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Biomedical subjects

M Spencer

Publications and source records attributed to M Spencer.

At least 19 recordsLinked to original sources

The history of malaria control in the southwest Pacific region, with particular reference to Papua New Guinea and the Solomon Islands.

A number of phases in the history of malaria control in the Southwest Pacific Region can be recognized. During the first phase (1898-1923) it was known that anopheline mosquitoes carried malaria, but as yet the identity of the local vectors had not been established. The incrimination of the vectors in 1923 gave a sound basis for control, which remained largely urban in location except for the distribution of the larvivorous fish Gambusia affinis. The exigencies of the Pacific War and the presence of large numbers of combat troops in malarious areas resulted in the establishment of Mobile Entomological Sections and Malaria Control Units, and the collection and collation of large amounts of entomological, epidemiological and parasitological information. Larval control measures, carried out with very large labour lines and with military precision, were effective. The availability of dichlorodiphenyltrichloroethane (DDT) in 1943 made attack on adult vector mosquitoes also possible; DDT was applied widely in Papua New Guinea and the Solomon Islands by spraying and misting with adulticidal devices in tents and buildings, and by release from aircraft. Atebrin and dimethylphthalate also became available in quantity, for the suppression and treatment of malaria and for personal protection against mosquitoes, respectively. The wartime successes gave hope for peacetime anti-malaria activities carried out within village communities, which to this stage had not been seriously attempted. By three years after the end of the war the World Health Organization, the South Pacific Commission, and local administrative structures had been set up. Extensive investigations into the nature and severity of malaria endemicity were undertaken and recorded. Initially malaria control remained localized and largely urban, and was carried out by conventional antilarval measures, but at the same time new anti-malaria compounds became available for prophylaxis and treatment. Uncertainty still remained as to the usefulness of indoor spraying with DDT against anophelines of the punctulatus group. By 1953 the results of detailed studies in test huts set up for the purpose were known to been couraging, and the decision was made in 1954 to begin in Netherlands New Guinea (West Irian) a pilot project of routine residual spraying with DDT in village houses.(ABSTRACT TRUNCATED AT 400 WORDS)

History, 19th Century

Dose-dependent responses to nerve growth factor by adult rat cholinergic medial septum and neostriatum neurons.

This study describes the relationship between the concentration of intraventricularly infused nerve growth factor (NGF) and several responses by axotomized cholinergic medial septum neurons and normal cholinergic neostriatal neurons of the adult rat. NGF infused for 14 days starting either immediately after a unilateral fimbria-fornix transection or after a 2-week delay period elicited similar dose-response relationships for the maintenance or restoration of ChAT and NGF receptor positivity and cell body size and for intraseptal 'sprouting' of the axotomized medial septum neurons. Thus, in the medial septum it appears that the expression of 'marker' molecules, cell body size and the induction of 'sprouting' are regulated by virtually the same concentrations of NGF in the two treatment strategies. This suggests that NGF has a general regulatory role and injured but untreated neurons remain fully susceptible to NGF at least up to 2 weeks after the lesion. A 14-day infusion with NGF also induced an above-normal cell body size (hypertrophy) both in axotomized medial septum and in intact striatal cholinergic neurons. The hypertrophic response of normal striatal neurons required less NGF than did that of medial septum neurons. Since the striatal response began to be detectable at a similar concentration as that required for the full maintenance or restoration of ChAT and NGF receptor positivity it could be seen as an unwanted side-effect. The definition of a sub-optimal dose with which a significant, but not maximal response can be elicited will allow future evaluations of potentially additive or synergistic actions by other agents.

Animals

Expression of a whey acidic protein transgene during mammary development. Evidence for different mechanisms of regulation during pregnancy and lactation.

