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Biomedical subjects

J H Wilson

Publications and source records attributed to J H Wilson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Human allogeneic vascular rejection after arterial transplantation and peripheral lymphoid reconstitution in severe combined immunodeficient mice.

BACKGROUND: Interspecies differences create important shortcomings in existing animal models used to describe in vivo events responsible for allograft rejection. Alloimmune destruction of human dermal microvessels, histologically consistent with rejection, has been demonstrated in human skin-grafted severe combined immunodeficient (SCID) mice receiving allogeneic human peripheral blood mononuclear cells (PBMC). We have now documented human alloimmune injury in a vascularized, SCID-human arterial transplantation model. METHODS: Fresh human artery was used to replace the CB.17 SCID/beige mouse infrarenal aorta. Seven days later, 3x10(8) human PBMC were administered intraperitoneally, and lymphocyte engraftment was considered successful when circulating human CD3+ cells were later identified in peripheral blood. RESULTS: Forty-six of 49 (94%) mice undergoing transplantation survived, including 14 controls with arterial grafts receiving no PBMC. Twenty-eight of 32 mice demonstrated circulating human CD3+ cells, 14 days after PBMC administration. Animals were killed at 14, 21, or 28 days after receiving allogeneic PBMC, and arteries were recovered for histology and immunohistology. All 14 control mice had patent transplanted grafts with normal vascular histology and no lymphoid infiltration. Damage to transplanted arteries among lymphocyte-engrafted mice was apparent by 14 and 21 days in some animals, whereas 16 of 22 exhibited moderate to severe intimal, medial, and/or adventitial lymphocytic infiltration with intimal expansion by day 28. The infiltrate consisted of HLA-A, -B, -C+, and -DR+, human CD3+ cells, approximately equally distributed as CD4+ and CD8+ subsets. Some infiltrating lymphocytes were cytolytic cells as demonstrated by perforin staining. The endothelium of transplanted human arteries exhibited endothelialitis, and the endothelial cells stained intensely with anti-HLA-A, -B, -C and anti-HLA-DR antibodies. The expanded intima was predominantly smooth muscle cells, staining positively for smooth muscle alpha-actin, HLA-A, -B, -C and HLA-DR. Medial necrosis was not observed. CONCLUSION: The results provide evidence of alloimmune-mediated vascular rejection in this human arterial transplantation model.

Adult↗
PubMed1999

A population-based case-cohort study of drug-associated agranulocytosis.

BACKGROUND: Agranulocytosis is a life-threatening disorder, often caused by drugs. Incidences or risks of drug-induced agranulocytosis are not well known, since it is rare. METHODS: To determine the risk of drug-associated agranulocytosis as a reason for admission to Dutch hospitals, we performed a population-based case-cohort study. Hospital discharge data came from the Dutch Centre for Health Care Information, Utrecht, which contains data on all general and university hospitals in the Netherlands. The reference cohort consisted of all persons in the catchment area of the Pharmaco Morbidity Record Linkage System (PHARMO RLS) in the Netherlands, composing a population of approximately 220 000 to 484 000 persons from 1987 through 1990. All admissions during that period with agranulocytosis or related diagnoses were included in the study (n = 923). The potential causes of agranulocytosis were assessed in all cases classified as probable or possible agranulocytosis. RESULTS: Discharge summaries were received of 753 admissions, of which 678 contained enough information for analysis. Of the 678,108 were classified as "agranulocytosis probable" or as "agranulocytosis possible." In 75 of these 108 cases, agranulocytosis had been the reason for admission. Fifteen patients had used methimazole within 10 days before developing agranulocytosis; 2, carbimazole; 9, sulfasalazine; 8, sulfamethoxazole-trimethoprim; 4, clomipramine hydrochloride; and 2, dipyrone with analgesics, yielding adjusted relative risks of agranulocytosis of 114.8 (for thyroid inhibitors combined) (95% confidence interval [CI], 60.5-218.6), 74.6 (95% CI, 36.3-167.8), 25.1 (95% CI, 11.2-55.0),20.0 (95% CI, 6.1-57.6), and 26.4 (95% CI, 4.4-11.1), respectively. CONCLUSIONS: The highest relative risks were found for thyroid inhibitors, sulfamethoxazole-trimethoprim, sulfasalazine, clomipramine, and dipyrone combined with analgesics.

Adult↗
PubMed1999

Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families.

The Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder in which gastrointestinal hamartomatous polyposis, mucocutaneous pigmentation, and a predisposition for developing cancer are transmitted in an autosomal dominant fashion. The recently identified LKB1/STK11 gene located at chromosome 19p13.3 is mutated in a number of PJS pedigrees. We performed mutation analysis in 19, predominantly Dutch, PJS families. In 12 of these families, we identified LKB1/STK11 mutations, none of which has been described before. These 12 novel LKB1/STK11 mutations consist of one nonsense mutation, three frameshift deletions, three frameshift insertions, two acceptor splice site mutations, and three missense mutations. In addition, we detected four polymorphisms in LKB1/STK11. In the remaining seven PJS families, we found no apparent abnormalities of the LKB1/STK1I gene, which could reflect the existence of locus heterogeneity in PJS. None of the mutations occurred in more than one family, and a number were demonstrated to have arisen de novo. The diverse array of mutations found, the apparent high mutation rate, as well as the existence of a possible second PJS locus, renders diagnostic or predictive genetic testing in individual patients difficult, although future identification of additional mutations or even gene(s) will help in increasing the yield of direct mutation analysis.

AMP-Activated Protein Kinase Kinases↗
PubMed1999

Incorporation and washout of orally administered n-3 fatty acid ethyl esters in different plasma lipid fractions.

The aim of the present study was to quantify the incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids after oral administration of n-3 fatty acid ethyl esters, since little is known about the rate and pattern of incorporation into plasma lipid fractions. In addition, we aimed to obtain preliminary information regarding EPA half-life, which is needed to establish an optimal dosing schedule. Five healthy volunteers ingested two 8.5 g doses of n-3 fatty acid ethyl esters daily for 7 d, supplying 6.0 g EPA/d and 5.3 g DHA/d. The fatty acid compositions of plasma phospholipids (PL), cholesteryl esters (CE) and triacylglycerols (TAG) were determined during supplementation and during a washout period of 7 d. Half-lives of EPA and DHA were calculated. The proportion of EPA in PL showed a 15-fold increase after 7 d (P < 0.001), while DHA showed a smaller increase (P < 0.01). In CE, EPA also increased (P < 0.05), while DHA did not increase at all. Remarkably, incorporation of DHA into TAG was even higher than that of EPA. Half-life of EPA in PL ranged from 1.63 to 2.31 d (mean 1.97 (SE 0.15) d), whereas mean half-life of EPA in CE was 3.27 (SE 0.56) d. In three subjects, washout of EPA and DHA from TAG seemed to follow a bi-exponential pattern, with a short half-life (< 1 d) in the initial phase and a half-life of several days in the second phase. In conclusion, EPA ethyl esters are rapidly incorporated into plasma lipids, especially into PL. The relatively long half-life of EPA in plasma would permit a dosing schedule with intervals of > or = 12 h in supplementation studies.

Adult↗
PubMed1999

Peutz-Jeghers syndrome: risks of a hereditary condition.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal-dominant disorder characterized by hamartomatous polyposis of the gastrointestinal tract and melanin pigmentation of the skin and mucous membranes. We review the clinical features of PJS with special emphasis on the risks for its gene carriers. METHODS: Review of the literature. RESULTS: Risks imposed by the presence of polyps in PJS patients include surgical emergencies like small bowel intussusception, and chronic or acute bleeding from the polyps. As the polyps in PJS are hamartomas, the disease had in the past always been thought not to have malignant potential. However, more and more reports suggest an association of PJS with both gastrointestinal and non-gastrointestinal tumours. Whether these malignancies originate from the polyps is not clear, but the frequent occurrence of some rare extra-intestinal malignancies such as tumours of the ovary (sex cord tumours with annular tubules), cervix (adenoma malignum) and testis (Sertoli cell tumours) indicates a general susceptibility for the development of malignancies. The PJS gene, which was recently identified to encode for the serine threonine kinase STK11, is therefore thought to act as a tumour-suppressor gene. CONCLUSIONS: PJS gene carriers not only run risks of polyp-induced gastrointestinal complications, but also are at increased risk of developing cancer, both within and outside the gastrointestinal tract. As genetic identification of asymptomatic gene carriers in this relatively rare disorder becomes possible, surveillance and screening protocols need to be developed for PJS patients and their relatives.

AMP-Activated Protein Kinase Kinases↗
PubMed1999

Drug-associated acute pancreatitis: twenty-one years of spontaneous reporting in The Netherlands.

