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Biomedical subjects

J D Harris

Publications and source records attributed to J D Harris.

At least 19 recordsLinked to original sources

Promoter-independent activation of heterologous virus gene expression by the herpes simplex virus immediate-early protein ICP27.

The herpes simplex virus (HSV) immediate-early protein ICP27 has been postulated to play an auxillary role in HSV. gene expression, augmenting or inhibiting the activation of different viral promoters by the other immediate-early proteins ICPO and ICP4. Here we show that ICP27 alone can up-regulate gene expression of a retroviral vector containing Moloney murine leukemia virus (MoMuLV) regulatory sequences. This is the first report of an effect of ICP27 on gene expression driven by heterologous virus regulatory sequences. The effect does not involve the region of ICP27 which inhibits gene activation of HSV early gene promoters by ICPO and ICP4, but rather is dependent on the same region of ICP27 as is required to augment the activation of HSV late gene promoters by ICPO and ICP4. This indicates that the two activation effects are likely to operate via the same mechanism. Activation by ICP27 is dependent on the 3' LTR and adjacent region of MoMuLV but is independent of the promoter in the 5' LTR which can be replaced by a heterologous promoter such as that of SV40 without affecting activation by ICP27. The significance of this effect for an understanding of the mechanism of action of ICP27 and its role in regulating the gene expression of HSV and potentially of other viruses is discussed.

3T3 Cells

A recombinant HIV provirus is synergistically activated by the HIV Tat protein and the HSV IE1 protein but not by the HSV IE3 protein.

To study the effects of regulatory proteins encoded by herpes viruses on the HIV long terminal repeat (LTR) in the presence or absence of HIV-encoded regulatory products, we prepared a proviral construct containing 5' and 3' HIV LTR, but lacking the coding sequences of any HIV proteins. This construct allowed the effects of herpesvirus regulatory proteins on the HIV LTR to be assessed in a construct similar to the HIV provirus whilst also allowing their interactions with HIV-encoded regulatory proteins to be studied. In this system, the herpes simplex virus (HSV) protein IE1 (ICPO) but not the IE3 (ICP4) protein can activate the HIV LTR, whereas both proteins are active on a single plasmid-borne HIV LTR. Although the activation of the LTR by IE1 is strongly stimulated by the HIV Tat protein, it can also be observed in the absence of Tat, indicating that HSV infection via IE1 has the potential to activate an entirely silent, latent HIV provirus.

Animals

Consistency and change in maternal child-rearing practices and values: a longitudinal study.

Although developmental psychologists frequently assume that parents change their child-rearing practices as their children develop, there is little research on this topic and virtually none involving parents of adolescents and a longitudinal, repeated-measures design. We examined changes in mothers' reported practices over time in regard to independence and control, expression of positive and negative affect, and disciplinary practices using items from the Child-Rearing Practices Report (CRPR). The CRPR was administered to the same mothers 5 times over an 8-year time period (from when their children were aged 7 or 8 years until they were 15-16 years old). A substantial degree of stability in behaviors and values was noted, even over the 8-year period. In addition, some practices increased or decreased with age, with most of the changes being consistent with prior theorizing and research, as well as commonsense notions related to child rearing.

Age Factors

Effects of high-frequency cue reduction on the comprehension of distorted speech.

Forty-five subjects with sharply sloping sensorineural high-frequency hearing losses were examined for comprehension with a tape containing sentences that had been time-compressed (250 words/min), interrupted, (50 msec on-50 msec off), and masked with speech-spectrum noise (+2 dB S/N) in that order. All subjects yielded normal speech reception thresholds, and generally normal scores on the Northwestern University Auditory Test No. 6. Distorted-speech testing was completed at 40 dB SL. Subjects with losses at 2 kHz and above were able to comprehend only 50, 65, and 68% of compressed, interrupted, and noise-masked sentences, respectively. In contrast, subjects with losses at 3 kHz and above performed poorer than normal controls by 11.3, 12.5, and 8% points respectively, while subjects within normal hearing sensitivity at 3 kHz performed as well as controls (maximum drop of 4.6 points with noise-masking). The multiplicative hypothesis was upheld in that the performance of subjects with severe high-frequency deficiencies was much poorer than one would predict on the basis of what is known about performance on these tests with either filtering alone or other distortions alone. These subjects, most especially those with severe frequency deficiencies, outperformed by up to 29 percentage points the mean scores of groups of normals given the same test items and distortion conditions, but listening through filtering that simulated the hearing loss of subjects in this study. It was suggested that hypacusics with high-frequency hearing losses can learn to use residual cues efficiently and that it is not altogether permissible to model sensorineural high-frequency losses with normal-hearing subjects using frequency filtering.

Adult

Multiplicative effects on sentence comprehension for combined acoustic distortions.

This study was designed to explore the effect on speech comprehension of combining two types of signal distortion. A tape of clearly-enunciated sentences in quiet was distorted in each of four ways: low-pass (LP) filtering, time compression, interruption, and noise masking. Data are reported on a population of normal-hearing young men for multiple-choice answer tests of colloquial sentences of either LP filtered at 1, 2, 3, or 4 kHz, time compressed by computer at 250 words/min, interrupted (50 msec on--50 msec off), masked by speech-spectrum noise at +2 dB S/N, or given each of the 12 possible combinations of LP filtering plus the other three distortions. Individual distortion conditions were adjusted to reduce speech comprehension performance to about 90% accuracy, Low-pass filtering above 1 kHz reduced comprehension by no more than five to 10 percentage points, but when LP filtering was added to the other distortions in turn, latent effects were uncovered. The reduction in comprehension with the combined distortions was much greater than the simple additive effects of the distortion and LP filtering by themselves. For example, LP filtering above 2 kHz produced no measurable effect on sentence comprehension but this same distortion in combination with noise masking reduced performance from 89.4 to 59.7% correct (where 25% was chance). This study further validates the multiply-compounded nature of simultaneous types of distortion. The use of LP filtering extends the multiplicative principle to the simulated case of high-frequency hearing losses.