Expression of the mouse whey acidic protein (WAP) gene is specific to the mammary gland, is induced several thousand-fold during pregnancy, and is under the control of steroid and peptide hormones. To study developmental regulation of the mouse WAP gene, a 7.2-kilobase (kb) WAP transgene, including 2.6 kb of 5'- and 1.6 kb of 3'-flanking sequences, was introduced into mice. Of the 13 lines of mice examined, 6 expressed the transgenes during lactation at levels between 3 and 54% of the endogenous gene. Although expression was dependent on the site of integration, the transgenes within a given locus were expressed in a copy number-dependent manner and were coordinately regulated. The WAP transgenes were expressed specifically in the mammary gland, but showed a deregulated pattern of expression during mammary development. In all six lines of mice, induction of the WAP transgenes during pregnancy preceded that of the endogenous gene. During lactation, expression in two lines increased coordinately with the endogenous gene, and in three other lines of mice, transgene expression decreased to a basal level. These data indicate that the 7.2-kb gene contains some but not all of the elements necessary for correct developmental regulation. At a functional level it appears as if a repressor element, which inactivates the endogenous gene until late pregnancy, and an element necessary for induction during lactation are absent from the transgene. Complementary results from developmental and hormone induction studies suggest that WAP gene expression during pregnancy and lactation is mediated by different mechanisms.

Animals

Recoverin: a calcium sensitive activator of retinal rod guanylate cyclase.

Vertebrate retinal photoreceptors recover from photoexcitation-induced hydrolysis of guanosine 3', 5'-monophosphate (cyclic GMP) by resynthesizing cyclic GMP, which reopens cation channels that have been closed by light. Activation of guanylate cyclase by light-induced depletion of cytosolic calcium is a key event in this recovery process. This cyclase has now been shown to be regulated by a 23-kilodalton calcium binding protein. The protein is present in both rod and cone photoreceptors and was named recoverin because it promotes recovery of the dark state. The amino acid sequence of recoverin exhibits three potential calcium binding sites (EF hands). That recoverin binds calcium was confirmed with calcium-45 and by observing calcium-induced changes in its tryptophan fluorescence. Recoverin activated guanylate cyclase when free calcium was lowered from 450 to 40 nM, an effect that was blocked by an antibody to recoverin. Thus, guanylate cyclase in retinal rods is stimulated during recovery by the calcium-free form of recoverin. A comparison of recoverin with other calcium binding proteins reveals that it may represent, along with the protein visinin, a family of proteins that are regulated by submicromolar calcium concentrations.

Amino Acid Sequence

Peripheral visual changes and spatial attention.

Three experiments are reported investigating the attentional effects of peripheral visual changes. In agreement with previous work, experiment 1 demonstrated facilitatory and inhibitory effects of a peripheral visual change on the latency of peripheral target detection. However, after a few minutes practice the facilitatory effect disappeared entirely. The inhibitory effect, though slightly reduced in later blocks, remained significant. Hence, the two effects are dissociable and not inter-dependent as argued by Maylor (1985). In experiments 2 and 3 the perceptual salience of the peripheral cue was manipulated. With a low energy, barely noticeable cue there was no reduction in either facilitation or inhibition as a function of practice. In contrast, the attentional effects of cues higher in energy tended to diminish with practice. Theoretical implications of these data are discussed.

Adult

A randomised placebo-controlled trial of topical cysteamine therapy in patients with nephropathic cystinosis.

Five patients with nephropathic cystinosis were evaluated to assess the ability of topical cysteamine to clear corneal cystine crystals. All patients were randomised to receive topical cysteamine 0.2% six times a day in one eye with normal saline in the other eye as a control. All five patients showed some improvement in visual symptoms (photophobia, blepharospasm and visual acuity) together with an improvement in corneal crystal density. Three of these also had an improvement in Snellen visual acuity and contrast sensitivity.

Adolescent

Membrane skeleton protein 4.1 in inner segments of retinal cones.

Retinal cone photoreceptors are polarized cells with discrete functional compartments. Little is known of the membrane-skeleton components in cones responsible for the maintenance of cellular morphology and compartmentalization of integral membrane proteins. The authors describe a high density of the membrane-skeleton protein 4.1 in the myoid region of cones in retinas of developing and adult frogs, and adult lizards, turtles, and chicks. In the developing retina, a discrete locus of protein 4.1 is first detected by immunocytochemistry in the cone myoid after the completion of photoreceptor synaptogenesis. Protein 4.1 immunoreactivity expands to line the plasma membrane of the myoid after cones attain their adult proportions. Nonerythroid alpha-spectrin and protein 4.1 colocalize in the cone myoid, and both are in close proximity to long bundles of f-actin that traverse the myoid and extend from the cone outer segment to the external limiting membrane. By analogy to the erythrocyte, where protein 4.1 modulates the interaction of spectrin and actin to regulate cell shape, the authors propose that protein 4.1 interacts with nonerythroid alpha-spectrin and f-actin in cones and plays a role in the maintenance of cone inner segment morphology.

