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Biomedical subjects

S J King

Publications and source records attributed to S J King.

At least 19 recordsLinked to original sources
PubMed2006

New discoveries of skeletal elements of Hadropithecus stenognathus from Andrahomana Cave, southeastern Madagascar.

Remains of what appears to be a single, subadult Hadropithecus stenognathus were recovered from a previously unexcavated site at Andrahomana Cave (southeastern Madagascar). Specimens found comprise isolated teeth and cranial fragments (including the frontal processes of the orbits), as well as a partial postcranial skeleton. They include the first associated fore- and hind-limb bones, confirming the hind-limb attributions made by Godfrey and co-workers in 1997, and refuting earlier attributions by Lamberton in 1937/1938. Of particular interest here are the previously unknown elements, including a sacrum, other vertebrae and ribs, some hand bones, and the distal epiphysis of a femur. We briefly discuss the functional implications of previously unknown elements. Hadropithecus displayed a combination of characters reminiscent of lemurids, others more like those of the larger-bodied Old World monkeys, and still others more like those of African apes. Yet other characteristics appear unique. Lemurid-like postcranial characteristics may be primitive for the Archaeolemuridae. Hadropithecus diverges from the Lemuridae in the direction of Archaeolemur, but more extremely so. Thus, for example, it exhibits a stronger reduction in the size of the hamulus of the hamate, greater anteroposterior compression of the femoral shaft, and greater asymmetry of the femoral condyles. Nothing in its postcranial anatomy signals a close relationship to either the Indriidae or the Palaeopropithecidae.

Animals↗
PubMed2006

What is the need for additional bladder surgery after bladder augmentation in childhood?

PURPOSE: Bladder augmentation has revolutionized the care of children with a neuropathic bladder but it remains a major surgical procedure. However, the need for subsequent bladder surgery has not been well defined in a large series with long-term followup. MATERIALS AND METHODS: We retrospectively reviewed the records of the first 500 bladder augmentations performed from 1978 to 2003 at our institution. Charts were reviewed for complications requiring additional surgery, including malignancy, bladder perforation, repeat augmentation, bowel obstruction and bladder calculi. Mean and median followup was 13.3 years. RESULTS: Complications occurred in 169 patients (34%) resulting in a total of 254 surgeries. The cumulative risk of further surgery at the bladder level was 0.04 operations per patient per year of augmentation. Three patients (0.6%) had transitional cell carcinoma, of whom all presented with metastatic disease and died. Bladder perforation occurred in 43 patients (8.6%) with a total of 53 events. Of the patients 16 (3.2%) required laparotomy for bowel obstruction and 47 (9.4%) required repeat augmentation. Bladder stones were treated in 75 patients (15%), who required a total of 125 surgeries. CONCLUSIONS: Bladder augmentation provides immeasurable improvements in quality of life but it requires lifelong dedication from the patient, family and health care providers. While the requirements for additional surgery are not trivial, 66% of our patients have not required any further surgery in the augmented bladder.

Child↗
PubMed2006

Treatment of the occult tethered spinal cord for neuropathic bladder: results of sectioning the filum terminale.

PURPOSE: Occult tethered cord syndrome applies to patients with signs and symptoms consistent with a caudal spinal cord malformation despite normal neuroimaging. Although several reports of successful surgical treatment exist, controversy remains with respect to patient selection and efficacy. We present a large series with excellent clinical followup, neuroimaging and urodynamic characterization. MATERIALS AND METHODS: We present our experience with 36 patients at a single institution with preoperative clinical findings, neuroimaging and urodynamics available. Postoperative outcomes were assessed clinically and with urodynamics. We determined predictive parameters to improve patient selection. RESULTS: Approximately 0.04% of pediatric urology clinic visits resulted in neurosurgical referral for the potential of an occult tethered cord. They occurred after failure of a mean of 2 years of aggressive medical management. Daytime urinary incontinence was present in 83% of patients and 47% had encopresis. Preoperative urodynamics were markedly abnormal in all patients with mean bladder capacity 55% of expected capacity. Clinical improvement in urinary symptoms was seen in 72% of patients with resolution of incontinence in 42%. Bowel symptoms improved in 88% of cases, including resolution of encopresis in 53% within 3 months of surgery. Urodynamic improvements were demonstrated in 57% of cases. We were unable to determine preoperative factors that were more likely associated with surgical success. CONCLUSIONS: In a highly select population with severe urinary and fecal dysfunction sectioning a normal-appearing filum terminale can result in significant improvement. We were unable to identify factors that may increase the chance of surgical success.

