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C McCulloch

Publications and source records attributed to C McCulloch.

At least 19 recordsLinked to original sources
PubMed2002

CSF tau protein phosphorylated at threonine 231 correlates with cognitive decline in MCI subjects.

In this longitudinal study of 77 patients with mild cognitive impairment (MCI), the authors analyzed whether levels of tau protein phosphorylated at threonine 231 (p-tau(231)) in CSF correlate with progression of cognitive decline. High CSF p-tau(231) levels at baseline, but not total tau protein levels, correlated with cognitive decline and conversion from MCI to AD. Independently, old age and APOE-epsilon 4 carrier status were predictive as well. Our data indicate that an increased p-tau(231) level is a potential risk factor for cognitive decline in patients with MCI.

Adult↗
PubMed2001

Venous gangrene of lower extremities and Staphylococcus aureus sepsis.

This is a study of the venous gangrene of lower extremities and Staphylococcus aureus sepsis. We report on a premature infant who developed phlegmasia cerulea dolens (PCD) in both lower extremities in association with S. aureus sepsis, resulting in gangrene of the right foot. Non-pitting edema and cyanosis of the digits of the right lower extremity were noted 48 hours after hypotension and severe shock due to S. aureus sepsis. Intravenous antibiotics, isotonic fluids, and heparin were administered. Twenty-four hours later, edema and ischemic changes of the first and fifth left toes were also noted. Doppler flow study showed flow signals in both right and left popliteal arteries. However, there were no Doppler signals in neither right nor left popliteal vein. Emergency fasciotomies were performed on both lower limbs. The progression of the gangrene was limited to the right foot. There was complete resolution of PCD in both lower extremities. To the best of our knowledge, the association of S. aureus sepsis with PCD and venous gangrene in an infant has not been reported previously. This case illustrates the need for early recognition of PCD and aggressive intervention.

Foot Diseases↗
PubMed2000

Template mixture models for direct cortical electrical interference data.

This paper introduces a statistical approach for high-level spatial analysis when there is little prior information about the shape or location of the region of interest in the underlying image and limited spatial resolution of the available data. Our work was motivated by a functional brain mapping technique called direct cortical electrical interference (DCEI) that gives binary observations at multiple sites throughout the brain. We estimate an underlying, binary spatial response function using a mixture of an unknown number of simple geometrical shapes (e.g. circles) with unknown centers and sizes to be estimated. Inference is made using reversible jump Markov chain Monte Carlo. The approach is illustrated with simulated examples and a real example with DCEI data.

Journal Article↗
PubMed2000

Biochemical and functional characterization of intercellular adhesion and gap junctions in fibroblasts.

Despite their significance in wound healing, little is known about the molecular determinants of cell-to-cell adhesion and gap junctional communication in fibroblasts. We characterized intercellular adherens junctions and gap junctions in human gingival fibroblasts (HGFs) using a novel model. Calcein-labeled donor cells in suspension were added onto an established, Texas red dextran (10 kDa)-labeled acceptor cell monolayer. Cell-to-cell adhesion required Ca(2+) and was >30-fold stronger than cell-to-fibronectin adhesion at 15 min. Electron micrographs showed rapid formation of adherens junction-like structures at approximately 15 min that matured by approximately 2-3 h; distinct gap junctional complexes were evident by approximately 3 h. Immunoblotting showed that HGF expressed beta-catenin and that cadherins and connexin43 were recruited to the Triton-insoluble cytoskeletal fraction in confluent cultures. Confocal microscopy localized the same molecules to intercellular contacts of acceptor and donor cells. There was extensive calcein dye transfer in a cohort of Texas red dextran-labeled cells, but this was almost completely abolished by the gap junction inhibitor beta-glycyrrhetinic acid and the connexin43 mimetic peptide GAP 27. This donor-acceptor cell model allows large numbers (>10(5)) of cells to form synchronous cell-to-cell contacts, thereby enabling the simultaneous functional and molecular studies of adherens junctions and gap junctions.

Cadherins↗
PubMed1998

Can we improve the uptake of gastroscopy in the population at risk for gastric cancer? The effect of home letter information.

