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Biomedical subjects

C Lloyd

Publications and source records attributed to C Lloyd.

At least 55 records · Page 3Linked to original sources
PubMed1996

Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation.

We have cloned a novel mouse CC chemokine cDNA from the lung during an allergic inflammatory reaction. The protein encoded by this cDNA is chemotactic for eosinophils, monocytes, and lymphocytes in vitro and in vivo. Based on its similarities in sequence and function with other CC chemokines, we have named it mouse monocyte chemotactic protein-5 (mMCP-5). Under noninflammatory conditions, expression of mMCP-5 in the lymph nodes and thymus is constitutive and is generally restricted to stromal cells. Neutralization of mMCP-5 protein with specific antibodies during an allergic inflammatory reaction in vivo resulted in a reduction in the number of eosinophils that accumulated in the lung. Moreover, mMCP-5 mRNA expression in vivo is regulated differently from that of other major CC chemokines in the lung during the allergic reaction, including Eotaxin. The presence of lymphocytes is essential for expression of mMCP-5 by alveolar macrophages and smooth muscle cells in the lung, and the induction of mMCP-5 RNA occurs earlier than that of the eosinophil chemokine Eotaxin during allergic inflammation. In contrast to Eotaxin, mRNA for mMCP-5 can be produced by mast cells. From these results, we postulate that mMCP-5 plays a pivotal role during the early stages of allergic lung inflammation.

Amino Acid Sequence↗
PubMed1996

The changing course of diabetic nephropathy: low-density lipoprotein cholesterol and blood pressure correlate with regression of proteinuria.

Diabetic nephropathy (DN) as manifested by persistent and clinically evident proteinuria, has long been considered an irreversible process that predicts a rapid decline in renal function. The observation of reversal of DN in several individuals enrolled in a prospective study of the natural course of diabetes complications challenged this view and led to the current investigation into the correlates of such regression of proteinuria. DN was defined as a median albumin excretion rate (AER) over 200 microg/min in two or three urine collections obtained at baseline, and again at 2 and 4 years of follow-up. Among 658 individuals with childhood-onset insulin-dependent diabetes mellitus (IDDM), 146 had DN at baseline. Nine subsequently died without renal failure, and 13 were lost to follow-up. Of the 124 subjects with at least survey follow-up data, 32 (24%) developed renal failure, and 78 of the remaining 92 provided full quantitative data. AER decreased by > or = 10-fold into the microalbuminuric (20 to 200 microg/min) or normal range (<20 microg/min) in 7 of these individuals and are called "regressors of proteinuria." Compared with the remaining 71 subjects, the strongest correlate of regression of proteinuria was an improvement in fasting plasma low-density lipoprotein cholesterol (LDL-C) in the 7 regressors (P < 0.008). Improved glycemic control was not a significant predictor of improved AER. Five of the 7 individuals with improved AER had a baseline median AER below 500 microg/min. When the 7 regressors of proteinuria were combined with an additional 38 individuals who also experienced smaller decreases in median AER, such improvement was associated with a more favorable systolic (or diastolic) blood pressure (BP) change (P < 0.01), and a decrease in plasma LDL-C level (P = 0.01). These data suggest that proteinuria in DN may substantially regress in approximately 6% and improve in at least 34% of individuals with IDDM over a 4-year period, often in association with a decrease in plasma LDL-C concentration or stabilization or improvement in BP. Furthermore, the data suggest that the nonreversibility threshold for diabetic nephropathy may be higher (500 mg/min) than previously reported (200 microg/min).

Adult↗
PubMed1996

Isolation of microtubule-associated proteins from carrot cytoskeletons: a 120 kDa map decorates all four microtubule arrays and the nucleus.