OBJECTIVE: Drugs are considered a rare cause of acute pancreatitis. We conducted a descriptive study to assess which drugs have been associated with acute pancreatitis in spontaneous adverse drug reaction reports in The Netherlands. METHODS: Our study is based on reports of drug-associated acute pancreatitis reported to the Netherlands Center for Monitoring of Adverse Reactions to Drugs and The Netherlands Pharmacovigilance Foundation LAREB between 1 January 1977 and 1 January 1998. We used an algorithm to validate the diagnosis and to assess the causal relationship between acute pancreatitis and use of the suspected drug. RESULTS: A total of 55 cases were available for review. We excluded 11 (20.0%) reports, as we could not confirm the diagnosis of acute pancreatitis. Another 10 (18%) cases were excluded, as the causal relationship with the suspected drug was unlikely. In the remaining 34 reports, acute pancreatitis was labeled as definite in 11 (32%) and as probable in 23 (68%). The age of the patients ranged from 17 to 84 yr with a median of 41; 24 (71%) patients were female. Of the 34 cases, 27 (79%) recovered, five (15%) died, and in two (6%) the outcome is unknown. Azathioprine, cimetidine, interferon-alpha, methyldopa, metronidazole, olsalazine, and oxyphenbutazon all had a definite causal relationship with acute pancreatitis. Doxycycline, enalapril, famotidine, ibuprofen, maprotiline, mesalazine, and sulindac had a probable causal relationship with acute pancreatitis. CONCLUSIONS: A variety of drugs was associated with acute pancreatitis in Dutch adverse drug reaction reports. Quantitative information about drug-induced pancreatitis is scanty. Epidemiological studies to assess the risk of drug-induced acute pancreas, therefore, are needed.

Acute Disease↗
PubMed1999

Adenosine triphosphate: established and potential clinical applications.

Adenosine 5'-triphosphate (ATP) is a purine nucleotide found in every cell of the human body. In addition to its well established role in cellular metabolism, extracellular ATP and its breakdown product adenosine, exert pronounced effects in a variety of biological processes including neurotransmission, muscle contraction, cardiac function, platelet function, vasodilatation and liver glycogen metabolism. These effects are mediated by both P1 and P2 receptors. A cascade of ectonucleotidases plays a role in the effective regulation of these processes and may also have a protective function by keeping extracellular ATP and adenosine levels within physiological limits. In recent years several clinical applications of ATP and adenosine have been reported. In anaesthesia, low dose adenosine reduced neuropathic pain, hyperalgesia and ischaemic pain to a similar degree as morphine or ketamine. Postoperative opioid use was reduced. During surgery, ATP and adenosine have been used to induce hypotension. In patients with haemorrhagic shock, increased survival was observed after ATP treatment. In cardiology, ATP has been shown to be a well tolerated and effective pulmonary vasodilator in patients with pulmonary hypertension. Bolus injections of ATP and adenosine are useful in the diagnosis and treatment of paroxysmal supraventricular tachycardias. Adenosine also allowed highly accurate diagnosis of coronary artery disease. In pulmonology, nucleotides in combination with a sodium channel blocker improved mucociliary clearance from the airways to near normal in patients with cystic fibrosis. In oncology, there are indications that ATP may inhibit weight loss and tumour growth in patients with advanced lung cancer. There are also indications of potentiating effects of cytostatics and protective effects against radiation tissue damage. Further controlled clinical trials are warranted to determine the full beneficial potential of ATP, adenosine and uridine 5'-triphosphate.

Adenosine Diphosphate↗
PubMed1999

The Alumni program: redefining continuity of care in psychiatry.

The Alumni Program is a novel approach to the continuing care and preventive treatment of clients with "chronic" mental illness. This approach demands a different conceptualization of outpatient psychiatric intervention. The infectious disease model has been deliberately replaced with a chronic illness model that more accurately reflects the course and natural history of psychiatric illness. The Alumni Program is similar to the approach employed with other chronic medical conditions like arthritis, asthma, or diabetes. The program has complementary roles for both specialty psychiatric clinicians and family practitioners. In addition, the program empowers clients and their families to play a key role in their own ongoing adaptation and adjustment to chronic illness while striving for optimal wellness.

Aftercare↗
PubMed1999

The family educator: a professional resource for families.

The family educator works with the client's family members to help in their understanding of their ill relative and to assist with managing the stress of the caregiver role. Families come to understand that they can join forces with the clinical team in helping their relative engage in a trial of treatment. Each treatment recommendation is explained to the family and decisions are arrived at by consensus through partnership meetings. Role modeling effective interaction approaches and providing assistance in generating alternative solutions to problematic situations are important functions of the family educator.

Family↗
PubMed1998

[Endoscopic treatment of Barrett esophagus].

