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Biomedical subjects

G Miller

Publications and source records attributed to G Miller.

At least 253 records · Page 14Linked to original sources

ZEBRA and a Fos-GCN4 chimeric protein differ in their DNA-binding specificities for sites in the Epstein-Barr virus BZLF1 promoter.

Epstein-Barr virus (EBV) encodes a protein, ZEBRA, which enables the virus to switch from a latent to a lytic life cycle. The basic domain of ZEBRA is homologous to the Fos/Jun oncogene family, and both proteins bind the canonical AP-1 site (TGAGTCA). However, ZEBRA does not contain a leucine zipper dimerization domain which has been shown to be necessary for DNA binding of Fos/Jun proteins. Additionally, ZEBRA binds to sites which deviate from the AP-1 consensus sequence. Thus, it was of interest to define the domain of the ZEBRA protein required for DNA binding. We have determined by mutagenesis that ZEBRA residues 172 to 227, representing the basic domain and a putative dimerization domain, are required for specific binding to AP-1 and divergent sites. Mutagenesis of the basic amino acids 178 to 180 or 187 to 189 abrogates ZEBRA binding to all DNA target sequences. These residues are conserved in Fos and are also necessary for Fos DNA-binding activity. We have found that a Fos-GCN4 chimera and ZEBRA have different cognate binding specificities. The autoregulated BZLF1 promoter contains three divergent AP-1 sequences, ZIIIA (TGAGCCA), ZIIIB (TTAGCAA), and Z-AP-1-octamer (TGACATCA). ZEBRA binds with high specificity to ZIIIA and ZIIIB but weakly to the Z-AP-1 octamer. Conversely, the Fos-GCN4 chimera recognizes only the Z-AP-1 octamer. ZEBRA binds the ZIIIA and ZIIIB sites together in a noncooperative fashion, while Fos-GCN4 binds these sites as a higher-order complex. Additionally, we have found that flanking sequences influence binding of Fos-GCN4 to a degenerate AP-1 site (TGAGCAA). The characteristic binding specificities of ZEBRA and cellular AP-1 proteins suggest that they differentially affect viral and cellular transcription.

Amino Acid Sequence↗

Reliability of three clinical measures of muscle tone in the shoulders and wrists of poststroke patients.

Muscle tone was tested at the shoulders and wrists of 49 randomly selected poststroke patients with the use of resting joint position (SJP and WJP), resistance to passive movement or stiffness (SRM and WRM), and angle of appearance of resistance (SAR and WAR). Subjects were tested while seated with their arm supported in a suspension sling adapted for free movement. Five of the first and immediately repeated measurement pairs showed strong correlations and interrater reliability (SJP, .839; WJP, .900; SRM, .886; WRM, .904; SAR, .884 [p less than .05]). The sixth (WAR) showed moderate reliability (.618, p less than .05). Resting joint position measurements were most reliable among subjects with higher tone. The joint first measured had a slight order effect on SRM among subjects with higher muscle tone. Its second measurements were slightly increased over the first among those subjects whose shoulders were measured first and slightly reduced when measured immediately after the wrist. Reliable means of clinical evaluation of muscle tone at the shoulder and wrist are available if the influence of level of tone and the mutual influence of muscles tested are prudently considered.

Aged↗

At-will employment doctrine--are patient care employers vulnerable?

This article analyzes the importance of changes in the at-will rule of employment law to hospital and other health care employers. A survey of wrongful termination cases brought against health care defendants is presented, and recommendations as to employment procedures are made.

Civil Rights↗

Work coding: beyond SIC and SOC, BOC and DOT.

Traditional coding schemes for occupational health related factors (eg, SIC, SOC, CAS) are structured similarly as hierarchical, exclusive, and exhaustive systems. Each is limited to information of one particular type (eg, industry) and, therefore, the relationships implicit in the coding scheme are limited. This study empirically determined that "natural" coding schemes used by occupational health professionals do not share these characteristics but are more akin to semantic network data bases. There is therefore a need to re-evaluate how occupational data are to be coded.

Databases, Factual↗

Rate of transmission of human immunodeficiency virus type 1 infection from mother to child and short-term outcome of neonatal infection. Results of a prospective cohort study.

