Biomedical subjects

Howard Bell

Publications and source records attributed to Howard Bell.

9 recordsLinked to original sources

PubMed2005

Amaurosis fugax: associations with heritable thrombophilia.

The aim of this study was to prospectively assess associations between amaurosis fugax, inherited thrombophilia, and acquired thrombophilia. Thrombophilia and hypofibrinolysis were studied in 11 cases (eight women, three men; all white) with amaurosis fugax, 57 +/- 17 years old, selected by the absence of abnormal brain magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), magnetic resonance venography (MRV), ipsilateral internal carotid artery plaque, atrial fibrillation, or cardiac thrombus. Cases were compared to 78 healthy adult white controls (53 +/- 18 years old) for serologic measures, and by polymerase chain reaction to 248 healthy white controls (78 adults, 170 children) for gene mutations. All 11 cases had one or more familial thrombophilic coagulation disorder including one heterozygous for the G1691A factor V Leiden mutation, two with low free protein S, four with high factor VIII, three with resistance to activated protein C, three homozygous for the C677T methylenetetrahydrofolate reductase (MTHFR) mutation, two compound C677T-A1298C MTHFR heterozygotes, and three with hypofibrinolytic 4G4G homozygosity for the PAI-1 gene. The case with factor VIII of 160% had two other thrombophilias (compound MTHFR C677T-A1298C heterozygosity, resistance to activated protein C), and hypofibrinolytic high Lp(a). Thrombophilic C677T MTHFR homozygosity or compound C677T-A1298C heterozygosity was present in five of 10 (50%) cases vs. 30 of 248 (12%) controls, Fisher's p (p(f)) = .005. Thrombophilic factor VIII was high in four of 10 (40%) cases vs. 0 of 38 controls, p(f) = .001. Thrombophilic hyperestrogenemia in five of the eight women (four exogenous estrogen, one pregnant) may have interacted with inherited thrombophilia-hypofibrinolysis, promoting thrombus formation. In cases selected by the absence of abnormal brain magnetic resonance imaging, significant ipsilateral internal carotid artery plaque, atrial fibrillation, or cardiac thrombus, we speculate that amaurosis fugax can be caused by reversible (by anticoagulation) retinal artery thrombi associated with heritable thrombophilia and/or hypofibrinolysis, often augmented by estrogen-driven acquired thrombophilia.

Adult↗

PubMed2005

Follow the water.

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Drug-Related Side Effects and Adverse Reactions↗

PubMed2004

Cloning, expression and functional characterisation of chitinase from larvae of tomato moth (Lacanobia oleracea): a demonstration of the insecticidal activity of insect chitinase.

Chitinases are vital to moulting in insects, and may also affect gut physiology through their involvement in peritrophic membrane turnover. A cDNA encoding chitinase was cloned from larvae of tomato moth (Lacanobia oleracea), a Lepidopteran pest of crops. The predicted protein contains 553 amino acid residues, with a signal peptide of 20 a.a. Sequence comparison showed 75-80% identity with other Lepidopteran chitinases. L. oleracea chitinase was produced as a functional recombinant enzyme in the yeast Pichia pastoris. A fusion protein containing chitinase joined to the N-terminus of snowdrop lectin (GNA) was also produced, to determine whether GNA could deliver chitinase to the haemolymph of Lepidopteran larvae after oral ingestion. The purified recombinant proteins exhibited similar levels of chitinase activity in vitro. Both proteins were highly toxic to L. oleracea larvae on injection, causing 100% mortality at low dose (2.5 microg/g insect). Injection of chitinase prior to the moult resulted in decreased cuticle thickness. The recombinant proteins caused chronic effects when fed, causing reductions in larval growth and food consumption by up to 60%. The oral toxicity of chitinase was not increased by attaching GNA in the fusion protein, due to degradation in the larval gut, preventing GNA acting as a "carrier".

Amino Acid Sequence↗

PubMed2004

Nonarteritic anterior ischemic optic neuropathy: associations with homozygosity for the C677T methylenetetrahydrofolate reductase mutation.

The association between nonarteritic anterior ischemic optic neuropathy (NAION) and coagulation disorders was prospectively assessed at least 3 months after the occurrence of ocular vascular events in 12 white patients in an outpatient clinical research center. Two community-based ophthalmologists evaluated the 12 NAION patients in the consecutive order of their referral. Polymerase chain reaction-complementary DNA assays of gene mutations associated with coagulation disorders and serologic coagulation measurements in study patients were compared with those in 36 healthy, normal race-, sex-, and age-matched controls, with 3 controls matched for each case. Of the 12 patients, 4 men and 8 women (mean age 62 +/- 15 years, 3 of them 55 years or older), 8 had unilateral NAION (bilateral in 4). The 12 patients with NAION were more likely than controls to demonstrate homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation (50% vs 11 %; Fisher's P =.009, with the likelihood of a type I error quite small, 0.9%). Our sample size had a power of 80% to detect this case-control difference in C677T MTHFR homozygosity at an alpha value of.05. Of the 12 NAION patients, 7 (58%) had at least 1 gene mutation in the C677T MTHFR, G1691A V Leiden, or G20210A prothrombin gene, compared with 5 of 36 controls (14%) (chi(2) = 9.48, P =. 002, with the likelihood of a type I error quite small, 0.2%). Our sample size had a power of 85% to detect this case-control difference at alpha =. 05. Of the 8 women with NAION, 5 (63%) first experienced the condition while taking hormone replacement therapy (n = 4) or during pregnancy (n = 1), with superposition of estrogen-induced thrombophilia on heritable thrombophilia and hypofibrinolysis. Confirmation of a causal relationship between coagulation disorders and NAION should facilitate its prevention and treatment and help protect against thrombi in other vascular beds.

Aged↗

PubMed2003