Adolescent↗
PubMed2005

Building complexity: an in vitro study of cytoplasmic dynein with in vivo implications.

BACKGROUND: Cytoplasmic dynein is the molecular motor responsible for most retrograde microtubule-based vesicular transport. In vitro single-molecule experiments suggest that dynein function is not as robust as that of kinesin-1 or myosin-V because dynein moves only a limited distance (approximately 800 nm) before detaching and can exert a modest (approximately 1 pN) force. However, dynein-driven cargos in vivo move robustly over many microns and exert forces of multiple pN. To determine how to go from limited single-molecule function to robust in vivo transport, we began to build complexity in a controlled manner by using in vitro experiments. RESULTS: We show that a single cytoplasmic dynein motor frequently transitions into an off-pathway unproductive state that impairs net transport. Addition of a second (and/or third) dynein motor, so that cargos are moved by two (or three) motors rather than one, is sufficient to recover several properties of in vivo motion; such properties include long cargo travels, robust motion, and increased forces. Part of this improvement appears to arise from selective suppression of the unproductive state of dynein rather than from a fundamental change in dynein's mechanochemical cycle. CONCLUSIONS: Multiple dyneins working together suppress shortcomings of a single motor and generate robust motion under in vitro conditions. There appears to be no need for additional cofactors (e.g., dynactin) for this improvement. Because cargos are often driven by multiple dyneins in vivo, our results show that changing the number of dynein motors could allow modulation of dynein function from the mediocre single-dynein limit to robust in vivo-like dynein-driven motion.

Animals↗
PubMed2005

Reduced bone density in cystic fibrosis: DeltaF508 mutation is an independent risk factor.

The aim of this cross-sectional study was to determine the prevalence and identify determinants of reduced bone mineral density (BMD) in adults with cystic fibrosis (CF). Adults (88) with CF (mean+/-SD age 29.9+/-7.7 yrs; forced expiratory volume in one second (FEV1) 58.2+/-21.5% of the predicted value) were studied. BMD at the lumbar spine (LS) and femoral neck (FN) and body composition were measured using dual-energy X-ray absorptiometry. Blood and urine were analysed for hormones, bone turnover markers, and the cytokines tumour necrosis factor-alpha, and interleukin-6 and -1beta. FEV1 (% pred); CF genotype; malnutrition; history of growth, development or weight gain delays; and corticosteroid use were analysed. BMD Z-scores were -0.58+/-1.30 (mean+/-SD) at the LS and -0.24+/-1.19 at the FN. Z-scores of <-2.0 were found in 17% of subjects. Subjects who were homozygous or heterozygous for the DeltaF508 mutation exhibited significantly lower Z-scores than those with no DeltaF508 allele. Multiple linear regression showed that the DeltaF508 genotype and male sex were independently associated with lower BMD at both sites. Other factors also independently associated with lower BMD included malnutrition, lower 25-hydroxyvitamin D level, lower fat-free mass and lower FEV1 (% pred). In conclusion, reduced bone mineral density in cystic fibrosis is associated with a number of factors, including DeltaF508 genotype, male sex, greater lung disease severity and malnutrition.

Adult↗
PubMed2001

Adaptive and phylogenetic significance of ontogenetic sequences in Archaeolemur, subfossil lemur from Madagascar.

Among the best known of recently extinct Malagasy lemurs is Archaeolemur, which is represented by many hundreds of specimens. The phylogenetic affinities of this taxon are unclear, especially in light of recent preliminary analysis of ancient DNA which does not support its previously accepted close relationship with the living Indridae. We examined the nearly complete skeletons of two adults and one juvenile and other less complete specimens to reconstruct aspects of the ontogeny of Archaeolemur. To compare the development of Archaeolemur to that of living strepsirrhines we collected data on Propithecus verreauxi, Eulemur fulvus, and Lemur catta. Additionally, because Archaeolemur exhibits some morphological convergences with distantly related papionins, we tested for convergence in the developmental patterns of Archaeolemur and Macaca fascicularis. Data include the status of tooth eruption, craniofacial sutural closure, and postcranial epiphyseal fusion, as well as linear measurements. We used discriminant function analysis and other tools to explore ontogenetic similarities and differences. The adaptive and phylogenetic significance of ontogenetic information is discussed. Our analysis shows that Archaeolemur displays a clear strepsirrhine pattern of development with only minor macaque convergences. Among the Strepsirrhini, Archaeolemur is slightly more similar developmentally to E. fulvus and L. catta than to P. verreauxi. Some of the distinctive features of the ontogeny of Archaeolemur may be related to diet, while others bear apparent testimony to a relatively rapid absolute pace of growth and development.

