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Biomedical subjects

T C Lo

Publications and source records attributed to T C Lo.

At least 19 recordsLinked to original sources
PubMed2001

Outcome of renal replacement therapy in the very elderly.

BACKGROUND: In a retrospective case-note and computer database analysis we assessed the outcome of very elderly patients (> or = 75 years old) with end-stage renal disease (ESRD) on renal replacement therapy (RRT). METHODS: Fifty-eight individuals aged 75 or over (group 1) commenced RRT between 1 January 1991 and 31 December 1995. Comparisons were made with other patients commencing RRT who were divided into two groups: group 2 (201 individuals 65-74 years old) and group 3 (379 patients <65 years old). All subjects were followed up until the point of assessment (30 June 1998), the time of death, or withdrawal from dialysis. Survival rates in the three groups were compared using Kaplan-Meier method. The number of hospital admissions, length of in-patient stay, and complications rate on RRT were assessed for group 1. RESULTS: One-year survival rates in groups 1, 2 and 3 were 53.5, 72.6, and 90.6% respectively and the 5-year survival rates were 2.4, 18.8, and 61.4% respectively. The very elderly spent 20% of their time in hospital, 46% had two co-morbid factors at the outset, and 26% developed multiple complications while on RRT. Withdrawal from dialysis remained the most common cause of death in this group of individuals (38%), followed by cardiovascular causes (24%) and infections (22%). CONCLUSION: Very elderly ESRD patients on RRT have a very poor outcome and, since they are the largest growing group of RRT patients, this has important implications for future health policies.

Adolescent↗
PubMed2001

A single point mutation in the V3 region affects protein kinase Calpha targeting and accumulation at cell-cell contacts.

Given the importance of intercellular adhesion for many regulatory processes, we have investigated the control of protein kinase Calpha (PKCalpha) targeting to the cell-cell contacts. We have previously shown that, upon treatment of the pituitary cell line GH3B6 with thyrotropin-releasing hormone (TRH) or phorbol 12-myristate 13-acetate (PMA), human PKCalpha (hPKCalpha) is selectively targeted to the cell-cell contacts (42). Here we show that the D294G mutation of hPKCalpha, previously identified in a subpopulation of human tumors, induces the loss of this selective targeting. The D294G mutant is instead targeted to the entire plasma membrane, including the cell-cell contacts, and the duration of the first rapid and transient translocation induced by TRH (42) is longer than that of the wild-type enzyme (93.3 versus 22.5 s), coinciding with the duration of the [Ca(2+)](i) increase. We found that in the presence or absence of PMA, RACK1 is never localized at the cell-cell contacts nor was it coimmunoprecipitated with hPKCalpha wild type or the D294G mutant. In contrast, PMA treatment or long-term TRH stimulation resulted in the presence of F-actin and beta-catenin at the cell-cell contacts and their exclusion from the rest of the plasma membrane. Upon disruption of the F-actin network with phalloidin or cytochalasin D, wild-type hPKCalpha translocates but did not accumulate at the plasma membrane and beta-catenin did not accumulate at the cell-cell contacts. In contrast, the disruption of the F-actin network affected neither translocation nor accumulation of the D294G mutant. These results show that the presence of PKCalpha at the cell-cell contacts is a regulated process which depends upon the integrity of both PKCalpha and the actin microfilament network.

Actins↗
PubMed2001

Re-irradiation for prophylaxis of heterotopic ossification after hip surgery.

Heterotopic ossification (HO) may occur after total hip arthroplasty, but fortunately most patients are asymptomatic. Rick factors for HO include previous HO, hypertrophic osteoarthritis, diffuse idiopathic skeletal hyperostosis, ankylosing spondylitis, Paget's disease and post-traumatic arthritis. Both pre-operative and post-operative radiotherapy are effective in the prevention of HO in 85-95% of high-risk patients treated. In the few patients who needed re-operation for a variety of reasons, we found that re-irradiation is possible and safe. These case reports present our experience with single dose re-irradiation of the hip in an attempt to prevent post-operative HO.

Adult↗
PubMed2001

Intraluminal brachytherapy for malignant endobronchial tumors: an update on low-dose rate versus high-dose rate radiation therapy.

