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Biomedical subjects

M Subramaniam

Publications and source records attributed to M Subramaniam.

71 records · Page 4Linked to original sources

Development of resistance to hearing loss from high frequency noise.

The effect of interrupted exposure on the development of progressive resistance to hearing loss from exposure to high frequency noise was studied using monaural chinchillas. The animals were exposed to an octave band noise centered at 4 kHz at 85 dB SPL for 6 h a day for ten consecutive days. Hearing thresholds were measured using evoked potential recording before and after each exposure. Results indicated a reduction in threshold shift with repeated exposures. This reduction in threshold shift or 'toughening' was more rapid for the high frequency exposures than the 'toughening' from similar low frequency exposures.

Acoustic Stimulation↗

The effect of exposure level on the development of progressive resistance to noise.

The effect of exposure level on the development of progressive resistance to temporary threshold shift caused by exposures to an octave band of noise centered at 0.5 kHz was explored using chinchillas. The animals were exposed to either 85, 95 or 100 dB SPL for six hours a day for ten days. Hearing thresholds were recorded electrophysiologically, prior to and after each daily exposure. A trend toward decreasing threshold shift with increase in the number of exposures was seen at all the levels. The amount of threshold shift appeared to depend upon the level as well as the test frequency. The findings are discussed in the light of results of previous studies and possible mechanisms involved in the process of 'toughening' are hypothesized.

Adaptation, Physiological↗

Impact noise: the importance of level, duration, and repetition rate.

The applicability of the equal energy hypothesis (EEH) to impact noise exposures was studied using chinchillas. Hearing thresholds were estimated by recording the evoked potentials from a chronic electrode implanted in the inferior colliculus. The animals were exposed to broadband impacts of 200-ms duration. The study was carried out in two parts. In experiment I, six exposure levels (107, 113, 119, 125, 131, and 137 dB SPL) and three repetition rates (4/s, 1/s and 1/4s) were employed. In the second experiment, the total duration of the exposure as well as the total energy were kept constant by trading level and rate. Results indicate that hearing loss resulting from exposure to impact noise does not conform to the predictions of the EEH. The permanent threshold shift as well as the hair cell loss are more or less equal across the lower peak exposure levels. However, both the hearing loss and the hair cell damage increase for exposures with higher peak levels. Furthermore, hearing loss and cochlear damage are dependent upon the rate of exposure. Thus the amount of hearing loss and hair cell damage appears to depend on the interaction of several factors including peak level, rate, and the susceptibility of the animal.

Animals↗

Sporadic Koro and marital dysharmony.

A case of Koro is described in a Malaysian Chinese man in the setting of martial dysharmony and sexual rejection. A distinction is suggested between the epidemic form of Koro and the Koro symptom occurring sporadically. Existence of the sporadic Koro syndrome is discussed and a unified classificatory system is proposed.

Adult↗

Rapid inhibition of the c-jun proto-oncogene expression in avian oviduct by estrogen.

The c-jun proto-oncogene codes for an important component of the AP-1 transcription factor complex which regulates the expression of many genes. This paper demonstrates that the steady state c-jun mRNA level in the avian oviduct is markedly decreased to 50% of control values within 30 minutes after estrogen injection into the animals. In the avian liver, the level is rapidly increased over 10 fold. Nuclear run-off transcription analysis demonstrates that the decrease in the c-jun mRNA levels in the avian oviduct occurs at least in part at the level of transcription. These changes are reproducible in repeat experiments. This response in the avian oviduct is unique since 1) it is the first demonstration of a steroid effect on c-jun expression in any animal system, 2) the changes in c-jun mRNA occur much more rapidly than most steroid responsive genes, and 3) it is the rare demonstration of an estrogen inhibition of the expression of a gene. A role for the c-jun proto-oncogene as an early regulatory gene in the cascade model for steroid action is proposed.

Animals↗

Evoked-response tone-on-tone masking in the chinchilla: effect of masker frequency.

Tone-on-tone masking patterns were measured at 0.5, 1, and 4 kHz using the auditory-evoked response from the inferior colliculus of the chinchilla. Masking profiles obtained with a masking level of 30 dB SPL were relatively symmetrical; however, as masker level increased, masking spread toward the high frequencies, particularly with the 0.5-kHz masker. For masker frequencies of 1 and 4 kHz, a low-threshold notch was observed in the masking profile 2/3 of an octave above the frequency of the masker. The low-threshold notch may represent a response to the distortion tone 2F1-F2. The notch was absent in the 0.5-kHz masking profile. The masking profiles obtained with the evoked response are somewhat wider, but otherwise qualitatively similar to those measured psychophysically in humans. Thus, the evoked-response procedure may provide a convenient way of evaluating the spread of masking and the presence of distortion tones in difficult-to-test subjects.

Acoustic Stimulation↗

Negative regulation of serum-responsive enhancer elements.

Transcription of the c-fos proto-oncogene and the cytoskeletal actin genes is induced within minutes of the addition of serum growth factors in a variety of cell types. Inhibitors of protein synthesis such as cycloheximide have been shown to dramatically potentiate the transcriptional response, an effect termed 'superinduction'. Although the stimulatory effect of serum has been shown to be transmitted through a cis-acting enhancer sequence termed a serum response element (SRE), the sequence element(s) responsible for mediating the effect of cycloheximide has not been identified. We now report that a synthetic copy of the c-fos SRE is sufficient to confer cycloheximide-dependent inducibility upon a heterologous promoter. This does not require the presence of serum, but several mutations in the SRE that impair serum-inducibility also impair cycloheximide-inducubility. These results imply that serum-responsive enhancer elements are negatively regulated by one or more labile proteins and that both positive and negative regulators of enhancer activity require a functional 'CArG box', a sequence domain previously implicated in muscle-specific transcription.

