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J Chapman

Publications and source records attributed to J Chapman.

At least 199 records · Page 11Linked to original sources
PubMed1997

Farnesol inhibits L-type Ca2+ channels in vascular smooth muscle cells.

Earlier experiments with animal and human arteries have shown that farnesol, a natural 15-carbon (C15) isoprenoid, is an inhibitor of vasoconstriction (Roullet, J.-B., Xue, H., Chapman, J., McDougal, P., Roullet, C. M., and McCarron, D. A. (1996) J. Clin. Invest. 97, 2384-2390). We report here that farnesol reduced KCl- and norepinephrine-dependent cytosolic Ca2+ transients in fura-2-loaded intact arteries. An effect on Ca2+ signaling was also observed in cultured aortic smooth muscle cells (A10 cells). In these cells, farnesol reduced KCl-induced [Ca2+]i transients and mimicked the inhibitory effect of Ca2+-free medium on the [Ca2+]i response to both 12,13-phorbol myristate acetate, a protein kinase C activator, and thapsigargin, a specific endoplasmic reticulum ATPase inhibitor. Perforated patch-clamp experiments further showed in two vascular smooth muscle cell lines (A10 and A7r5), a reversible, dose-dependent inhibitory effect of farnesol on L-type Ca2+ currents (IC50 = 2.2 microM). Shorter (C10, geraniol) and longer (C20, geranylgeraniol) isoprenols were inactive. L-type Ca2+ channel blockade also occurred under tight (gigaohm) seal configuration using cell-attached, single-channel analysis, thus suggesting a possible action of farnesol from within the intracellular space. We finally demonstrated that farnesol did not affect Ca2+-sensitive pathways implicated in smooth muscle contraction, as tested with alpha-toxin permeabilized arteries. Altogether, our results indicate that farnesol is an inhibitor of vascular smooth muscle Ca2+ signaling with plasma membrane Ca2+ channel blocker properties. The data have implications for the endogenous and pharmacological regulation of vascular tone by farnesol or farnesol analogues.

Animals↗
PubMed1997

Tumour growth modifies intravascular polyamine transport by plasma lipoproteins in the mouse.

Polyamines are polycationic compounds which are implicated in cell division and tumor growth. We have evaluated the potential role of plasma lipoproteins in the transport of major polyamines, spermine, spermidine and putrescine, and the effect of tumor growth on such transport. Plasmas of healthy male BL6/DBA2 mice and of mice bearing Lewis lung carcinoma (3LL) were fractionated by isopycnic density gradient ultracentrifugation, and polyamine content determined in lipoprotein fractions. Spermidine was the most abundant polyamine in the lipoproteins of both control and tumor-bearing mice and was principally associated with HDL (d: 1.046-1.136 g/ml); approx. 40% of total plasma polyamines was lipoprotein-associated in control mice and 60% in cancerous mice. Only minor amounts were transported by LDL (< 10% of total lipoprotein-associated polyamines), while VLDL were devoid of these substances. Marked elevations of circulating levels of LDL were found in 3LL grafted mice: in these particles however, the contents of spermidine and spermine were significantly reduced. A preferential uptake of polyamines by red blood cells could in part explain this marked reduction of LDL polyamine content, but the consequence of this reduction on the net electrical charge and biochemical function of LDL remains unknown. Elevations of plasma LDL and HDL levels in 3LL-grafted mice underlie the finding that only minor modification was detected in the putrescine content of these particles. However, it is evident that elevated total amounts of putrescine were present in the plasma of such animals. Finally, the density profile of polyamines was modified in cancerous mice in which a shift to transport in lighter apo.AI-containing HDL particles was observed for spermidine; an even more marked shift was found for spermine. In conclusion, our data demonstrate that HDL particles constitute the major plasma vehicle for polyamine transport in both control and in tumor-bearing mice.

Animals↗
PubMed1997

Simultaneous pancreas and kidney transplant rejection: separate or synchronous events?