Actins

Membrane skeleton protein 4.1 in developing Xenopus: expression in postmitotic cells of the retina.

Membrane skeleton protein 4.1 plays a key role in modulating the interactions of spectrin, actin, and integral membrane proteins in erythroid and nonerythroid cells. We have investigated its structure and expression during embryonic development of Xenopus laevis. An analysis of the complete 2758-nucleotide sequence and predicted translation of 801 amino acids (85.5 kDa) of X. laevis oocyte protein 4.1 reveals that, within overlapping regions, oocyte protein 4.1 is 74% identical to a composite amino acid sequence of human erythroid and lymphoid protein 4.1 and has an identity similar to that of amino acid motifs variably expressed in either human erythroid or lymphoid protein 4.1 S1 nuclease protection analysis demonstrates the presence of a single species of protein 4.1 transcript in embryos. Antibodies produced against X. laevis protein 4.1 fusion protein recognize two bands of 180 and 115 kDa on Western blots of X. laevis embryos and retina and, using immunocytochemical techniques, label the developing retina most intensely. In vitro transcription of a cDNA construct fully encoding X. laevis protein 4.1 yields a synthetic mRNA which, when translated in vitro, produces a polypeptide that comigrates on SDS-polyacrylamide gels with the 115-kDa form of embryos and retina. Protein 4.1 is found exclusively in photoreceptors following the terminal mitosis of retinal neurons. When retinal synaptogenesis is complete, protein 4.1 is also expressed in the inner retina. In adult amphibian retinas, protein 4.1 is detected in photoreceptors, bipolar cells, and ganglion cell axons. As these cell types have previously been shown to express spectrin, actin, and ankyrin, it is likely that the membrane skeleton of erythrocytes and retinal cells share functional similarities.

Amino Acid Sequence

Design and testing of external fixator bone screws.

In external fixation, bone screw loosening still presents a major clinical problem. For this study, the design factors influencing the mechanics of the bone-screw interface were analysed and various experimental screws designed with the intention of maximizing the strength and stiffness of the inserted screw. Push-in, pull-out and bending tests were then carried out on the three experimental screws, and on two commercially available screws in both a synthetic material and in cadaveric bone; photoelastic tests on different screw threadforms were also performed. The results of the push-in and pull-out tests indicate that both the screw threadform and cutting head have a significant effect on the holding strength of the screw. The photoelastic tests show that most of the applied load is distributed over the first few threads closest to the load, and that the area between the thread crests is subjected to high shear stresses.

Biomechanical Phenomena

Long-term follow-up of the ileoanal anastomosis in children and young adults.

The purpose of this study was to carry out a long-term study of the ileoanal anastomosis (IAA) in children and young adults, comparing the straight IAA to the J pouch. One hundred twenty-one young people who had undergone IAA were studied, with 114 available for long-term follow-up. One hundred one were 18 years and under. Forty-nine patients had a straight IAA and 72 had a J-pouch reservoir. There were no deaths. After surgery, three children had intraabdominal sepsis and one had pelvic sepsis, but it did not lead to excision of the IAA. The mean stool frequency in all 114 patients was 5.0 +/- 2.5 per day and 1.2 +/- 1.1 at night. The mean number of stools for the straight IAA was 6 per day and 2.1 at night. The mean number of stools for the straight IAA with balloon dilations was 5.8 per day and 1.2 at night, and for the J pouch it was 4 per day and 1 at night. Patients with both the J pouch and straight IAA had good to excellent sensation, with patients with the J pouch always able to distinguish flatus from stool in 87% of patients and almost always in 13%. Daytime continence was very good in both groups. Moderate nighttime loss of stool occurred in 10 patients, 6 with a straight IAA and 4 with a J pouch. Ninety-five percent of the 114 patients were satisfied or very satisfied, with most children with a J pouch very satisfied. The J pouch remains the procedure of choice in young people.

