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Biomedical subjects

D S Taylor

Publications and source records attributed to D S Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1998

Alström syndrome. Report of 22 cases and literature review.

OBJECTIVE: The authors report 22 cases of Alström syndrome (AS), which is the largest series to date. Only 37 cases have been reported in the world literature since 1959. The authors review the clinical features and compare these with the overlapping condition of Bardet-Biedl syndrome. Their aim is to clarify the AS phenotype and to increase awareness of the early features. DESIGN: A retrospective case series. PARTICIPANTS: All patients (22) with a diagnosis of AS admitted to the authors' hospital in the past 10 years were included in this review. INTERVENTION: This is principally a review of ocular features, but other features are recorded and discussed. MAIN OUTCOME MEASURES: Features noted included age at onset of visual symptoms, presence of photophobia, visual acuity, and electroretinogram findings. Nonocular features recorded included cardiac status, weight and height, hearing, and presence of diabetes mellitus. RESULTS: Cardiomyopathy presenting in infancy has only been recognized recently to be a feature of AS. Of the authors' cases, 18 of 22 had infantile cardiomyopathy. In the authors' tertiary referral institution, there is an ascertainment bias toward younger patients and especially those with pathology that is other than ocular pathology. In addition, AS is difficult to recognize in childhood without the development of infantile cardiomyopathy. Alström syndrome often is not recognized until diabetes mellitus develops in the second or third decade. Initially, a diagnosis of cone-rod dystrophy, achromatopsia, Leber's congenital amaurosis, or Bardet-Biedl syndrome may be made. In AS, there is a severe infantile retinal dystrophy. The electroretinogram is absent or attenuated with better preserved rod than cone function. The retinal dystrophy is progressive with the patient's visual acuity of 6/60 or less by 10 years of age and no light perception by 20 years of age. CONCLUSIONS: A diagnosis of AS should be considered in infantile cone and rod retinal dystrophy, particularly if the weight is above the 90th percentile (16 of 18 cases) or if there is an infantile cardiomyopathy (18 of 22 cases).

Abnormalities, Multiple↗
PubMed1998

Comparison of pattern-onset, -reversal and -offset VEPs in treated amblyopia.

PURPOSE: There are differences in the properties of visual evoked potentials (VEPs) to various forms of pattern stimulation and it is not clear how these differences reflect macular and parmacular function in amblyopic and normal eyes. We assessed pattern-onset, -reversal and -offset VEPs from amblyopic eyes and compared them with the responses from the fellow eyes, and from controls, to gauge the relative effectiveness of these stimulus modes. METHODS: The three modes of pattern stimulation were presented sequentially in a single recording run to enable direct comparisons to be made for identical recording conditions. Half-field stimulation was used, as this elicits components over the ipsilateral and contralateral occipital scalp relative to the stimulated half-field, which reflect stimulation of macular and paramacular areas of the visual field. Eighteen amblyopes treated by occlusion and 20 control children were studied. RESULTS: Multivariate analysis of variance showed significant differences between ambylopic and fellow eyes in amblyopes: pattern-onset components were significantly attenuated and ipsilateral reversal components were significantly prolonged in amblyopic eyes. When fellow eyes of amblyopes were compared with the eyes of controls, the reversal P100 and offset P110 and N165 components showed significant differences. CONCLUSIONS: Ipsilateral reversal components and onset CII and contralateral P105 were the most affected in amblyopic eyes. The subnormal findings for the fellow eyes of amblyopes suggest that occlusion may have a long-standing physiological effect on the patched eye, not normally clinically apparent.

Adolescent↗
PubMed1998

Phase I/II trial of PIXY321 (granulocyte-macrophage colony stimulating factor/interleukin-3 fusion protein) for treatment of inherited and acquired marrow failure syndromes.

Fourteen paediatric patients with advanced amegakaryocytic thrombocytopenia (AMT) or other bone marrow (BM) failure syndromes were enrolled on one of two phase I/II dose escalation studies of PIXY321. PIXY321 was administered subcutaneously in doses ranging from 250 to 750 mg/m2/d. No dose-limiting toxicity was observed. Peak absolute neutrophil count (ANC) was higher than baseline in all patients. Most transfusion-independent patients demonstrated elevation in haematocrit and/or platelet count. Trilineage haemopoietic responsiveness was evident in the three transfusion-independent patients. In these paediatric populations PIXY321 is well tolerated and merits consideration as a potential therapy.

Adolescent↗
PubMed1998

Familial congenital saccade initiation failure and isolated cerebellar vermis hypoplasia.