Adaptation, Physiological↗
PubMed2001

Qualitative analysis of the care of children in hospital in four countries-Part 1.

As part of a large study of the care of children in Australian, British, Indonesian, and Thai hospitals, qualitative methods were used to examine differences influenced by culture. Two groups were surveyed: parents of hospitalized children, and staff caring for them. Vignettes were used to invoke discussion, and content analysis was used to examine the data. Subjects were interviewed singly, or in focus groups. These interviews were audiotaped and transcribed verbatim. The data were explored by using content analysis to extract themes of understanding of cultural experiences. This article is the first of a two-part series, and includes a review of the literature, description of the methods used, and results of the parents' interviews. The staff results and discussion will be published in Part 2. Analysis revealed that parents in all countries were primarily concerned with treating the child's illness and the child's recovery. Parents were concerned with their work (employment), but this was a much larger consideration in Indonesia and Thailand, where no social security systems exist, than in Australia and Britain. Communication with staff was the most commonly mentioned theme for parents, indicating that irrespective of the culture in which the care was given, good communication between parents and staff was of paramount importance.

Adolescent↗
PubMed2001

Distribution and genetic diversity of suilysin in Streptococcus suis isolated from different diseases of pigs and characterization of the genetic basis of suilysin absence.

Streptococcus suis is an economically important pathogen of pigs responsible for a variety of diseases including meningitis, septicemia, arthritis, and pneumonia, although little is known about the mechanisms of pathogenesis or virulence factors associated with this organism. Here, we report on the distribution and genetic diversity of the putative virulence factor suilysin, a member of the thiol-activated toxin family of gram-positive bacteria. On the basis of PCR analysis of over 300 isolates of S. suis, the suilysin-encoding gene, sly, was detected in 69.4% of isolates. However, sly was present in a considerably higher proportion of isolates obtained from cases of meningitis, septicemia, and arthritis (>80%) and isolates obtained from asymptomatic tonsillar carriage (>90%) than lung isolates associated with pneumonia (44%). With the exception of serotypes 1, 14, and 1/14, there was no strong correlation between the presence of suilysin and serotype. Analysis of the genetic diversity of suilysin by restriction fragment length polymorphism and sequence analysis found that the suilysin gene, where present, is highly conserved with a maximum of 1.79% diversity at the nucleotide level seen between sly alleles. Assays of hemolytic activity and hybridization analysis provided no evidence for a second member of the thiol-activated toxin family in S. suis. Inverse PCR was used to characterize regions flanking sly, which in turn allowed the first characterization of the equivalent region in a strain lacking sly. Sequence comparison of these regions from sly-positive (P1/7) and sly-negative (DH5) strains indicated that two alternative arrangements are both flanked by genes with highest similarity to haloacid dehalogenase-like hydrolases (5' end) and putative N-acetylmannosamine-6-phosphate epimerases (3' end). However, sly appears to be completely absent from the alternative arrangement, and a gene of unknown function is located in the equivalent position. Finally, PCR analysis of multiple sly-positive and -negative strains indicated that these two alternative genetic arrangements are conserved among many S. suis isolates.

Amino Acid Sequence↗
PubMed2000

Dynactin increases the processivity of the cytoplasmic dynein motor.

Cytoplasmic dynein supports long-range intracellular movements of cargo in vivo but does not appear to be a processive motor protein by itself. We show here that the dynein activator, dynactin, binds microtubules and increases the average length of cytoplasmic-dynein-driven movements without affecting the velocity or microtubule-stimulated ATPase kinetics of cytoplasmic dynein. Enhancement of microtubule binding and motility by dynactin are both inhibited by an antibody to dynactin's microtubule-binding domain. These results indicate that dynactin acts as a processivity factor for cytoplasmic-dynein-based motility and provide the first evidence that cytoskeletal motor processivity can be affected by extrinsic factors.

Adenosine Triphosphatases↗
PubMed2000

Caring for adolescent females with anorexia nervosa: registered nurses' perspective.