The purpose of the treatment of Barrett epithelium in the distal oesophagus is to reduce or even eliminate the increased risk of malignant degeneration in it. This can be achieved by removing the Barrett epithelium, whether or not dysplastic, and to have it replaced by normal squamous epithelium. Drug treatment or surgical antireflux treatment of Barrett epithelium has hardly any effect on the length of the Barrett epithelium or on the occurrence of malignancy. Various forms of endoscopic ablative therapy (laser coagulation, multipolar electrocoagulation, photodynamic therapy and argon plasma coagulation), in combination with antireflux treatment enable removal of the Barrett epithelium with regeneration of squamous epithelium. However, islets of Barrett epithelium may be found beneath the regenerated squamous epithelium and there is also the possibility of malignant potential of pluripotent stem cells left behind in the oesophagus. Future studies will have to afford insight into long-term results, the costs, the side effects of the various methods of treatment and the quality of life of patients during and after treatment of the Barrett oesophagus.

Argon↗
PubMed1998

Triplex targets in the human rhodopsin gene.

We have explored the application of triplex technology to the human rhodopsin gene, which encodes a G-protein-linked receptor involved in the genetic disorder autosomal dominant retinitis pigmentosa (ADRP). Our results support the hypothesis that most human genes contain high-affinity triplex sites and further refine the rules governing identification and successful targeting of triplex-forming oligonucleotides (TFOs) to these sites. Using a computer search for sites 15 nucleotides in length and greater than 80% purine, we found 143 distinct sites in the rhodopsin gene and comparable numbers of sites in several other human genes. By applying more stringent criteria, we selected 17 potential target sites in the rhodopsin gene, screened them with a plasmid binding assay, and found 8 that bound TFOs with submicromolar affinity (Kd = 10(-)9-10(-)7 M). We compared purine (GA) and mixed (GT) TFOs at each site, and found that GA-TFOs consistently bound with higher affinity, and were less sensitive to pyrimidine interruptions in the target strand. High G-content favored high-affinity binding; only sites with >54% G-content bound TFOs with Kd </= 10(-)8 M.

Binding Sites↗
PubMed1998

5-Aminolaevulinic acid-induced protoporphyrin IX accumulation in tissues: pharmacokinetics after oral or intravenous administration.

UNLABELLED: In this study, the biodistribution of 5-aminolaevulinic acid (ALA) and accumulation of protoporphyrin IX (PpIX) in rats have been examined. Two groups of 21 WAG/Rij rats are given 200 mg/kg ALA orally or intravenously. Six rats serve as controls. At 1, 2, 3, 4, 6, 12 and 24 h after ALA administration, ALA and porphyrin concentrations are measured in 18 tissues and fluids. Liver enzymes and renal-function tests are measured to determine ALA toxicity. In both groups ALA concentration is highest in kidney, bladder and urine. After oral administration, high concentrations are also found in duodenal aspirate and jejunum. Mild, short-lasting elevation of creatinine is seen in both treatment groups. Porphyrins, especially PpIX, accumulate mainly in duodenal aspirate, jejunum, liver and kidney (> 10 nmol/g tissue), less in oesophagus, stomach, colon, spleen, bladder, heart, lung and nerve (2-10 nmol/g tissue), and only slightly in plasma, muscle, fat, skin and brain (< 2 nmol/g tissue). In situ synthesis of porphyrins rather than enterohepatic circulation contributes to the PpIX accumulation. Confocal laser scanning microscopy shows selective porphyrin fluorescence in epithelial layers. Peak levels and total production of porphyrins are equal after oral and intravenous ALA administration. IN CONCLUSION: administration of 200 mg/kg ALA results in accumulation of photosensitive concentrations of PpIX, 1 to 6 h after ALA administration, in all tissues except muscle, fat, skin and brain. Knowledge of the time-concentration relationship should be helpful in selecting dosages, routes of administration and timing of ALA photodynamic therapy.

Administration, Oral↗
PubMed1998

Type-II renal tubular acidosis and ventricular tachycardia in a horse.

A 14-year-old Arabian mare was admitted for lethargy, anorexia, and low fecal output. On the basis of laboratory, physical examination, and electrocardiographic findings, diagnoses of type-II renal tubular acidosis (RTA), impaction of the large colon, and ventricular tachycardia were made. Diagnosis of type-II RTA was based on measurement of a low fractional excretion value for potassium and fractional excretion value for sodium within the reference range. In contrast, horses with type-I RTA have high fractional excretion values for sodium and fractional excretion values for potassium within reference ranges. Treatment consisted of intravenous and oral administration of sodium bicarbonate, intravenous administration of fluids, and oral administration of mineral oil and docusate sodium. Acidosis improved, and ventricular tachycardia resolved with resolution of acidosis. Oral administration of bicarbonate was continued after discharge. The mare had several relapses, which were associated with anorexia and low intake of supplemental bicarbonate. The mare was found dead 2 months after discharge.

