Search PubMed⌕ Search

Biomedical subjects

David J Williams

Publications and source records attributed to David J Williams.

65 records · Page 4Linked to original sources
PubMed2002

Synthesis of a homoleptic niobium(V) thiolate complex and the preparation of niobium sulfide via thio "sol-gel" and vapor phase thin-film experiments.

Reaction of [Nb(NMe(2))(5)] with 10 equiv of 2,6-Me(2)C(6)H(3)SH in toluene results in the formation of red crystals of [Nb(SC(6)H(3)Me(2)-2,6)(5)]. Crystal structure analysis of [Nb(SC(6)H(3)Me(2)-2,6)(5)] showed that the niobium center adopts a distorted trigonal bipyramidal geometry. Niobium disulfide, NbS(2), has been successfully prepared via a thio "sol-gel" process using [Nb(SC(6)H(3)Me(2)-2,6)(5)] as the metal source. In contrast, vapor phase thin-film studies revealed that [Nb(SC(6)H(3)Me(2)-2,6)(5)] functions as a single-source precursor to NbS films.

Journal Article↗
PubMed2002

Characterization of a murine gene encoding a developmentally regulated cytoplasmic dual-specificity mitogen-activated protein kinase phosphatase.

Mitogen-activated protein kinases (MAPKs) play a vital role in cellular growth control, but far less is known about these signalling pathways in the context of embryonic development. Duration and magnitude of MAPK activation are crucial factors in cell fate decisions, and reflect a balance between the activities of upstream activators and specific MAPK phosphatases (MKPs). Here, we report the isolation and characterization of the murine Pyst3 gene, which encodes a cytosolic dual-specificity MKP. This enzyme selectively interacts with, and is catalytically activated by, the 'classical' extracellular signal-regulated kinases (ERKs) 1 and 2 and, to a lesser extent, the stress-activated MAPK p38alpha. These properties define the ability of this enzyme to dephosphorylate and inactivate ERK1/2 and p38alpha, but not JNK (c-Jun N-terminal kinase) in vivo. When expressed in mammalian cells, the Pyst3 protein is predominantly cytoplasmic. Furthermore, leptomycin B causes a complete redistribution of the protein to the nucleus, implicating a CRM (chromosomal region maintenance)1/exportin 1-dependent nuclear export signal in determining the subcellular localization of this enzyme. Finally, whole-mount in situ hybridization studies in mouse embryos reveal that the Pyst3 gene is expressed specifically in the placenta, developing liver and in migratory muscle cells. Our results suggest that this enzyme may have a critical role in regulating the activity of MAPK signalling during early development and organogenesis.

Amino Acid Sequence↗
PubMed2002

Unified route to the palmarumycin and preussomerin natural products. Enantioselective synthesis of (-)-preussomerin G.

The total syntheses of eight members of the palmarumycin family have been achieved, with identification of the absolute stereochemistry for three of these natural products. In addition, the ras-farnesyl transferase inhibitor (-)-preussomerin G has been synthesized, achieving the first enantioselective route for accessing this family of natural products. Highlights of the synthetic work include an asymmetric epoxidation of a cyclic enone in excellent yield and enantiomeric excess and a potentially biomimetic oxidative spirocyclization for the introduction of the bis-spiroketal array unique to the preussomerin natural products.

Biological Products↗
PubMed2002

Associations between human liver and kidney cadmium content and immunochemically detected CYP4A11 apoprotein.