The poor outlook for gastric cancer in Britain is largely due to late diagnosis. Earlier diagnosis will require both easy access to endoscopy and increased public awareness of dyspeptic symptoms. We used information by personal letter to encourage reporting of potentially significant symptoms in patients over 40 years of age. The aim of this study was to measure the acceptability and effect on gastroscopy rates of home letter information. Patients over 40 registered with 12 general practices were used in the study (practice population 80,000). Patients over 40 from another nine practices (practice population 46,500) acted as controls. A letter encouraging consultation for new dyspeptic symptoms was sent to all study subjects. Gastroscopy rates were compared in both study and control populations. Questionnaires on symptoms were sent to 500 study subjects. The principal outcome measure was the gastroscopy rate in people over 40 in both populations, before and during the intervention. The gastroscopy rate was 23% higher in the study than in the control population during the study (3.32 vs. 2.7%, P = 0.00016, chi 2 = 14.25). Gastroscopy uptake increased by 85% from 1991/2 to 1993/4 in the study group and by 34% in the control group (chi 2 = 14.02, P = 0.00018). Thirty-one per cent of questionnaire respondents had dyspeptic symptoms; only 3% had 'significant' symptoms of between 2 and 52 weeks duration. Home letters are an acceptable and efficient method of increasing gastroscopy uptake in dyspeptic patients over 40.

Adult↗
PubMed1997

Interleukin 1-induced calcium signalling in chondrocytes requires focal adhesions.

The cytokine interleukin 1 (IL-1) is an important mediator of connective-tissue destruction in arthritic joints but the mechanisms by which IL-1 mediates signal transduction in chondrocytes is poorly understood. Previous results have indicated that IL-1 receptors co-localize with focal adhesions [Qwarnstrom, Page, Gillis and Dower (1988) J. Biol. Chem. 263, 8261-8269], discrete adhesive domains of cells that function in cell attachment and possibly in signal transduction. We have determined whether focal adhesions restrict IL-1-induced Ca2+ signalling in primary cultures of bovine chondrocytes. In cells grown for 24 h on fibronectin, the basal intracellular Ca2+ ion concentration ([Ca2+]i) was 100+/-3 nM. Optimal increases of [Ca2+]i above baseline were induced by 10 nM IL-1 (183+/-30 nM above baseline). There was no significant difference between cells plated on fibronectin or type II collagen (P>0.2; 233+/-90 nM above baseline). Ca2+ transients were significantly decreased by the inclusion of 0.5 mM EGTA in the bathing buffer (74+/-11 nM above baseline), and 1 microM thapsigargin completely blocked Ca2+ transients. Cells plated on poly-(l-lysine) or suspended cells showed no Ca2+ increases, whereas cells grown on fibronectin exhibited IL-1-induced Ca2+ responses that corresponded temporally to the time-dependent cell spreading after plating on fibronectin. Cells plated on poly-(l-lysine) and incubated with fibronectin-coated beads exhibited vinculin staining in association with the beads. In identical cell preparations, IL-1 induced a 136+/-39 nM increase of [Ca2+]i above baseline in response to 10 nM IL-1beta. There were no IL-1-induced Ca2+ increases when cells on poly-(l-lysine) were incubated with fibronectin-coated beads for only 15 min at 37 degrees C, in cells maintained for 3 h at 4 degrees C, in cells incubated with BSA beads for 3 h at 37 degrees C, or in cells pretreated with cytochalasin D. Labelling of IL-1 receptors with 125I-IL-1beta showed 3-fold more specific labelling of focal adhesion complexes in cells incubated with fibronectin-coated beads compared with cells incubated with BSA-coated beads, indicating that IL-1 receptor binding or the number of IL-1 receptors was increased in focal adhesions. These results indicate that, in chondrocytes, IL-1-induced Ca2+ signalling is dependent on focal adhesion formation and that focal adhesions recruit IL-1 receptors by redistribution in the cell membrane.

Animals↗
PubMed1997

Single cell analysis of intracellular osteopontin in osteogenic cultures of fetal rat calvarial cells.

Osteopontin (OPN), a major component of the bone matrix, is expressed at different stages of bone formation. To determine possible relationships between OPN expression and stages of osteogenic cell differentiation, we have performed single cell analyses of intracellular OPN in early (proliferating), subconfluent (differentiating), and mature (mineralizing) cultures of fetal rat calvarial cells (FRCC) using a combination of flow cytometry and confocal microscopy. At each culture stage, a high proportion (60-98%) of cells were immunoreactive for OPN (OPN+ve). Each of these populations also included a small proportion of OPN-ve cells which were characterized by their small size, low granularity, high proliferative capacity, and enhanced osteogenic potential. The OPN+ve cells displayed two distinct patterns of intracellular immunostaining: a perinuclear distribution typical of secreted proteins and a perimembrane distribution in which patches of OPN were concentrated at the cell surface. Perimembranous staining predominated in migrant cells, which contained greater than tenfold higher levels of OPN than nonmigrant cells as separated in a Boyden chamber. When cell proliferation was high (day 2), most cells were OPN + ve. At all culture stages the intensity of OPN staining was increased as cells progressed through the cell cycle. As cells differentiated and started to form matrix (days 4 and 6), the mean cell expression of OPN was also increased (fourfold), independent of changes in total cell protein. However, despite the association of OPN with osteogenic cells, we were surprised to find that a high proportion (60%) of fetal skin fibroblasts were also immunoreactive for OPN. The expression of OPN by these cell populations was confirmed by RT-PCR, and a strong correlation was observed between the quantitative flow cytometry data and Western blot analysis of cell extracts in which the high and low phosphorylated isoforms of OPN were observed. These studies, therefore, have identified several phenotypes in FRCC cultures that are based on OPN expression: small OPN-ve cell populations enriched in osteogenic precursors, differentiating osteogenic cells that synthesize and secrete OPN, and migrating stromal cells characterized by a perimembranous OPN staining pattern.