Although the evolution from low-dose rate (LDR) to high-dose rate (HDR) brachytherapy for malignant endobronchial tumors was presumably based on economy, patient convenience, and radiation protection, our experience with both modalities permits assessment of the pros and cons of each technique. In November 1991, our HDR remote afterloading brachytherapy unit became operational. By that time, we had treated 110 patients (group 1) with malignant endobronchial obstruction with LDR brachytherapy. Since then, all patients have been treated with HDR brachytherapy. The outcome of our first 110 patients (group 2) treated with HDR brachytherapy is presented in this communication, using group 1 as the historic control group. In group 1, patients were treated with 1 or 2 sessions of 30-60 Gy, each calculated at a 1-cm radius. In group 2, patients received 3 or 4 weekly treatments of 7 Gy, each calculated at a 1-cm radius. The majority of patients in each group had previously received a full course of external beam irradiation, and a history of laser bronchoscopy was also similar for the 2 groups. Differences in bronchoscopic response rate (82% vs. 96%, respectively) and complications (3.6% vs. 2.7%, respectively) were statistically insignificant between the LDR group and the HDR group. We believe HDR brachytherapy is the state-of-the-art modality in intraluminal therapy for endobronchial malignancies.

Journal Article↗
PubMed2000

A case of isolated ACTH deficiency presenting with hypercalcaemia.

A 76-year-old man presented with a subacute history of weight loss, malaise and anorexia. Laboratory investigations revealed serially increasing hypercalcaemia, correlating with deterioration in his clinical status. He was subsequently shown to have hypocortisolaemia, which improved with the administration of intravenous steroids. Subsequent biochemical testing revealed the endocrinological defect to be one of isolated ACTH deficiency, which, unlike Addison's disease, does not classically include hypercalcaemia in its presentation.

Adrenal Cortex Diseases↗
PubMed1999

Radiation therapy for heterotopic ossification.

Heterotopic ossification is a common complication after bone and joint surgery. If the disease progresses, it may cause pain and disability, eventually defeating the purpose of surgery in the first place. Today, prophylactic treatment is indicated after surgery. Both nonsteroidal antiinflammatory drugs and radiation therapy are effective. Radiation therapy is associated with fewer side effects and is preferred. Single-dose postoperative irradiation has been found to be as effective as fractionated radiation therapy.

Humans↗
PubMed1999

Characterization of insertions of IS476 and two newly identified insertion sequences, IS1478 and IS1479, in Xanthomonas campestris pv. campestris.

Thirty-two plasmid insertion mutants were independently isolated from two strains of Xanthomonas campestris pv. campestris in Taiwan. Of the 32 mutants, 14 (44%), 8 (25%), and 4 (12%) mutants resulted from separate insertions of an IS3 family member, IS476, and two new insertion sequences (IS), IS1478 and IS1479. While IS1478 does not have significant sequence homology with any IS elements in the EMBL/GenBank/DDBJ database, IS1479 demonstrated 73% sequence homology with IS1051 in X. campestris pv. dieffenbachiae, 62% homology with IS52 in Pseudomonas syringae pv. glycinea, and 60% homology with IS5 in Escherichia coli. Based on the predicted transposase sequences as well as the terminal nucleotide sequences, IS1478 by itself constitutes a new subfamily of the widespread IS5 family, whereas IS1479, along with IS1051, IS52, and IS5, belongs to the IS5 subfamily of the IS5 family. All but one of the IS476 insertions had duplications of 4 bp at the target sites without sequence preference and were randomly distributed. An IS476 insertion carried a duplication of 952 bp at the target site. A model for generating these long direct repeats is proposed. Insertions of IS1478 and IS1479, on the other hand, were not random, and IS1478 and IS1479 each showed conservation of PyPuNTTA and PyTAPu sequences (Py is a pyrimidine, Pu is a purine, and N is any nucleotide) for duplications at the target sites. The results of Southern blot hybridization analysis indicated that multiple copies of IS476, IS1478, and IS1479 are present in the genomes of all seven X. campestris pv. campestris strains tested and several X. campestris pathovars.

Amino Acid Sequence↗
PubMed1998

Alteration of myogenic regulatory components in a rat myoblast GLUT 3(-) mutant.