The results of simultaneous pancreas and kidney transplantation (SPK) cannot be matched by pancreas transplantation alone (PTA), in part because an independent diagnosis of pancreas graft rejection remains difficult. The relationship between rejection of the pancreas and rejection of the kidney is poorly understood, and it is not known whether simultaneous transplantation of both organs confers true protection to either graft. To study these questions, reliable canine allotransplant models of kidney transplantation alone (KTA), PTA, and SPK were established. Sixty-seven mongrel dogs received KTA (n=21), PTA (n=23), or SPK (n=23) with either no immunosuppression, low-dose cyclosporine (CsA)-based immunosuppression, or high-dose CsA-based immunosuppression. Needle core biopsy (NCB) and fine needle aspiration biopsy (FNAB) were performed at 0, 2, 4, 7, 9, 11, 14, 21, and 30 days or at the time of graft failure. Pancreas and kidney graft survival after SPK was significantly shorter in dogs given low-dose CsA than in dogs given high-dose CsA (pancreas, P<0.04; kidney, P<0.03). Concurrent NCBs and FNABs were performed on 227 occasions in pancreas grafts and 229 occasions in kidney grafts. The time to initial evidence of rejection by NCB was not different in any immunosuppressed group. Synchronous rejection occurred in 73% of immunosuppressed SPK biopsies. Kidney-only rejection occurred in 23% of biopsies and pancreas-only rejection occurred in only 3% after SPK. All markers of pancreas graft rejection were poor, with the most sensitive being NCB of the simultaneously transplanted kidney. In summary, recipients of SPK required more immunosuppression than recipients of PTA, and improved PTA survival should be achievable with more sensitive markers of rejection. Markers of kidney rejection were the most sensitive indicators of pancreas rejection, and independent pancreas rejection was uncommon after SPK.

Animals↗
PubMed1997

Pathophysiological implication of the structural domains of lipoprotein(a).

Numerous epidemiological studies have shown that lipoprotein(a) (Lp(a)) is an independent risk factor for the premature development of cardiovascular disease. In spite of such evidence, the structural and functional features of this atherogenic, cholesterol-rich particle are not clearly understood. We have demonstrated the presence of two distinct structural domains in apolipoprotein(a) (apo(a)), which are linked by a flexible and accessible region located between kringles 4-4 and 4-5. We have isolated the Lp(a) particle following removal of the N-terminal domain by proteolytic cleavage; the residual particle, containing the C-terminal domain (comprising the region from Kr 4-5 to the protease domain), is linked to apo B-100 by disulphide linkage, and is termed 'mini-Lp(a)'. Mini-Lp(a) exhibited the same binding affinity to fibrin as the corresponding Lp(a). This finding indicated that the kringles responsible for fibrin binding are restricted to Kr 4-5 to Kr 4-10, an observation consistent with the failure of the N-terminal domain to bind to fibrin. N-terminal fragments of apo(a) have been detected in the urine of normal subjects, thereby indicating that part of the catabolism of Lp(a), which is largely indeterminate, could occur via the renal route.

Animals↗
PubMed1997

Examination of four 123I-labeled piperidine-based sigma receptor ligands as potential melanoma imaging agents: initial studies in mouse tumor models.

The development of sigma (sigma) receptor radioligands has become the focus of research over the past few years due to their potential uses in nuclear medicine. It has been shown that a wide variety of human tumor cell lines express sigma receptors, including malignant melanoma and tumors of the colon, lung, brain, breast and testes. To provide potential probes for the in vivo SPECT examination of sigma receptor densities, we have synthesized a series of halogenated 4-(phenoxymethyl)piperidines and related compounds as high affinity sigma receptor ligands. Four of these have been labeled with I-123 and evaluated in vivo in mouse tumor models. All four radioligands were synthesized no-carrier-added using oxidative radioiododestannylation methods and specific activities > 74,000 MBq/mumol were obtained. Radiochemical yields were 55-83% EOS and radiochemical purities were > 98%. All four tracers were initially screened in vivo using distribution studies in nude mice with B16 melanoma tumors (8-12 mm diameter in the flank). In all four studies, high uptake (up to 0.90 +/- 0.42 %ID, 12.99 +/- 4.28 %ID/g at 48 h) and excellent retention of radioactivity in tumor tissues was exhibited for as long as 48 h post-injection (PI). In the B16 melanoma model, the most promising results were obtained with [123I]-1-(2-hydroxyethyl)-4-(iodophenoxymethyl)piperidine (123I-3), for which tumor/tissue ratios were significantly > 1.0 by 4 h PI for most organs and increased thereafter. Tumor/tissue ratios at 48 h were as follows: blood, 68.4; muscle 31.7; brain, 7.4; lung, 6.3; liver, 1.3. In subsequent studies, 123I-3 was evaluated in nude mice with A375 human malignant melanoma. As in the B16 model, high uptake and prolonged retention of radioactivity in tumor tissues was noted. These results indicate that 123I-3 shows promise as a SPECT ligand for the detection of malignant melanoma.

Animals↗
PubMed1997

The incorporation of mannoproteins in the cell wall of S. cerevisiae and filamentous Ascomycetes.

