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Biomedical subjects

B Chapman

Publications and source records attributed to B Chapman.

At least 19 recordsLinked to original sources
PubMed1997

Selective sensitization to the psychosis-inducing effects of cocaine: a possible marker for addiction relapse vulnerability?

Patients in inpatient rehabilitation for uncomplicated cocaine dependence were asked whether, compared with the time of their first regular use, they could now identify changes in the effects of similar doses of cocaine. We asked about a spectrum of cocaine effects "then" and "now" and whether the same amount of drug caused effects to occur to about the same degree, less intensely (tolerance), or more intensely (sensitization). Nearly half our sample developed predominantly paranoid psychoses in the context of cocaine use. Sensitization was consistently linked only to psychosis-related cocaine effects. It has been proposed that mesolimbic dopaminergic sensitization might contribute to addiction severity. A preliminary followup of patients who were sensitized or nonsensitized to psychosis development suggests that rehospitalization for treatment of addiction may be more frequent in the sensitized group.

Adult↗
PubMed1997

The effect of tenidap on cytokines, acute-phase proteins, and virus load in human immunodeficiency virus (HIV)-infected patients: correlation between plasma HIV-1 RNA and proinflammatory cytokine levels.

Proinflammatory cytokines may be important in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) disease. Tenidap decreases interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF) production by peripheral blood mononuclear cells and decreases IL-6 plasma levels in rheumatoid arthritis patients. In this randomized double-blind study, 43 HIV-1-infected patients received tenidap (120 mg) or placebo daily for 6 weeks and then crossed over to the alternative therapy for an additional 6 weeks. Mean entry CD4 cell count was 140/microL. Analyses were performed on cytokines, acute-phase proteins, virus load, and CD4 cell counts. With the exception of small differences in plasma TNF levels, tenidap had no significant effect on these indices. Significant correlations of plasma IL-6 and TNF levels with HIV-1 RNA were noted. Six patients discontinued tenidap due to rash. The effects of tenidap in HIV-1 infection contrast to results in arthritis patients, in whom tenidap decreased plasma levels of IL-6 and acute-phase proteins.

Acute-Phase Proteins↗
PubMed1996

Development of orientation preference maps in ferret primary visual cortex.

The development of orientation preference maps was studied in ferret primary visual cortex using chronic optical imaging of intrinsic signals. The emergence and maturation of the maps were examined over time in single animals. The earliest age at which cortical domains selectively responsive to particular stimulus orientations were observed varied considerably between individuals, from postnatal day 31 to 36. In all cases, the earliest maps seen were low-contrast, with regions of orientation-specific activity that were difficult to distinguish from noise. These early maps matured over a period of several days into the high-contrast, patchy maps typical of adult animals. The structure of the orientation maps was remarkably constant over time. The indistinct features in the earliest maps were always patches of the same sizes and shapes and at the same locations as in the maps obtained in subsequent recording sessions. Details of the more mature maps, including the relative intensities of individual iso-orientation domains, were also constant from one recording session to another over periods of several weeks. The patterning of iso-orientation domains in ferret primary visual cortex thus is established early in development and remains stable over time, unaffected by either normal visual experience or the anatomical rearrangements of geniculocortical afferents into eye-specific domains.

Age Distribution↗
PubMed1996

Admission criteria for inpatient substance abuse/dependence rehabilitation: implications for managed care.

In view of recent trends toward the replacement of traditional inpatient rehabilitation programs with nonresidential services, we examined the extent to which patients currently admitted to inpatient rehabilitation for alcohol or drug abuse/dependence met published criteria suggesting a preferential need for inpatient or residential care. Over 90% of almost 300 veterans with a primary DSM-III R diagnosis of alcohol or substance abuse/dependence, admitted to six New York Metropolitan Area Veterans Administration Medical Centers for inpatient rehabilitation, met at least one criterion dimension considered indicative of a need for such services, with over two-thirds meeting two or more dimensions. These findings suggest a continuing need for initial primary inpatient or residential rehabilitation for such patients.

Adult↗
PubMed1995

Evolutionary reengineering of the phosphofructokinase active site: ARG-104 does not stabilize the transition state in 6-phosphofructo-2-kinase.