Myogenesis is a complex process characterized by both biochemical and morphological differentiation. Recent transfection studies suggested a close relationship between the GLUT 3 transporter and the myogenic ability of rat skeletal L6 myoblast. In this study, the myogenic properties of GLUT 3- mutants were examined. Studies using three different GLUT 3- mutants (D2, D9 and D23) revealed that these mutants were defective not only in the GLUT 3 transporter, but also in the expression of myogenesis-associated genes. The properties of mutant D23 were further characterized. Overexpression of an exogenous functional GLUT 3 transporter was unable to restore the myogenic defects of this mutant. This mutant was subsequently found to be altered in components acting on at least two different sites of the L6 myogenic pathway. Transfection studies revealed that mutant D23 was deficient in component(s) essential for the myogenin promoter activity. The second component was required for the transcription of muscle-specific protein genes, as overexpression of myogenin was unable to rescue the inability of this mutant to express muscle-specific genes and to form myotubes. Mutant D23 was therefore thought to be deficient in a regulatory component which controlled the expression of GLUT 3, myogenin and muscle-specific genes.

Animals↗
PubMed1998

The role of the GLUT 4 transporter in regulating rat myoblast glucose transport processes.

Previous studies revealed an inverse relationship between GLUT 1 and GLUT 4 expression in rat myoblasts [L. Xia, Z. Lu, T.C.Y. Lo, J. Biol. Chem., 268 (1993) 23258-23266]. It was not clear whether these were coincidental or causal occurrences. To examine the regulatory roles of the GLUT 4 isoform, rat L6 myoblasts were transfected with full length GLUT 4 cDNAs (2.5 kb) in the sense or antisense orientation. L6 myoblasts transfected with the GLUT 4 sense cDNA (L6/G4S transfectants) possessed much elevated levels of both endogenous GLUT 4 transcripts (1.4 kb and 2.8 kb). Transport and immunofluorescence studies showed that this GLUT 4 sense cDNA was responsible for a functional GLUT 4 transporter. L6 cells transfected with the GLUT 4 antisense cDNA (L6/G4A transfectants) possessed only 6% of the L6 level in day 6 cultures. These antisense transfectants were essentially devoid of any functional GLUT 4 transporter. The activation of transcription of the endogenous GLUT 4 gene in L6/G4S myoblasts suggested auto-regulation of GLUT 4 expression. GLUT 3 expression and activity were not altered in both sense and antisense GLUT 4 transfectants. More interestingly, GLUT 1 expression was reduced in L6/G4S myoblasts, whereas it was elevated in L6/G4A myoblasts. This was the first direct evidence indicating GLUT 4 might play an important role in suppressing GLUT 1 expression.

Animals↗
PubMed1998

The effect of the nasopharyngeal air cavity on x-ray interface doses.

We investigated the impact of air cavities in head and neck cancer patients treated by photon beams based on clinical set-ups. The phantom for investigation was constructed with a cubic air cavity of 4 x 4 x 4 cm3 located at the centre of a 30 x 30 x 16 cm3 solid water slab. The cavity cube was used to resemble an extreme case for the nasal cavity. Apart from measuring the dose profiles and central axis percentage depth dose distribution, the dose values in 0.25 x 0.25 x 0.25 cm3 voxels at regions around the air cavity were obtained by Monte Carlo simulations. A mean dose value was taken over the voxels of interest at each depth for evaluation. Single-field results were added to study parallel opposed field effects. For 10 x 10 cm2 parallel opposed fields at 4, 6 and 8 MV, the mean dose at regions near the lateral interfaces of the cavity cube were decreased by 1 to 2% due to the lack of lateral scatter, while the mean dose near the proximal and distal interfaces was increased by 2 to 4% due to the greater transmission through air. Secondary build-up effects at points immediately beyond the air cavity cube are negligible using field sizes greater than 4 x 4 cm2. For most head and neck treatment, the field sizes are usually 6 x 6 cm2 or greater, and most cavity volumes are smaller than our chosen dimensions. Therefore, the influence of closed air cavities on photon interface doses is not significant in clinical treatment set-ups.

Air↗
PubMed1997

Use of transport mutants to examine the identity and expression of GLUT isoforms in rat cardiac myoblasts.