This present study was undertaken to assess potential effects of cadmium on CYP4A11 apoprotein in human liver and kidney as detected by Western blotting using a highly specific anti-peptide antibody. Liver and kidney cortex samples were autopsy specimens of 37 individuals (26 males and 11 females) whose ages ranged from 3 to 89 years. All were Caucasians who had not been exposed to cadmium in the workplace. Reduced CYP4A11 apoprotein levels were found in chronic hepatitis samples and in liver samples showing fatty changes. In contrast, increased CYP4A11 apoprotein levels were found in liver samples having higher cadmium content compared to the lower cadmium content samples. Increased CYP4A11 levels were also found in liver samples from female donors, compared to male donors; the difference being attributable to higher female liver cadmium burden. In distinction to liver, lowered CYP4A11 levels were seen in the kidney cortex samples which have high cadmium content. It is proposed here that the difference between the absolute cadmium burden of the liver and kidney samples may be responsible for the different patterns of expression of CYP4A11 in these two tissues. Further, since cadmium exposure may be associated with derangement in blood pressure control, it is interesting to note the possible relationship between altered CYP4A11-dependent production of arachidonic acid hydroxy and epoxy metabolites in kidney cortex and altered control of blood pressure. Our findings provide a possible link between these observations.

Adolescent↗
PubMed2002

Direct conversion of macrocyclic furans into macrocyclic isothiazoles.

The first calixhetarenes with more than one heteroatom in the constituent rings are prepared in one step by treatment of calix[4]furan 1a and calix[6]furan 1b with ethyl carbamate, thionyl chloride and pyridine to give 2, 3, 4 and 5, 6, 7 respectively; these products have been characterised by X-ray crystallography which reveals that in 2 all eight heteroatoms lie on one face of the macrocyle.

Journal Article↗
PubMed2002

Rapid and complete occlusion of a heat and moisture exchange filter by pulmonary edema (clinical report).

PURPOSE: A case of near fatal obstruction of a breathing system is described, due to occlusion of a heat and moisture exchange filter in a patient with pulmonary edema. Previous reports have described cases of mechanical obstruction to fresh gas flow due to an accumulation of a bolus of fluid within the filter housing. However, in this case, the cause of occlusion was due to the protein and cell debris contained in a small amount of pulmonary edema fluid interacting with the filter membrane. CLINICAL FEATURES: Obstruction occurred rapidly and without warning, and was difficult to differentiate from the more common diagnoses of bronchospasm or tension pneumothorax. Outwardly the filter appeared normal, and routine protocol for emergency management of suspected breathing system obstruction initially failed to identify the site of occlusion. CONCLUSION: Minimal contamination by proteinaceous fluid may cause rapid and complete occlusion of a breathing system filter. Blockage of the breathing system filter and catheter mount should be considered in cases of unexplained breathing system occlusion. The use of a fresh breathing system without a filter for each patient, as recommended by The American Center for Disease Control and the American Society of Anesthesiologists, would have prevented this scenario from occurring.

Adult↗
PubMed2002

Vascular responsiveness to brachial artery infusions of phenylephrine during isoflurane and desflurane anesthesia.

UNLABELLED: Compared with equi-minimum alveolar anesthetic concentration (MAC) isoflurane, desflurane is associated with greater levels of sympathetic nerve activity in humans but similar reductions in blood pressure. To explore these divergent effects, we evaluated vascular alpha(1)-adrenoceptor responses in the human forearm during isoflurane and desflurane anesthesia to determine if alpha(1)-adrenoceptor responses were more substantially attenuated during desflurane administration. Bilateral forearm venous occlusion plethysmography was used to examine arterial blood flow and to determine changes in forearm vascular resistance during brachial artery infusions of saline and phenylephrine (0.2, 0.4, 0.8, and 1.6 microg/min) in 22 conscious subjects and during anesthesia with 0.65 and 1.3 MAC isoflurane or desflurane. Infusion of phenylephrine into the brachial artery increased the forearm vascular resistance in a dose-dependent manner. The arterial response to phenylephrine was significantly attenuated by 0.65 and 1.3 MAC desflurane and similarly attenuated during 1.3 MAC isoflurane (P < 0.05). Impaired arterial alpha(1)-adrenoceptor responsiveness occurred during desflurane. However, this effect was statistically similar (P > 0.05) to the impaired responses during isoflurane. Blood pressure decreases during volatile anesthesia may be, in part, caused by decreased alpha(1)-adrenoceptor responsiveness. IMPLICATIONS: alpha-receptors on blood vessels regulate constriction and dilation and therefore modulate blood pressure. This research indicates that vasoconstriction via the alpha(1)-receptor vascular response is impaired during isoflurane and desflurane anesthesia.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Cadmium levels in the lung, liver, kidney cortex, and urine samples from Australians without occupational exposure to metals.