Acidosis, Renal Tubular↗
PubMed1998

The intermediate filament protein, vimentin, in the lens is a target for cross-linking by transglutaminase.

Mere addition of Ca2+ to a lens cortical homogenate (bovine) generates a series of products composed of a variety of high molecular weight vimentin species. The Ca2+-induced cross-linking of this cytoskeletal element seems to be mediated by the intrinsic transglutaminase of lens, because the reaction could be blocked at the monomeric state of vimentin by the inclusion of small synthetic substrates of the enzyme dansylcadaverine or dansyl-epsilon-aminocaproyl-Gln-Gln-Ile-Val. These compounds are known to compete against the Gln or Lys functionalities of proteins that would participate in forming the Nepsilon(gamma-glutamyl)lysine protein-to-protein cross-links. The cytosolic transglutaminase-catalyzed reactions could be reproduced with purified bovine lens vimentin and also with recombinant human vimentin preparations. Employing the latter system, we have titrated the transglutaminase-reactive sites of vimentin and, by sequencing the dansyl-tracer-labeled segments of the protein, we have shown that residues Gln453 and Gln460 served as acceptor functionalities and Lys97, Lys104, Lys294, and Lys439 as electron donor functionalities in vimentin. The transglutaminase-dependent reaction of this intermediate filament protein might influence the shape and plasticity of the fiber cells, and the enzyme-catalyzed cross-linking of vimentin, in conjunction with other lens constituents, may contribute to the process of cataract formation.

Amino Acid Sequence↗
PubMed1998

Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974-1994).

In this descriptive study, all 425 reports were included concerning drug-associated agranulocytosis as registered between 1974 and 1994 in the files of the Drug Safety Unit of the Dutch Inspectorate for Health Care. All reports were analysed as to the probability of agranulocytosis or neutropenia according to previously defined criteria. Subsequently, the causal relationship between exposure and outcome was assessed. It concerned 149 men and 271 women. One hundred and twelve reports were unclassifiable because age, gender, or total number of leukocytes at the time of reaction were unknown. In 100 reports agranulocytosis was probable, in 78 possible, in 8 reports neutropenia was probable, in 20 reports neutropenia was possible, and in 107 reports agranulocytosis or neutropenia were unlikely. In the 13 reports of probable agranulocytosis or neutropenia with a certain causal relationship, causative drugs were cimetidine, dipyrone, sulphasalazine, methyldopa, spironolactone, propylthiouracil (2), thiamazole, sulphamethoxazole with trimethoprim, gentamicin, a combination preparation containing aminophenazone, benzylpenicillin and indomethacin. The individual drugs most often reported to cause agranulocytosis or neutropenia were: dipyrone (19), mianserin (15), sulphasalazine (13), sulphamethoxazole with trimethoprim (11), the group of penicillins (9), cimetidine (8), the thiouracil derivatives (8), phenylbutazone (8), and penicillamine (8). Agranulocytosis is a serious and fairly frequently reported adverse reaction. The reporting system of the Drug Safety Unit can be used very well for signal generation concerning adverse reactions to drugs.

Adult↗
PubMed1998

Triplex-directed modification of genes and gene activity.

Oligonucleotides offer enormous potential for manipulating gene function in cells and, as such, constitute a promising new class of pharmaceutical agents. Oligonucleotides that form triple helices (triplexes) at specific DNA sequences in defined genes can be used to reduce transcription selectively, to introduce site-specific mutations or to stimulate gene-specific targeted recombination.

Animals↗
PubMed1998

Targeted recombination at the Chinese hamster APRT locus using insertion versus replacement vectors.

In this study, we have examined the effects of targeting vector configuration and site of vector linearization on the frequency of targeted recombination at the endogenous CHO APRT locus, and have analyzed the types and class distributions of APRT+ recombinants obtained in APRT targeting experiments employing uncut circular, insertion-type (ends-in), and replacement-type (ends-out) configurations of the same pAG7 targeting vector, including configurations produced by introduction of a double-strand break (DSB) at sites either within, or at the 5' or 3' boundaries of APRT targeting homology. Our results suggest that: 1) plasmid-chromosome targeted recombination in mammalian cells may not be stimulated to the same degree by a DSB in the targeting vector as by a DSB in the chromosomal target; 2) recombinant class distributions are highly dependent upon targeting vector configuration; and 3) one-sided invasion mechanisms may play a significant role in homologous recombination in mammalian cells.

Adenine Phosphoribosyltransferase↗