Biomedical subjects

G W Hunter

Publications and source records attributed to G W Hunter.

15 recordsLinked to original sources

PubMed2002

Interstitial microdeletion of chromosome 1p in two siblings.

Two half-siblings are described with what we believe to be the second and third cases identified of the microdeletion, del(1)(p32.1p32.3). Both siblings had a tethered cord and had mental retardation, but otherwise their phenotypic presentations were quite different. The sister had failure to thrive, congenital dysplasia of the hip, absent corpus callosum, Chiari I malformation, and syringomyelia. The brother experienced neonatal seizures secondary to a hemorrhagic stroke. He had an accessory thumb, inguinal hernia, cryptorchidism, urinary reflux, and cholelithiasis. Although these children have only delayed development in common with the previously reported case, they help to further define chromosomal deletions in this area of chromosome 1. As yet, no clear phenotypic picture has emerged.

Adolescent↗

PubMed2001

Role of cysteine residues in structural stability and function of a transmembrane helix bundle.

To study the structural and functional roles of the cysteine residues at positions 36, 41, and 46 in the transmembrane domain of phospholamban (PLB), we have used Fmoc (N-(9-fluorenyl)methoxycarbonyl) solid-phase peptide synthesis to prepare alpha-amino-n-butyric acid (Abu)-PLB, the analogue in which all three cysteine residues are replaced by Abu. Whereas previous studies have shown that replacement of the three Cys residues by Ala (producing Ala-PLB) greatly destabilizes the pentameric structure, we hypothesized that replacement of Cys with Abu, which is isosteric to Cys, might preserve the pentameric stability. Therefore, we compared the oligomeric structure (from SDS-polyacrylamide gel electrophoresis) and function (inhibition of the Ca-ATPase in reconstituted membranes) of Abu-PLB with those of synthetic wild-type PLB and Ala-PLB. Molecular modeling provides structural and energetic insight into the different oligomeric stabilities of these molecules. We conclude that 1) the Cys residues of PLB are not necessary for pentamer formation or inhibitory function; 2) the steric properties of cysteine residues in the PLB transmembrane domain contribute substantially to pentameric stability, whereas the polar or chemical properties of the sulfhydryl group play only a minor role; 3) the functional potency of these PLB variants does not correlate with oligomeric stability; and 4) acetylation of the N-terminal methionine has neither a functional nor a structural effect in full-length PLB.

Alanine↗

PubMed1999

Lysophosphatidylcholine modulates catalytically important motions of the Ca-ATPase phosphorylation domain.

Catalytically important motions of the Ca-ATPase, modulated by the physical properties of surrounding membrane phospholipids, have been suggested to be rate-limiting under physiological conditions. To identify the nature of the structural coupling between the Ca-ATPase and membrane phospholipids, we have investigated the functional and structural effects resulting from the incorporation of the lysophospholipid 1-myristoyl-2-hydroxy-sn-glycerol-3-phosphocholine (LPC) into native sarcoplasmic reticulum (SR) membranes. Nonsolubilizing concentrations of LPC abolish changes in fluorescence signals associated with either intrinsic or extrinsic chromophores that monitor normal conformational transitions accompanying calcium activation of the Ca-ATPase. There are corresponding decreases in the rates of calcium transport coupled to ATP hydrolysis, suggesting that LPC may increase conformational barriers associated with catalytic function. Fluorescence anisotropy measurements of the lipid analogue 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) partitioned into SR membranes indicate that LPC does not significantly modify lipid acyl chain rotational dynamics, suggesting differences in headgroup conformation between LPC and diacylglycerol phosphatidylcholines. Complementary measurements using phosphorescence anisotropy of erythrosin isothiocyanate at Lys464 on the Ca-ATPase provide a measure of the dynamic structure of the phosphorylation domain, and indicate that LPC restricts the amplitude of rotational motion. These results suggest a structural linkage between the cytosolic phosphorylation domain and the conformation of membrane phospholipid headgroups. Thus, changes in membrane phospholipid composition can modulate membrane surface properties and affect catalytically important motions of the Ca-ATPase in a manner that suggests a role for LPC generated during signal transduction.

Adenosine Triphosphate↗

PubMed1999

Phosphatidylethanolamine modulates Ca-ATPase function and dynamics.

Phospholipids containing phosphoethanolamine (PE) headgroups within biological membranes have been suggested to be important with respect to the functional regulation of membrane proteins, including the Ca-ATPase in sarcoplasmic reticulum (SR). To investigate the role of PE headgroups in modulating the catalytic activity of the Ca-ATPase, we have reconstituted the Ca-ATPase into unilamellar liposomes containing defined amounts of dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC). The enzymatic activity of the Ca-ATPase progressively increases upon incorporation of increasing amounts of PE into reconstituted vesicles, and approaches that characteristic of native SR membranes. To identify structural changes that correlate with enzyme activation, we have used frequency-domain phosphorescence spectroscopy to measure the rotational dynamics of erythrosin isothiocyanate covalently bound to Lys464 in the phosphorylation domain of the Ca-ATPase. Progressive increases in the rotational dynamics of the phosphorylation domain result from the incorporation of increasing amounts of DOPE, and correlate with enhanced enzymatic function. These results suggest that PE headgroups induce dynamic structural rearrangements involving the phosphorylation domain that modify the rates of nucleotide utilization. In contrast, no changes in the rotational dynamics of the lipid acyl chains are observed irrespective of the PE content. Therefore, the enhanced ATP hydrolytic activity associated with the incorporation of DOPE into these proteoliposomes is the result of specific noncovalent interactions involving PE phospholipid headgroups and the Ca-ATPase.