Two different spontaneous glucose transport (GLUT) mutants were used to examine the identity and properties of proteins involved in rat cardiac myoblast glucose transport processes. The parental clone, H9C2, possessed a high (HAHT) and a low (LAHT) affinity hexose transport process, and the GLUT 1, 3 and 4 isoforms. Mutant RCM was devoid of HAHT, the GLUT 3 transcript, and a 41 kDa protein recognizable by an anti-mouse GLUT 3 Ab. Mutant EZ-4 was impaired in the GLUT 3 and 4 isoforms, and in HAHT and LAHT. These studies demonstrated a close association of the GLUT 3 and 4 isoforms with the HAHT and LAHT processes, respectively. Both GLUT 3 and 4 isoforms were regulated in opposite ways during myogenesis, and both GLUT 3 mutants were impaired in myogenesis. Despite its normal GLUT 1 transcript level, mutant EZ-4 was devoid of an efficient carrier-mediated glucose transport process, thus suggesting that the GLUT 1 transporter was inoperative in rat cardiac myoblasts. Unlike the rat skeletal. L6 GLUT 1 isoform, expression of the rat cardiac GLUT 1 isoform was not affected by glucose starvation, and was not reduced in multinucleated myotubes. These studies demonstrated the usefulness of transport mutants in determining the identity, expression and property of GLUT isoforms and their association with specific transport processes.

Animals↗
PubMed1997

Involvement of the GLUT 3 transporter in myogenic regulation.

We have recently demonstrated a close relationship between the GLUT 3 transporter and the myogenic ability of rat skeletal L6 myoblasts [1]. This investigation examined the effects of over- and under-expression of the GLUT 3 transporter on both biochemical and morphological differentiation. L6 transfectants expressing two to five times the normal L6 GLUT 3 transcript level were impaired in the expression of myogenesis-associated genes, such as myogenin, MLC, MHC and TnT, and in myotube formation. Similar defects were also observed in myoblast mutants expressing less than 20% of the normal GLUT 3 level. Forced expression of an exogenous GLUT 3 cDNA could partially rescue the myogenic defect of these GLUT 3 mutants. However, such myogenic defects were not observed in L6 GLUT 3 antisense transfectants expressing 39% of the normal L6 GLUT 3 level. These data suggest that myogenic differentiation will proceed only within a critical level of the GLUT 3 transporter. The optimal GLUT 3 content for myogenesis ranges from around 2 x 10(5) to 5 x 10(5) molecules per cell in day 2 cultures; GLUT 3 levels outside this range have a negative effect on myogenesis. Our data suggest that GLUT 3 may regulate myogenesis by modulating the levels of signal transducers required for expression of myogenin and muscle-specific contractile protein genes.

Animals↗
PubMed1996

Effects of 2-deoxy-d-glucose on the functional state of the rat myoblast GLUT 1 transporter.

Based on the rationale that internalized 2-deoxy-D-glucose (dGlc) is toxic to cells, glucose transport (GLUT) defective myoblast mutants have been isolated by their ability to grow in glucose-free medium containing dGlc. Recent studies revealed that the GLUT 1 transport process was activated when GLUT 3-GLUT 4-mutants were grown in glucose-free medium. It was therefore puzzling why these GLUT3-GLUT4-myoblasts could survive in the presence of dGlc during the mutant selection process. The present study revealed that GLUT 1 transport affinity in dGlc-grown cells was at least four folds lower than that in control cells. This loss of GLUT 1 transport activity was apparent only after exposure to the toxic sugar analogues for more than 10 hrs. This dGlc-mediated effect was not due to competitive inhibition by the residual dGlc carried over from growth medium, changes in glycolytic enzymes, nor accumulation of the negatively charged dGlc-6-PO4. In fact, GLUT 1 transcript level was elevated in dGlc-treated cells. Both immunoprecipitation and immunoblotting studies indicated that the size of the GLUT 1 transporter in dGlc-grown myoblasts was reduced from 52 kDa to that of the unglycosylated form (38 kDa). These findings suggest that growth in the presence of dGlc inhibits glycosylation of the GLUT 1 transporter, thus reducing its transport affinity. This inability of the GLUT 1 transporter to take up dGlc may therefore explain why GLUT 3-GLUT 4-mutants are able to grow in the presence of the toxic dGlc during the mutant selection procedure.

3-O-Methylglucose↗
PubMed1996

Case report: radiation prevention of heterotopic ossification after bone and joint surgery in sites other than hips.

Five patients were given single dose irradiation in an attempt to prevent heterotopic ossification after bone and joint surgery in sites other than hips. All patients were at risk for the development of post-operative heterotopic ossification. Two patients were treated with 6 Gy and three patients were treated with 7 Gy the day after operation. No complications were encountered. Post-operative heterotopic ossification did not develop in patients who received 7 Gy, whereas treatment failed in the two patients who received 6 Gy. Because this is a case report study, no conclusion could be made. Further investigation is needed to assess the efficacy of post-operative single dose irradiation in heterotopic ossification prophylaxis in sites other than hips in high risk patients.

