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Biomedical subjects

H H Lim

Publications and source records attributed to H H Lim.

At least 55 records · Page 3Linked to original sources

Operative treatment of acetabular fractures.

A retrospective review of 23 patients with acetabular fractures operated upon between January 1985 and December 1990 was conducted. Eighteen patients were available for assessment of functional outcome. Radiological results were also evaluated. The majority of the patients were male and the average age was 35 years. Three-quarters of the patients had an injury to another system. Three-quarters of the patients were operated upon within two weeks and only two patients had complications directly related to the operation. Radiological result was excellent or good in 61%, fair in 22%, and poor in 16% of the patients. Functional score was excellent or good in 72%, fair in 16% and poor in 11%. In summary, operative treatment of acetabular fracture is a safe and acceptable method of managing displaced acetabular fractures.

Acetabulum↗

The CDC42 homologue from Caenorhabditis elegans. Complementation of yeast mutation.

A Caenorhabditis elegans cDNA encoding a homologue of the p21 ras-related CDC42, designated as CDC42Ce, was isolated from a nematode mixed stage cDNA library. The encoded protein of 188 amino acid residues has 85% identity to both human G25K and CDC42Hs and 79 and 76% identity to the yeast CDC42Sp and CDC42Sc proteins, respectively. The CDC42Ce cDNA maps to a position on C. elegans chromosome II in close proximity to lin-26, a cell lineage gene. The CDC42Ce cDNA hybridizes to 2- and 1.5-kilobase mRNAs. Their expression is developmentally regulated with highest levels at the embryonic stage, decreasing progressively during development except for an increase of the more abundant 1.5-kilobase mRNA at the L3 stage. The glutathione S-transferase/CDC42Ce fusion protein expressed in Escherichia coli displays both GTP binding and intrinsic GTPase activities. The GTPase activity of CDC42Ce is moderately stimulated by human n-chimaerin, a GTPase-activating protein for the related p21 rac1. The CDC42Ce protein complements the temperature-sensitive lethal mutation cdc42-1 in yeast Saccharomyces cerevisiae. These data suggest that CDC42Ce is the C. elegans homologue of the yeast CDC42. The developmental expression pattern of mRNA and is biochemical properties of its encoded protein which are closely related to CErac1 suggest that the two p21s might be involved in related biological processes.

Amino Acid Sequence↗

A new member of the ras superfamily, the rac1 homologue from Caenorhabditis elegans. Cloning and sequence analysis of cDNA, pattern of developmental expression, and biochemical characterization of the protein.

A new member of the ras superfamily, designated CErac1 has been identified. The CErac1 cDNA clone was isolated from a Caenorhabditis elegans mixed stage library and encodes a protein of 191 amino acids with 82 and 79% identity to human rac1 and rac2 proteins, respectively. The CErac1 cDNA maps to a position on C. elegans chromosome IV in close proximity to cha-1, a choline acetyltransferase gene. The CErac1 cDNA hybridizes to two mRNAs (1.7 and 0.9 kilobases). Their expression is developmentally regulated, that of the more abundant 1.7 kilobases being highest at the embryonic stage and decreasing dramatically during development with 10% of the embryonic level in adult nematodes. The glutathione-S-transferase/CErac1 fusion protein expressed in Escherichia coli binds GTP and exhibits intrinsic GTPase activity. The GTPase activity of the CErac1 protein is stimulated by human n-chimaerin, a GTPase-activating protein for p21 rac1. These data suggest a role of CErac1 in C. elegans early development. The conserved biochemical properties indicate that further characterization of CErac1 by genetic analysis will be helpful in elucidating not only its role in the signal transduction, but also the biological function of its mammalian homologues.

Amino Acid Sequence↗

Detection of HSP 72 synthesis after acoustic overstimulation in rat cochlea.

