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Biomedical subjects

J Howarth

Publications and source records attributed to J Howarth.

At least 19 recordsLinked to original sources
PubMed2004

Metabolic and structural viability of precision-cut rat lung slices in culture.

1. The principal objective was to evaluate the functional and structural integrity of precision-cut rat lung slices in culture over 72 h. 2. Lung slices metabolized 7-ethoxycoumarin in a time-dependent fashion, the major metabolites being the sulphate and glucuronide of 7-hydroxycoumarin with very low levels of the free compound. Prior treatment of rats with beta-naphthoflavone elevated markedly the rate of metabolism. The optimum slice thickness, as exemplified by the metabolism of 7-ethoxycoumarin, was about 600 microm. 3. Lung slices retained metabolic viability towards 7-ethoxycoumarin for 8 h, but after this point a marked decline in metabolic activity was noted. However, very low levels of activity were still evident following a 72 h incubation. 4. Morphological examination of lung slices revealed nuclear degeneration and loss of tissue architecture following 24h incubation. When cellular integrity was assessed using lactate dehydrogenase, a time-dependent leakage was evident with maximum loss occurring within 24h; longer incubations did not result in further leakage. 5. It is concluded that precision-cut rat lung slices, of 600 microm thickness, can be maintained metabolically viable in culture for some 8 h.

Animals↗
PubMed2001

Intermolecular interactions in two (ferrocenylmethyl)benzimidazoles incorporating the 4-MeOC6H4 and 3,4-(MeO)2C6H3 groups: analysis of MeO-C-C distortions from ideal 120 degrees geometry.

The title compounds, 1-ferrocenylmethyl-2-(4-methoxyphenyl)-1H-benzimidazole, [Fe(C5H5)(C20H17N2O)], (I), and 2-(3,4-dimethoxyphenyl)-1-ferrocenylmethyl-1H-benzimidazole, [Fe(C5H5)(C21H19N2O2)], (II), are model electroactive compounds for anion sensor and antimalarial applications. Distortions from the ideal 120 degrees angle about the MeO-C-C groups are evident, with angles of 115.1 (2) and 125.0 (2) degrees in (I), and 115.9 (2) and 124.6 (2) degrees, and 115.7 (2) and 125.1 (2) degrees in (II). The main intermolecular hydrogen bonds in (I) comprise C-H.N and C-H.pi(C5H5) interactions, while in (II), only weak C-H.pi(imidazole) and C-H.pi(arene) interactions are present.

Journal Article↗
PubMed2000

Simple 1,2-aminoalcohols as strain-specific antimalarial agents.

We report here the in vitro activity of a selection of 1, 2-aminoalcohol-containing compounds against cloned strains of human Plasmodium falciparum. These compounds exhibit moderate antimalarial activity but a high degree of strain specificity, preferentially inhibiting a chloroquine-resistant strain of the organism.

Animals↗
PubMed2000

The use of cluster sampling to determine aid needs in Grozny, Chechnya in 1995.

War broke out in Chechnya in November 1994 following a three-year economic blockade. It caused widespread destruction in the capital Grozny. In April 1995 Medical Relief International--or Merlin, a British medical non-governmental organisation (NGO)--began a programme to provide medical supplies, support health centres, control communicable disease and promote preventive health-care in Grozny. In July 1995 the agency undertook a city-wide needs assessment using a modification of the cluster sampling technique developed by the Expanded Programme on Immunisation. This showed that most people had enough drinking-water, food and fuel but that provision of medical care was inadequate. The survey allowed Merlin to redirect resources earmarked for a clean water programme towards health education and improving primary health-care services. It also showed that rapid assessment by a statistically satisfactory method is both possible and useful in such a situation.

Cluster Analysis↗
PubMed1998

Ethnicity study and non-selective screening for haemoglobinopathies in the antenatal population of central Manchester.

The objective of this study was to determine the frequency of ethnic groups within the antenatal population in central Manchester and thereby ensure that the haemoglobinopathy service was targeting the correct population and their needs. Ethnic data collection records of 6718 patients were analysed over a 7 month period. Of these 62.3% stated that they were White, 13.2% Asian, 7.9% Black, 3.8% Chinese or 'other ethnic groups' and 12.7% gave no information about their ethnic background. A subset of 1144 patients were screened for haemoglobinopathies over a 1 month period. The incidence of haemoglobinopathies within the screened population was 2.62%, and comprised 0.69% beta thalassaemia trait, 1.22% sickle cell trait, 0.43% haemoglobin C trait and 0.26% haemoglobin D trait. The total incidence of haemoglobinopathies was highest within the Black population (18.2%), followed by the no information group (5.6%), Asian (3.35%) and white (0.26%). The high proportion of ethnic minorities and the significant carrier frequency in the no information group, support our view that non-selective screening should be offered to the antenatal population of central Manchester.