The authors undertook this study to assess levels of cadmium exposure in the general population. Samples of lung, liver, and kidney were obtained from 61 cadavers (43 males, 18 females; 2-89 yr of age, mean age = 38.5 yr) who died from accidental causes and who were subject to postmortem examinations at the John Tonge Centre for Forensic Sciences, Queensland Health Scientific Services, Brisbane, Australia, in 1997 and 1998. Samples of bladder urine were also obtained from 22 cadavers. Tissue and urine samples were analyzed for cadmium, zinc, and copper with inductively coupled plasm (ICP) mass spectrometry. The overall mean values for cadmium in the lung, liver, and kidney cortex samples were 0.13, 0.95, and 15.45 microg/gm wet tissue weight. The average renal cadmium level in subjects with high lung-cadmium levels (n = 13) was 6 microg/gm wet tissue weight higher than that of similarly aged subjects who had medium lung-cadmium levels (n = 30). In females, the average level of cadmium in the liver was 74% greater than in males, and the average liver cadmium in females with high lung-cadmium levels was 100% higher than in males in the same age range who had the same high lung-cadmium levels. Renal cadmium accumulation tended to be greater in females than in males who were in the same age range and who had similar lung-cadmium levels, a result that suggested that there was a higher absorption rate of cadmium in females. The mean value for a urinary cadmium excretion of 2.30 microg/gm creatinine was found in a subset of samples that had a mean age of 39 yr and a renal cortex cadmium concentration of 18.6 microg/gm wet tissue weight. Urinary cadmium excretion rates were correlated more strongly with lung and kidney cadmium content than with age or liver cadmium levels. The results suggest that urinary cadmium excretion may be increased in smokers and could provide some estimate of body cadmium burdens in future Australian epidemiological studies.

Adult↗
PubMedDate not supplied

Snakebite mortality at Port Moresby General Hospital, Papua New Guinea, 1992-2001.

OBJECTIVE: Fatal snakebites at Port Moresby General Hospital (PMGH), Papua New Guinea (PNG), were examined to identify interventions that may improve patient survival. DESIGN: Retrospective case series. SUBJECTS AND SETTING: Inpatients at PMGH who presented with snakebite, had evidence of envenomation, and died as inpatients between 1 January 1992 and 31 December 2001. OUTCOME MEASURES: Number and cause of fatalities; ventilation bed-days; antivenom timing, dose and price. RESULTS: 87 deaths occurred among 722 snakebite admissions to the intensive care unit (ICU). Of these 722 patients, 82.5% were ventilated, representing 45% of all ventilated ICU patients and 60% (3430/5717) of all ICU ventilator bed-days. The median duration of ventilation in fatal snakebite cases was significantly less than in non-fatal cases for children (3.0 v. 4.5 days) and adults (3.0 v. 5.0 days). The case-fatality rate for children (14.6%) was significantly greater than that for adults (8.2%). Sixty fatalities were examined in detail: 75% received blood products; 53% received antivenom (mostly a single ampoule of polyvalent), but only 5% received antivenom < or = 4 hours post-bite. Major causes of death included respiratory complications (50%), probable intracerebral haemorrhage (17%), and renal failure (10%). Antivenom unit costs increased significantly over the decade; in 2000 an ampoule of polyvalent antivenom was 40-fold more expensive in PNG than in Australia on a gross domestic product (A dollars) per capita basis. CONCLUSIONS: Management of severe snakebite is a major challenge for PMGH. Improved antivenom procurement and use policies (including increased use of appropriate monovalent antivenoms), combined with targeted snakebite education interventions (community- and hospital-based), are key interventions to reduce the ongoing toll from snakebite.

Adolescent↗