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M Holt

Publications and source records attributed to M Holt.

At least 37 records · Page 2Linked to original sources

Ecological risk assessment of endocrine disruptors.

The European Centre for Ecotoxicology and Toxicology of Chemicals proposes a tiered approach for the ecological risk assessment of endocrine disruptors, integrating exposure and hazard (effects) characterization. Exposure assessment for endocrine disruptors should direct specific tests for wildlife species, placing hazard data into a risk assessment context. Supplementing the suite of mammalian screens now under Organization for Economic Cooperation and Development (OECD) validation, high priority should be given to developing a fish screening assay for detecting endocrine activity in oviparous species. Taking into account both exposure characterization and alerts from endocrine screening, higher tier tests are also a priority for defining adverse effects. We propose that in vivo mammalian and fish assays provide a comprehensive screening battery for diverse hormonal functions (including androgen, estrogen, and thyroid hormone), whereas Amphibia should be considered at higher tiers if there are exposure concerns. Higher tier endocrine-disruptor testing should include fish development and fish reproduction tests, whereas a full life-cycle test could be subsequently used to refine aquatic risk assessments when necessary. For avian risk assessment, the new OECD Japanese quail reproduction test guideline provides a valuable basis for developing a test to detecting endocrine-mediated reproductive effects; this species could be used, where necessary, for an avian life-cycle test. For aquatic and terrestrial invertebrates, data from existing developmental and reproductive tests remain of high value for ecological risk assessment. High priority should be given to research into comparative endocrine physiology of invertebrates to support data extrapolation to this diverse fauna.

Amphibians↗

Calcium/calmodulin-dependent phosphorylation and activation of human Cdc25-C at the G2/M phase transition in HeLa cells.

The human tyrosine phosphatase (p54(cdc25-c)) is activated by phosphorylation at mitosis entry. The phosphorylated p54(cdc25-c) in turn activates the p34-cyclin B protein kinase and triggers mitosis. Although the active p34-cyclin B protein kinase can itself phosphorylate and activate p54(cdc25-c), we have investigated the possibility that other kinases may initially trigger the phosphorylation and activation of p54(cdc25-c). We have examined the effects of the calcium/calmodulin-dependent protein kinase (CaM kinase II) on p54(cdc25-c). Our in vitro experiments show that CaM kinase II can phosphorylate p54(cdc25-c) and increase its phosphatase activity by 2.5-3-fold. Treatment of a synchronous population of HeLa cells with KN-93 (a water-soluble inhibitor of CaM kinase II) or the microinjection of AC3-I (a specific peptide inhibitor of CaM kinase II) results in a cell cycle block in G2 phase. In the KN-93-arrested cells, p54(cdc25-c) is not phosphorylated, p34(cdc2) remains tyrosine phosphorylated, and there is no increase in histone H1 kinase activity. Our data suggest that a calcium-calmodulin-dependent step may be involved in the initial activation of p54(cdc25-c).

Benzylamines↗

Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene.

A large English family with autosomal dominant segregation of presenile dementia, ataxia and other neuropsychiatric features is described. Diagnoses of demyelinating disease, Alzheimer's disease, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome have been attributed to particular individuals at different times. An Irish family, likely to be part of the same kindred, is also described, in which diagnoses of multiple sclerosis, dementia, corticobasal degeneration and new variant CJD have been considered in affected individuals. Molecular genetic studies have enabled the classification of this disease at the molecular level as one of the group of inherited prion diseases, with the substitution of valine for alanine at codon 117 of the prion protein gene (PRNP). Only three other kindreds have been described world-wide with this mutation and only limited phenotypic information has been reported. Here we describe the phenotypic spectrum of inherited prion disease (PrPA117V). The diversity of phenotypic expression seen in this kindred emphasizes the logic of molecular classification of the inherited prion diseases rather than classification by specific clinicopathological syndrome. Indeed, inherited prion disease should be excluded by PRNP analysis in any individual presenting with atypical presenile dementia or neuropsychiatric features and ataxia, including suspected cases of new variant CJD.

Adult↗

An evaluation of a new analyser for inhaled nitric oxide administration.

We examined the ability of a new combined nitric oxide (NO)/nitrogen dioxide (NO2) electrochemical analyser (PrinterNOx, Micro Medical Limited, Chatham, Kent, England) to measure NO and NO2 concentrations. The PrinterNOx was compared to a chemiluminescence analyser (42H, Thermo Environmental Instruments Inc, Franklin MA, U.S.A.). NO and NO2 were generated in a standard ventilator circuit using a paediatric ventilator (900C, Siemens Elema, Sweden) connected to an artificial lung (260li, TTL Test Lung, Michigan Instruments, MI, U.S.A.). Forty-four paired NO measurements ranging from 2.56 ppm to 74.6 ppm and 50 paired NO2 measurements ranging from 0.0 ppm to 5.39 ppm were obtained. For the measurement of NO the PrinterNOx showed a tendency to overestimate the chemiluminescence analyser. Regression analysis showed a close relationship between the two analysers with r2 = 0.9981 and a regression equation of y = 1.1658 x +0.0197. In the more clinically important range of 0-25 ppm, r2 increased to 0.9996 with a regression equation of y = 1.1984 x -0.4657. Conversely the PrinterNOx underestimated the chemiluminescence analyser for the measurement of NO2. The regression equation describing this relationship was y = 0.879 x -0.0447 (r2 = 0.9993). We conclude that the PrinterNOx is of sufficient accuracy to be of clinical use in the administration of NO.