Arg-104 of the kinase domain of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase was mutated to alanine, the mutant enzyme expressed in E. coli with a T7 RNA polymerase-based expression system, and purified to homogeneity by Blue-Sepharose and Q-Sepharose chromatography. The mutant enzyme exhibited a 200-fold increase in Km for fructose-6-phosphate, no change in Km for ATP, and a 2-3-fold increase in catalytic rate. The results indicate that Arg-104, along with Arg-195, are the principal binding site residues for the 6-phosphate group of fructose-6-phosphate. In contrast to the corresponding residue in the related E. coli 6-phosphofructo-1-kinase, Arg-104 did not stabilize the transition state at pH 7-9. The Arg-104 mutation also decreased Fru-2,6-P2ase activity without affecting substrate inhibition, which suggests that this mutation affects the bisphosphatase active site conformation and/or substrate access to it.

Arginine↗
PubMed1995

High-dose pentoxifylline in patients with AIDS: inhibition of tumor necrosis factor production. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.

Tumor necrosis factor-alpha (TNF) may activate human immunodeficiency virus (HIV), antagonize zidovudine activity, and contribute to AIDS wasting syndrome. Pentoxifylline decreases TNF production. In cell culture, pentoxifylline decreases HIV replication and gene expression. Since an AIDS Clinical Trial Group study suggested that pentoxifylline (400 mg thrice daily) is safe in AIDS patients and decreases TNF mRNA levels in peripheral blood mononuclear cells (PBMC), a second cohort received 800 mg thrice daily for 8 weeks. During treatment, the median decrease in TNF production by PBMC cultured with 0.1 microgram/mL lipopolysaccharide (LPS) was 40%. The median change in TNF mRNA was a 34% decrease. Pentoxifylline did not affect HIV levels as detected by quantitative microculture or serum p24 antigen measurements, nor did it alter zidovudine pharmacokinetics. The most common toxicity was gastrointestinal. Pentoxifylline at dosages of less than thrice-daily 800 mg is well tolerated and may decrease TNF mRNA levels and LPS-induced TNF production.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Evidence for a causal relationship between the structure, size, and load of calcium pyrophosphate dihydrate crystals, and attacks of pseudogout.

OBJECTIVE: To investigate any relationship between the nature, size, and numbers of synovial fluid (SF) calcium pyrophosphate dihydrate (CPPD) crystals, and attacks of pseudogout. METHODS: Knee SF was aspirated from nine selected patients, first during an attack of pseudogout (acute sample) and again later when the attack had subsided (interval sample). CPPD crystals were extracted, weighed, examined by high resolution transmission electron microscopy (HRTEM), and characterised by size and crystal habit (monoclinic or triclinic). Structural analysis was carried out by x ray powder diffraction (XRD) and the proportions of monoclinic to triclinic CPPD were estimated from densitometric measurements of selected key reflections. RESULTS: The mean crystal size, by HRTEM, indicated that the crystals in the acute sample were larger than those in the interval sample. The ratio of monoclinic to triclinic CPPD, whether estimated from their morphological appearance by HRTEM, or from XRD, was greater in the acute than in the interval sample in all nine patients. The total amount of extracted mineral varied, but in every patient the concentration of CPPD per ml of fluid, and the total mineral per joint, were greater in the acute sample than in the interval sample. CONCLUSION: In this highly selected group of patients, the large numbers of CPPD crystals associated with attacks of pseudogout included a greater proportion of monoclinic crystals, and larger crystals, than those present when inflammation had subsided. A special, phlogistic population of crystals may exist, originating in different joint tissues, or cleared in a different manner, than the more common populations of smaller crystals with a greater proportion of triclinic CPPD, seen in chronic disease.

Acute Disease↗
PubMed1994

Submicroscopic crystals in osteoarthritic synovial fluids.

OBJECTIVES: To investigate the hypothesis that synovial fluid (SF) from patients with osteoarthritis (OA) may contain calcium phosphate crystals that are either too small, or too few in number to be identified by conventional light microscopy techniques. METHODS: Twelve SF from 11 patients with established knee OA, five SF from patients with rheumatoid arthritis (RA), and two control samples of SF from patients with pseudogout were subjected to an enzyme/hypochlorite extraction procedure. The patients with OA and RA had no radiographic evidence of chondrocalcinosis, or SF crystals on polarised light microscopy. Extracted material was examined and analysed by analytical electron microscopy (AEM) and x ray powder diffraction (XRD). RESULTS: Mineral was found in 11 of 12 OA samples, ranging from 2-120 micrograms/ml SF. Analytical electron microscopy revealed calcium pyrophosphate dihydrate (CPPD) crystals in five (confirmed by XRD in three) and basic calcium phosphates (BCP) in eight (five on XRD). Two samples with confirmed CPPD contained some rods with a mean length below 100 nm. The majority of BCP clusters were also less than 100 nm in diameter. BCP was detected in 1/5 RA samples. Control samples contained CPPD crystals of the expected size range of 0.42-17.9 microns. CONCLUSIONS: The data indicate that many OA SF may contain CPPD or BCP crystals which are too small or too few in number to be identified by conventional techniques. Crystal deposition is not an 'on-off' phenomenon in OA.

