Search PubMed⌕ Search

Biomedical subjects

J Fletcher

Publications and source records attributed to J Fletcher.

At least 217 records · Page 12Linked to original sources
PubMed1988

HLA-DR and DQ DNA polymorphisms in subjects of Asian Indian and white Caucasian origin.

There is a close correspondence between serologically defined DR types and DR beta chain restriction fragment length polymorphisms (RFLPs). There is also an association between DR types and DQ alpha and DQ beta RFLPs because of linkage disequilibrium. We present the results of an analysis of DR beta, DQ alpha and DQ beta RFLPs in Asian Indians and white Caucasian subjects. DR beta RFLPs were similar in the two groups. Clearly distinguishable DR beta patterns were observed for DR1, 2, 3, 4, 5, 7 and w10. The DR beta patterns associated with DR3 were, however, also found with w6. The DR7 DR beta patterns were also found with w9. For DR specificities 1, 3, 4, 5, 7 and w10, the associated DQ alpha and DQ beta RFLPs were similar in both racial groups, but for DR2, however, marked differences were found. The DR2-positive white Caucasian subjects all possessed a single DQ alpha/DQ beta combination whereas the DQ alpha/DQ beta patterns in DR2-positive Asian Indians showed considerable heterogeneity. The pattern seen in white subjects was present in only a minority of Asians. DR-DQ relationships clearly vary in different racial groups. RFLP analysis of HLA-linked diseases in different populations should prove to be an important technique in identifying the primary genetic factor(s) in these disorders.

Genetic Linkage↗
PubMed1988

Neutrophil function in patients on continuous ambulatory peritoneal dialysis.

Frequent and recurrent episodes of peritonitis are a major cause of morbidity in patients on continuous ambulatory peritoneal dialysis (CAPD). One factor contributing to this problem may be an abnormality of neutrophil function in these patients. We have therefore quantified phagocytosis and killing by circulating and peritoneal neutrophils from patients on CAPD with and without peritonitis. Circulating neutrophils from uninfected patients showed reduced phagocytosis of both Staphylococcus epidermidis and Candida guilliermondii because of an opsonic defect in CAPD serum and because of a defect of the neutrophils themselves. In contrast, phagocytosis by circulating and peritoneal neutrophils from patients with peritonitis was normal. Intracellular killing of C. guilliermondii was normal in all groups of neutrophils but killing of S. epidermidis, the organism most commonly isolated in CAPD peritonitis, was reduced. The possible mechanisms for the enhanced neutrophil activity seen in peritonitis, and for the decreased killing of S. epidermidis in contrast to normal killing of C. guilliermondii are discussed. A defect in killing of S. epidermidis may explain why peritonitis caused by this organism can be difficult to erradicate.

Adolescent↗
PubMed1988

HLA class II DNA genotypes in Graves' disease: clues to inheritance of the HLA-linked component of susceptibility.

Restriction fragment length polymorphism analysis using DQ alpha, DQ beta and DR beta cDNA probes was performed in Graves' disease patients and control subjects. The following restriction fragment patterns were increased in frequency in patients compared with control subjects: 10 + 7.0 + 4.0kb DR beta/TaqI fragments (66% vs 32%; P less than 0.01; corrected P less than 0.06), 7.0 + 4.0kb DQ beta/BamHI fragments (55% vs 15%; P less than 0.001; corrected P less than 0.006), and a DQ alpha/TaqI 4.6kb fragment (75% vs 36%; P less than 0.005; corrected P less than 0.02). These associations could be accounted for by the known association of the B8-DR3 haplotype with the disorder. No non-DR3-related restriction fragment pattern was associated with the disease using any of the probes with restriction enzymes TaqI and BamHI. The 10 + 7.0 + 4.0kb DR beta/TaqI restriction pattern was identified in 23 of 35 Graves' disease patients. All 23 subjects were heterozygous for this pattern. This was inconsistent with simple recessive inheritance of the DR3-associated component of disease susceptibility (P = 0.01). The implications of these findings are discussed with reference to models for the inheritance of the HLA-linked component of Graves' disease susceptibility.

DNA Probes, HLA↗
PubMed1988

Malignant hyperthermia in myotonia congenita.

We report a family in which two sisters with myotonia congenita (MyC) were referred for malignant hyperthermia (MH) evaluation after each developed muscle rigidity with anesthesia. Halothane contracture testing of skeletal muscle in both was consistent with MH susceptibility. A third sister without clinical evidence of MyC was negative on contracture testing. These results suggest an association between MyC and MH susceptibility.

Adult↗
PubMed1988

Human cytochrome P-450 PB-1: a multigene family involved in mephenytoin and steroid oxidations that maps to chromosome 10.

The cytochrome P-450 monooxygenase system possesses catalytic activity toward many exogenous compounds (e.g., drugs, insecticides, and polycyclic aromatic hydrocarbons) and endogenous compounds (e.g., steroids, fatty acids, and prostaglandins). Multiple forms of cytochrome P-450 with different substrate specificities have been isolated. In the present paper we report the isolation and sequence of a cDNA clone for the human hepatic cytochrome P-450 responsible for mephenytoin (an anticonvulsant) oxidation. The mephenytoin cytochrome P-450 is analogous to the rat cytochrome P-450 form termed PB-1 (family P450C2C). We also report that human PB-1 is encoded by one of a small family of related genes all of which map to human chromosome 10q24.1-10q24.3. The endogenous role of this enzyme appears to be in steroid oxidations. This cytochrome P-450 family does not correspond to any of the hepatic cytochrome P-450 gene families previously mapped in humans.