This phenomenological study was undertaken to explore in depth the experiences of registered nurses caring for adolescent anorexic females within paediatric wards of general hospitals in Victoria, Australia. A qualitative design underpinned by the philosophy of Edmund Husserl was employed for this study. Audio taped in-depth interviews with five registered nurses working within the public health care system were conducted. Using Colaizzi's procedural steps of analysis, six themes of meaning were explicated. They were: (a) personal core values of nurses; (b) core values challenged; (c) emotional turmoil; (d) frustration; (e) turning points; and (f) resolution. These themes, when taken together, described the essence of the journey undertaken by registered nurses who cared for adolescent anorexic females. The findings of this study indicated that there is a need for extensive registered nurse preparation, on-going support, and development of education programmes to enable registered nurses to care for these patients with greater understanding. Further, the participants identified the need for new care regimes and protocols to be developed that incorporated new ways of thinking. They also expressed a desire to be have greater involvement in the planned care of their patients.

Adolescent↗
PubMed2000

Real time imaging reveals a peroxisomal reticulum in living cells.

We have directly imaged the dynamic behavior of a variety of morphologically different peroxisomal structures in HepG2 and COS-7 cells transfected with a construct encoding GFP bearing the C-terminal peroxisomal targeting signal 1. Real time imaging revealed that moving peroxisomes interacted with each other and were engaged in transient contacts, and at higher magnification, tubular peroxisomes appeared to form a peroxisomal reticulum. Local remodeling of these structures could be observed involving the formation and detachment of tubular processes that interconnected adjacent organelles. Inhibition of cytoplasmic dynein based motility by overexpression of the dynactin subunit, dynamitin (p50), inhibited the movement of peroxisomes in vivo and interfered with the reestablishment of a uniform distribution of peroxisomes after recovery from nocodazole treatment. Isolated peroxisomes moved in vitro along microtubules in the presence of a microtubule motor fraction. Our data reveal that peroxisomal behavior in vivo is significantly more dynamic and interactive than previously thought and suggest a role for the dynein/dynactin motor in peroxisome motility.

Animals↗
PubMed1999

Sex differences in development of morphine tolerance and dependence in the rat.

RATIONALE: Several investigators have shown that male rodents are more sensitive than females to morphine's antinociceptive effects. OBJECTIVE: The present study was conducted to determine whether this sex difference is stable after chronic morphine treatment. RESULTS: Acutely administered morphine produced significantly greater hotplate and tail withdrawal antinociception in males than in females. In contrast, there were no sex differences in morphine's hotplate or tail withdrawal effects under repeated (1-week interval) dosing conditions. In a separate group of rats, after 2 weeks of twice-daily morphine treatment (10-20 mg/kg per injection), the ED50 for morphine's antinociceptive effects increased approximately 6.9-fold in males versus only 3.7-fold in females; chronic morphine treatment also disrupted the estrous cycle of females. In a separate group of rats treated with 10 mg/kg morphine twice daily for 5 days, treatment with naloxone (1.0 mg/kg) on day 6 produced greater withdrawal scores in males than in females. CONCLUSIONS: These experiments demonstrate sex differences in development of tolerance to and dependence on morphine in the rat.

Analgesics, Opioid↗
PubMed1999

Appendicovesicostomy and newer alternatives for the Mitrofanoff procedure: results in the last 100 patients at Riley Children's Hospital.

PURPOSE: We present our experience using the various Mitrofanoff techniques to create a continent catheterizable stoma as an adjunct to continent urinary tract reconstruction in children and young adults. MATERIALS AND METHODS: Between 1990 and 1998 a Mitrofanoff procedure was performed at our institution in 55 male and 45 female patients with a mean age of 10.5 years. The etiology of incontinence was diverse but more than 90% of the patients had neurogenic bladder, the epispadias-exstrophy complex or a cloacal anomaly. Surgery included appendicovesicostomy in 57 cases, a Yang-Monti ileovesicostomy in 21, continent vesicostomy in 21 and formation of a tapered ileal segment as a catheterizable channel in 1. Simultaneously bladder augmentation was performed in 52 patients, bladder neck reconstruction was done in 48 and a Malone antegrade colonic enema stoma was constructed for fecal incontinence in 17. RESULTS: The abdominal stoma is continent in 98 of our 100 patients. Mean followup is 2 years (range 2 months to 8 years) with the longer followup in the appendicovesicostomy group. One patient with stomal incontinence who underwent revision is now dry. Postoperative complications requiring an additional procedure developed in 20 patients, including stomal stenosis in 12. Continent vesicostomy was most prone to stomal problems (6 of 21 patients, 29%). CONCLUSIONS: The Mitrofanoff procedure is a reliable technique for creating a continent catheterizable urinary stoma. Appendicovesicostomy continues to be our first option for this procedure, although we have also had good results with the Yang-Monti ileovesicostomy and continent vesicostomy. These newer options have allowed preservation of the appendix for the Malone antegrade colonic enema stoma procedure in patients with urinary and fecal incontinence.