Actins↗

Evidence that the functional beta-actin gene is single copy in most mice and is associated with 5' sequences capable of conferring serum- and cycloheximide-dependent regulation.

Hybridization to synthetic oligonucleotides representing conserved regions in the promoter and first intron of several vertebrate beta-actin genes was used to discriminate between what appears to be a single functional beta-actin gene and numerous pseudogenes in the mouse genome. Sequences derived from the 5' end of this gene were shown to confer serum-inducible expression upon a heterologous reporter gene when transfected into mouse fibroblasts. Moreover, these sequences rendered reporter gene expression superinducible by a combination of serum and cycloheximide. These experiments indicate that the 5' end of the mouse beta-actin gene contains sequence elements which mediate the stimulatory effects of serum growth factors and which are responsive to both positive and negative regulators of gene expression.

Acetyltransferases↗

Effect of cycloheximide and growth factors on gene expression in quiescent mouse embryo fibroblasts.

Gene expression in quiescent mouse embryo fibroblasts was studied by labelling the cells with [14C] amino acids and analysing the proteins by electrophoresis in polyacrylamide gradient gels containing sodium dodecyl sulfate. Cycloheximide (CH) pretreatment of the cells was found to induce the synthesis of four proteins of molecular weights 72,000, 68,000, 42,000, and 29,000. These proteins were induced by CH both in serum-arrested and serum-stimulated cells. Addition of platelet-derived growth factor to serum-arrested quiescent cells also induced the synthesis of these proteins. Addition of CH and fetal calf serum (20%) to quiescent cells resulted in a dramatic increase in the synthesis of actin and another protein of molecular weight 29,000. The 29,000-dalton protein was present in higher quantities in the nuclei of induced cells. This protein appeared to be an early protein whose synthesis was transiently induced in quiescent cells within 3 hours of addition of 20% fetal calf serum (FCS). The synthesis of this protein was virtually turned off at 5-6 hours after the addition of serum. However, if CH or a combination of CH and FCS was present, a continuous synthesis of the 29 K protein was observed.

Animals↗

A serum-induced 29 Kd protein of mouse embryo fibroblasts is tightly bound to the chromatin.

Treatment of quiescent cultures of mouse embryo fibroblasts with 20% fetal calf serum (FCS) or cycloheximide (CH) resulted in the induction of a nuclear protein of molecular weight 29 000 daltons. The 29 Kd protein induced by these two agents was found to be tightly bound to the chromatin since it was not released from the chromatin by a combination of 2.5 M NaCl and 3.2 M urea. The chromatin associated CH-induced 29 Kd protein and the 29 Kd protein obtained from serum-induced cells displayed similar N-chlorosuccinimide cleavage patterns. Pulse-chase experiments indicate a half-life of an hour for the 29 Kd protein. The kinetics of induction of the 29 Kd protein in the early hours of mitogen addition, short half-life, nuclear localisation and strong association with chromatin suggest that this protein may have important roles in cell proliferation, possibly as a mediator of mitogen action.

Amino Acids↗

Intracellular and secreted proteins of density-inhibited, serum-arrested and proliferating mouse embryo cells.

Short-term labelling of secondary cultures of mouse embryo fibroblasts with [14-C] aminoacids enabled the identification and quantitation of proteins specific for quiescent and proliferative stages. Intracellular and secreted proteins of cells maintained under different growth conditions were resolved in high resolution SDS-polyacrylamide gradient gels. Two proteins, identified as fibronectin and procollagens and a 34 000 D polypeptide were found to be secreted by all three types (density-arrested, serum arrested and proliferating) of cells. Both types of arrested cells exclusively secreted a 375 000 D protein while the proliferating cells specifically secreted a 48 000 D polypeptide. During progression of cells from quiescence to proliferation, two intracellular proteins showed major variations. A 205 000 D intracellular protein was found to be synthesized in higher amounts by proliferating cells than by arrested cells. Another protein, identified as actin, showed a marked increase in synthesis following the release of cells from serum arrest. The arrested cells showed reduced levels of actin synthesis and the turning-off process in the synthesis of actin was found to be relatively slow as the cells entered into quiescence.

Actins↗

Effects of serum, cycloheximide and actinomycin D on protein secretion by quiescent mouse embryo fibroblasts.

Quiescent secondary cultures of Swiss mouse embryo fibroblasts secrete several proteins in response to the addition of 20% fetal calf serum (FCS). Of these proteins, a polypeptide of molecular weight (Mr) 48,000 (48 K) was identified in the medium within an hour of mitogenic stimuli. In the next hour an additional protein of Mr26,000 (26 K) appeared in the medium. These two proteins were absent in the conditioned medium of quiescent cells. A third protein of molecular weight 45,000 (45 K) was found in small quantities in the conditioned medium of quiescent cells but a 2-3 fold increase in the level of this protein was observed in the medium of stimulated cells. The level of the serum-induced 45 K protein was much higher in the medium of cells that were treated with cycloheximide (CH) and FCS than that found in the medium of cells treated with FCS alone. A 40,000 dalton protein was found to be a quiescence specific protein which was observed in large amounts in the medium of quiescent cells; the level of this protein gradually declined in the conditioned medium as the cells entered into the proliferative phase. Actinomycin D specifically inhibited the level of the 45 K secreted protein and a 29 K intracellular protein when added along with CH. In contrast to the inhibition of the synthesis of mitogen induced proteins, actinomycin D super-induced the intracellular and extracellular levels of the matrix proteins fibronectin and procollagens.

Animals↗