PubMed HealthSearch

Biomedical subjects

F Jones

Publications and source records attributed to F Jones.

At least 37 records · Page 2Linked to original sources

Involvement of arginine residues in the activation of calmodulin-dependent 3',5'-cyclic-nucleotide phosphodiesterase.

Pretreatment of an affinity-purified, brain calmodulin (CaM)-dependent phosphodiesterase (EC 3.1.4.17) with p-hydroxyphenylglyoxal (pHPG), a specific arginine-modifying reagent, resulted in a time-dependent loss in CaM-stimulated hydrolysis of cyclic AMP and cyclic GMP with no change in basal, CaM-independent activity. The loss in CaM-stimulated activity was preceded by a transient increase in CaM-dependent activity. Phenylglyoxal was 10-fold more effective than pHPG in promoting the loss of CaM-stimulated activity with a second-order rate constant of 13.3 M-1 min-1. Other arginine-modifying reagents, 1,2-cyclohexanedione and 2,3-butanedione, were not effective. The pHPG-modified enzyme was activated by 100 microM lysophosphatidylcholine to levels comparable to CaM-stimulated activity. The arginyl-modified enzyme was also activated by chymotrypsin and trypsin but not to the extent of the untreated enzyme stimulated with CaM. The presence of CaM during chemical modification with pHPG protected the enzyme from inactivation. Both the extent of activation and the amount of CaM necessary for 50% maximal activation were affected by pHPG treatment of the enzyme. The approximate number of modified arginines estimated by [7-14C]phenylglyoxal incorporation and amino acid analysis after complete inactivation of CaM stimulation was seven residues per catalytic subunit assuming enzyme homogeneity. The Stokes radius and sedimentation coefficient of the enzyme were unchanged by the modification. These results suggest that arginine residues are critical for functional interaction between phosphodiesterase and CaM and that controlled modification can selectively alter CaM-stimulated enzyme activity.

3',5'-Cyclic-AMP Phosphodiesterases

Role of cytoplasmic vacuoles in varicella-zoster virus glycoprotein trafficking and virion envelopment.

Varicella-zoster virus (VZV) encodes several glycoproteins which are present on both mature viral envelopes and the surfaces of infected cell membranes. Mechanisms of VZV glycoprotein transport and virion envelopment were investigated by both continuous radiolabeling and pulse-chase analyses with tritiated fucose in VZV-infected cells. We studied in detail the large cytoplasmic vacuoles which were present in infected cells but absent from uninfected cells. The specific activity in each subcellular compartment was defined by quantitative electron microscope autoradiography, using a cross-fire probability matrix analysis to more accurately assess the individual compartment demarcated by the silver grains. By these techniques, we documented a progression of activity originating in the Golgi apparatus and traveling through the post-Golgi region into virus-induced cytoplasmic vacuoles and finally to areas of the cellular membrane associated with the egress of viral particles. Significant amounts of radiolabel were not observed in the nucleus, and only low levels of radiolabel were associated with the cellular membrane not involved with the egress of viral particles. In addition, immunolabeling of Lowicryl-embedded VZV-infected cells demonstrated the presence of VZV glycoproteins within cytoplasmic vacuole membranes as well as on virion envelopes. These observations suggested that cytoplasmic vacuoles harbored VZV-specified glycoproteins and were also the predominant site of VZV virion envelopment within the infected cell. Neither enveloped nor unenveloped viral particles were observed within the Golgi apparatus itself.

Autoradiography

The effects of an anti-I-Ab antibody on murine host resistance to Listeria monocytogenes.

Infection with Listeria monocytogenes stimulates T cell proliferation and T cell-derived lymphokine production. The release of lymphokines, in turn, "activates" macrophages, enhancing their bactericidal capacity. Because prior studies suggest that I-A+ accessory cells play a critical role in this pathway, we assessed the effects of an anti-I-A antibody on the murine host resistance to listerial infection. To this end, we infused Listeria into control C57BL/6 mice (I-Ab haplotype) and mice of the same strain which had been pretreated 18 hr earlier with D3137 (a monoclonal IgG2a anti-I-Ab,d antibody). Preliminary studies demonstrated that this antibody can markedly inhibit antigen-induced proliferation of Listeria-dependent T cells in vitro and (at a dose of 1 mg/animal) can markedly reduce I-A expression on splenocytes in vivo. Even though D3137 pretreatment prevented the splenomegaly normally observed after Listeria infusion into mice, it protected animals infused with otherwise lethal concentrations of Listeria. Because antibody-treated animals had sevenfold fewer organisms in their spleens 18 hr after infection and 1000-fold fewer organisms than control animals 3 days after infection, improved survival resulted from an antibody-induced increase in the bactericidal capacity of the MPS. Protection was not noted when C1.18.4 (an IgG2a myeloma protein without known antibody activity) was infused into C57BL/6 mice or when D3137 was infused in B10.BR (I-Ak) mice. D3137 also protected (B10 X B10.BR)F1 mice (which are hybrids bearing I-Ab and I-Ak), suggesting that complete blockade of antigen presentation is not a prerequisite for its protective action. Further studies into the mechanism for these effects may provide new insights into the pathophysiology of MPS activation in response to immunologic challenge.