Animals↗
PubMed1989

Excitatory effect of morphine and opioid peptides in the rat isolated colon.

Morphine and the opioid peptides cause isolated segments of rat colon to contract and relax rhythmically. This study re-examines two hypotheses to explain this phenomenon: Release of 5-hydroxytryptamine (5-HT)/acetylcholine by morphine or inhibition of a tonically active non-adrenergic, non-cholinergic (NANC) inhibitory mechanism. Rhythmic contractions induced by morphine (5 x 10(-6) M) were naloxone sensitive (10(-6) M) but unaffected by methysergide (10(-6) M), atropine (10(-6) M) or pretreatment of rats with p-chlorophenylalanine (200 mg kg-1 i.p. for four days) which lowered the 5-HT level in the colon from 3.73 +/- 0.83 mg g-1 in controls to 0.41 +/- 0.06 mg g-1 (P less than 0.001). The pattern of rhythmic contractions produced by morphine was unlike those produced by 5-HT (5 x 10(-6) M), acetylcholine (5 x 10(-6) M) or potassium chloride (30 mM). Tetrodotoxin (10(-6) M), apamin (10(-8) M), clonidine (2 x 10(-8) M), phentolamine (10(-5) M) or oxprenolol (10(-5) M) caused rhythmic contractions which were unaffected by naloxone. Clonidine contractions were inhibited by yohimbine (10(-7) M) but not by prazosin (10(-6) M). Electrical field stimulation at the peak of a contraction induced by morphine, apamin or clonidine, produced an inhibitory response which was unaffected by atropine, phentolamine, propranolol and guanethidine (all 10(-5) M). It persisted in colon segments from the rats with reserpine or 6-hydroxydopamine. These results suggest that neither the 5-HT/acetylcholine hypothesis nor inhibition of the NANC mechanism adequately explains the excitatory effect of morphine in the rat colon.

Acetylcholine↗
PubMed1988

Pathological study in a female carrier of choroideremia.

We present the pathological findings in one eye of a 68-year-old woman with choroideremia. There was widespread malformation of the outer receptor segments. A second retinal finding was patches of atrophy, involving loss of the retinal outer cell layer. The pigment epithelium was intact, although there were areas showing depigmentation of the cells. The choriocapillaris was present. The findings suggest that the primary defect in choroideremia lies at the retina-pigment epithelium interface. Possible mechanisms are discussed.

Aged↗
PubMed1986

Effects of 30% intestinal resection on whole population cell kinetics of mouse intestinal epithelium.

The intestine remaining after resection undergoes a well known compensatory response. Crypts and villi grow in size, and the number of proliferating cells in a crypt increases. The crypt labeling index, however, is unchanged, which is thought to suggest that the growth fraction also remains unchanged and hence that the system is enlarged, but otherwise the new steady-state is similar to that of the controls. It is also generally accepted that no new crypts or villi are added to the adapting bowel. In this study we applied recently developed tools to study the response of the intestinal epithelium as a whole. Thus, the effects of 30% intestinal resection on whole population cell kinetics were determined by using flow cytometry, Coulter particle counting, and simple morphometric techniques. In addition to the classic response, we found an increase in the rate of crypt production, which was due mainly to a shorter crypt replication cycle. Thus, new crypts were produced at a faster rate in the resected animals than in the transected controls. This resulted in an expansion of the crypt cell population in the epithelium following resection. There was a corresponding expansion of the cycling cell population and thus an increase in the growth fraction of the resected epithelium. We conclude that for the crypt population, the classic story is correct with the exception that new crypts are added to the epithelium after resection. However, for the epithelium as a whole, the classic story is misleading as there appears to be an increase in the growth fraction of the epithelium after intestinal resection.