The purpose of this study was to determine if high intensity acoustic stimulation would induce HSP 72 in rat cochlea. The animals were exposed to 110 dB SPL broad band noise for 1.5 h and sacrificed 4, 6 and 8 h after stimulation. Immunocytochemistry and western blotting were used to detect the expression of HSP 72 in the cochlear tissues. Western blots showed an intense 72 kD band in the noise exposed animals compared to a very light band in non-stimulated control animals. Immunocytochemical results in the cochlea revealed noise induced HSP 72 immunoreactive staining of outer hair cells. Only a few immunoreactive stained inner hair cells were seen and spiral ganglion cells were not stained. These results indicate that acoustic overstimulation can induce the expression of HSP 72 in outer hair cells of the rat cochlea. HSP 72 may serve as a marker for cellular stress and potential damage and may be involved in protection from insult.

Acoustic Stimulation↗

Alpha 2-chimerin, an SH2-containing GTPase-activating protein for the ras-related protein p21rac derived by alternate splicing of the human n-chimerin gene, is selectively expressed in brain regions and testes.

n-Chimerin (alpha 1-chimerin) is a brain GTPase-activating protein (GAP) for the ras-related p21rac. We now report the occurrence of another form of chimerin, termed alpha 2-chimerin. This is the product of an alternately spliced transcript of the human n-chimerin gene encoding an N-terminal SH2 (src homology 2) domain in addition to the phorbol ester receptor and GAP domains. alpha 1- and alpha 2-chimerin mRNAs were expressed differently. In the rat brain, only alpha 1-chimerin mRNA was expressed in cerebellar Purkinje cells, although both alpha 1- and alpha 2-chimerin mRNAs occurred in neurons in the cerebral cortex, hippocampus, and thalamus. Only alpha 2-chimerin RNA was expressed in rat testes, in early pachytene spermatocytes. A 45-kDa SH2-containing chimerin corresponding to the alpha 2 form was purified from rat brain. As with Escherichia coli 45-kDa recombinant alpha 2-chimerin, purified brain alpha 2-chimerin exhibited racGAP activity which was stimulated by phosphatidylserine. The recombinant SH2 domain bound several 32P-labelled phosphoproteins of PC12 cells, whose phosphorylation increased in response to trophic factors, including nerve growth factor. To examine the relationships of alpha 1- and alpha 2-chimerin transcripts, human genomic DNA clones were characterized. In alpha 2-chimerin mRNA, a 3' splice acceptor site within exon 1 of alpha 1-chimerin mRNA was used, replacing its 5' untranslated region and N-terminal coding sequence. The single human n-chimerin gene was mapped to chromosome 2q31-q32.1, colocalizing with the CRE-BP1 transcription factor gene (2q32). It contained several splice junctions conserved with the sequence-related protein kinase C and bcr genes. alpha 2-Chimerin is only the second SH2-containing GAP and the first example of an SH2 domain generated by alternate splicing.

Alternative Splicing↗

Developmental regulation and neuronal expression of the mRNA of rat n-chimaerin, a p21rac GAP:cDNA sequence.

Human n-chimaerin is a GTPase-activating protein (GAP) for p21rac and a phorbol ester receptor. We have isolated rat n-chimaerin cDNA and investigated the cellular and developmental pattern of mRNA expression in the brain. There is extensive sequence conservation with human n-chimaerin in the coding region and the first 400 nucleotides of the 3'-untranslated region (UTR) (90% and 83% identity respectively). The rat cDNA encodes an additional 35 N-terminal amino acids compared with the reported human cDNA, which has a 5'-UTR sequence inversion and a 41-nucleotide deletion including the putative initiator methionine. The rat cDNA encodes a 334-amino acid protein (38200 M(r), pI 8.04) with 97% amino acid sequence identity with the human protein, after correction of the human 5'-DNA sequence. n-Chimaerin mRNA was detectable in embryonic rat brain at day 15 and increased in amount postnatally from birth to 20 days, coincident with cellular differentiation and synaptogenesis. n-Chimaerin mRNA is restricted to neurons, with highest concentrations in hippocampal pyramidal cells, granule cells of the dentate gyrus and cortical neurons. In the cerebellum the mRNA was detected only in Purkinje neurons. The pattern and specificity of mRNA expression suggests an important role for n-chimaerin in neuronal signal-transduction mechanisms.