The underlying lesion in congenital saccade initiation failure (c-SIF) ('congenital ocular motor apraxia', 'Cogan's apraxia') is uncertain. Often no abnormality can be found, yet in others a midline cerebellar abnormality has often been reported. We examined this cerebellar association in a brother and sister. In addition to standard ophthalmological and neurological examinations, both siblings underwent ocular motor testing and neuroradiological investigations including CT and MRI. Both siblings exhibited the typical signs of c-SIF, including headthrusting, synkinetic blinking, missed-nystagmus quick phases, mild developmental delay, and speech difficulties. CT and MRI revealed cerebellar vermis hypoplasia in the brother, but appeared normal in the sister. No other neuroradiological abnormalities were detected. These cases highlight the wide variability in the association of vermis abnormalities with c-SIF, despite the inheritance and similar clinical manifestations. They show that either: (1) the vermis is causal in saccade triggering, but that c-SIF may result from very subtle damage that is beyond MRI resolution in some cases; or (2) that a vermis abnormality per se is not causative but only a marker of another subtle abnormality, either structural or possibly biochemical.

Apraxias↗
PubMed1998

Saccadic strategies in children with hemianopia.

Multiple hypometric (undershooting) saccades are generally reported as a compensatory strategy in adults with homonymous hemianopia. However, hypermetric (overshooting) saccades have been reported to develop spontaneously as a beneficial strategy in response to predictable targets. We examined the saccades of 10 children (aged 5 to 16 years) with homonymous hemianopia to determine the type of compensatory eye-movement strategies employed 6 months to 16 years after hemianopia onset. Homonymous hemianopia was identified using perimetry and/or pattern visual evoked potentials and supported with results of neuroimaging. Eye movements were recorded using bitemporal electrooculography. Saccades were elicited to a red light source in a semipredictable paradigm. We found that hypermetria was not a consistent compensatory strategy in our patients. In spite of the predictability of our paradigm and the long follow-up period, multiple hypometric saccades into the blind field appeared to be the preferred strategy.

Adolescent↗
PubMed1998

The nanophthalmic macula.

AIMS: To define an unusual macular appearance found in association with nanophthalmos. METHODS: A case review. RESULTS: Seven children (aged 8 months to 17 years) with nanophthalmos were examined. They all exhibited the same clinical findings of an unusual yellow macula appearance with retinal folds and crowded optic discs. Visual electrophysiology performed in four cases was normal. CONCLUSION: A distinctive yellow macular pigmentation with associated chorioretinal folds and crowded optic discs is present in nanophthalmos. It is proposed that the retinal folds are due to a disparity between scleral and retinal growth while the macula discoloration is due to a congenital abnormality in arrangement or position of the luteal pigment and is not degenerative. Included in this case series is the second case in the literature of nanophthalmos associated with Kenny's syndrome. Inheritance of nanophthalmos appears to be autosomal recessive.

Abnormalities, Multiple↗
PubMed1998

Optic disc anomalies and frontonasal dysplasia.

AIMS: To document the optic disc abnormalities in patients with frontonasal dysplasia in association with basal encephalocele. METHODS: Names and hospital numbers of patients with midline clefts were obtained from the ophthalmology and genetics database. Six patients were identified who had the following common findings: midline facial cleft with midline cleft lip and palate; hypertelorism; absent corpus callosum; basal (sphenoethmoidal) encephalocele; and pituitary deficiency (five out of six cases). Ophthalmic examination was performed with fundal photography where possible. RESULTS: Two patients had unilateral and one a bilateral peripapillary staphyloma. Two patients had bilateral optic disc hypoplasia and one appeared to have a peripapillary staphyloma in one eye and a morning glory disc in the other. CONCLUSION: Optic disc abnormalities were found in all patients with this constellation of clinical findings. This association appears to represent a distinct subgroup within the spectrum of frontonasal dysplasia. The presence of midline facial anomalies and any dysplastic disc should alert the physician as to the presence of an encephalocele.

Abnormalities, Multiple↗
PubMed1997

Stimulation of activin A expression in rat aortic smooth muscle cells by thrombin and angiotensin II correlates with neointimal formation in vivo.