Adolescent

Structure, organization, and expression of the rat cardiac myosin light chain-2 gene. Identification of a 250-base pair fragment which confers cardiac-specific expression.

The present study characterized the structure, organization, and expression of the rat cardiac myosin light chain (MLC) -2 gene. The rat cardiac MLC-2 gene has seven exons which display complete conservation with the exon structure of the rat fast twitch skeletal MLC-2 gene. A 250-base pair (bp) sequence of the 5'-flanking region contains CArG motifs and additional cis elements, each greater than 10 bp in length, which were conserved in sequence and relative position with the chick cardiac MLC-2 gene. A series of MLC-2/luciferase fusion genes consisting of nested 5' deletions of the MLC-2 5'-flanking region were constructed and transfected into primary neonatal rat myocardial cells and a non-myocardial cell line (CV-1), demonstrating that this 250 bp of the MLC-2 5'-flanking region was sufficient to confer cardiac specific expression on a luciferase reporter gene. This study suggests the presence of important proximal regulatory sequences in the MLC-2 5'-flanking region which are capable of directing the cardiac specific expression of the rat cardiac myosin light chain-2 gene.

Amino Acid Sequence

Depression and Alzheimer's disease.

In his classic case, Alzheimer described cognitive symptoms such as amnesia, aphasia, and apraxia and noncognitive symptoms such as delusions and agitation. Recent studies have suggested that depression also occurs in Alzheimer's disease. In this study, 144 patients who met criteria for Alzheimer's disease were examined for depression on a modified version of the Present State Examination. The prevalence rate of major depression was 17%. The depressed Alzheimer's disease patients were more cognitively impaired and more disabled than the nondepressed patients. Studies are needed to clarify the etiology and treatment of depression in Alzheimer's disease.

Aged

Semantic activation and implicit memory in Alzheimer disease.

Patients with Alzheimer disease (AD) invariably display pronounced deficits in verbal memory when retention is tested explicitly. The present study examined the possibility that tasks which require memory only implicitly would be performed normally. Moderately demented patients with probable AD were severely impaired in free recall of a word list. On a subsequent word association test, the AD patients were less likely than normals to give items from the recall list as their word associations. The results suggest that implicit verbal memory, as well as explicit memory, is impaired in AD. While the magnitude of the activation effect was significantly reduced in AD patients, it was uncorrelated with recall performance or a measure of global cognitive functioning. Memory activation may thus depend on neural circuitry outside the traditional (i.e. temporo-limbic) memory system.

Aged

Distribution of membrane proteins in mechanically dissociated retinal rods.

Solitary rods were isolated from frog retinas by mechanical dissociation. Typically, the rods cleave sclerad to the nucleus and consist of outer segments with attached partial inner segments with either tapered or rounded profiles. Light and electron microscopy reveal that the outer and inner segments of rods with tapered inner segments, like rods in the intact retina, are joined by a single connecting cilium. In contrast, the outer and inner segments of rods with rounded inner segments are fused, with no extracellular cleft between the two segments. Opsin distribution was studied in both unfused and fused rods by light and electron microscopic immunocytochemistry. Extensive surface labeling is restricted to the outer segments of tapered rods, as observed in vivo. In contrast, both inner and outer segments of rods with rounded inner segments (fused) label heavily with anti-opsin. Thus opsin, a mobile membrane protein, diffuses from the outer to the inner segment of fused rods. Segregated distribution of opsin in unfused rods suggests that the connecting cilium and/or its associated structures may normally act as a diffusion barrier between the outer and inner segments to mobile membrane proteins such as opsin. Immunofluorescence studies demonstrate that Na+/K+ ATPase is restricted in distribution to the inner segment and calycal processes of both fused and unfused isolated rods, as observed in vivo. Maintenance of its restricted distribution in fused cells indicates that Na+/K+ ATPase is not mobile and may be tethered in the surface membrane of the inner segment.

Animals

Office management of urinary stomas.

The postoperative care of stoma patients is truly life long. With the excellent stoma equipment available, no patient should be a "stoma cripple." New advances in continent reservoirs will improve patient acceptance and lessen the fear associated with stomas. Finally, close follow-up by both the enterostomal therapy nurse and the surgeon is essential for the complete care of the stoma patient.

Ambulatory Care