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Biomedical subjects

G Miller

Publications and source records attributed to G Miller.

At least 199 records · Page 11Linked to original sources
PubMed1994

The interleukin-1 receptor antagonist (rhIL-1ra) protects against cerebral infarction in a rat model of hypoxia-ischemia.

We assessed the cerebral protective effects of the competitive interleukin-1 antagonist rhIL-1ra in 7-day-old rats that were subjected to brain hypoxia-ischemia by unilateral carotid artery ligation and subsequent exposure to 2 h of 7.5% O2-balanced N2. This procedure leads to atrophy in the cerebral hemisphere ipsilateral to carotid occlusion, with prominent foci of neuronal infarction in the striatum. Systemic administration of 100 mg/kg of rhIL-1ra before and/or after the hypoxic exposure limited the insult. The results indicate that rhIL-1ra has potent neuroprotective properties against morphologic brain injury from hypoxia-ischemia. rhIL-1ra may prove to be clinically useful in protecting against hypoxia-ischemia-related disorders.

Animals↗
PubMed1994

EEG changes during open heart surgery on infants aged 6 months or less: relationship to early neurologic morbidity.

In a prospective study, we analyzed the intraoperative electroencephalographic (EEG) changes during open heart surgery with deep hypothermia in 66 infants aged 6 months or younger, 70% of whom were neonates. Suppression of amplitude and continuity at the nadir of temperature reduction and following rewarming, and the appearance of periodic paroxysmal activity, was compared with neurologic abnormalities before and following operation, patient characteristics, and operation variables. EEG changes disclosed no relationship to abnormal neurologic findings, age at operation, type of anesthetic, duration of cardiopulmonary bypass (CPB), duration of low-flow CPB or cooling, temperature at circulatory arrest (HCA) or low flow, or nasopharyngeal-venous return temperature differences. EEG suppression following rewarming was associated with the use of thiopentone and duration of HCA. Use of thiopentone was also related to decreased levels of alertness at the end of the first postoperative week. We could not demonstrate any association between operation variables, including duration of HCA, and postoperative neurologic findings which include abnormalities of tone, alertness, seizures, generalized pyramidal signs, choreoathetosis, and hemiparesis. Severe hypotonia before operation was associated with continuing severe hypotonia during the postoperative period. EEG changes during cooling for open heart surgery on infants appear to be physiologic, and these plus EEG suppression following HCA or low-flow CPB are not useful predictors of early neurologic morbidity.

Brain Damage, Chronic↗
PubMed1994

Human subcutaneous adipose tissue shows site-specific differences in fatty acid composition.

Adipose tissue was obtained from six women undergoing liposuction twice at 6-mo intervals. Samples obtained bilaterally from abdomen, inner thigh, and outer thigh had fatty acids quantified by gas chromatography. There were no important differences between sides or over time. The saturates 14:0, 16:0, 18:0, and 20:0 were higher in abdominal adipose than in outer thigh (P < 0.002 for all); 16:1 and 18:1 omega 9 were lower in abdomen vs outer thigh (P < 0.01), whereas 18:1 omega 7 and 20:1 omega 9 were unchanged. Polyunsaturates 18:2 omega 6, 20:3 omega 6, and 20:4 omega 6 were higher in outer thigh than in abdomen (P < 0.06), and inner thigh values were intermediate. These changes in fatty acid composition resulted in lower mean triglyceride melting points from abdomen to inner thigh to outer thigh, and suggest that temperature may influence the selection process determining the variation in adipose fatty acid composition with anatomical location. Because the site-specific differences included essential fatty acids, selective uptake as well as potential differences in in situ fatty acid modification are indicated.

Abdomen↗
PubMed1994

Association between genetic variation at the APO AI-CIII-AIV gene cluster and familial combined hyperlipidaemia.

By using chemical cleavage mismatch analysis and the single strand conformation polymorphism technique, DNA fragments of the apo CIII gene, including the 5' flanking region and all the exons, were screened for sequence changes underlying the observed association between familial combined hyperlipidaemia (FCHL) and the apo AI-CIII-AIV gene cluster in affected individuals from eight FCHL families. A C1100-T transition in the wobble position of codon 14 in exon 3 and a T3206-G transversion in the non-translated region of exon 4 were identified, occurring in four and all probands, respectively. Using these variants and the G-75-A transition in the apo AI promoter, co-segregation of the gene cluster with hyperlipidaemia could be excluded in all eight families (lod score - infinity at theta = 0). No support for co-segregation was obtained using the affected pedigree member method of linkage analysis (overall T = -0.77 for f(p) = 1 [symbol: see text] p). The frequencies of T1100 and G3206 in a group of 55 patients with combined hyperlipidaemia were 0.35 and 0.52, respectively, which were significantly higher compared to 360 controls (0.21, p < 0.01 and 0.35, p < 0.005 respectively). In patients homozygous for the T1100 allele, levels of plasma triglyceride were 2.5-fold higher (868 mg/dl) than those homozygous for the C1100 allele (337 mg/dl), while patients heterozygous for the polymorphism had intermediate values (443 mg/dl) (p < 0.01). A similar association was seen in controls (p < 0.04). The three polymorphisms studied were in strong linkage disequilibrium in both the group of CHL patients and the unrelated individuals. This study confirms the association between common variation in the gene cluster and differences in plasma lipid levels in the general population and in patients with combined hyperlipidaemia, but fails to confirm co-segregation with FCHL, suggesting the role of other genetic or environmental factors in the aetiology of FCHL.