Vasoactive GTP-binding protein-coupled receptor agonists (e.g., angiotensin II [AII] and alpha-thrombin) stimulate the production of mitogenic factors from vascular smooth muscle cells. In experiments to identify mitogens secreted from AII- or alpha-thrombin-stimulated rat aortic smooth muscle (RASM) cells, neutralizing antibodies directed against several growth factors (e.g., PDGF and basic fibroblast growth factor [basic FGF]) failed to inhibit the mitogenic activity of conditioned media samples derived from the cells. In this report, we found that polyclonal neutralizing antibodies directed against purified human placental basic FGF reduced the mitogenic activity of AII-stimulated RASM cell-conditioned media and in immunoblot experiments identified a 26-kD protein (14 kD under reducing conditions) that was distinct from basic FGF. After purification from RASM cell-conditioned medium, amino acid sequence analysis identified the protein as activin A, a member of the TGF-beta superfamily. Increased activin A expression was observed after treatment of the RASM cells with AII, alpha-thrombin, and the protein kinase C agonist PMA. In contrast, PDGF-BB or serum caused only a minor induction of this protein. Although activin A alone only weakly stimulated RASM cell DNA synthesis, it demonstrated a potent comitogenic effect in combination with either EGF or heparin-binding EGF-like growth factor in the RASM cells, increasing DNA synthesis by up to fourfold. Furthermore, in a rat carotid injury model, activin A mRNA was upregulated within 6 h after injury followed by increases in immunoreactive protein detected in the expanding neointima 7 and 14 d later. Taken together, these results indicate that activin A is a vascular smooth muscle cell-derived factor induced by vasoactive agonists that may, either alone or in combination with other vascular derived growth factors, have a role in neointimal formation after arterial injury.

Activins↗
PubMed1997

Eye movement abnormalities in a case of Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder that is characterised by the presence of multiple vocal, facial, and motor tics which change with time, and a number of other behavioural phenomena. Previous studies have not revealed any ocular-motor abnormalities. We report the eye movement studies of a patient with TS, using electrooculography and simultaneous video recording. Intrusive saccades occurred during smooth pursuit and optokinetic nystagmus. Reflexive and voluntary saccades were dysmetric and there was a complete failure of antisaccades. These abnormalities are characteristic of disease of the frontal lobes and basal ganglia. We review the literature with respect to the eye movement abnormalities associated with TS.

Adolescent↗
PubMed1996

Cooperation between core binding factor and adjacent promoter elements contributes to the tissue-specific expression of interleukin-3.

Tissue-specific expression of interleukin-3 (IL-3) is mediated via cis-acting elements located within 315 base pairs of the transcription start. This is achieved in part through the positive activities of the AP-1 and Elf-1 sites in the IL-3 promoter. The contribution to T cell-specific expression by other promoter sites was assessed in a transient expression assay with IL-3 promoter constructs linked to a luciferase gene, focusing initially on the core binding factor (CBF) site, which is footprinted in vivo upon T cell activation. Activity of the CBF site is shown to be critically dependent on the adjacent activator site Act-1. Together the Act-1 and CBF sites form a functional unit (AC unit) with dual activity. The AC unit is demonstrated to enhance basal activity of promoters both in fibroblasts and T cells. This activity is further inducible in activated T cells, but not in fibroblasts. In addition to the already identified NIP repressor site, evidence is presented for a second repressor region that restricts promoter activity in fibroblasts. Finally, a novel positive regulatory element has been mapped in the IL-3 promoter between nucleotide -180 and -210 that leads to increased expression in T cells. Together these results demonstrate that T cell expression of IL-3 is not specified by the activity of a single tissue-specific element, but instead involves multiple interacting elements that provide both specific positive regulation in T cells and specific negative regulation in fibroblasts.

3T3 Cells↗
PubMed1996

Thrombin receptor activation elicits rapid protein tyrosine phosphorylation and stimulation of the raf-1/MAP kinase pathway preceding delayed mitogenesis in cultured rat aortic smooth muscle cells: evidence for an obligate autocrine mechanism promoting cell proliferation induced by G-protein-coupled receptor agonist.