In yeast, glucanase extractable cell wall proteins are anchored to the plasma membrane at an intermediate stage in their biogenesis via a glycosylphosphatidylinositol (GPI) moiety before they become anchored to the wall glucan via a beta 1,6-glucan linkage. The mechanism of the membrane processing step of cell wall proteins is not known. Here, we report that Ascomycete filamentous fungi involved in food spoilage such as Aspergillus, Paecilomyces and Penicillium, also contain GPI membrane-anchored proteins some of which are processed by an endogenous phospholipase C activity. Furthermore, similar to the situation in yeast, their cell walls contain mannoproteins which are linked to the glucan backbone through a beta 1,6-glucan linkage. Interestingly, one mould which contains a significant amount of non covalently linked beta 1,6-glucosylated cell wall proteins, is much more sensitive towards beta 1,3-glucanases and membrane perturbing peptides than the others.

Ascomycota↗
PubMed1997

Magical ideation and social anhedonia as predictors of psychosis proneness: a partial replication.

The authors compared college students identified by high scores on the Magical Ideation Scale (M. Eckblad & L. J. Chapman, 1983) and the Revised Social Anhedonia Scale (MagSoc; n = 28; M. Eckblad, L. J. Chapman, J. P. Chapman, & M. Mishlove, 1982) with control participants (n = 20) at a 10-year follow-up assessment in an attempt to replicate L. J. Chapman, J. P. Chapman, T. R. Kwapil, M. Eckblad, and M. C. Zinser's (1994) report of heightened psychosis proneness in MagSoc individuals. The MagSoc group exceeded the control group on severity of psychotic-like experiences; ratings of schizotypal, paranoid, and borderline personality disorder symptoms; and rates of mood and substance use disorders. Two of the MagSoc participants but none of the control participants developed psychosis during the follow-up period (a nonsignificant difference). Consistent with L. J. Chapman et al.'s findings, the groups did not differ on rates of personality disorders or relatives with psychosis.

Adult↗
PubMed1997

Interlaboratory variation in the detection of clinically significant alloantibodies against human platelet alloantigens.

This report describes the results of eight workshop exercises which were designed to test the proficiency of laboratories in the detection of antibodies to human platelet antigens (HPA). Detection of the most clinically significant alloantibody, anti-HPA-1a, is adequate. However, despite improvements in consistency of test results between laboratories over the last 3 years, there is still a high probability that clinically significant antibodies against other HPA alloantigens will not be detected.

Antigens, Human Platelet↗
PubMed1997

Report on the second international granulocyte serology workshop.

BACKGROUND: The methods of granulocyte antibody and antigen detection have improved considerably since the First International Granulocyte Serology Workshop. STUDY DESIGN AND METHODS: Thirteen laboratories participated in the Second International Granulocyte Serology Workshop. The study was designed to meet five goals: 1) establishment of antigen-typed granulocyte panels, 2) determination of the proficiency of granulocyte antibody detection by laboratory and by technique, 3) identification of granulocyte antibodies present in uncharacterized sera, 4) genotyping of NA antigens by DNA-based techniques, and 5) collection and exchange of information to standardize granulocyte antibody screening. RESULTS: NA1-, NA2- and NB1-specific antibodies were detected by more than two-thirds of the participants with the granulocyte immunofluorescence test (GIFT) but by fewer than two-thirds with the granulocyte agglutination test (GAT). The determination of the NB2-, 5b-, and Fc gamma RIIIb-specific antibodies was the most problematic. Ninety percent of the participants were not able to identify NB2 antibodies in sera with suspected NB2 specificity. The 5b antibodies were only detected by laboratories that performed the GAT. Isoantibodies to Fc gamma RIIIb were identified when the monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA) assay or an Fc gamma RIIIb-deficient panel cell was available. In 4 of 11 uncharacterized sera, the presence of NA1, NA2, and Fc gamma RIIIb antibodies could be confirmed by the MAIGA assay. In polymerase chain reaction with sequence-specific primers (PCR-SSP), the NA genotypes of all DNA samples were correctly determined. CONCLUSION: A combination of the GIFT and GAT is still the best means of antibody detection. The MAIGA assay allows identification of isoantibodies to Fc gamma RIIIb or alloantibodies to NA antigens. The NA genotype can be reliably determined by PCR-SSP. Cell panels should cover NA1, NA2, NB1, 5b, and, if possible, SH.

Antigens, CD↗
PubMed1997

Clinical, radiographic, and pathologic features of medical calcific sclerosis in the breast.

