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Biomedical subjects

J Love

Publications and source records attributed to J Love.

At least 37 records · Page 2Linked to original sources

Short communication: developmental control of Xa21-mediated disease resistance in rice.

The rice resistance gene Xa21 confers resistance against the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo). The molecular genetic mechanism controlling the integration of the Xa21-mediated disease resistance response with the developmental program in rice is under study in this model system. Reproducible means of infecting plants at certain developmental stages were designed based on the timing of full expansion of the leaf. Xa21-resistance progressively increases from the susceptible juvenile leaf 2 stage through later stages, with 100% resistance at the adult leaf 9/10 stage. We found that Xa21 expression is independent of plant developmental stage, infection with Xoo, or wounding. Expression of the Xa21 gene transcript is not correlated with expression of Xa21 disease resistance indicating that the developmental regulation of Xa21-resistance is either controlled post-transcriptionally or by other factors.

Gene Expression↗

Missense mutations in the most ancient residues of the PAX6 paired domain underlie a spectrum of human congenital eye malformations.

Mutations of the human PAX6 gene underlie aniridia (congenital absence of the iris), a rare dominant malformation of the eye. The spectrum of PAX6 mutations in aniridia patients is highly biased, with 92% of all reported mutations leading to premature truncation of the protein (nonsense, splicing, insertions and deletions) and just 2% leading to substitution of one amino acid by another (missense). The extraordinary conservation of the PAX6 protein at the amino acid level amongst vertebrates predicts that pathological missense mutations should in fact be common even though they are hardly ever seen in aniridia patients. This indicates that there is a heavy ascertainment bias in the selection of patients for PAX6 mutation analysis and that the 'missing' PAX6 missense mutations frequently may underlie phenotypes distinct from textbook aniridia. Here we present four novel PAX6 missense mutations, two in association with atypical phenotypes: ectopia pupillae (displaced pupils) and congenital nystagmus (searching gaze), and two in association with more recognizable aniridia phenotypes. Strikingly, all four mutations are located within the PAX6 paired domain and affect amino acids which are highly conserved in all known paired domain proteins. Our results support the hypothesis that the under-representation of missense mutations is caused by ascertainment bias and suggest that a substantial burden of PAX6 -related disease remains to be uncovered.

Amino Acid Sequence↗

Endemic infection with HTLV-IIB in Venezuelan Indians: molecular characterization.

The peripheral blood of 41 Yaruro and Guahibo Indians from Venezuela was examined for HTLV antibodies and DNA. Twenty-five samples (61%) were found to be infected with HTLV-IIB. The sensitivities of the serologic and DNA polymerase chain reaction (PCR) analyses were 80% and 96%, respectively. Epidemiologic studies supported both sexual and perinatal transmission of the virus. Sequence analyses of the HTLV-IIB strains from these Indians indicate that they are unique relative to HTLV-II detected in other groups of humans. HTLV-IIB-G2 isolated from a Guahibo Indian is the most divergent HTLV-IIB strain relative to the prototype HTLV-II NRA.

Adolescent↗

A new set of primers for mutation analysis of the human PAX6 gene.

Mutations in the human PAX6 gene are an important cause of dominantly inherited congenital malformations of the eye, including aniridia, Peters' anomaly, keratitis, and isolated foveal hypoplasia. To satisfy the need for efficient detection of PAX6 mutations, we have developed a new set of oligonucleotides for genomic SSCP based on the recently completed genomic sequence of the entire human PAX6 gene. We also describe PAX6 mutations in eight aniridia patients, five of which are novel.

Blood Cells↗

A 5-year clinical review of bond failure with a light-cured resin adhesive.