Treatment of quiescent rat aortic smooth muscle cells with either alpha-thrombin or a thrombin receptor-derived agonist peptide (SFLLRNP) resulted in pronounced increases in [3H]thymidine incorporation that were concentration dependent and reached a maximum of approximately 15-fold above serum-starved controls. However, in contrast to FBS, PDGF-BB, or basic fibroblast growth factor (bFGF), that initiated DNA synthesis promptly after 16-19 h, thymidine incorporation in response to thrombin was delayed by an additional 3-6 h. Delayed mitogenesis correlated with the appearance of a potent mitogenic activity in conditioned media samples obtained from thrombin-stimulated rat aortic smooth muscle cells, as assayed using Swiss 3T3 fibroblasts. This activity was not inhibited by neutralizing antibodies directed against PDGF or bFGF. Furthermore, in the Swiss 3T3 cells, simple addition of either alpha-thrombin or SFLLRNP failed to elicit a significant mitogenic response. In signal transduction studies, both thrombin and SFLLRNP treatment led to rapid tyrosine phosphorylation of proteins with apparent molecular masses of 42, 44, 75, 120, and 190 kD, respectively, as assessed by antiphosphotyrosine immunoblotting. The overall pattern of protein tyrosine phosphorylation was distinct from that observed after PDGF-BB addition. Activation of Raf-1 and the mitogen-activated protein (MAP) kinases p44mapk and p42mapk was also observed. However, the time course and duration of Raf-1/MAP kinase activation after thrombin stimulation were similar to those elicited by PDGF-BB. Taken together, our results indicate that thrombin-stimulated vascular smooth muscle proliferation is delayed and requires the de novo expression of one or more autocrine mitogens. In addition, the rapid induction of discrete intracellular signaling mechanisms by thrombin, including the Raf-1/MAP kinase pathway, appears to be insufficient alone to promote vascular smooth muscle cell mitogenesis.

Animals↗
PubMed1996

The role of ERG/VEP and eye movement recordings in children with ocular motor apraxia.

Ocular motor apraxia (OMA) is characterised by an intermittent inability to initiate voluntary saccades, and a failure to produce optokinetic and vestibular quick phases. Some patients have no other abnormalities (idiopathic OMA), whereas in others it appears associated with a variety of neurological conditions which may affect the sensory visual pathway. Electroretinograms (ERGs), flash and pattern visual evoked potentials (VEPs) and eye movements were assessed in 53 children with OMA (age range 17 days to 14 years) to determine their efficacy in helping to distinguish between idiopathic and non-idiopathic cases. Seven patients (13.2%) had idiopathic OMA and the remaining 46 (86.8%) had other associated clinical conditions. All patients had episodes of absent quick phases ('lock up') during optokinetic nystagmus (OKN) and/or vestibular testing. Flash ERGs were abnormal in only 7 patients (13.2%); 6 had syndromes involving a pigmentary retinopathy (Joubert's, Bardet-Biedl, infantile Refsum's, Kearns-Sayre's), and the seventh had a cone dystrophy with vermis hypoplasia. VEPs were normal in all 7 patients with idiopathic OMA. Thirty-three (72%) patients with OMA in association with neurological conditions had abnormal VEPs and 13 had normal VEPs (28%). There was a significant positive correlation between VEP abnormality and poor OKN gain. VEP/ERG testing and eye movement studies are useful when OMA is suspected as they help in distinguishing isolated idiopathic cases from those with more widespread neurological abnormalities.

Adolescent↗
PubMed1995

Digital flexor tendon lacerations in horses: 50 cases (1975-1990).

The medical records of 50 horses examined because of lacerations of the tendon of the superficial or deep digital flexor muscle were reviewed to determine whether any injury or treatment factors could be associated with outcome. Median age of horses treated was 4.5 years (range, 1.5 years to 15 years), and the median follow-up time was 5 years (range, 1.5 to 16 years) after injury. Horses were considered to have survived if they were alive more than 1 year after injury. Twelve of 16 horses that had 1 or the other tendon transected survived; 13 of 16 horses that had both tendons transected survived; and 14 of 18 horses that had partial tendon disruptions of 1 or both tendons survived. Of the 39 surviving horses, 27 horses returned to their original use, and 32 horses were sound for riding. Nine horses with 1 or both tendons transected were being used for athletic activities. Lacerated tendons were sutured in 16 horses, and 15 of these survived. Tendons were not sutured in 34 horses, and 24 of these survived. We were not able to detect any association between outcome and tendon sheath involvement or between outcome and limb involvement (forelimb vs hind limb).

Animals↗
PubMed1995

The optokinetic response differences between congenital profound and nonprofound unilateral visual deprivation.