Adolescent↗
PubMed1999

Molecular characterization of equine isolates of Streptococcus pneumoniae: natural disruption of genes encoding the virulence factors pneumolysin and autolysin.

Although often considered a strict human pathogen, Streptococcus pneumoniae has been reported to infect and cause pneumonia in horses, although the pathology appears restricted compared to that of human infections. Here we report on the molecular characterization of a group of S. pneumoniae isolates obtained from horses in England and Ireland. Despite being obtained from geographically distinct locations, the isolates were found to represent a tight clonal group, virtually identical to each other but genetically distinguishable from more than 120 divergent isolates of human S. pneumoniae. A comprehensive analysis of known pneumococcal virulence determinants was undertaken in an attempt to understand the pathogenicity of equine pneumococci. Surprisingly, equine isolates appear to lack activities associated with both the hemolytic cytotoxin pneumolysin, often considered a major virulence factor of pneumococci, and the major autolysin gene lytA, also considered an important virulence factor. In support of phenotypic data, molecular studies demonstrated a deletion of parts of the coding sequences of both lytA and ply genes in equine pneumococci. The implications of these findings for the evolution and pathogenicity of equine S. pneumoniae are discussed.

Animals↗
PubMed1998

Kinetics of uptake and elimination of silicic acid by a human subject: a novel application of 32Si and accelerator mass spectrometry.

Silicon is possibly important in human physiology in protecting against the toxic effects of aluminium, but the kinetics of uptake and excretion of silicic acid, the bioavailable form, are not well characterised. We have used 32Si as a tracer in a human uptake experiment to determine a gastrointestinal uptake factor for silicic acid, and to elucidate the kinetics of renal elimination. Urine collections were made for extending intervals from 2 to 12 h over 2 days following ingestion by a single human subject of a neutral silicic acid solution containing tracer levels of 32Si (t1/2 approximately 150 y). Silicon was isolated as SiO2 and the 32Si content determined by accelerator mass spectrometry (AMS), using a gas-filled magnet technique to eliminate a prolific isobaric interference from 32S. Silicon uptake appears to have been essentially complete within 2 h of ingestion. Elimination occurred by two simultaneous first-order processes with half-lives of 2.7 and 11.3 h, representing around 90% and 10%, respectively, of the total output. The rapidly eliminated 32Si was probably retained in the extracellular fluid volume, whilst the slower component may represent intracellular uptake and release. Elimination of absorbed 32Si was essentially complete after 48 h and was equivalent to 36% of the ingested dose. This establishes only a lower limit for gastrointestinal absorption as, although there was no evidence for longer term retention of additional 32Si, the possibility could not be excluded by these results.

Administration, Oral↗
PubMed1998

Location of aluminium and gallium in human neuroblastoma cells treated with metal-chelating agent complexes.

The subcellular location of aluminium is unknown, probably because of difficulties in investigating aluminium biochemistry and the use of varied experimental approaches of uncertain sensitivity. We have studied levels of uptake and the localization of gallium and of aluminium in cultured human neuroblastoma cells treated with soluble metal complexes (mainly Al- or Ga-EDTA), radiolabeled with 26Al or 67Ga, respectively. Crude nuclei and cytoplasm were obtained by two separate methods, and DNA, RNA, and proteins were prepared from the nuclei by centrifugation in high salt; also, cytosol and noncytosol were separated using a nondissociating method. Levels of uptake were of similar order for the two metals-on average about 50 pmol/10(6) cells for aluminium and 120 pmol/10(6) cells for gallium, after 4 to 8 days treatment at 250 microM, and approximately 50 to 70% of the metal was found in the cytosol. About 20% of the aluminium and 10 to 25% of the gallium was associated with nuclear protein. A lower proportion was bound to DNA and to nuclear RNA. In cells treated with gallium-citrate/transferrin mixtures, 30 to 35% of the gallium in the cytosol was bound to protein, at least 35 being loosely bound; the main gallium-associated protein was probably intracellular transferrin. The remaining 65 to 70% of the metal in the cytosol was in low-molecular-weight form, and we suggest that the latter metal could affect structures such as the cytoskeleton and also metabolic processes in the cytoplasm. The similarity in distribution of the two metals supports the use of gallium as a "surrogate" for aluminium, at least in cell culture studies.

Aluminum↗