The purpose of this study was to investigate the time to first failure of stainless steel orthodontic brackets (Ormco Corp, Glendora, Calif) bonded with a light-cured resin adhesive (Transbond, 3M Unitek, Monrovia, Calif) and assess whether time to failure was related to the patient's age at the start of treatment or sex, the proficiency of the individual placing the brackets, or the presenting malocclusion. Data on 548 patients with 7118 bonded brackets were analyzed. Survival analysis was carried out on a single bracket per patient. In each patient, the first bracket to fail was studied. In cases where no brackets failed, the bracket with the shortest follow-up time was analyzed and handled as a censored observation in the formal analysis. Median time until first bracket failure was 442 days, and an overall failure rate of 6% was recorded. There were no significant differences in time to first failure of brackets with respect to the sex or age of the patient at the start of treatment (p = 0.168, and p = 0.261, respectively), operator proficiency in placing brackets (p = 0.189), or presenting malocclusion (p = 0.052). Performance of brackets bonded with Transbond does not appear to vary significantly according to the variables examined.

Adolescent↗

Conflicting values in oral health care.

It was demonstrated that a group of professionals representing diverse values with regard to oral health care can work effectively to identify pivotal issues and even reach consensus on ethical issues. Where consensus cannot be reached, it is still possible to make progress by clarifying positions. Consensus was reached on a statement regarding adequacy of care for patients whose insurance coverage is less than what the dentist considers appropriate.

Attitude of Health Personnel↗

Combined SSCP/heteroduplex analysis in the screening for PAX6 mutations.

We demonstrate the use of combined SSCP and heteroduplex analysis in the detection of PAX6 mutations using non-radioactive silver staining. A panel of aniridia patients was screened by this approach and we show that a greater number of mutations was detected than would have been found by running each technique alone. Six previously unreported aniridia mutations in PAX6 are also described..

Aniridia↗

Degenerate and specific PCR assays for the detection of bovine leukaemia virus and primate T cell leukaemia/lymphoma virus pol DNA and RNA: phylogenetic comparisons of amplified sequences from cattle and primates from around the world.

Degenerate and specific PCR assays were developed for bovine leukaemia virus (BLV) and/or primate T cell leukaemia/lymphoma viruses (PTLV). The degenerate assays detected all major variants of the BLV/PTLV genus at a sensitivity of 10-100 copies of input DNA; the specific systems detected 1-10 copies of input target. Sensitivity was 100% in specific DNA-PCR assays done on peripheral blood from seropositive BLV-infected cattle and HTLV-I- or HTLV-II-infected humans, and 62% in RNA/DNA-PCR assays on sera from BLV seropositive cattle. The pol fragments from 21 different BLV strains, isolated from cattle in North and Central America, were cloned and sequenced, and compared to other published BLV and PTLV pol sequences. BLV and PTLV sequences differed by 42%. Sequence divergence was up to 6% among the BLV strains, and up to 36% among the PTLV strains (with PTLV-I and PTLV-II differing among themselves by 15% and 8%, respectively). Some cows were infected with several BLV strains. Among retroviruses, BLV and PTLV sequences formed a distinct clade. The data support the interpretation that BLV and PTLV evolved from a common ancestor many millennia ago, and some considerable time before the PTLV-I and PTLV-II strains diverged from each other. The dissemination of the BLV strains studied probably resulted from the export of European cattle throughout the world over the last 500 years. The relatively similar mutation rates of BLV and PTLV, after their various points of divergence, suggest that there could be a much wider genetic range of BLV than has currently been defined.

Amino Acid Sequence↗

Absence of human herpes virus 8 DNA sequences in large granular lymphocyte (LGL) leukemia.

The etiology of large granular lymphocyte (LGL) leukemia is uncertain. Recently, a Kaposi's sarcoma-associated herpes virus, denoted as human herpes virus 8 (HHV-8), has been identified. Some data suggest that HHV-8 and Epstein-Barr virus (EBV) may interact to induce malignant transformation. Infection with EBV has been implicated in the pathogenesis of some cases of LGL leukemia. Therefore, we performed PCR analyses for HHV-8 detection in samples from nineteen patients with LGL leukemia; three of these samples contained the EBV genome. We could not detect HHV-8 sequences in any of these patients. Therefore, HHV-8 infection is not involved in the pathogenesis of T-LGL leukemia.

