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Biomedical subjects

G Miller

Publications and source records attributed to G Miller.

At least 379 records · Page 21Linked to original sources

Follow-up of pre-term infants: is correction of the developmental quotient for prematurity helpful?

Developmental quotients, measured on the Griffiths' scales, of 114 preterm infants of less than 34 wk gestation are compared with abnormal neurological findings at 1 yr of cerebral palsy, dystonia, and motor delay. The developmental quotient (DQ) uncorrected for prematurity more readily distinguishes the abnormal infant than the corrected DQ. It is recommended that while developmental follow-up still uses scales originally standardised on older preterm and full-term infants the uncorrected developmental quotient is also used. Ideally normative data on the preterm infant should be compiled as a basis for assessing development in these infants.

Cerebral Palsy↗

Correlation of neurologic assessment in the preterm newborn infant with outcome at 1 year.

A prospective study was undertaken of the outcome at 1 year in 129 preterm infants of less than 34 weeks gestation (range 27 to 34 weeks) who underwent detailed neurologic assessment and ultrasound scanning in the neonatal period and again at 40 weeks postmenstrual age, and an independent neurodevelopmental assessment at 12 months chronologic age. Of the 129 infants, 37 (29%) had ultrasound evidence of periventricular hemorrhage. At 40 weeks postmenstrual age the infants were classified as neurologically normal, abnormal, or borderline on the basis of the neurologic examination. Of the 62 infants considered normal at 40 weeks, 57 (91%) were assessed as normal at one year, compared to only 14 (35%) of the 39 infants considered abnormal (P less than 0.001). Ten (85%) of the 12 normal infants with associated periventricular hemorrhage were normal at 1 year, compared to 47 (94%) of the 50 normal infants without periventricular hemorrhage, whereas 5 (25%) of 20 abnormal infants with associated periventricular hemorrhage and 9 (47%) of the 19 without periventricular hemorrhage were normal at 1 year. There was no direct correlation in individual cases between the severity of neurologic deficit and the presence or severity of periventricular hemorrhage. Infants with a cluster of abnormal signs were more likely to have later dystonia or cerebral palsy than those with marked hypotonia but no other abnormality.

Cerebral Hemorrhage↗

The maturation of the auditory brainstem response compared to peripheral nerve conduction velocity in preterm and full-term infants.

The maturation of the auditory brainstem response in preterm and full-term infants is compared with that of nerve conduction velocity. There is a linear relationship between wave I latency, the peripheral component of the response, and nerve conduction velocity, but the negative correlation is not high. A poor negative correlation exists between the I-V interval, an index of brainstem transmission, and nerve conduction velocity. The factors governing the maturation of central transmission along the auditory pathway in the brainstem are not related to myelination of peripheral nerves. Abnormal nerve conduction velocities are not related to any particular abnormal brainstem response in a stable external environment.

Auditory Pathways↗

Identification of Epstein-Barr nuclear antigen polypeptide in mouse and monkey cells after gene transfer with a cloned 2.9-kilobase-pair subfragment of the genome.

A new antigenic polypeptide was identified in mouse L cells and in monkey COS-1 cells in which Epstein-Barr nuclear antigen (EBNA) was expressed as the result of gene transfer with cloned fragments of Epstein-Barr virus (EBV) DNA. The same-size protein (Mr, approximately equal to 78,000) was seen in stably transformed mouse cells harboring only the BamHI K fragment [approximately equal to 5.2 kilobase pairs (kbp)] or its BamHI/HindIII subfragment, I1f (approximately equal to 2.9 kbp). Thus, the latter DNA fragment is sufficient to code for the protein. In transfected COS cells, a deletion mutant of the I1f fragment (approximately equal to 2.3 kbp) gave rise to a truncated protein (Mr, approximately equal to 52,000), whereas the BamHI K fragment yielded a full-sized Mr 78,000 species. This finding indicates that EBNA is encoded by viral genes. In Burkitt lymphoma lines or in immortalized lymphocytes, variation in the size of the I1f fragment correlated with the apparent molecular weight of the EBNA polypeptide. EBNA is truncated in two Burkitt lymphoma lines, Raji (Mr, 67,000) and P3JHR-1 (Mr, 70,000), which have deletion mutant I1f genes. EBNA in human lymphoid cells bearing a complete I1f fragment as part of the entire EBV genome is the same size (Mr, 78,000) as EBNA found after gene transfer of I1f alone into mouse or monkey cells. Therefore, these expression systems make an authentic EBNA after transfer of the appropriate EBV genes.

Animals↗

Infectious mononucleosis: a polyclonal B cell transformation in vivo.