Adult↗
PubMed1994

Activation of the Epstein-Barr virus BMRF1 and BZLF1 promoters by ZEBRA in Saccharomyces cerevisiae.

ZEBRA has been shown to activate model reporter genes consisting of synthetic oligomerized ZEBRA response elements upstream of a minimal CYC1 promoter fused to beta-galactosidase in the yeast Saccharomyces cerevisiae. Here it is shown that in S. cerevisiae ZEBRA activates transcription of natural Epstein-Barr virus promoters. Two Epstein-Barr virus promoters were shown to be activated by ZEBRA in S. cerevisiae: Zp, the promoter that regulates expression of BZLF1, which encodes ZEBRA; and EAp, the promoter controlling expression of BMRF1, which encodes diffuse early antigen, EA-D. These observations indicate that neither mammalian-specific nor virally encoded coactivators are obligatory for ZEBRA to stimulate expression from these two promoters. Zp was also strongly activated by endogenous yeast factors. EAp was not activated by yeast factors. The results show that in S. cerevisiae and in B cells, ZEBRA dominates the response of EAp; ZEBRA plus endogenous cell factors activate Zp.

Antigens, Viral↗
PubMed1994

Long-term MRI changes in brain after pediatric open heart surgery.

We performed magnetic resonance imaging (MRI) on the brain and neurologic examinations on 23 children after open heart surgery for congenital heart disease. Twenty children also had psychometric assessments. Examinations were performed at a mean age of 66 months (range, 26 to 180 months). Age at operation was less than 1 month in 43% and more than 6 months in 45%. Abnormal scans were found in 17 (74%) and showed diffuse findings consistent with hypoxic-ischemic encephalopathy, with or without areas of cortical infarction; focal cortical infarction alone; and (in one patient) callosal agenesis and abnormal neuronal migration. Normal IQ and neurologic examinations were found in all six of those who had a normal MRI, and five of six children with changes consistent with focal cortical infarction without diffuse change had a normal neurologic examination. Cerebral palsy and mental retardation was common in the group with diffuse abnormality (in eight of nine children), and this was more likely to occur in those who underwent prolonged (> 45 minutes) hypothermic circulatory arrest and operation during early infancy (P = .004). Focal cortical findings without diffuse changes were more likely in those who underwent open heart surgery without hypothermic circulatory arrest and were older than 6 months at operation, and these children were less likely to have frank neurodevelopmental sequelae. Thus, in our population, focal cortical lesions were common after open heart surgery, and, in addition, diffuse brain abnormality on MRI plus neurologic sequelae were common after prolonged hypothermic circulatory arrest.

Adolescent↗
PubMed1994

Inhibitory effects of antagonists of bombesin/gastrin releasing peptide (GRP) and somatostatin analog (RC-160) on growth of HT-29 human colon cancers in nude mice.

Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with somatostatin analog (RC-160), bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095 and RC-3440). In three separate experiments somatostatin analog RC-160 (50 micrograms/day) released from microgranules significantly reduced tumor growth. Bombesin/GRP antagonists, RC-3095 and RC-3440 injected subcutaneously (s.c.) twice daily at a dose of 10 micrograms had the greatest and consistently significant inhibitory effect on tumor growth. RC-3095 given once daily s.c. at a dose of 20 micrograms was less effective. RC-3095 also inhibited metastatic tumor growth after intrasplenic injection of HT-29 cells in nude mice. Specific binding sites of somatostatin, bombesin and epidermal growth factor (EGF) were detected on intact HT-29 cells or on the membranes from HT-29 tumor xenografts. The inhibitory effects of bombesin antagonists on tumor growth were consistently linked with a significant down-regulation of EGF receptors. Bombesin/GRP antagonists and somatostatin analogs could be considered for the development of new hormonal therapies for colon cancer.