Medial calcific sclerosis (MCS), a nonocclusive calcification of the media of small to medium-sized muscular arteries, may occur in the breast. To ascertain whether MCS causes difficulty with mammographic interpretation of breast calcifications and to determine its clinical and pathologic associations, we reviewed the records and biopsy specimens from 62 patients who had had screening mammography and breast biopsy, lumpectomy, or mastectomy. Ten specimens from 7 patients showed MCS. Average age of patients without MCS was 48.8 years, and that of the 7 patients with MCS was 61.3 years. Microcalcifications were found in 25 of 62 mammograms (34%). Of the 7 patients with MCS, 2 had hypertension, 1 diabetes mellitus, 2 diabetes mellitus and hypertension, and 2 neither hypertension nor diabetes mellitus. In 5 specimens, calcification only was associated with MCS. In 2 of these specimens, the mammographic calcifications were thought to be suggestive of malignancy on the basis of clustering and spiculation. One of the 2 was benign on histopathology; the other was malignant. Overall, carcinoma was identified in 3 of 7 patients with MCS (compared with 11 of 55 patients without MCS) and in 2 of 5 specimens (2 patients) with mammary MCS as the only type of calcification. The mammographic appearance of the microcalcification in MCS may suggest malignancy.

Adult↗
PubMed1997

Antenatal corticosteroid prescribing: setting standards of care.

OBJECTIVE: Despite widespread recognition that prenatal administration of corticosteroids dramatically reduces perinatal mortality and morbidity, clinical practice in this area remains less than ideal. We therefore reviewed our practice to identify reasons for this and to determine attainable standards of care. DESIGN: Retrospective case record review. SETTING: Level three maternity unit in Edinburgh, UK. POPULATION: All women admitted at gestations of 24 to 34 weeks and 6 days inclusive, and all women receiving corticosteroids in one institution, over a 10-month period. MAIN OUTCOME MEASURES: The number and clinical features of women delivering before and after 35 weeks of pregnancy who had received corticosteroids. RESULTS: Seven hundred and two women were admitted during the study period; case records were available for 688 of these. One hundred and ninety-two women (28%) delivered before 35 weeks of gestation, of whom 123 (64%) had received dexamethasone. Of 69 women who received no steroids 30 (43%) were in hospital for more than 24 hours before delivery. Overall, 29% of women receiving dexamethasone delivered after 35 weeks of gestation and 42 (24%) women treated with dexamethasone received more than one course. While the grade of admitting doctor did not affect prescribing, there were other significant differences that may help guide future practice. CONCLUSIONS: This study provides some guidance for optimising corticosteroid prescribing and for the development of clinical practice guidelines. Approximately 80% of women should be able to receive at least some corticosteroids prior to delivery before 35 completed weeks of pregnancy.

Delivery, Obstetric↗
PubMed1997

Serum amyloid A and high density lipoprotein participate in the acute phase response of Kawasaki disease.

In this study we report changes in HDL concentration and composition in acute and convalescent Kawasaki disease. Notable reductions in plasma HDL-cholesterol (0.54 +/- 0.2 mmol/L, normal level 0.7-1.81 mmol/L) and apolipoprotein A-I (apoA-I) (56 +/- 28 mg/dL, normal level 141 +/- 22 mg/dL) were observed in all 24 patients studied during the acute phase of Kawasaki disease. These changes were accompanied by the marked appearance of serum amyloid A (SAA) protein in the plasma, associated with HDL3-like lipoprotein particles. The distribution of apoA-I was analyzed in five patients and showed a significant increase in lipid-free apoA-I in the bottom fraction (28.8 +/- 4.1%, normal range 10-15%), suggesting displacement of apoA-I from the HDL particles by SAA. Within 2 wk after acute Kawasaki disease, levels of HDL-cholesterol and apoA-I returned to the normal range, and SAA disappeared from the plasma. The HDL of patients with Kawasaki disease was markedly enriched in triglyceride even in the absence of changes in total plasma triglyceride. The core composition of HDL returned to the normal range more slowly than the plasma HDL-cholesterol and apoA-I levels. This suggests that Kawasaki disease has a profound effect on the lipoprotein profile acutely and a more subtle sustained effect on the HDL composition. We interpret these changes as manifestations of the acute phase response in Kawasaki disease.

Acute-Phase Reaction↗
PubMed1996

Farnesyl analogues inhibit vasoconstriction in animal and human arteries.