Amino Acid Sequence↗

Central projection of the sensory fibres of the recurrent laryngeal nerve of the cat.

There have been few studies of the central projection of the sensory fibres of the recurrent laryngeal nerve into the medulla oblongata. In the present study terminal degeneration was observed in both the nucleus of the tractus solitarius and the nucleus of the spinal tract of the trigeminal nerve after transection of the nerve and after injection of a lectin, Ricinus communis agglutinin (RCA). Degeneration was observed to be more extensive after RCA injection than after nerve transection. In both instances, however, degeneration was observed bilaterally.

Animals↗

Human brain n-chimaerin cDNA encodes a novel phorbol ester receptor.

A human brain-specific cDNA encoding n-chimaerin, a protein of predicted molecular mass 34 kDa, has sequence identity with two different proteins: protein kinase C (PKC) at the N-terminus and BCR protein [product of the breakpoint-cluster-region (BCR) gene, involved in Philadelphia chromosome translocation] at the C-terminus [Hall, Monfries, Smith, Lim, Kozma, Ahmed, Vannaisungham, Leung & Lim (1990) J. Mol. Biol. 211, 11-16]. The sequence identity of n-chimaerin with PKC includes the cysteine-rich motif CX2CX13CX2CX7CX7C, and amino acids upstream of the first cysteine residue, but not the kinase domain. This region of PKC has been implicated in the binding of diacylglycerol and phorbol esters in a phospholipid-dependent fashion. Part of this cysteine-rich motif (CX2CX13CX2C) has the potential of forming a 'Zn-finger' structure. Phorbol esters cause a variety of physiological changes and are among the most potent tumour promoters that have been described. PKC is the only known protein target for these compounds. We now report that n-chimaerin cDNA encodes a novel phospholipid-dependent phorbol ester receptor, with the cysteine-rich region being responsible for this activity. This finding has wide implications for previous studies equating phorbol ester binding with the presence of PKC in the brain.

Amino Acid Sequence↗

Novel human brain cDNA encoding a 34,000 Mr protein n-chimaerin, related to both the regulatory domain of protein kinase C and BCR, the product of the breakpoint cluster region gene.

A novel human brain complementary DNA sequence encodes n-chimaerin, a 34,000 Mr protein. A single cysteine-rich sequence CX2CX13CX2CX7CX7C in the N-terminal half of n-chimaerin shares almost 50% identity with corresponding sequences in the C1 regulatory domain of protein kinase C. The C-terminal half of n-chimaerin has 42% identity with the C-terminal region (amino acid residues 1050 to 1225) of BCR, the product of the breakpoint cluster region gene involved in Philadelphia (Ph') chromosome translocation. n-Chimaerin mRNA (2.2 x 10(3) base-pairs) is specifically expressed in the brain, with the highest amounts being in the hippocampus and cerebral cortex. The mRNA has a neuronal distribution and is expressed in neuroblastoma cells, but not in C6 glioma or primary astrocyte cultures. The similarity of two separate regions of n-chimaerin to domains of protein kinase C and BCR has intriguing implications with respect to its evolutionary origins, its function in the brain and potential phorbol-ester-binding properties.

Amino Acid Sequence↗

Forward masking patterns produced by intracochlear electrical stimulation of one and two electrode pairs in the human cochlea.

