 to -13 kcal/mol at pH 8. The heat of formation of the chymotrypsin-indole complex is a nearly constant -6 kcal/mol over most of the same pH range. alpha-Chymotrypsin has been purified by pH gradient elution from an immobilized lima bean inhibitor column. Solutions of the enzyme up to 400 microM, prepared in this manner, have a zero heat of dilution from pH 5 to 8 in 0.1 M KCl, with or without added 0.05 M Tris, N-(tris[hydroxy-methyl]methyl-2-amino) ethanesulfonic acid, 4-morpholineethanesulfonic acid, or acetate buffers. Binding of phenylethane boronic acid causes a pH-dependent decrease in proton binding to chymotrypsin; the decrease in proton binding evoked by formation of the indole complex is much less, with a much smaller pH dependence. The calorimetric and proton-binding results are applied to a model for boronic acid binding (Hanai, K. (1976) J. Biochem. (Tokyo) 79, 107-116). We conclude that the thermodynamics of formation of the trigonal boronic acid complex are quite similar to those for the formation of the noncovalent complex formed by indole and related ligands. The trigonal-tetrahedral tautomerism in the boronic acid-chymotrypsin complex is characterized by thermodynamic changes similar to those accompanying the binding of virtual substrates to chymotrypsin.

Boronic Acids↗

Studies of cervicovaginal smears for the presence of actinomycetes.

Cytologic and direct fluorescent antibody techniques were used to detect the presence of Actinomyces israelii and Arachnia propionica in cervicovaginal smears collected from 100 women, 94 of whom did not use intrauterine contraceptive devices. In no case were these organisms found. The possible significance of these results is discussed.

Actinomyces↗

Copper, iron, and zinc contents of human milk at early stages of lactation.

The Cu, Fe, and Zn contents of early milk from 102 American mothers were examined in relation to stage of lactation, intake of prenatal mineral supplements, maternal age, parity, and previous history of lactation. A total of 412 samples was collected at three stages of lactation: early transitional (4 to 7 days postpartum); transitional (10 to 14 days postpartum); and mature (30 to 45 days postpartum). For the transitional and mature stages, representative samples of late evening (PM) and early morning (AM) feedings were collected. Diurnal variation in concentration was observed only for Fe. Concentrations of all elements decreased significantly at successive stages of lactation with Zn showing the greatest decline. Cu, Fe, and Zn contents (means +/- SEM) were 104.1 +/- 5.4, 96.5 +/- 6.5, and 520 +/- 20 micrograms/100 g in early transitional milk; 93.9 +/- 3.6, 85.4 +/- 4.5, and 410 +/- 10 micrograms/100 g in transitional milk, and 84.7 +/- 3.8, 76.1 +/- 3.8, and 290 +/- 10 micrograms/100 g in mature milk, respectively. No significant relationship was found between levels of Cu and Zn in milk and whether mothers had taken dietary supplements containing these elements. In addition, no significant correlations were found between maternal age, parity, or previous history of lactation and the elemental content of milk. Based on these data, it was estimated that fully breast-fed infants would receive approximately 0.11, 0.10, and 0.50 mg/kg per day of Cu, Fe, and Zn, respectively, during the neonatal period.

Circadian Rhythm↗