Adult

Optimum threshold crossings and time-window validation in threshold pure-tone computerized audiometry.

Two versions of the "10 dB down-5 dB up" rule were computerized: (1) with a "lax" time-window response validation in which a subject had to press and release a button within the window of 15-3750 ms after onset of a 1-s tone in his earphone (this was designed to stimulate the condition often found in manual audiometry) and (2) with a "strict" condition in which he had to respond within 60-795 ms after onset of the tone and release the button within 15-750 ms following the tone. A threshold-seeking run was continued using 5-dB steps until the threshold had been crossed six times. With 24 subjects it was found that 13 of 288 runs did not yield the "ASHA" criterion (three ascending series ending on the same hearing level (HL), out of any six or fewer consecutive series), but of these 13 runs all but one run did meet the "ANSI" criterion (two ascending series ending on the same HL, out of any three or fewer consecutive series). The ANSI Hearinnd yielded essentially the same means. An ANSI HTL was established within four or fewer ascending series for 95% or more of the runs, while an average of five extra stimuli was needed to pursue the run until an ASHA HTL was achieved (a savings of nearly 5 min per person). It was recommended that the ANSI Criterion for HTL be adopted for many audiometric situations, that a maximum of four ascending series be completed in any single threshold-seeking run, and that rather strict time windows be set within which onset and offset responses may register.

Adolescent

Intermitochondrial bridge junctions in fat body cells of the pre-hatch larvae of the forest tent caterpillar Malacosoma disstria HBN.

An electron microscopic feature of fat body cells of diapausing Malacosoma disstria pre-hatch caterpillars, experimentally held at certain controlled time-and-temperature conditions, is an elaborate bridge junction, between mitochondria, strikingly similar in appearance to the septate junction which has frequently been described as occurring between cells of many invertebrate species. It is suggested that the intermitochondrial unctions may well represent elaborate forms of interaction between organelles in order to enhance metabolic efficiency in times of stress.

Adipose Tissue

Liposarcoma of spermatic cord.

Four patients with myxoid liposarcoma of the spermatic cord are presented, three of whom have survived longer than five years. Wide local excision is usually the treatment of choice with radiotherapy reserved for control of either extensive local disease or following incomplete removal of the lesion.

Aged

Temperature-sensitive Escherichia coli mutant producing a temperature-sensitive sigma subunit of DNA-dependent RNA polymerase.

A gene affecting the sigma subunit of DNA-dependent RNA polymerase is tightly linked to dnaG at 66 min on the Escherichia coli chromosome. In order to create an easily selectable marker in this region, we inserted transposon-10, which carries a gene determining resistance to tetracycline (tet) near 66 min, and the order tolC-dnaG-sigma-tet was determined. We used frequency of contransduction with tet as a criterion to screen a collection of spontaneous temperature-sensitive Escherichia coli mutants that might affect the sigma subunit. One such mutant was found to map at the sigma locus. The sigma subunit isolated from this mutant is unstable at 46 degrees C in vitro and has an altered electrophoretic mobility. The temperature sensitivity of RNA synthesis in this mutant indicates that most transcription in E. coli is sigma dependent.

Chromosome Mapping

Proem to a quantum leap in audiometric data collection and management.

A revolution began in 1961 when Weiss first mated a minicomputer to an audiometer. Today's technology offers a number of aids to the audiometrist in standardizing stimulus presentation patterns, objectifying and validating responses, computing HTL from a response pattern, computing significant threshold shifts from baseline audiograms, computing percentage binaural hearing impairment for a person, etc. Audiometers can be made which self-calibrate and are fail-safe. Furthermore, a revolution has occurred in replacing an audiogram written record, for example a card, with a system in which the audiometer transfers HTL data directly into computer storage without the possibility of transcription error. A group of turnkey and interlocking terminals allows the audiometric data of any individual serviced to be retrieved and/or updated from any terminal in the system. This paper lists commercial models simulating standard manual audiometry, models computerizing Bekesy audiometry, and some experimental models on yet other principles. Psychometric methods and methods for response validation suitable for audiometry are discussed, and out of many possible suggestions a few are offered for audiometric paradigms which may go beyond simulation of ASHA guidelines and ANSI specifications for manual threshold audiometry in order to take advantage of the power available from the computer as a tool in audiometry. For example, a computer can scan the responses of as many as 32 subjects simultaneously, offer each an adaptive program based on his response, and printout HTL's in conventional audiometric format.

Adolescent

A gene from Escherichia coli affecting the sigma subunit of RNA polymerase.

The RNA polymerase sigma subunits of Escherichia coli K, E. coli C, and Salmonella typhimurium can be resolved by electrophoresis. Using this technique, we have analyzed Salmonella strains carrying F' plasmids from E. coli K in order to map the gene for the sigma factor. Partial diploid analyses show the location of the sigma gene at 62-66 min on the E. coli genetic map. This gene is cotransducible with toIC and dnaG, at 66 min.

Chromosome Mapping