England↗
PubMed1997

The preparation of a molecular imprinted polymer to 7-hydroxycoumarin and its use as a solid-phase extraction material.

A molecular imprinted polymer (MIP) was prepared to 7-hydroxycoumarin (7-OHC). A number of preparation parameters were examined by ultraviolet (UV) spectroscopy, including the amount of solvent used for reaction, equilibration time, selectivity and capacity of material. The polymer which showed the most selectivity for 7-OHC was then packed into cartridges and used as a solid-phase extraction sorbent. An extraction procedure was then developed from first principles. The cartridges were examined for selectivity of 7-OHC over some other members of the coumarin family. 7-OHC was then extracted from urine using this solid-phase extraction (SPE) method, and its concentration determined using capillary zone electrophoresis (CZE). The method was found to be linear over the range 10-50 micrograms ml-1. Inter- and Intra-assay precision studies were performed to validate the method.

Drug Compounding↗
PubMed1997

Konzo associated with war in Mozambique.

We report an epidemic of konzo, symmetric spastic paraparesis associated with cassava consumption and cyanide exposure: 384 patients were treated in rehabilitation centres; the prevalence rate in a badly affected area was 30/1000. Most patients were children over 3 and women. Owing to war, communities turned to bitter cassava as their staple and took shortcuts in its processing. When the war ended, they continued to depend on inadequately processed bitter cassava. The epidemic lasted 2 years (the last year of war and the first of peace) with peaks each year during the cassava harvest. Although most cases were reported from rural inland areas, patients also came from small towns and the coast. School children had raised urinary thiocyanate and linamarin and low inorganic sulphate concentrations. Urinary thiocyanate values were lower than those previously reported in konzo epidemics, probably because we collected specimens before the cassava harvest and epidemic peak. The necessary conditions for konzo were present: intensive cultivation of bitter casava, insufficient processing, a probable high cyanide intake, and a low intake of protein-rich foods.

Adolescent↗
PubMed1994

Assignment and calcium dependence of methionyl epsilon C and epsilon H resonances in cardiac troponin C.

The 10 Met methyl groups in recombinant cardiac troponin (cTnC) were metabolically labeled with [13C-methyl]Met and detected as 10 individual cross-peaks using two-dimensional heteronuclear single- and multiple-quantum coherence (HSMQC) spectroscopy. The epsilon C and epsilon H chemical shifts for all 10 Met residues were sequence-specifically assigned using a combination of HSMQC and systematic conversion of the Met residues to Leu. The only negative functional consequence of these changes was seen when both Met 45 and 81 were mutated. Binding of Ca2+ to the high affinity C-terminal sites III and IV induced relatively large changes in the epsilon H and epsilon C chemical shifts of all Met residues in the C-terminal domain as well as small but significant changes in the chemical shifts of epsilon H Met 47 and Met 81 in the N-terminal half of cTnC. Binding of Ca2+ to the low affinity N-terminal site II induced large changes in the epsilon H and epsilon C chemical shifts of Met 45, Met 80, and Met 81. Binding of Ca2+ to site II had no effect on the chemical shifts of Met residues located in the C-terminal domain. The nature of the chemical shift changes of Met residues in the N- versus the C-terminal halves of cTnC were consistent with different Ca(2+)-induced conformational changes in these domains. Thus, the assigned methyl Met chemical shifts can serve as useful structural markers to study conformational transitional in free cTnC and potentially after association with small ligands, peptides, and other troponin subunits.

Calcium↗
PubMed1993

Lipolytic activity and degradation of rapeseed oil and rapeseed by spoilage fungi.

Aspergillus, Eurotium and Penicillium spp. from rapeseed were able to grow and produce lipases over a range of water activities (aw) at both 15 and 25 degrees C on tributyrin agar. The ability to produce lipases was not directly related to growth rate. The clearing zone: growth rate ratios gave lipase indices which varied markedly between test fungi and with aw. The fungi with the highest indices were Aspergillus candidus and Aspergillus versicolor and Penicillium expansum and Penicillium hordei. The Aspergillus spp. generally grew faster on a 1% crude rapeseed oil at 25 degrees C and 0.995 and 0.95 aw than on the tributyrin agar. P. hordei degraded the rapeseed oil more rapidly than Eurotium amstelodami or Penicillium aurantiogriseum, with optimum activity at 0.98 aw. E. amstelodami was the least effective at degrading the rapeseed oil under all aw conditions. The lipase indices were compared with the ability of the test fungi to degrade irradiated rapeseed. Dry matter loss over 4-week periods were greater at 25 than 15 degrees C, regardless of aw. At 15 degrees C, Penicillium spp. caused significantly greater dry matter losses than Aspergillus spp. A. niger degraded rapeseed faster than other Aspergillus spp. tested at 0.98 aw, but at 0.95 and 0.90 aw there was little difference between species.