A method for biochemically isolating microtubule-associated proteins (MAPs) from the detergent-extracted cytoskeletons of carrot suspension cells has been devised. The advantage of cytoskeletons is that filamentous proteins are enriched and separated from vacuolar contents. Depolymerization of cytoskeletal microtubules with calcium at 4 degrees C releases MAPs which are then isolated by association with taxol stabilized neurotubules. Stripped from microtubules (MTs) by salt, then dialysed, the resulting fraction contains a limited number of high molecular weight proteins. Turbidimetric assays demonstrate that this MAP fraction stimulates polymerization of tubulin at concentrations at which it does not self-assemble. By adding it to rhodamine-conjugated tubulin, the fraction can be seen to form radiating arrays of long filaments, unlike MTs induced by taxol. In the electron microscope, these arrays are seen to be composed of mainly single microtubules. Blot-affinity purified antibodies confirm that two of the proteins decorate cellular microtubules and fulfil the criteria for MAPs. Antibodies to an antigenically related triplet of proteins about 60-68 kDa (MAP 65) stain interphase, preprophase band, spindle and phragmoplast microtubules. Antibodies to the 120 kDa MAP also stain all of the MT arrays but labelling of the cortical MTs is more punctate and, unlike anti-MAP 65, the nuclear periphery is also stained. Both the anti-65 kDa and the anti-120 kDa antibodies stain cortical MTs in detergent-extracted, substrate-attached plasma membrane disks ('footprints'). Since the 120 kDa protein is detected at two surfaces (nucleus and plasma membrane) known to support MT growth in plants, it is hypothesized that it may function there in the attachment or nucleation of MTs.

Animals↗
PubMed1995

MMK2, a novel alfalfa MAP kinase, specifically complements the yeast MPK1 function.

Mitogen-activated protein (MAP) kinases are serine/threonine protein kinases that are activated in response to a variety of stimuli. Here we report the isolation of an alfalfa cDNA encoding a functional MAP kinase, termed MMK2. The predicted amino acid sequence of MMK2 shares 65% identity with a previously identified alfalfa MAP kinase, termed MMK1. Both alfalfa cDNA clones encode functional kinases when expressed in bacteria, undergoing autophosphorylation and activation to phosphorylate myelin basic protein in vitro. However, only MMK2 was able to phosphorylate a 39 kDa protein from the detergent-resistant cytoskeleton of carrot cells. The distinctiveness of MMK2 was further shown by complementation analysis of three different MAP kinase-dependent yeast pathways; this revealed a highly specific replacement of the yeast MPK1(SLT2) kinase by MMK2, which was found to be dependent on activation by the upstream regulators of the pathway. These results establish the existence of MAP kinases with different characteristics in higher plants, suggesting the possibility that they could mediate different cellular responses.

Amino Acid Sequence↗
PubMed1995

Plant morphogenesis. Life on a different plane.

Arabidopsis ton mutant cells do not make the bands of microtubules that normally predict cell-division planes; the planes are irregular, yet seedlings develop to maturity. Is cellular morphogenesis important for plant form?

Arabidopsis↗
PubMed1995

Familial posterior lenticonus.

Posterior lenticonus tends to be unilateral and there is no evidence that this is a familial condition. We report three cases of bilateral posterior lenticonus in boys. The mothers of all three cases had posterior lenticular changes, less severe than their sons. We suggest that bilateral posterior lenticonus may be inherited in an X-linked fashion.

Cataract↗
PubMed1995

The basal keratin network of stratified squamous epithelia: defining K15 function in the absence of K14.

Keratin 5 and keratin 14 have been touted as the hallmarks of the basal keratin networks of all stratified squamous epithelia. Absence of K14 gives rise to epidermolysis bullosa simplex, a human blistering skin disorder involving cytolysis in the basal layer of epidermis. To address the puzzling question of why this disease is primarily manifested in skin rather than other stratified squamous epithelia, we ablated the K14 gene in mice and examined various tissues expressing this gene. We show that a key factor is the presence of another keratin, K15, which was hitherto unappreciated as a basal cell component. We show that the levels of K15 relative to K14 vary dramatically among stratified squamous epithelial tissues, and with neonatal development. In the absence of K14, K15 makes a bona fide, but ultrastructurally distinct, keratin filament network with K5. In the epidermis of neonatal mutant mice, K15 levels are low and do not compensate for the loss of K14. In contrast, the esophagus is unaffected in the neonatal mutant mice, but does appear to be fragile in the adult. Parallel to this phenomenon is that esophageal K14 is expressed at extremely low levels in the neonate, but rises in postnatal development. Finally, despite previous conclusions that the formation of suprabasal keratin filaments might depend upon K5/K14, we find that a wide variety of suprabasal networks composed of different keratins can form in the absence of K14 in the basal layer.

Amino Acid Sequence↗
PubMed1995

Impact of altered actin gene expression on vinculin, talin, cell spreading, and motility.