DNA, Viral↗

Value of gastroscopy without a prior consultation.

Upper endoscopy is the most accurate and cost effective tool available to physicians when confronted with a patient with dyspepsia. Access to this procedure in Canada is generally limited by the requirement to see a consultant physician before the procedure can be performed. This review, in a question and answer style, builds a case for the introduction of open access endoscopy in Canada. Endoscopy is an effective and valid diagnostic test. Consultants are no better at deciding who requires endoscopy than general practitioners. Clinical patterns of dyspepsia are not a valid guideline for appropriate use of endoscopy. There is value in a normal endoscopy in terms of changes to medical treatment, reassurance, lower consultation and medical clinic attendance rates--and radiation exposure is avoided. After endoscopy, normal patients tend to make 41% fewer physician visits, prescriptions decrease by 71%, and 66% feel better and are more productive at work. Open access endoscopy is cost effective, even when American costs are used. Open access endoscopy should not overrun endoscopy suites if we use the British experience as a guide. The endoscopist would only require a limited history and physical examination to determine safety of the procedure. Follow-up and management is the responsibility of the referring physician, and this must be communicated to the patient and referring physician. The Canadian Association of Gastroenterology needs to draw up guidelines along with the Canadian Medical Practitioners Association for the adoption of this practice.

Canada↗

The BSE crisis.

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Animals↗

Calcium, calmodulin and protein kinase C dependence of platelet shape change.

Platelet shape change (PSC) represents the initial phase of platelet activation and is normally investigated in ethylene diamine tetraacetic acid (EDTA) containing platelet rich plasma (PRP); EDTA is a potent chelator of calcium and therefore reduces ionized calcium to negligible levels. It is therefore assumed that it is a process independent of calcium. To test the hypothesis that PSC may be dependent upon intracellular calcium, we examined the effect of 8-(N,N-Diethylamino) octyl 3,4,5-Trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of intercellular calcium mobilization on PSC. It produced a dose dependent inhibition of PSC. We then examined whether PSC was dependent upon calmodulin and protein kinase C, a calcium dependent enzyme which is cardinal to platelet aggregation. Both calmidazolium, a specific inhibitor of calmodulin, and H-9, a specific inhibitor of protein kinase C, produced dose dependent inhibition of PSC. Finally, we investigated whether GP IIb/IIIa receptor which binds fibrinogen was involved in PSC; DMP 728 [(cyclic [D-2-amino-butyryl-N2-methyl-L-arginyl-glycyl-L-aspartyl-3- (a min o-methyl-benzoic acid], methanesulfonic acid salt] a potent GP IIb/IIIa receptor antagonist was without any effect on PSC. We conclude that PSC is a calcium, calmodulin and protein kinase C dependent process like platelet aggregation but that it does not require extracellular calcium or the participation of platelet GP IIb/IIIa complex.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

A rapid and sensitive method of identification of HTLV-II subtypes.

There are 2 subtypes of human T-cell lymphoma/leukemia virus type II (HTLV-II), A and B. HTLV-II is increasingly associated with rare forms of lymphocytic neoplasia and a neurodegenerative disorder, characterized by hyperspasticity and ataxia. We have used PCR to amplify, clone and sequence 140 bp of the pol gene from many isolates of HTLV-IIA and HTLV-IIB from around the world. Analysis of these and other published sequence established that all HTLV-IIA sequences contained a unique Hinf I site and all HTLV-IIB sequences a unique Mse I site. A rapid and specific oligomer restriction (OR) assay was developed utilizing the primer pair SK110/SK111 and subsequent digestion with these enzymes. Concordance between sequenced and OR-based subtyping of DNA amplified by PCR was absolute among 22 HTLV-II isolates tested. Further OR or sequence analyses on an additional 30 other isolates indicated that the majority of North American non-indian HTLV-II isolates were subtype A, while all Paleo-Amerindian samples, including those from the Seminole of Florida; the Guaymi from Panama; and the Toba, Chorote, Wichi, and Chulupe of Argentina, belonged to subtype B. The SK110/SK111 PCR-OR format should facilitate molecular epidemiology studies of HTLV-II infection and allow for subtype stratification in assessing the sensitivity and specificity of HTLV detection formats and HTLV-II disease association.