Anesthesiology↗

Successful embolization of persistent endoleak from a patent inferior mesenteric artery.

PURPOSE: To report the successful endovascular occlusion of a persistent endoleak owing to collateral perfusion in a 1-year-old bifurcated aortic endograft. METHODS AND RESULTS: An 81-year-old man underwent endovascular repair of a 5.5-cm abdominal aortic aneurysm (AAA) with a bifurcated stent-graft in 1995; collateral perfusion of the excluded aneurysm by retrograde filling of the patent inferior mesenteric artery (IMA) was noted postoperatively. At his 1-year follow-up, the mid-sac endoleak persisted on contrast-enhanced computed tomography. Using the superior mesenteric artery for access, the stump of the IMA was successfully embolized with glue. CONCLUSIONS: This case, which highlights the importance of documenting a patent IMA prior to AAA endografting, illustrates one option for the management of persistent collateral perfusion of endovascularly excluded aneurysms.

Adhesives↗

Allelic loss and the progression of breast cancer.

To study genetic changes and the evolution of breast cancer, we assayed for loss of heterozygosity (LOH) in 12 sets of synchronous carcinoma in situ (CIS) and invasive cancer, compared to normal control DNA. Microsatellite markers were used, which map to each nonacrocentric autosomal arm. Eight tumor sets demonstrated LOH of the same allele in both concurrent invasive cancer and ductal CIS, for a total of 18 chromosomal loci. Three of nine tumor sets showed LOH on 11p. In two of these sets, LOH was seen on 11p only in the invasive tumor, not the corresponding CIS. One of these tumors also exhibited allelic loss in the invasive tumor for 4 loci, all of which were retained in the noninvasive tumor. For two tumor sets, LOH was mirrored in matched ductal CIS, invasive tumor, and lymph node metastasis. The maintenance of LOH for certain loci throughout the stages of breast cancer suggests clonality of the cancer cells.

Breast Neoplasms↗

Allelic loss on a chromosome 17 in ductal carcinoma in situ of the breast.

Multiple tumor suppressor genes are implicated in the oncogenesis and progression of invasive carcinoma of the breast. To investigate the chronology of genetic changes we studied loss of heterozygosity on chromosome 17 in ductal carcinoma in situ, a preinvasive breast cancer. A microdissection technique was used to separate tumor from normal stromal cells prior to DNA extraction and loss of heterozygosity was assayed mainly using simple sequence repeat polymorphism markers and the polymerase chain reaction. Loss of heterozygosity on 17p was observed in 8 of 28 tumors (29%) when compared with normal control DNA, whereas no loss was seen on 17q, suggesting that at least one locus on 17p is involved early in the development of breast cancer.

Alleles↗

Bonding of amalgam to tooth structure: tensile adhesion and microleakage tests.

Amalgam can be bonded to etched enamel by a thin coat of Panavia resin cement with a resulting mean bond strength of 1404 psi to enamel and 469 psi to dentin as tested in tension. Less microleakage was observed in resin-bonded amalgam restorations than in Copal varnish-lined or unlined restorations. The technique could be used clinically with possible implications for cavity design, fracture resistance of restored teeth, and recurrent caries. These properties as well as the variables affecting bond strength need further exploration.

Acid Etching, Dental↗

The National WIC Evaluation: evaluation of the Special Supplemental Food Program for Women, Infants, and Children. IV. Study methodology and sample characteristics in the longitudinal study of pregnant women, the study of children, and the food expenditures study.

The longitudinal study of pregnant women enrolled a national probability sample of 5,205 women first certified for WIC and 1,358 comparable low-income pregnant women in 174 WIC clinics located in 58 areas in the contiguous 48 states and in 55 prenatal clinics without WIC programs in counties with low program coverage. The women completed 24-h dietary recalls, histories of food expenditures, health care utilization, health and sociodemographic status, and anthropometric assessment. At late-pregnancy follow-up 3,967 WIC and 1043 control women were interviewed and 853 WIC and 762 control women completed 1-wk food expenditure diaries. Birth outcome was abstracted (from hospital records) for 3,863 WIC and 1058 control women. Anthropometry, dietary intake, health, and use of health services were related to WIC among 2,619 random low-income preschoolers. Psychological development was assessed in 526 children aged 4 and 5 y. Control women had higher income, education, and employment status; therefore, WIC program benefits probably were underestimated.

Child Nutritional Physiological Phenomena↗

The National WIC Evaluation: evaluation of the Special Supplemental Food Program for Women, Infants, and Children. V. Longitudinal study of pregnant women.

The major associations with the Special Supplemental Food Program for Women, Infants, and Children (WIC) in pregnancy were increased intake of protein, iron, calcium, and vitamin C (four of five targeted nutrients) and of energy, magnesium, phosphorus, thiamin, riboflavin, niacin, vitamin B-6, and vitamin B-12; reversal of low weight gain in early pregnancy; smaller fat stores in late pregnancy; reduced frequency of premature rupture of the uterine membranes; larger infant head circumference with no effect on birth weight and length; increased birth weight and head circumference with better program quality; and lower fetal mortality of appreciable but not significant magnitude. Incremental energy intake was comparable to that in most small-scale supplementation trials. There was no evidence of effects on frequency of prenatal care, use of alcohol or tobacco, the intention to breast-feed, or the rate of breast-feeding. Maternal alcohol intake was associated with depressed infant head circumference, over and above effects on birth weight and length.

Anthropometry↗