BACKGROUND: The occurrence of monocular naso-to-temporal optokinetic nystagmus (OKN) asymmetry, as a reflection of the immature oculomotor system in infants, and its persistence with early onset monocular visual deprivation, is well known. This asymmetry has been linked with poor binocular function and attributed to disruption of the development of binocular cortical projections to the pretectum. Optokinetic nystagmus symmetry in patients with congenital uniocular total pattern vision deprivation has not been fully investigated. METHODS: The authors compared the optokinetic responses in six children with "profound" uniocular visual deprivation, who were born with untreated conditions (microphthalmos and persistent hyperplastic primary vitreous), with ten aphakic children treated early for congenital unilateral cataracts (nonprofound unilateral visual deprivation). Eye movements were recorded using dc-electro-oculography, and OKN was elicited using a full-field patterned curtain. Flash and pattern visual-evoked responses were also measured in each subject. RESULTS: Latent nystagmus was present in six children in the nonprofound group, whereas none was detected in the profound group. All children in the nonprofound group showed statistically significant monocular naso-to-temporal asymmetry for either eye. Subjects in the profound group had symmetric OKN. CONCLUSIONS: The authors conclude that unequal input from the two eyes and interocular rivalry lead to OKN asymmetry. Their results suggest that if vision from one eye is so negligible that it does not compete with the neuroanatomic connections of the fellow eye, then the input from this eye remains undisturbed, and OKN remains symmetric.

Adolescent↗
PubMed1995

Neuroradiological and eye movement correlates in children with intermittent saccade failure: "ocular motor apraxia".

Ocular motor apraxia (OMA) is a clinical sign involving the intermittent inability to initiate saccades, and a failure of quick phases during optokinetic nystagmus (OKN) and vestibular nystagmus (VN). Some patients have no other associated abnormalities (idiopathic), whereas others have a variety of neurological conditions. We quantified the severity of the saccade failure and correlated it with neuro-radiological and other oculomotor findings in 62 children (aged 17 days - 14 years). Saccades, smooth pursuit, OKN and VN were recorded using electrooculography and the extent of "locking up" (absent quick phases during OKN and VN) was measured. Saccades were usually hypometric. Pursuit and OKN gains were normal in the majority of the idiopathic cases but were low in those with other neurological conditions. Twenty-four patients had essentially normal scans, whereas 38 had abnormal scans: Delayed myelination, cerebellar abnormalities (particularly involving the vermis), and agenesis of the corpus callosum were the most common findings. A significant positive correlation was present between increasing neuro-radiological deficits and severity of "locking up" during OKN. Principal component analysis showed that brainstem and cerebellar vermis abnormalities were the main factors involved. A pathophysiological basis of OMA is discussed in the light of animal and clinical studies.

Adolescent↗
PubMed1995

Angiotensin II stimulation of rapid paxillin tyrosine phosphorylation correlates with the formation of focal adhesions in rat aortic smooth muscle cells.

Angiotensin II is a potent vasoconstrictor that has been also implicated in vascular hyperproliferative diseases, including atherosclerosis and restenosis following angioplasty. Treatment of cultured, serum-starved rat aortic smooth muscle cells with angiotensin II causes rapid protein tyrosine phosphorylation that precedes cell mitogenesis. We have identified two of the phosphoproteins as paxillin (75 kilodaltons) and the tyrosine kinase pp125Fak, both components of actin-associated focal adhesion sites. Angiotensin II stimulated a 5-fold increase in the tyrosine phosphorylation of paxillin and a smaller (1.5-fold) increase in pp125Fak tyrosine phosphorylation. Paxillin tyrosine phosphorylation was evident within 1 minute, and was maximal after 10 minutes. Similar elevated protein tyrosine phosphorylation levels of paxillin were obtained with exposure of the rat aortic smooth muscle cells to peptides endothelin-1 and alpha-thrombin that function, as angiotensin II, through binding to members of the seven transmembrane domain G protein coupled receptors. Angiotensin II treatment also stimulated the production of a well-ordered actin-containing stress fiber network and prominent paxillin-containing focal adhesions. The focal adhesions stained intensely with anti-phosphotyrosine antibody suggesting the tyrosine phosphorylation of paxillin and cytoskeletal reorganization were tightly coupled. Angiotensin II receptor occupancy has been shown previously to lead to protein kinase C activation. However, compared to angiotensin II stimulation, a smaller, delayed increase in paxillin tyrosine phosphorylation was observed following direct protein kinase C activation by the phorbol ester phorbol 12-myristate-13-acetate. Paxillin tyrosine phosphorylation was selective for certain agonists since no increase in tyrosine phosphorylation of this protein was observed following exposure to the potent mitogen PDGF. Thus, actin-based cytoskeletal changes involving sites of cell adhesion to the extracellular matrix may play an important role in normal and pathophysiologic smooth muscle cell growth regulation in response to certain angiotensin II-type vasoactive agonists.

Angiotensin II↗