Argentina↗

Complete disruption of the main pancreatic duct: endoscopic management.

BACKGROUND: Complete disruption of the main pancreatic duct is an unusual event in the course of acute or chronic pancreatitis. Endoscopic management has already proven effective in the treatment of partial ruptures. METHODS: Thirteen patients presented over a 7-year period with acute (9 patients) or chronic (4 patients) pancreatitis complicated by complete disruption of the main pancreatic duct and cyst formation. Endoscopic treatment was attempted in 12. Treatment varied depending on the site of the rupture and accessibility of the pseudocyst and consisted either of transpapillary drainage (3), cystogastrostomy (3), cystoduodenostomy (2), or combined procedures (4) when one of these procedures did not induce significant decrease in collection size. Long-term results were obtained by observing the patients with ultrasound, CT, ERCP, and clinical evaluation. RESULTS: Short-term results were excellent with complete cyst resolution and clinical recovery in all but one patient treated by endoscopy. Two patients had pseudocyst infection successfully treated by drainage and antibiotics. Long-term follow-up was available for 11 patients (mean duration, 30.2 months; range, 12 to 72 months) without relapsing clinical symptoms or pseudocyst. CONCLUSIONS: Endoscopic management is effective and safe for treating patients with complete main pancreatic duct disruption. A double drainage combining transpapillary drainage and cystoenterostomy must be done in selected instances, especially when rupture occurs in the setting of chronic pancreatitis with stricture or stone distal to the rupture.

Acute Disease↗

Cholangiographic findings in deteriorating primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: The evolution of primary sclerosing cholangitis (PSC) is difficult to predict, and ERCP may be helpful in diagnosing its complications and treating them. Few descriptions of cholangiographic findings during the course of the disease have yet appeared. We report here on our experience in the management and follow-up by ERCP of six patients with deteriorating PSC. PATIENTS AND METHODS: Between 1981 and 1992, PSC was diagnosed in 18 patients. Clinical, biochemical, and cholangiographic findings were recorded during the follow-up period. An initial group of 12 patients had a good clinical and biochemical course (mean 56 months) and did not require systematic control ERCPs. A second group of six patients, showing cholangiographic features similar to those of the first group at presentation, developed clinical and biochemical deterioration within a mean period of 43 months (range 6-96). RESULTS: These six patients had a significant elevation of serum bilirubin and at ERCP showed worsening bile duct lesions, with marked strictures and a subsequent increase in the maximum duct diameter in both the extrahepatic and intrahepatic ducts compared to the initial ERCPs. In two of these six patients, the strictures were due to a superimposed cholangiocarcinoma. Endoscopic drainage was unsuccessful, transplantation impracticable due to extrahepatic spread, and both patients died three and five months, respectively, after diagnosis of cholangiocarcinoma. By contrast, four patients with dominant extrahepatic duct involvement benefited from endoscopic procedures (mean follow-up 19 months) without any recurrence of cholangitis and without requiring long-term antimicrobial treatment. The follow-up checks included regular ERCPs performed every six months for duct and stent assessment, and cytology brushing. CONCLUSIONS: Since there are no effective means of early and accurate detection of cholangiocarcinoma, the use of ERCP to compare the course of cholangiographic lesions over time may be of interest. Patients with extrahepatic duct involvement may benefit from endoscopic therapy. By contrast, in patients with dominant intrahepatic duct disease and a deteriorating clinical status, attempts at endoscopic therapy are not helpful, and liver transplantation needs to be considered promptly.

Adult↗