Adenocarcinoma↗
PubMed1994

Neonatal pontomedullary disconnection with aplasia or destruction of the lower brain stem: a case of pontoneocerebellar hypoplasia?

We report a neonate who presented with marked hypotonia and absent suck reflex. MR demonstrated complete absence of the pons as well as absence of a basilar artery flow void. Our case exhibits features similar to those described in previous reports of pontoneocerebellar hypoplasia, but with a more severe degree of pontine involvement. The associated vascular findings suggest a vascular insult to the brain stem as the cause.

Basilar Artery↗
PubMed1993

Serine-173 of the Epstein-Barr virus ZEBRA protein is required for DNA binding and is a target for casein kinase II phosphorylation.

An Epstein-Barr virus-encoded protein, ZEBRA, mediates the switch from latency to the viral lytic life cycle. ZEBRA's domain structure and DNA binding specificity resemble that of cellular transcriptional activators such as c-Fos/c-Jun. We show that ZEBRA, like c-Jun, is phosphorylated by casein kinase II (CKII). The principal site of phosphorylation is serine-173 (S173), five amino acids upstream of the basic DNA recognition domain. CKII phosphorylation abrogated ZEBRA's capacity to bind its target DNA sequences. S173 is a functional component of ZEBRA's DNA binding domain, since mutation of S173 to alanine (S173A) reduced DNA binding in vitro to 10% of wild-type levels. Transcriptional activation of a native viral promoter in vivo by mutant S173A was also reduced markedly. Reversible phosphorylation of S173 is likely to be an important means of regulating ZEBRA's activity in vivo.

Alanine↗
PubMed1993

Data collection and changing health care systems. 1. United Kingdom.

The adoption of "Read Clinical Codes" for computerised patient records could profoundly alter the nature and quality of Western medicine in the next decade. The increasing awareness of the need for a standardised coding system has led to the funding of a pilot project to test Read codes in Australian general practice. Read codes are a comprehensive nomenclature of clinical terms incorporating over 100,000 codes in a structured hierarchical form. Designed by a general practitioner, they are now owned, controlled, and developed by the British National Health Service (NHS). Selected as the basis for clinical coding across the NHS, they form the cornerstone of computerised patient records. Computer use has been encouraged in general practice in the UK, with financing schemes and functional inducements resulting in 70% of practices being at least partly computerised, and 84% of these using Read codes. Their promotion has been backed by a major development program to broaden the codes to include all clinical specialities, nursing, and professions allied to medicine. The codes will require significant adaptation for Australian use, including the development of an administrative chapter and a pharmaceutical classification. The impact of information management systems on health care in the UK has relevance for the continuing development of the Australian National Health Information Strategy and for future record keeping in general practice in Australia. If the trial proves successful, the adoption of Read codes as a standard for information management in patient medical records will need to be considered.

Abstracting and Indexing↗
PubMed1993

Data collection and changing health care systems. 2. New Zealand.

Radical changes planned in the New Zealand health system aim to improve its cost effectiveness, quality and consumer responsiveness. These changes will take place despite a paucity of data on the use of resources and outcomes. Data collection systems are to be introduced into hospitals and primary care with the use of the Read clinical codes (RCC) in addition to ICD-9-CM (International classification of disease--clinical modification) and ICPC (International classification of primary care). This paper discusses the proposed changes to the New Zealand health care system and describes their effect on the present and future data collection methods in general practice.

Abstracting and Indexing↗
PubMed1993

Changing Epstein-Barr viral ZEBRA protein into a more powerful activator enhances its capacity to disrupt latency.

The Epstein-Barr viral transcriptional activator ZEBRA induces expression of viral early lytic genes when introduced into cells bearing latent Epstein-Barr virus. We show here that a ZEBRA-herpes simplex viral protein 16 (VP16) fusion protein induces early viral lytic gene expression in Epstein-Barr virus-containing cells more efficiently than does wild-type ZEBRA. The fusion protein is also a more powerful transcriptional activator in these cells, as assayed with reporter constructs. Our experiments also suggest that ZEBRA manifests a function required for full activity on certain natural promoters but not on promoters bearing oligomerized ZEBRA binding sites; this function cannot be provided by VP16.

Cells, Cultured↗
PubMed1993

SCH 38057: a picornavirus capsid-binding molecule with antiviral activity after the initial stage of viral uncoating.