Animals

Attention, autonomic arousal, and personality in behaviorally disordered children.

This study assessed the construct validity of the Revised Behavior Problem Checklist (RBPC) by measuring attention, autonomic arousal, and personality in 40 behaviorally disordered children aged 7 to 15 years. Conduct Disorder and Socialized Aggression subscales were characterized by high Psychoticism, Impulsivity, and Lie personality scores, by lower heart rate levels, and by more errors on a continuous performance reaction-time task. Conversely, Attention Problems, Anxiety Withdrawal, and Motor Excess were characterized by greater variability in reaction times. Conduct Disorder alone was related to an external locus of control, while only Attention Problems was characterized by low scores on the WISC Freedom from Distraction factor. These differential relationships suggest (a) support for the construct validity of the RBPC, (b) that antisocial behavior and hyperactivity/attention deficits are dissociated disorders, and (c) that hyperactivity/attention deficits may be characterized by fluctuations in the allocation of attentional resources rather than a core structural deficit in attention.

Adolescent

Genetic analysis of spontaneous resistance to ampicillin in Neisseria gonorrhoeae.

Step-wise intrinsic resistance to ampicillin in Neisseria gonorrhoeae was analyzed genetically by DNA-mediated transformation experiments. A first-step ampicillin-resistant (Ampr1) mutant and a second-step ampicillin-resistant (Ampr2) mutant generated during sequential selection were used in these studies. Each selection step was accompanied by an approximate twofold increase in resistance. Four amp alleles were found to account for full resistance of the Ampr2 phenotype. All four amp alleles lie among a cluster of genes which code for ribosomal functions. This region has the map order rif str fus tet cam. First-step resistance was caused by two amp alleles, ampA2 and ampB1, neither of which independently caused detectable ampicillin resistance. Outcrossing of the ampA2 or the ampB1 mutation resulted in wild-type susceptibility to ampicillin. Mapping studies indicate that ampB1 lies between str and fus, whereas ampA2 lies to the right of cam. Second-step resistance required two mutations, ampC3 and ampD4, in addition to ampB1 and ampA2. Transformation of ampC3 to ampC3+ in an Ampr2 mutant resulted in the Ampr1 phenotype. Both ampC3 and ampD4 showed transformation linkage to rif and str. ampC3 was positioned at a site between rif and str. ampD4 apparently occupied a site, outside of the rif-str region, proximal to rif and distal to str. We postulate the gene order to be ampD rif ampC str ampB fus tet cam ampA.

Alleles

Subpopulations of B cells distinguished by cell surface expression of Ia antigens. Correlation of Ia and idiotype during activation by cloned Ia-restricted T cells.

We have investigated in vitro the induction of antibody responses to phosphorylcholine (PC) by cloned T helper (Th) cell lines. The cloned Th cells are antigen specific, in this case ovalbumin (OVA), self-Ia recognizing, and induce antibody secretion only if the hapten, PC, is physically linked to the carrier (OVA) molecule. The plaque-forming cell (PFC) response generated in the presence of cloned Th cells is idiotypically diverse with 5-40% of the secreting B cells bearing the TEPC-15 (T15) idiotype. The interaction of the cloned Th cells and unprimed B cells requires recognition of B cell surface Ia glycoproteins for all B cells activated to secrete anti-PC antibody, whether they be T15-bearing or not. More importantly, however, effective interaction between a cloned Th cell and a B cell is determined by the quantity of B cell surface Ia glycoproteins. Our results indicate that quantitative differences in B cell surface Ia antigens are directly related to B cell activation by the cloned Th cell. The high Ia density B cells are most easily activated by cloned Th cells, and these appear to be mainly non-T15-bearing. These data suggest that the failure of cloned Th cells to effectively activate T15-bearing B cells in vitro may be due to the lower relative Ia density of these B cells and therefore to their inability to interact effectively with cloned Ia-recognizing Th cells. These results imply that monoclonal T cells may distinguish between T15-bearing and non-T15-bearing B cells based on their Ia density.

Animals

A cloned, antigen-specific, Ia-restricted Lyt-1+,2- T cell with suppressive activity.