Recent studies have suggested that nonsterol, mevalonate-derived metabolites are implicated in the control of vascular tone and blood pressure. Because of the metabolic importance of farnesyl pyrophosphate, a 15-carbon (C15) intermediate of the cholesterol pathway, the vasoactive properties of the farnesyl motif were investigated. Two farnesyl analogues were used: farnesol, the natural dephosphorylated form of farnesyl pyrophosphate, and N-acetyl-S-trans,trans-farnesyl-L-cysteine (AFC), a synthetic mimic of the carboxyl terminus of farnesylated proteins. Both compounds inhibited NE-induced vasoconstriction in rat aortic rings at micromolar concentration. Their action was rapid, dose dependent, and reversible. Shorter (C10) and longer (C20) isoprenols as well as N-acetyl-S-geranyl-L-cysteine (C10) did not inhibit the response to NE. In contrast, N-acetyl-S-geranylgeranyl-L-cysteine (C20), exhibited vasoactive properties similar to AFC. It was further demonstrated that AFC and farnesol inhibited KCl and NaF-induced contractions, suggesting a complex action on Ca2+ channels and G protein-dependent pathways. Finally, the effect of farnesol and AFC on the NE response was reproduced in human resistance arteries. In conclusion, mevalonate-derived farnesyl analogues are potent inhibitors of vasoconstriction. The study suggests that farnesyl cellular availability is an important determinant of vascular tone in animals and humans, and provides a basis for exploring farnesyl metabolism in humans with compromised vascular function as well as for using farnesyl analogues as regulators of arterial tone in vivo.

Animals↗
PubMed1996

Sphingomyelin-derived lipids differentially regulate the extracellular signal-regulated kinase 2 (ERK-2) and c-Jun N-terminal kinase (JNK) signal cascades in airway smooth muscle.

In ASM cells platelet-derived growth factor stimulates rapid transient sphingosine phosphate formation, the activation of extracellular signal-regulated kinase 2 (ERK-2), the phosphorylation of p70(56K), and a ninefold increase in DNA synthesis. In contrast, this growth factor fails to activate c-Jun N-terminal kinase (JNK). Based upon these findings, we have tested whether the sphingomyelin-derived sphingolipids play a role in growth factor signalling by assessing their effect on ERK-2, JNK, and p70(56K). We demonstrate that sphingosine phosphate induces the activation of ERK-2, is ineffective against JNK, and fails to induce the phosphorylation of p70(56K). The latter may explain why it is a poor mitogen when added directly to ASM cells. In contrast, sphingosine and cell-permeable ceramides elicit the prominent tyrosyl phosphorylation and activation of JNK, are poor stimulators of ERK-2, and do not induce the phosphorylation of p70(56K). Therefore, the specificity of signalling through either ERK-2 or JNK cascades may be determined by the rapid agonist-dependent interconversion of these sphingomyelin-derived lipids. This may also provide a dynamic mechanism that enables growth factors and cytokines to elicit pleiotropic cell responses, such as proliferation and cell survival. For instance, both ceramide and sphingosine will elicit growth arrest via activation of JNK, whereas sphingosine phosphate will potentiate growth-factor-stimulated DNA synthesis, a consequence of the activation of ERK-2, Furthermore, under certain conditions, sphingosine and ceramide stimulate cAMP formation, a negative modulator of cell growth, whereas sphingosine phosphate depresses cAMP, thereby enhancing its own growth-promoting properties. From these studies, it is evident that sphingosine phosphate displays a signalling profile that is consistent with it mediating part of the action of platelet-derived growth factor.

Animals↗
PubMed1996

General practitioners' management of acute back pain: a survey of reported practice compared with clinical guidelines.

OBJECTIVE: To compare general practitioners' reported management of acute back pain with 'evidence based' guidelines for its management. DESIGN: Confidential postal questionnaire. SETTING: One health district in the South and West region. SUBJECTS: 236 general practitioners; 166 (70%) responded. OUTCOME MEASURES: Examination routinely performed, 'danger' symptoms and signs warranting urgent referral, advice given, and satisfaction with management. RESULTS: A minority of general practitioners do not examine reflexes routinely (27%, 95% confidence interval 20% to 34%), and a majority do not examine routinely for muscle weakness or sensation. Although most would refer patients with danger signs, some would not seek urgent advice for saddle anaesthesia (6%, 3% to 11%), extensor plantar response (45%, 37% to 53%), or neurological signs at multiple levels (15%, 10% to 21%). A minority do not give advice about back exercises (42%, 34% to 49%), fitness (34%, 26% to 41%), or everyday activities. A minority performed manipulation (20%) or acupuncture (6%). One third rated their satisfaction with management of back pain as 4 out of 10 or less. CONCLUSIONS: The management of back pain by general practitioners does not match the guidelines, but there is little evidence from general practice for many of the recommendations, including routine examination, activity modification, educational advice, and back exercises. General practitioners need to be more aware of danger symptoms and of the benefits of early mobilisation and possibly of manipulation for persisting symptoms. Guidelines should reference each recommendation and discuss study methodology and the setting of evidence.

Acute Disease↗