We obtained spontaneous formation of Epstein-Barr virus-transformed B lymphocyte colonies from the blood of four patients with mononucleosis with the use of soft-agar medium. The colonies were propagated into separate cell lines and analyzed for their immunoglobulin secretion. Of 52 such lines, 44 produced immunoglobulin composed of a single class of heavy chain and single type of light chain. Among these clonal transformants, 27 (62%) of 44 produced mu-chain, 13 (29%) of 44 produced gamma-chain, and 4 (9%) of 44 produced alpha-chain. Analysis of light-chain secretion revealed that of the 44 cell clones secreting complete, monoclonal immunoglobulin products, 31 produced kappa-chain and 13 produced gamma-chain. One clone secreted mu-heavy chain and no light chain, an observation suggesting the clone is a pre-B cell phenotype. Seven lines derived from clones had aberrant patterns of immunoglobulin secretion that produced either two heavy chains or two light chains. B lymphocytes in different states of immunoglobulin gene expression are, therefore, transformed in vivo by Epstein-Barr virus.

Antibodies, Viral↗

Radioisotope studies of neurogenic bladder in multiple sclerosis.

Urinary dysfunction is a frequent and often serious manifestation of multiple sclerosis. If ignored, urinary tract pathology can cause disabling symptoms and life-threatening complications. Symptomatic relief and preventative measures are available once the underlying neurogenic pathology has been identified. The conceptualization of the categories "Failure to Store," "Failure to Empty," or "Combined" provide practical diagnostic and treatment catagories. One important diagnostic test to help define treatment parameters is the radioisotope renal/residual urine study.

Adult↗

Epstein-Barr virus with heterogeneous DNA disrupts latency.

By cloning the HR-1 Burkitt lymphoma line, we previously uncovered two distinct biological variants of nontransforming Epstein-Barr virus (EBV). The most commonly cloned variant has a low rate of spontaneous viral synthesis and is unable to induce early antigen in Raji cells (EAI-). A rare variant spontaneously releases virus which is capable of inducing early antigen in Raji cells (EAI+). Since EAI- virus lacks heterogeneous DNA (het-) and EAI+ virus contains heterogeneous DNA (het+), we suggested that spontaneous viral synthesis and induction of early antigen are biological properties which correlate with the presence of het sequences. The present experiments provide three new lines of experimental evidence in favor of this hypothesis. (i) Revertant subclones of the EAI+ het+ variant which have lost the het DNA concomitantly lost EAI ability. Thus, het DNA is not stably associated with the cells as are the episomes. (ii) het DNA was acquired by two het- subclones of the HR-1 line after superinfection with EAI+ virus. After superinfection, these clones synthesized EAI+ het+ virus. Thus, het DNA may be maintained in the HR-1 line by cell-to-cell spread. (iii) Virus with het DNA activated full expression of endogenous latent EBV of the transforming phenotype in a line of immortalized neonatal lymphocytes designated X50-7. By use of restriction endonuclease polymorphisms unique to both the superinfecting and endogenous genomes, we show that the genome of the activated virus resembles that of the virus which was endogenous to X50-7 cells. This result suggests that het sequences result in transactivation of the latent EBV. het DNA had homology with EBV sequences which are not normally contiguous on the physical map of the genome. het DNA was always accompanied by the presence of DNA of nonheterogenous HR-1. Thus, het DNA is a form of "defective" EBV DNA. However, the biological effect of this defective DNA is to enhance rather than to interfere with EBV replication. This is a novel property of defective virus.

Antigens, Viral↗

Expression in COS-1 cells of Epstein-Barr virus nuclear antigen from a complete gene and a deleted gene.

In a previous study the BamHI-K fragment of Epstein-Barr virus DNA was shown to induce a nuclear antigen, Epstein-Barr virus nuclear antigen (EBNA), when cotransfected with the herpes simplex virus thymidine kinase gene into mouse LTK- cells. We have now inserted the BamHI-K fragment and a BamHI/HindIII subfragment, I1f , into shuttle vectors containing the origin of replication of simian virus 40. These plasmids have been introduced into COS-1, which are monkey kidney cells transformed by an origin-defective simian virus 40 genome. This expression system permitted rapid characterization of antigens, mRNAs, and proteins related to EBNA. The same-sized EBNA protein (approximately 78,000) was made after transfection with BamHI-K (5.2 kilobase pairs [kbp]) or the I1f subfragment (2.9 kbp). A deletion of about 600 bp occurred when the I1f fragment was propagated on the pSV2 plasmid in Escherichia coli. The deleted fragment gave rise to a smaller protein (approximately 52,000). These data provide evidence that EBNA is encoded by the 2.9-kbp I1f and is not an induced cellular protein. Nuclear antigen and polypeptide expression occurred equally well when the Epstein-Barr virus DNA was cloned on PSV2 -gpt or pSVOd . The latter plasmid lacks sequences allowing for efficient early gene transcription as well as splicing and polyadenylation signals which are present in pSV2 . Preliminary mapping of the EBNA gene transcripts demonstrated that two mRNAs (2.9 and 2.4 kilobases [kb]) are homologous to the I1f fragment. Taken together, the data suggest that the 2.9-kbp I1f fragment contains the structural gene for EBNA synthesis. COS-1 cells will thus provide a valuable system in which to analyze functional domains of the EBNA gene.

Animals↗

Ladder angle and ankle flexion while climbing.