The correlation between cell surface antigen phenotype and function is one of the cornerstones of modern cellular and clinical immunology. It is based on the collective experience of many investigators examining populations of T cells. The availability of cloned lines of T cells now allows us to ask whether all cells sharing cell surface antigen phenotype are functionally equivalent. We have examined a large number of antigen-specific, self-Ia recognizing, cloned Lyt-1+,2- T cell lines for their ability to help B cells proliferate and secrete antibody in response to antigen. All of these lines induced antigen-specific, Ia-restricted B cell proliferation. One line did not induce antibody secretion. This line, indeed suppressed the plaque-forming cell response of B cells helped by any of the other cloned T cell lines tested. Suppression in this system had all the characteristics of classical T cell help, apart from the ultimate outcome. That is, the suppressor cell acted upon the B cell in a manner that was antigen-specific, Ia-restricted, and required hapten-carrier linkage. We interpret our results as supporting the basic paradigm of an association of cell surface antigen phenotype with function, with an important proviso. Not all Ly1, Ia-restricted T cells may be capable of helper function, and some in fact may be suppressive. Experimental conditions favoring the generation of such cells, or disease states in which such cells reside within the Ly1 or T4+ subset, may give rise to disparities between phenotype and function similar to that observed here at the clonal level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Syringomyelia as a sequel to traumatic paraplegia.

Ten cases of post-traumatic paraplegia are described in whom syringomyelia symptoms have supervened. Five patients have been operated upon after investigation. Operative results have been encouraging. A discussion of likely pathogenetic mechanisms is presented.

Adolescent

Predicting offspring vulnerability to psychopathology from parents' test data.

Interpretation of parents' psychological test data was used to predict vulnerability to psychopathology of male offspring ages 4, 7, and 10. Families were chosen for the study according to the previous psychiatric diagnosis of at least one parent. The prediction of procedure was styled after methods used in previous studies with adolescent and young adult offspring. Vulnerability was measured by a global rating score obtained from the Rochester Adaptive Behavior Inventory, a scale based on behavioral observations of the offspring's behavior. Evaluation of 11 families at each age level resulted in significantly accurate predictions at the 10-year-old level, but less than significantly accurate predictions at the 7- and 4-year-old levels. These findings have important implications for the family development of schizophrenia and related disorders.

Adult

Medication compliance in hyperactive children.

Medication compliance was studied over an 18-week period in 12 male children, ages 6 to 12 years, who were receiving medication for "hyperactivity." Subjects were randomly assigned to receive placebo (PB), d-amphetamine (AMP), and methylphenidate (MPH) for 6 weeks each in a triple-blind, crossover design. Urine samples were obtained weekly and assayed for MPH and AMP to assess compliance. Individual patient compliance varied from 0.00% to 100% (x = 67%) while taking MPH and from 20% to 83% (x = 60%) while taking AMP. The percent of patients compliant for a given week varied from 55% to 80% (x = 67%) when taking MPH and from 25% to 83% (x = 61%) when taking AMP. Significant positive noncompliance also occurred; ie, MPH was found in urine during the PB period in five of 12 individuals. Poor compliance in taking medication may explain, in part, the variable and conflicting results reported in many studies of the effect of medication on improving the behavior of hyperactive children.

Attention Deficit Disorder with Hyperactivity

The effects of hypophysectomy and continuous food restriction, begun at ages 70 and 400 days, on collagen aging, proteinuria, incidence of pathology and longevity in the male rat.

Hypophysectomy in young male Wistar rats aged 70 days, followed by cortisone acetate replacement therapy throughout life, retarded the rate of aging of tail tendon collagen fibres, inhibited the development of certain diseases of old age (renal disease, cardiac enlargement, hind limb paralysis, and various endocrine and non-endocrine tumors) and significantly prolonged the duration of life. Almost identical anti-aging effects were obtained by lowering the food intake of intact rats to that of hypophysectomized rats, from age 70 days until death. Hypophysectomy in middle age, at 400 days, even with cortisone acetate replacement therapy, produced a sharp increase in the mortality rate; the surviving rats exhibited significantly reduced aging of collagen fibres and of the kidney as measured by protein excretion. Food restriction begun at 400 days also inhibited renal aging, but had no demonstrable effect on collagen aging during the first 100 days. These studies suggest that procedures such as hypophysectomy and food restriction do not switch off an aging mechanism in youth but probably exert a continuing inhibitory influence on certain aging processes throughout life.

Aging

Parotid and whole-mouth secretion in response to viewing, handling, and sniffing food.

There was no significant change in flow rates of parotid saliva in nineteen of twenty subjects while they viewed photographs of lemons, or in fourteen of twenty subjects while they cut lemons in a glove box. Neither parotid nor whole-mouth secretion changed from baseline when subjects viewed fresh lemons and lemonade presented in a plastic box. Further, no significant changes in whole-mouth secretion rates were observed when subjects viewed photographs of two appetizing foods, or of fresh doughnuts in a plastic box, even though subjects knew they could eat the doughnuts after the experiment. In most cases, sniffing of the lemons or of the doughnuts resulted in increased flow rates. Subjects demonstrated large differences in their patterns of affective responses to full-strength and diluted lemon juice, which were independent of salivary flow. In the absence of olfactory or tactile stimulations, few subjects altered parotid or whole-mouth secretion rates in response to viewing food or photographs of food. A reevaluation of findings on 'psychic' stimulation of saliva may be in order to ascertain the role of olfactory, tactile, and even trigeminal clues in salivary response to food stimuli.

Citrates