Adult↗
PubMed1995

Use of hexose transport mutants to examine the expression and properties of the rat myoblast GLUT 1 transport process.

Rat L6 myoblasts were recently shown to possess the GLUT 1, 3 and 4 transporters, and not the GLUT 2 isoform [1]. This investigation examined the expression and properties of the GLUT 1 isoform. GLUT 1 transcript level was significantly reduced in cells grown at high densities and during myogenic differentiation. A comparison of the GLUT 1 and 4 transcript levels in myogenesis-competent and impaired cells revealed an inverse relationship between these two isoforms. This relationship was confirmed by studies using two independent spontaneous GLUT 3- GLUT 4- mutants, M1 and M3. These mutants possessed very high level of the GLUT 1 isoform, but negligible amount of the GLUT 3 and 4 isoforms. GLUT 1 expression was also subject to positive regulation. Glucose starvation was found to increase not only the levels of the GLUT 1 transcript and transporter, but also the intrinsic activity of the GLUT 1 transporter. Studies with M1 and M3 mutants revealed that the GLUT 1 transporter was not functional in glucose-grown cells, even though it was present at a very high level in the plasma membrane. This transporter became functional when cells were starved for glucose. The functional GLUT 1 transporter had an apparent Km value of around 0.9 mM, and was sensitive to cytochalasin B, phloretin, phlorizin and pCMBS.

3-O-Methylglucose↗
PubMed1995

Low dose rate versus high dose rate intraluminal brachytherapy for malignant endobronchial tumors.

Although the evolution from low dose rate to high dose rate brachytherapy for malignant endobronchial malignancies was primarily based on economy, patient convenience, and radiation protection, the difference in therapeutic index, if any, between these two modalities must be kept in mind. Our experience with both methods permits assessment of the feasibility of replacing low dose rate brachytherapy with high dose rate brachytherapy. Results with our first 110 patients (group 1) treated with low dose rate brachytherapy (133 procedures) were compared with results with our initial 59 consecutive patients (group 2) treated with high dose rate brachytherapy (161 procedures). In group 1, patients were treated with one or two sessions of 30-60 Gy each calculated at a 1 cm radius. In patients in group 2, we aimed at three weekly sessions of 7 Gy each calculated at a 1 cm radius. External beam irradiation therapy had previously been given to 88% of patients in group 1 and to 85% of patients in group 2. Laser bronchoscopy was performed in 36% of patients in group 1 and in 24% of patients in group 2 before brachytherapy. Clinical or bronchoscopic improvement was noted in 72% of patients in group 1 and in 85% of patients in group 2 (p > 0.05). Complication rates were low and comparable. Survival was similar in both groups (median < 6 months). Although both low dose rate and high dose rate brachytherapy appear equally effective in palliation for malignant endobronchial obstruction, we are now practicing the latter exclusively.

Aged↗
PubMed1995

Single-dose irradiation for the prevention of heterotopic ossification after total hip arthroplasty. A comparison of doses of five hundred and fifty and seven hundred centigray.

One hundred and seven hips (ninety-four patients) that had risk factors associated with the development of heterotopic ossification after total hip arthroplasty were treated with a single dose of radiation after the operation in an attempt to prevent the formation of heterotopic bone. A study was conducted to compare the efficacy of a single dose of 550 centigray (nineteen hips) with that of a single dose of 700 centigray (eighty-eight hips). Heterotopic ossification developed in twelve (63 per cent) of the nineteen hips that were treated with 550 centigray; grades 1, 2, and 3, according to the classification of Brooker et al., developed in four hips each. Two of the patients who received 550 centigray were symptomatic. Heterotopic ossification developed in nine (10 per cent) of the eighty-eight hips that were treated with 700 centigray; the lesion was grade 1 in six, grade 2 in one, and grade 3 in two. None of the patients who received 700 centigray were symptomatic. We concluded that single-dose irradiation consisting of 550 centigray is inadequate for the prevention of heterotopic ossification in high-risk patients after total hip arthroplasty. We recommend a dose of 700 centigray as effective prophylaxis for these patients.

Adult↗