Aged↗
PubMed1993

Nonaffinity purification of recombinant gp120 for use in AIDS vaccine development.

The gene encoding the major envelope glycoprotein of the HIV-SF2 isolate was engineered for the secretion of recombinant gp120 (rgp120SF2) from permanent Chinese hamster ovary (CHO) cell lines. Cellular production methods were scaled up and a method for purification of the secreted glycoprotein was devised. Mild purification conditions were selected in order to preserve the native structure of the protein. rgp120SF2 exhibits a molecular weight of 120 kDa in reduced or nonreduced SDS gels; thus the polypeptide chain is intact. Deglycosylated rgp120SF2 has the predicted molecular weight of the polypeptide backbone, 54 kDa. Gel-filtration HPLC in a nondenaturing buffer at neutral pH yields a molecular weight estimate of approximately 120 kDa. Purified rgp120 closely resembles authentic viral gp120 by several physical, chemical, and immunochemical tests. rgp120SF2 reacts strongly with human HIV-positive sera, monoclonal antibodies reactive with HIV-SF2 and HIV-MN viral envelope, and a human virus-neutralizing monoclonal antibody that maps to a conserved discontinuous epitope on HIV-1 gp120. Purified rgp120SF2 forms a 1:1 molecular complex with soluble recombinant human CD4 (rCD4) receptor, as demonstrated by gel-filtration HPLC; binding is high affinity (Kd approximately 2 x 10(-9) M).

AIDS Vaccines↗
PubMed1993

Pentoxifylline decreases tumor necrosis factor expression and serum triglycerides in people with AIDS. NIAID AIDS Clinical Trials Group.

Tumor necrosis factor-alpha (TNF)-cachectin increases the expression of the human immunodeficiency virus (HIV), reverses the therapeutic efficacy of zidovudine (ZDV), and may contribute to the wasting syndrome. Pentoxifylline (Trental) decreases TNF activity; in cell culture, it decreases HIV replication and down-regulates expression of the HIV long terminal repeat (LTR). Therefore, pentoxifylline was administered to 25 patients with advanced AIDS in this AIDS Clinical Trial Group study (ACTG #160), the goal of which was to investigate the ability of the drug to decrease TNF expression and HIV replication in this patient population. One patient discontinued drug treatment because of toxicity. Data were analyzed on the 17 patients who completed the 8-week study treatment with pentoxifylline, 400 mg, thrice daily. The median pretreatment CD4+ lymphocyte count was 32 cells/mm3. Fasting serum triglycerides, which have previously been shown to correlate with levels of interferon-alpha and/or TNF, fell on average by 66 mg/dl (p = 0.06). TNF mRNA levels in peripheral blood mononuclear cells fell in 10 of 16 patients (p = 0.02). HIV load decreased and increased significantly in four and one patients, respectively, but did not change in the group as a whole. This study demonstrates the safety of pentoxifylline in AIDS patients and its ability to decrease triglycerides and TNF mRNA levels.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Development of orientation selectivity in ferret visual cortex and effects of deprivation.

The orientation selectivity of cells in ferret primary visual cortex was studied during normal development and in animals deprived of vision or of visual cortical activity. In normal animals from the age when visual responses were first recorded (postnatal day 23) through postnatal week 5, only about 25% of cells showed orientation-selective responses. By postnatal week 7, cortical responses had matured to an adult-like state, with approximately 75% of cells clearly selective for orientation. This development of orientation selectivity was not merely a reflection of the development of cortical cell responsiveness: at all ages studied, there was no correlation between responsiveness and selectivity. Infusion of TTX into visual cortex to silence neuronal activity completely blocked the maturation of orientation selectivity. Visual deprivation by bilateral lid suture impaired but did not completely block the normal development of orientation selectivity. We conclude that the maturation of orientation-selective responses in ferret primary visual cortex requires cortical neuronal activity, and that normal development requires visually driven activity.

Animals↗
PubMed1992

Expression of a cytomegalovirus IE-1-factor VIII cDNA hybrid gene in transgenic mice.