The activity of a new water-soluble molecule, SCH 38057, against picornaviruses is described. SCH 38057 inhibited plaque formation of selected entero- and rhinoviruses in a range of 10.2 to 29.1 microM (50% endpoint) and had a therapeutic index of 10 against poliovirus type 2 (polio 2) in HeLa cells. When administered orally or subcutaneously, SCH 38057 protected mice infected with either coxsackievirus B3 (CVB3) or echovirus-9 from mortality. The molecule provided a low level of protection against thermal inactivation of virus, indicating that SCH 38057 interacts with the picornavirus capsid. Binding studies with [3H]SCH 38057 revealed that the molecule binds to CVB3 and human rhinovirus 14 (HRV14) in a ratio of 29 and 19 molecules per viral particle, respectively. The affinity constant for SCH 38057 binding to CVB3 was 7.0 x 10(-4) M. When added to cultures of infected cells at 3 h after infection, SCH 38057 markedly inhibited viral RNA synthesis. This finding with lack of inhibition of attachment and loss of infectious virus after attachment were interpreted to indicate that, although SCH 38057 binds to the viral capsid, the molecule exerts its antiviral effect after the initial stage of picornavirus uncoating, i.e., after conversion of the 156S infectious viral particle to smaller subviral species.

Animals↗
PubMed1993

An epidemiologic study of nosocomial infections in a pediatric long-term care facility.

OBJECTIVE: To determine the incidence of hospital-acquired (nosocomial) infection in pediatric long-term care facilities. DESIGN: Prospective cohort. SETTING: An 87-bed pediatric long-term care facility. PATIENTS: All patients receiving long-term care at Bloorview Children's Hospital during the study period. RESULTS: Infection developed in 40.1% of patients (n = 456). The nosocomial infection rate per 1000 patient days (mean, 7.84) varied substantially, from 1.66 in May 1988 to 16.37 day in April, 1989. The proportional frequencies of infections were as follows: respiratory, 41.6% (37.0% upper, 4.6% lower); urinary tract, 31.0%; skin, 15.6% (gastric tube site 5.0%, other 10.6%), eyes, 6.4%; gastrointestinal, 3.5%; and other, 1.5%. Of those infections for which an organism was recovered (48.5%), pathogens included Escherichia coli (22.5%), Enterococcus (14.8%), Staphylococcus (14.8%), Streptococcus (11.2%), Klebsiella (10.5%), Pseudomonas (10.1%), Proteus (4.3%), yeast (4.3%), Salmonella (0.7%), Clostridium difficile (0.4%), and other (6.2%). CONCLUSIONS: The incidence and nature of infections in pediatric long-term care facilities differs from those in acute care facilities. Physicians should become familiar with the infection rates in the populations whom they treat. Control requires compliance with currently recognized effective strategies as well as innovative practical approaches to respiratory disease. Behavioral problems related to frequent clean, intermittent catheterization in young adults need to be addressed.

Adolescent↗
PubMed1993

Autoreactive T cells from a type I diabetic recognize multiple class II products.

Mononuclear cells obtained from a child at the acute presentation of type I diabetes were stimulated in vitro with human insulin followed by IL-2 and IL-4. All of the T-cell clones isolated from this stimulation were autoreactive, recognizing autologous B cells in the absence of insulin or other exogenous antigens. Eleven CD4+ clones were studied in detail to identify the class II MHC antigens stimulating these autoreactive cells. The donor was heterozygous for DR3DQw2 and DR4DQw3.2 haplotypes, a combination of alleles with a greatly increased risk for type I diabetes. The clones demonstrated skewed recognition of class II antigens. Three clones appeared to recognize a peptide derived from one class II beta chain (DR beta 1, DR4Dw4) presented by another class II beta chain (DR beta 4, DRw53). Three clones were stimulated by cells expressing DPw4 molecules. Only one clone recognized a product derived from the DR3 haplotype. In contrast to both antigen-specific and autoreactive T-cell clones derived from normal individuals, many of the autoreactive T cells isolated from this subject were stimulated by class II molecules other than DR beta 1. The results support the hypothesis that autoreactive T cells recognize autologous peptides in association with MHC and some of these peptides are derived from self MHC molecules.

Acute Disease↗
PubMed1993

Differentiating acute appendicitis from pelvic inflammatory disease in women of childbearing age.

A retrospective study was performed to evaluate the usefulness of various historical, clinical, and laboratory findings in differentiating acute appendicitis from pelvic inflammatory disease (PID) in women of childbearing age. The records of all female patients presenting to the emergency department with abdominal pain who were found to have histologically proven appendicitis (n = 80) or PID confirmed on endocervical culture (n = 71) were reviewed. Clinically useful indicators favoring appendicitis included the presence of anorexia and the onset of pain later than day 14 of the menstrual cycle. Indicators favoring PID included a history of vaginal discharge, urinary symptoms, prior PID, tenderness outside the right lower quadrant, cervical motion tenderness, vaginal discharge on pelvic examination, and positive urinalysis. Despite these indicators, differentiating acute appendicitis from PID remains difficult.

Acute Disease↗