Animals↗
PubMed1986

Recurrent corneal erosion, microcystic epithelial dystrophy, map configurations and fingerprint lines in the cornea.

A 45-year-old lady presented with a recurrent corneal erosion. On closer examination, she was found to have epithelial microcysts and fingerprint dystrophy. Pathologic material from the affected cornea showed microcysts, protrusions of basement membrane and evidence of poor adhesion between the basement membrane and the epithelial cells, as well as between the epithelial cells themselves. The case demonstrated the clinical and pathologic features of recurrent corneal erosion, microcystic disease and fingerprint dystrophy of the cornea, together with the pathologic findings of map dystrophy. The authors suggest that these four diseases are various expressions of a clinicopathologic entity, epithelial basement membrane corneal dystrophy. A pathologic explanation for recurrent corneal erosion is apparent.

Cornea↗
PubMed1985

Corneal changes in Fabry's disease: a clinico-pathologic case report of a heterozygote.

Fabry's disease is an X-linked recessive inborn error of metabolism, caused by a deficiency of alpha galactosidase A. This report describes a heterozygote patient with multiple system problems diagnosed eventually as Fabry's disease by the ocular findings. The clinical diagnosis was confirmed by enzymatic assay. Our report emphasizes: The variability of the non-ocular manifestations in the heterozygote of Fabry's disease. The diagnosis of Fabry's disease in our patient was made by the ophthalmologist. The ultra-structural changes in the cornea and conjunctiva of the heterozygote confirm those reported in the literature; in addition we describe changes in the goblet cells. The clinical and ultra-structural similarities of the deposits in Fabry's disease, Chloroquin keratopathy and Amiodarone keratopathy are striking and will be discussed.

Adult↗
PubMed1984

Colour vision in long-standing diabetes mellitus.

In 12 long-standing insulin-dependent diabetics with background diabetic retinopathy their 100-hue colour vision scores were positively related to the degree of retinopathy and negatively to fasting blood glucose levels. However, the 100-hue colour vision scores and types were not significantly different from those of normal subjects matched for age, sex, and social class.

Adult↗
PubMed1984

Ultrastructural changes in the cornea and conjunctiva of a heterozygous woman with Fabry's disease.

Heterozygous females with Fabry's disease show a typical whorled pattern in the corneal epithelium. The patient presented in this paper also had symptoms of polymyositis, necrotizing vasculitis and angiokeratomas. The diagnosis was made from the corneal changes. Electron microscopy revealed intracytoplasmic electron-dense deposits made up of lamellar stacks of uniform periodicity similar to myelin. These were present not only in the corneal epithelium but also in the epithelium, goblet cells, endothelium and mural cells of blood vessels in the conjunctiva. The material in the goblet cells may account for the known presence of ceramide trihexoside in the tears.

Adult↗
PubMed1984

Amiodarone-induced ultrastructural changes in human eyes.

Ocular observations in a series of 100 patients treated with amiodarone, along with the pathological changes observed in the eye tissues of two patients treated with this drug, are described in this paper. In the latter two patients intracytoplasmic membrane-bound lamellar bodies similar to myelin were observed by electron microscopy not only in the corneal epithelium and fibroblasts, the conjunctiva and the lens, but also in the corneal endothelium, the iris, the ciliary body, the choroid and the retina. It is suggested that patients taking amiodarone in high dosage for long periods have their eyes and retinal function monitored.

Amiodarone↗
PubMed1983

Pathological and surgical examination of the handling of the lacerated eyeball.

A survey of 85 lacerated eyeballs pointed to six elements that had led to destruction of the globe: poor wound closure, hypotony, hemorrhage, lens remnants, fibrosis and antigen exposure. Guidelines for the repair of such globes were established on the basis of the pathological findings. The techniques necessitate great care and require the use of a microscope, a vitreous aspiration cutter and fine sutures. Adequate time must be set aside for the surgery, since anything less than careful and complete repair can lead to disaster. The quality of the primary repair is likely to be what defines the excellence of the final result.

Eye↗
PubMed1982

Amiodarone-induced cornea verticillata.

Among 37 patients treated with amiodarone, an antiarrhythmic drug, a typical keratopathy developed in 35, none of whom had ocular complaints. The keratopathy resembled that seen with Fabry's disease and chloroquine use, as did the membrane-bound lamellar bodies detected by electron microscopy in all layers of the corneal epithelium in the one patient with marked keratopathy in whom a corneal biopsy was performed; membrane-bound bodies, mostly granular, were also noted within this patient's stromal keratocytes. The possible pathogenesis of the keratopathy as a type of drug-induced lipidosis is discussed.

Adult↗