Ascomycota↗
PubMed1993

Monitoring of iron requirements in renal patients on erythropoietin.

We studied 38 patients (9 haemodialysis, 18 peritoneal dialysis, 11 advanced renal failure) over the first 12 weeks of erythropoietin therapy. In 14 iron-overloaded patients (ferritin > 500 micrograms/l the haemoglobin (+/- SEM) increased from 6.74 +/- 0.27 to 9.85 +/- 0.36 g/dl (P < 0.0001) entirely by mobilizing iron reserves (reduced from 1,220 +/- 73 to 739 +/- 111 mg, P < 0.0001). In the 24 non-overloaded patients (ferritin < 500 micrograms/l) the haemoglobin rose similarly from 7.04 +/- 0.18 to 10.70 +/- 0.36 g/dl (P < 0.0001), partly from iron reserves (depleted from 200 +/- 74 to -44 +/- 77 mg, P = 0.016) and partly from oral iron supplements (305 +/- 110 mg). In the overloaded patients the ferritin declined from 1057 micrograms/l (geometric mean, range 504-3699) to 317 micrograms/l (42-1505, P < 0.0001). In the non-overloaded patients it declined from 82 micrograms/l (8-461) to 45 micrograms/l (5-379, P = 0.016). The transferrin saturation (TS) in the overloaded patients appeared to decline from 38.3 +/- 7.2% to 24.0 +/- 3.7% but this was not statistically significant. In the non-overloaded the TS was unchanged (23.3 +/- 2.4 before and 28.1 +/- 3.6% after treatment). Considering all 38 patients together, the haemoglobin correlated negatively with the ferritin (r = 0.3731, P < 0.001) but not with the TS. The TS correlated with the serum ferritin initially (r = 0.75, P < 0.001) but not after the first 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of blood volume on the blood pressure of predialysis and peritoneal dialysis patients treated with erythropoietin.

Twenty-seven patients with renal failure (16 on CAPD and 11 predialysis) were treated with erythropoietin. At 12 weeks, the mean haemoglobin concentration (+/- SEM) in the CAPD patients had increased from 7.07 +/- 0.20 to 10.88 +/- 0.45 g/dl (two-tailed paired t test, P < 0.0001) and in the predialysis patients from 6.90 +/- 0.35 to 10.05 +/- 0.47 g/dl (P < 0.0001). Predialysis patients were taking more antihypertensive medication at baseline. No increase was required in either group after erythropoietin; there was no change in blood pressure in the CAPD patients, though in the predialysis patients the systolic blood pressure rose slightly from 132 to 146 mmHg (P = 0.029) and the mean blood pressure from 95 to 103 mmHg (P = 0.028). In 12 patients (6 on CAPD and 6 predialysis) the red cell volume, plasma volume, and total blood volume were measured before and after treatment. In the CAPD patients there was a marked expansion of the red cell volume from 912 +/- 127 to 1471 +/- 222 ml (P = 0.004) and a concomitant contraction of the plasma volume from 3932 +/- 250 to 3178 +/- 326 ml (P = 0.005), leaving the blood volume unchanged from 4843 +/- 352 to 4649 +/- 503 ml. Predialysis patients had a similar expansion of the red cell volume from 733 +/- 59 to 1304 +/- 161 ml (P = 0.017) but no contraction of the plasma volume (from 3417 +/- 354 to 3314 +/- 260 ml), so that the blood volume tended to expand from 4149 +/- 347 to 4618 +/- 414 ml (P = 0.053).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1990

NADPH-cytochrome P-450 reductase. Physical properties and redox behavior in the absence of the FAD moiety.

NADPH-cytochrome P-450 reductase contains one molecule each of FMN and FAD. The FAD moiety has been selectively removed, producing the FMN reductase. The FMN reductase is stable and enzymatic activity is reconstituted with either FAD or FMN. FMN remains tightly bound, but can both dissociate from the FMN site and bind to the vacant FAD site. The amount of FMN bound in the FAD site is minimal under specific experimental conditions. There are at least two conformational subpopulations of the FMN reductase; NADP dissociates readily from one but extremely slowly from the other. Rapid dissociation of NADP is regained upon reconstitution with FAD. The one-electron redox state of the FMN reductase is thermodynamically stabilized, though to a lesser degree than in the holoreductase. When two-electron reduced FMN reductase is exposed to oxygen, a stable species with an absorbance peak at 580 nm forms rapidly and quantitatively. This species has been identified by electron paramagnetic resonance spectroscopy as the neutral radical of FMN and is indistinguishable from the air-stable radical of the holoreductase. The redox behavior of the FMN reductase is in agreement with properties proposed previously for the FMN site.

Animals↗