In an attempt to determine the rate of transmission of infection from human immunodeficiency virus type 1 (HIV-1) antibody-positive women to their offspring and to describe the short-term outcome of perinatal infection, we enrolled 62 infants in a prospective cohort study during a 30-month period and followed them up for an additional 6 months. The clinical, immunologic, and serologic status of the children was assessed prospectively. Fourteen subjects were symptomatic: 3 had acquired immunodeficiency syndrome, 5 had signs and symptoms that were compatible with HIV-1 infection (Centers for Disease Control, Atlanta, Ga, class P2A), and 6 had ill-defined symptoms that could not be definitely attributed to HIV. Our data indicated that the maximum rate of vertical transmission of HIV-1 infection in New Haven, Conn, was less than 30%, and the rate of HIV-1-associated disease occurring during the first 3 years of life was 16%. The mean and median time to loss of maternal antibody, as detected by Western blot in seroreverters, was approximately 7 months, and the half-life of passive antibody was 38 days. A continued close follow-up of children in the cohort studied, and others like it, is critical to learn the full range of outcomes of HIV infection in the pediatric population.

Acquired Immunodeficiency Syndrome↗

Neurologic manifestations in 18q- syndrome.

We report a mother and son with a deletion at 18q22.3. Both have the typical manifestations of the 18q- syndrome. In addition, both have an action tremor which became apparent in childhood. The mother subsequently developed chorea and dysmetria in late adolescence. Magnetic resonance imaging of their brains showed poor myelination of the central white matter tracts with relatively normal myelination of the corpus callosum. We propose that these neurologic findings are most likely due to a failure of expression of the myelin basic protein gene.

Abnormalities, Multiple↗

Spinal cord ganglioglioma presenting as hydrocephalus.

We report a case of a 5 year old boy with a spinal cord ganglioglioma and hydrocephalus. The insidious onset with back stiffness and hamstring tightness, the diagnosis by magnetic resonance imaging, and the treatment by total excision is described. An adequate proven explanation for the hydrocephalus is lacking. Mechanisms which have been proposed include impaired cerebrospinal fluid absorption from increased cerebrospinal fluid protein, and arachnoiditis.

Child, Preschool↗

Maternal reproductive histories in ataxic cerebral palsy.

Maternal reproductive histories of fetal wastage in 36 cases of ataxic cerebral palsy and in a control group of 60 mothers were compared. There was no significant difference between the groups. A history of fetal loss did not accompany this cerebral palsy syndrome where prenatal factors play an important role.

Abortion, Spontaneous↗

Experimental investigation of the scaphoid strain during wrist motion.

The scaphoid is the most frequently fractured of the carpal bones [Taleisnik, J., The Wrist, Churchill Livingstone, New York (1985)]. This project was undertaken to qualitatively evaluate the strain in the scaphoid during wrist motion using a newly developed strain gage method. Strain gage rosettes were mounted within the scaphoid and the range of motion of the hand was monitored using a custom designed electrogoniometer and data acquisition system. Ten specimens were utilized for this study. Results indicated that supination/pronation (S/P) of the forearm did not affect the strain in the scaphoid. A map of the strain in the waist of the scaphoid, as a function of flexion/extension (F/E) and radial/ulnar deviation (R/U), was generated. The contour plot of scaphoid strain vs range of motion (ROM) shows a valley where strains are low. Minimum scaphoid strain was found near neutral F/E and 15 degrees of ulnar deviation.

Adult↗

Inhibition of specific binding of EBNA 1 to DNA by murine monoclonal and certain human polyclonal antibodies.

EBNA 1 was expressed as a nonfusion protein in Escherichia coli under control of the lac promoter. The major immunoreactive EBNA 1 proteins migrated as two doublets with molecular masses of about 39/41 and 49/51 kDa. Gel mobility shift experiments showed that these products exhibit the sequence-specific DNA binding on ori P previously characterized for a 28-kDa lambda N-fusion protein encompassing the carboxy third of the EBNA 1 protein. Three monoclonal antibodies previously found to react with EBNA 1 were shown to block binding of DNA by the EBNA 1 products expressed in bacteria. The same monoclonal antibodies also blocked specific DNA binding by EBNA 1 produced in Burkitt lymphoma cells infected by EB virus. Fab fragments of two monoclonal antibodies inhibited DNA binding by EBNA 1, indicating that the antibodies recognize an epitope of the protein that is involved in the recognition of DNA, or another domain crucial for DNA binding such as a dimerization site. Some but not all human antisera with antibody to EBNA 1 neutralized specific binding of EBNA 1 to DNA. These findings will help to map the residues of the EBNA 1 protein which are essential for specific binding of DNA.

Animals↗