Calcium-Transporting ATPases↗

PubMed1998

Phospholipid acyl chain rotational dynamics are independent of headgroup structure in unilamellar vesicles containing binary mixtures of dioleoyl-phosphatidylcholine and dioleoyl-phosphatidylethanolamine.

We have examined relationships between phospholipid headgroup structure and acyl chain dynamics, and their respective roles in modulating the physical properties of biological membranes. Fluorescence lifetime and anisotropy measurements were used to assess structural changes involving the lipid acyl chains in homogeneous populations of small and large unilamellar vesicles containing binary mixtures of dioleoyl-phosphatidylcholine (PC) and dioleoyl-phosphatidylethanolamine (PE) in the liquid-crystalline (Lalpha) phase. These measurements involve three different fluorescent lipid analogs containing diphenylhexatriene (DPH) linked to either a trimethylamine moiety (i.e., TMA-DPH) or the sn-1 position of monostearoyl-phospholipids containing PC or PE headgroups (i.e., DPH-PC and DPH-PE). The average lifetimes, rotational correlation times, and order parameters associated with DPH-PC and DPH-PE are virtually identical, and are not affected by alterations in the PE content of the membrane. These results suggest that the average cross-sectional areas of the phospholipid acyl chains of DOPE and DOPC relative to the membrane normal are similar in these unilamellar vesicles. Since PC headgroups are larger than those of PE, differences in the relative orientation of the phosphocholine and phosphoethanolamine moieties relative to the membrane surface probably function to maintain optimal van der Waals contact interactions between acyl chains. On the other hand, the average lifetime associated with TMA-DPH, whose chromophoric group is near the membrane surface, increases with increasing PE content. The position of TMA-DPH relative to the membrane surface does not change, since the rotational dynamics of TMA-DPH are independent of the PE concentration. Therefore, alterations in the average lifetime of TMA-DPH results from polarity differences near the membrane surface at the level of the glycerol backbone. These results are discussed in terms of how differences in the average conformation of the glycerol backbones or phospholipid headgroups of PE and PC have the potential to regulate membrane function.

Molecular Structure↗

PubMed1982

Control of schistosomiasis japonica in the Nagatoishi area of Kurume, Japan.

A pilot experiment using NaPCP as a molluscicide to control schistosomiasis japonica was initiated in 1950--51 in Nagatoishi-cho, Kurume, Japan, where 1,050 persons lived behind dikes built to prevent flooding from the Chikugo River. They farmed 60 ha of rice, and 72.9% of them were infected with schistosomiasis. At the end of 2 years, 99.5% of the snails (Oncomelania h. nosophora) were controlled and new cases dropped from 30--35 per year to 5 and 0 at the end of the 1st and 2nd year, respectively. Mollusciciding was continued by Japanese, and paddy irrigation ditches were lined with concrete by 1958. Land reclamation, involving conversion of cultivated land in the river bottom to a golf course, resulted in virtual elimination of infected snails from this area and, when found, snails were uninfected. Using immunologic tests (intradermal, complement fixation, and circumoval precipitation) plus multiple stool examinations in 1972 and 1978, it was possible to demonstrate a marked decrease in cases of schistosomiasis in children 15 years of age or younger. These results were significantly different (P less than 0.001) from those found in similar tests run in 1940 and 1966. By 1978 all children in the Nagatoishi area of Kurume, Japan, were negative for Schistosoma japonicum infection.

Adult↗

PubMed1976

Satisfaction with medical care during pregnancy and delivery.

Societal attitudes toward the medical profession are apparently undergoing a change from awe and total respect to a more critical assessing of accountability and credibility. Based on mass media reports and the increasing number of malpractice suits, it would appear that a rational, unbiased review of medical doctors, hospital personnel, and care received is in order. This review should be concerned with technical aspects of medicine as determined by highly competent professionals and the consumer's view of the medical care he receives. The latter review should logically be taken directly to the consumers of medical care to determine their satisfaction with the care they received. Because of the varied areas of specialty within the medical profession, there are different types of relationships between doctors and their patients. The obstetrician, for instance, is usually associated with pregnancy as a joyful event, in contrast to a surgeon whose diagnosis may seldom be accompanied by joy. Satisfaction with medical care could thus be expected to vary according to the area of specialty and may be related to factors over which doctors have no control, factors which initially bring the patient to the doctor for care. The degree of anxiety related to the patient's condition could also be expected to contribute to the degree of satisfaction expressed by the patient.

Consumer Behavior↗

PubMed1975