39 children 4 to 8 yr. of age were filmed while ascending and descending ladders positioned at 90, 67, 40, 24, 14, and 0 degree from horizontal. Analysis indicated that the greatest range of motion, i.e., variability, took place at angles of 90, 67, and 40 degrees, and at each angle the deviation was from dorsito plantar flexion. While results showed that at each angle more dorsiflexion was exhibited ascending than descending, minimal plantar flexion was noted so most movement occurred in the dorsiflexion range. The greatest deviation (and near maximal movement) was in dorsiflexion at the horizontal (0 degree) position. Implications for design of play apparatus were presented.

Ankle Joint↗

Latent herpesviruses of humans.

The herpesviruses that infect humans characteristically establish a latent infection that may be reactivated later. The consequences of reactivation range from asymptomatic shedding to severe disseminated infection. Varicella-zoster and herpes simplex viruses are both highly neurotropic, establishing nonreplicating infections in sensory ganglia. Latent herpes simplex virus is known to reside in neurons, and the virus-cell interactions involved have been defined to an extent. Cytomegalovirus and Epstein-Barr virus interact with peripheral blood leukocytes. Latent cytomegalovirus infection of human leukocytes has not been proved, although studies in a murine model have implicated B lymphocytes as a repository of latent virus. Epstein-Barr virus is known to persist in a non-replicating state as extrachromosomal DNA in B lymphocytes and to cause "immortalization" of the infected cell; persistence of the viral genome in epithelial cells may also result in malignant transformation, such as nasopharyngeal carcinoma.

Animals↗

Fatal Epstein-Barr-virus-associated proliferation of donor B cells after treatment of acute graft-versus-host disease with a murine anti-T-cell antibody.

Two patients with acute leukemia were treated with chemoradiotherapy and allogeneic bone marrow transplantation. Despite the prophylactic use of methotrexate after grafting, both patients developed severe graft-versus-host disease that was refractory to treatment with methylprednisolone. The graft-versus-host disease was then treated with a monoclonal antibody, 64.1, that reacts with a p19 antigen on human T cells. The disease responded dramatically to this treatment, but both patients subsequently developed a fatal polyclonal lymphoproliferative disorder arising in donor-derived B cells. Hybridization studies showed Epstein-Barr virus in both tumors. The combined effect of severe end-stage graft-versus-host disease and potent immunosuppressive therapy probably resulted in a progressive immunodeficiency syndrome that abrogated the T-cell-mediated surveillance mechanism that normally modulates the proliferation of Epstein-Barr-virus-infected B lymphocytes.

Adult↗

Fractures and dislocations about the hip in head-injured adults.

Twenty-nine of 591 head-injured adults (4.9%) sustained concomitant injuries about the hip. Three hip injuries were undetected during initial hospitalization (10%). Sixteen patients (55%) developed varying amounts of heterotopic ossification about the injured hip. Eleven of 23 hips (41%) treated by nonoperative methods developed heterotopic ossification. Six hips underwent open reduction and five developed heterotopic bone (83%). The severity of injury, especially central acetabular and posterior fracture-dislocations, increased the occurrence and amount of heterotopic bone. Ipsilateral hemiplegia did not seem to influence the incidence or amount of heterotopic ossification. As the amount of heterotopic ossification increased, the range of hip motion decreased.

Adolescent↗

Effect of whole herd anthelmintic treatment on milk production of dairy cows.

Fifteen of 29 commercial dairy herds were given a series of anthelmintic treatments. The remaining herds were untreated to provide a measure of seasonal variation. In the treated herds all milking cows were treated once in the summer and the autumn and three times at monthly intervals in late winter and early spring. Any other animals grazing the same area were similarly treated. No herds had been treated with anthelmintics in the preceding year and mean herd lactations for that year were used as covariate corrections. This experimental design had the potential to detect differences in production of the order of 5 X 7 per cent (P = 0.05). Although levels of subclinical parasitism were low, anthelmintic treatment increased milk fat production by 10.8 kg (8.3 per cent) in heifers. Average response in mature cows was much smaller (3.1 per cent) and not significant. Apparent milk fat responses in individual herds were variable with no relationship to level of production in the previous year.

Abomasum↗

Central-nervous-system lymphoma related to Epstein-Barr virus.

We have studied five cases suggesting a relation between Epstein-Barr virus infection and primary lymphoma of the central nervous system. A 48-year-old man had primary lymphoma of the central nervous system in the absence of systemic lymphoma or immunosuppression. Development of the tumor was associated with serologic evidence suggesting a recent primary infection with Epstein-Barr virus. DNA preparations from tumor tissue, but not from adjacent normal brain tissue, contained Epstein-Barr virus genomes when hybridized with a probe consisting of the BamHI K fragment of Epstein-Barr virus strain FF41. Evaluation of serum samples from four additional patients with central-nervous-system lymphoma revealed patterns of Epstein-Barr virus-specific antibody that were suggestive of an ongoing infection with EBV. Our results suggest induction of the lymphoma by Epstein-Barr virus.

Antibodies, Viral↗