A construct containing the 5' end of the human cytomegalovirus major immediate early gene fused to the human coagulation factor VIII cDNA was used to produce transgenic mice. Two out of five transgenic lines transcribed the construct. The expression was consistently seen in a limited number of tissues and was highest in muscle tissues. This is in contrast to the almost ubiquitous activity demonstrated in earlier studies with the IE-1 enhancer/promoter. Human factor VIII protein was detected immunochemically in muscle tissues at levels several times higher than in human plasma.

Animals↗
PubMed1992

Diencephalic idiopathic gliosis: an unusual hypothalamic syndrome of dermopathy, diarrhea and growth arrest.

This case report of a 16-year-old girl describes the association of chronic diarrhea and lower limb dermopathy with an unusual and widespread gliosis within hypothalamic and other diencephalic structures. This syndrome to our knowledge has not been previously reported. Hypothalamic disease was suggested during life by examination findings of sustained hypothermia, altered sleep-wake cycles and abnormal cortisol diurnal rhythms. Profound growth arrest from the age of 8 yr (growth velocity < 1.4cm/yr) despite normal levels of growth hormone and response to physiological stimuli were additional unusual features. Autopsy after sudden death at 16 yr showed extensive gliosis in hypothalamic and adjacent diencephalic structures with proportionately little neuronal loss--suggesting an unidentified stimulus to glial proliferation. In the absence of evidence of other organ dysfunction it is suggested that dermopathy and chronic diarrhea in this case may have an autonomic basis. The impaired tissue response to growth hormone could be due to chronic hypothermia or involvement of some other (unidentified) hypothalamic factor regulating growth velocity.

Adolescent↗
PubMed1992

Origin of orientation tuning in the visual cortex.

The results of recent experiments have thrown new light on the neuronal connections underlying orientation-selective responses in the primary visual cortex of adult animals. The pattern of afferent input from the lateral geniculate nucleus to the cortex appears to be specific for orientation, while intracortical inhibitory connections appear to be non-specific in this respect. Experimental and theoretical studies have suggested that the development of cortical cell orientation tuning is an activity-dependent process.

Animals↗
PubMed1991

Induction of specific storage organelles by von Willebrand factor propolypeptide.

Endothelial cells store the multimeric adhesive glycoprotein von Willebrand factor (vWf), which promotes the formation of a platelet plug at the site of vessel injury. To investigate the packaging of vWf into the granules called Weibel-Palade bodies, we expressed pro-vWf cDNA and cDNA lacking the prosequence in a variety of cell lines. Storage granules formed only in cells that contain a regulated pathway of secretion. Furthermore, packaging required the prosequence. Pro-vWf, lacking the C-terminal region involved in interchain disulfide bonding, formed granules. We conclude that the signal for storage is universal in that an adhesive glycoprotein can be stored by a hormone-secreting cell; the storage of vWf is independent of its covalent multimeric structure; the unusual rod shape of Weibel-Palade bodies is due to vWf; and the vWf propolypeptide is necessary for the formation of vWf storage granules.

Animals↗
PubMed1991

Neutrophil activation by Helicobacter pylori.

Helicobacter pylori infection of the stomach is accompanied by a persistent polymorphonuclear leukocyte (PMNL) infiltrate of the mucosa. The aim of this work was to study the activation of human PMNL by substances produced by H pylori. Filtered H pylori conditioned media stimulated a significant PMNL oxidative burst (p less than 0.002). This was equal to 26% of the maximal response stimulated by the PMNL chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 mumol/l). The response to FMLP was prolonged by the combined presence of complement inactivated human anti-H pylori plasma and conditioned medium (p less than 0.002). High pressure liquid chromatography of an extract of conditioned medium showed a fraction that stimulated PMNL, eluted, and antigenically cross reacted with FMLP. Washed H pylori cells, and those opsonised with complement inactivated human anti-H pylori plasma, did not induce a significant oxidative burst. Opsonized H pylori, however, prolonged the oxidative burst induced by FMLP (p less than 0.02). In conclusion, H pylori synthesizes and secretes a substance, probably FMLP, that may account for the PMNL accumulation that accompanies H pylori infections. Immune complexes composed of H pylori antigen and specific antibody potentiate the PMNL oxidative burst. This combination of H pylori derived products, and host PMNL and antibodies, may be involved in the mucosal damage observed in H pylori associated gastritis.

Antibodies, Bacterial↗