Previous studies have demonstrated a strong correlation between the expression of vinculin and the shape and motility of a cell (Rodriguez Fernandez et al., 1992a, b, 1993). This hypothesis was tested by comparing the expression of vinculin and talin with the motility of morphologically altered myoblasts. These mouse C2 myoblasts were previously generated by directly perturbing the cell cytoskeleton via the stable transfection of a mutant-form of the beta-actin gene (beta sm) and three different forms of the gamma-actin gene; gamma, gamma minus 3'UTR (gamma delta'UTR), and gamma minus intron III (gamma delta IVSIII) (Schevzov et al., 1992; Lloyd and Gunning, 1993). In the case of the beta sm and gamma-actin transfectants, a two-fold decrease in the cell surface area was coupled, as predicted, with a decrease in vinculin and talin expression. In contrast, the gamma delta IVSIII transfectants with a seven-fold decrease in the cell surface area showed an unpredicted slight increase in vinculin and talin expression and the gamma delta 3'-UTR transfectants with a slight increase in the cell surface area showed no changes in talin expression and a decrease in vinculin expression. We conclude that changes in actin gene expression alone can impact on the expression of vinculin and talin. Furthermore, we observed that these actin transfectants failed to show a consistent relationship between cell shape, motility, and the expression of vinculin. However, a relationship between talin and cell motility was found to exist, suggesting a role for talin in the establishment of focal contacts necessary for motility.

Actins↗
PubMed1995

Behavioral disturbance in dementia.

Fifty-seven subjects with moderate to severe dementia (49 with Alzheimer's disease) were rated twice, 8 weeks apart, using the Mini-Mental State Examination (MMSE), the Blessed Information-Memory-Concentration Test (BIMC), and the Stockton Geriatric Rating Scale (SGRC). Only three subjects lived at home; the rest were in long-stay hospital beds or nursing homes. For 29 subjects, the first rating coincided with their referral to a comprehensive geriatric psychiatry service. The main hypothesis, that the level of behavioral disturbance would correlate positively with the level of cognitive impairment, was strongly confirmed. This finding may reflect the severity of dementia in the study sample. The correlations between MMSE and BIMC scores were .87 at entry and .92 at exit, suggesting that the two measures were broadly equivalent, although both had marked floor effects. Test-retest reliability was high for all three measures. Overall, medication was of limited effectiveness in managing severe behavioral disturbance, highlighting the need for introducing effective behavioral programs.

Aged↗
PubMed1994

Exacerbations of childhood asthma and ozone pollution in Atlanta.

Asthma prevalence and mortality due to asthma have been increasing during the last decade, and both the rates and the increases in rates have been higher for blacks than whites and higher for children than adults. Whether environmental factors such as air pollution contribute to these increases is unknown. The purpose of this study was to examine the relationship between emergency visits to a hospital for childhood asthma and exposure to ozone in an indigent, predominantly black population. Data were collected by abstracting clinical records for all children with asthma or reactive airway disease in one public hospital during the summer of 1990. From June 1, 1990, to August 31, 1990, 609 visits were made by children aged 1 to 16 years to an emergency clinic for treatment of asthma or reactive airway disease. Monitoring data indicated that maximum ozone levels equalled or exceeded 0.11 ppm on 6 days during the study period. The average number of visits for asthma or reactive airway disease was 37% higher on the days after those 6 days (from 6:00 PM to 6:00 PM the next day) than on other days (95% CI, RR = 1.02-1.73). The results of the study suggest that among black children from low-income families, asthma may be exacerbated following periods of high ozone pollution.

Adolescent↗
PubMed1994

Excitatory amino acids, free radicals and the pathogenesis of motor neuron disease.

The cause of motor neuron disease (MND) remains unknown, but the pathogenic involvement of excitatory amino acid (EAA) neurotransmitters and related exogenous compounds has been proposed. We discuss current concepts of the mechanisms of action of EAAs and the evidence for links between these neurotransmitters and free radical hypotheses of neuronal damage. These concepts are especially pertinent following reports of mutations in the gene encoding the free radical scavenging enzyme, copper-zinc superoxide dismutase, in familial MND. New approaches to treatment are suggested by advances in understanding of the disease.

Animals↗
PubMed1993

Rhabdomyosarcoma cell line can be used for the isolation of soluble acetylcholine receptor and for assaying blocking and modulating autoantibodies.