Three psychophysical forward masking studies were conducted on a multichannel cochlear implant patient. The first study investigated the masking pattern produced by a bipolar electrode pair at different stimulus currents. It was found that the masking pattern for a single-masker bipolar electrode pair had a maximum located at an electrode position where the masker and probe coincided. The spread of the masking pattern was not symmetrical about the maximum. The amount of masking decreased very rapidly toward the apical direction and less rapidly toward the basal direction from the position of the maximum. As the stimulus current increased, the amount of masking at the maximum increased and the masking pattern broadened toward the base. The second study investigated the masking pattern produced by the activation of single bipolar electrode pairs with different spatial extents. The spatial extent of a bipolar electrode pair is defined as the distance between the apical and basal electrode members of the bipolar pair. With a small spatial extent (1.5 mm), the more basal electrode pairs (higher threshold and smaller dynamic range) produced broader masking patterns than the more apical electrode pairs (lower threshold and wider dynamic range), suggesting that there was more current spread at the basal region. With a larger spatial extent (4.5 mm), an additional secondary masking maximum was observed in the vicinity of the apical electrode member of the masker; this was observed only when the apical electrode member lay within the low-threshold apical region. The third study investigated the masking patterns produced by two loudness balanced bipolar masker electrode pairs activated within a stimulus period (inverse of the pulse repetition rate). The biphasic current pulses delivered to the two electrode pairs were nonoverlapping in time. It was found that, at any probe electrode position, the amount of masking produced by the two combined bipolar electrode pairs approximately followed the greater of the two maskings produced respectively by the two individual bipolar masker electrode pairs.

Cochlea↗

Synthetic vowel studies on cochlear implant patients.

Speech perception studies were conducted on three cochlear implant patients to investigate the relative merits of six speech processing schemes for presenting speech information to these patients. Electrical stimuli, described in this article as synthetic vowels, were constructed using tabulated data of formant frequencies of natural vowels. The six schemes differed in the number of formant frequencies encoded on the electrical signal dimension of electrode position, and/or in the range of electrode position used for encoding each formant frequency. Eleven synthetic vowels (i, I, E, ae, a, c, U, u, v, E, D) were used and were presented in a single-interval procedure for absolute identification. Single-formant vowels were used in two of the six schemes, two-formant vowels in three schemes, and three-formant vowels in the remaining scheme. The confusion matrices were subjected to conditional information transmission analysis on the basis of previous psychophysiological findings. Comparisons among the schemes in terms of the analyzed results showed that training, experience, and adaptability to new speech processing schemes were major factors influencing the identification of synthetic vowels. For vowels containing more than one formant, the information about each formant affected the perception of the other formants. In addition, there appeared to be differences between the perceptual processes for vowels containing more than one formant and the processes for single-formant vowels. Taking into consideration the effects of training, experience, and adaptability, the three-formant speech processing scheme appeared, on the basis of perceptual performance comparisons among the six schemes, to be the logical choice for implementation in speech processors for cochlear implant patients.

Aged↗

Concentrations of lead in maternal blood, cord blood, and breast milk.

Lead concentrations in maternal blood, umbilical cord blood, and breast milk from 114 women who were not occupationally exposed to lead were determined by graphite atomic absorption spectrophotometry. The mean concentrations of lead in maternal blood, umbilical cord blood and breast milk were 0.7, 0.55, and 0.23 mumol/l, respectively. A significant correlation was observed between maternal and umbilical cord blood (r = 0.63). A lower correlation was noted between maternal blood and breast milk (r = 0.29). These results suggest that lead freely crosses the placental barrier from mother to fetus and the transfer of this heavy metal from maternal tissues to breast milk is possible, but the metabolic mechanisms are more complicated. In addition, a longitudinal study was conducted of concentrations of lead in breast milk in nine lactating women. Results suggested no significant change in the content of lead in breast milk during early lactation.

Female↗

Rice millers' syndrome: a preliminary report.

A study was carried out to determine the health effects of rice husk dust in Malaysian rice millers. The study population consisted of 122 male Malay workers from three rice mills, with 42 controls of similar age, sex, ethnic group, and agricultural work background. Interviews using standardised questionnaires, physical examination, total and differential white cell counts, chest radiographs, and lung function tests were performed on each of the millers and the controls. Environmental dust monitoring was also carried out in the three rice mills. Clinical, haematological, and radiological findings suggest that a distinct clinical syndrome seems to be associated with exposure to rice husk dust. The manifestations of this "rice millers' syndrome" include acute and chronic irritant effects affecting the eyes, skin, and upper respiratory tract; allergic responses such as nasal catarrh, tightness of chest, asthma, and eosinophilia; and radiological opacities in the chest, probably representing early silicosis or extrinsic allergic alveolitis.

Adolescent↗