Animals↗
PubMed1988

On truth telling.

Explore the source record for details and available documents.

Ethics, Medical↗
PubMed1987

The HLA-D associations of type 1 (insulin-dependent) diabetes in Punjabi Asians in the United Kingdom.

Type 1 (insulin-dependent) diabetes is less common in Asian Indians than in white Caucasoids. Forty-five Punjabi Asians with Type 1 diabetes and 96 racially matched control subjects were HLA-DR typed. DR3 was increased in diabetic patients vs control subjects (82% vs 38%, p less than 10(-5)) with relative risk 7.7 and etiological fraction 0.72. DR4 was increased in diabetic patients vs control subjects (31% vs 7%, p less than 0.003) with relative risk 5.7 and etiological fraction 0.26. DR2 showed a negative association (relative risk 0.19, etiological fraction -0.28), as did DR7 (relative risk 0.21, etiological fraction -0.33). HLA-DQ beta-chain gene probing using restriction enzyme BamHI in 43 diabetic patients and 90 control subjects showed that the DR1-associated 6.2 and 3.2 kb fragments were less common in diabetic patients than in the control subjects (12% vs 36%, p less than 0.02). A 12 kb fragment was associated with DR4 in both diabetic patients and control subjects. DR3 is the major susceptibility factor for Type 1 diabetes in Punjabi Asians and DR4 is a second marker. Gene probing indicates that the same DR4 subset is associated with the condition as in white Caucasoids. DR1 and its associated DQ beta restriction fragments are reduced in Asian Type 1 diabetic patients making it unlikely that DR1 haplotypes carry a predisposing factor in this racial group. We conclude that the genetic component of Type 1 diabetes in Punjabis shows differences from that of the white Caucasoid population and that the lower frequency of DR4 in this population may contribute to the lower prevalence of Type 1 diabetes.

Diabetes Mellitus, Type 1↗
PubMed1987

Vincristine and etoposide: an effective chemotherapy regimen with reduced toxicity in extensive small-cell lung cancer.

Chemotherapy prolongs survival of patients with small-cell lung cancer, but very few are cured, and the treatment is unpleasant. Thirty patients, 28 with advanced disease, were treated with etoposide 250 mg/m2 orally, daily for 5 days, plus vincristine 2 mg intravenously on the first day, the cycle being repeated 3-weekly, to a maximum of 6. There was a response rate of 70%, a median survival of 249 days, and an 11% 2-year survival. Symptomatic side-effects were less pronounced than with most other regimens of comparable efficacy.

Aged↗
PubMed1987

The dangers of premature extubation after severe birth asphyxia.

The records of all 91 neonates with asphyxia who were referred to the Royal Children's Hospital in 1982 and 1983 were reviewed and information was obtained on their subsequent neurological outcome. Thirty children had been extubated after their initial resuscitation, before transfer to the Royal Children's Hospital; 21 of these children had been extubated despite the fact that they had taken more than 5 min to take their first breath, and 11 (52%) of them died (while none of the nine infants who breathed within 5 min died). A paediatrician was involved with two-thirds of the 21 children who were extubated despite having more than 5 min to breathe. Twelve children required cardiac massage; seven of them were extubated and then reintubated before transfer, and six of the seven infants died. These findings suggest that many paediatricians are not aware of the importance of continuing ventilatory support in neonates who have suffered a severe asphyxial insult. Asphyxiated babies who require cardiac massage, and babies who do not start breathing within 5 min of birth, should not be extubated as soon as they have established regular respiration; they should remain intubated and be transferred to an intensive care unit.

Asphyxia Neonatorum↗
PubMed1987

Filter Paper Dot-Immunobinding Assay for Detection of Spiroplasma citri.

A rapid filter paper dot-immunobinding assay was adapted to detect the wall-less mollicute Spiroplasma citri in medium, plants, or insects. Filter paper spotted with sample was incubated first in dilute antiserum, then in protein A-peroxidase, and finally in a substrate of 4-chloro-1-naphthol plus hydrogen peroxide. The detection limit averaged 2.3 x 10 CFU/ml in cultures, and S. citri was detected in single infected leafhoppers. This assay was less sensitive but more rapid and economical than an enzyme-linked immunosorbent assay.

Journal Article↗
PubMed1987

Effect of dialysate fluids on phagocytosis and killing by normal neutrophils.

Inadequate host defenses may partly explain the problem of recurrent peritonitis in patients on continuous ambulatory peritoneal dialysis. It has been suggested that these defenses may be adversely affected by the fluids used for dialysis, and so we examined the effects of unused, effluent, and infected peritoneal dialysis fluids on phagocytosis and killing by normal neutrophils. We used a clinical isolate of Staphylococcus epidermidis as the test organism, as this organism is the most commonly cultured in continuous ambulatory peritoneal dialysis peritonitis; we also used a fungal species, Candida guilliermondii. There was no phagocytosis of either organism in unused dialysate because of lack of opsonins and low pH. Phagocytosis in effluent dialysate did not occur because of inadequate opsonin levels and was variable in infected effluents, depending on quantities of immunoglobulins present. Intracellular killing of both test organisms was normal in unused dialysate in the presence of 5% normal serum, but was reduced in effluent and infected dialysates because of factors inhibiting killing by neutrophils. These factors adversely affected the killing of S. epidermidis more than that of C. guilliermondii. These results may explain why peritonitis recurs, particularly peritonitis due to S. epidermidis, because organisms could be sequestered within the neutrophils and thus be protected from antibiotic action. Reinfection of the peritoneal cavity would then take place following neutrophil breakdown, causing a clinical relapse.

Candida↗