We found that the Rhabdomyosarcoma (RD) cell line expresses human acetylcholine receptor (AChR) based on the following evidences: 1. Soluble AChR can be isolated from RD cells following the isolation procedure for AChR from human muscle; 2. Intact RD cells bind to alpha-bungarotoxin (alpha Butx) in a time-dependent and saturable fashion. The apparent dissociation constant (5.3 x 10(-10) M) is very similar to that reported for TE671 cells, which is known to express AChR; 3. Like fresh muscle culture, RD cells not only bind but also internalize 125I-alpha Butx. Soluble AChR from RD cells can be labeled specifically with 125I-alpha Butx and then used to quantify binding autoantibodies in myasthenic patients. We also demonstrate that blocking antibodies can be detected in sera from patients with myasthenia gravis (MG) using RD cells and the ability of RD cells to internalize alpha Butx. Consequently, RD cells can be used as a reliable source for obtaining soluble AChR and as a replacement for rodent or human muscle cultures in measuring blocking and modulating antibodies.

Autoantibodies↗
PubMed1993

Noncoding regions of the gamma-actin gene influence the impact of the gene on myoblast morphology.

We have addressed the question of whether two highly conserved noncoding regions of the gamma-actin gene are of functional importance. Human gamma-actin gene constructs deleted for either the entire 3' untranslated region (UTR) and 3' flank or intron III sequences were transfected into mouse myoblasts and the resulting clones were analyzed for cell morphology and actin protein expression. Transfectants carrying the gamma-actin gene deleted for the 3' end (gamma 22) exhibited numerous long pseudopods and increased surface area. In contrast, transfectants expressing the gamma-actin gene deleted for intron III (gamma 156) were rounded with blebs over the cell surface and showed decreased surface area. The relative expression of beta- to gamma-actin protein decreased for both transfectant types. The total actin protein levels remained constant for the gamma 22 cells but decreased for the gamma 156 cells. The results indicate that alterations to transfectant cell morphology can be influenced by the presence or absence of different noncoding regions in the transfected gamma-actin gene. The mechanisms by which noncoding regions of the gamma-actin gene influence the impact of the gene are unknown. Nevertheless, these noncoding regions are isoform specific and highly conserved in evolution. We propose that the functional significance of the different actin isoforms may involve the properties of these noncoding regions in addition to the differences in protein sequence.

Actins↗
PubMed1993

Differential regulation of tropomyosin isoform organization and gene expression in response to altered actin gene expression.

Phenotypically altered C2 myoblast cells, generated by the stable transfection of human nonmuscle actin genes (Schevzov, G., C. Lloyd, and P. Gunning. 1992. J. Cell Biol. 117:775-786), exhibit a differential pattern of tropomyosin cellular organization and isoform gene expression. The beta-actin transfectants displaying a threefold increase in the cell surface area, showed no significant changes in the pattern of organization of the high M(r) tropomyosin isoform, Tm 2, or the low M(r) tropomyosin isoform, Tm 5. In contrast, the gamma- and beta sm-actin gene transfectants, exhibiting a twofold decrease in the cell surface area, had an altered organization of Tm 2 but not Tm 5. In these actin transfectants, Tm 2 did not preferentially segregate into stress fiber-like structures and the intensity of staining was greatly diminished. Conversely, a well-defined stress fiber-like organization of Tm 5 was observed. The pattern of organization of these tropomyosin isoforms correlated with their expression such that a profound decrease in Tm 2 expression was observed both at the transcript and protein levels, whereas Tm 5 remained relatively unchanged. These results suggest that relative changes in nonmuscle actin gene expression can affect the organization and expression of tropomyosin in an isoform specific manner. Furthermore, this apparent direct link observed between actin and tropomyosin expression suggests that nonpharmacological signals originating in the cytoskeleton can regulate cytoarchitectural gene expression.

Actins↗
PubMed1993

The helping relationship: the application of Carkhuff's model.

Research has shown that good interpersonal skills are a prerequisite for a helping relationship to be effective. Carkhuff's helping model provides a framework in which to examine the nature of the helping relationship. The core helper dimensions and phases of helping are outlined. It is suggested that by incorporating this model into occupational therapy practice the delivery of care will be enhanced.

Allied Health Personnel↗