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Biomedical subjects

J M Lai

Publications and source records attributed to J M Lai.

15 recordsLinked to original sources
PubMed2001

Lysophosphatidic acid promotes phorbol-ester-induced apoptosis in TF-1 cells by interfering with adhesion.

When exposed to PMA, the erythroblastic cell line TF-1 and its cytokine-independent variant D2 cells can be induced to undergo differentiation and apoptosis. In this study we investigated the mechanism responsible for the differential responses to PMA induction and show that serum present in the medium has a major role in promoting PMA-induced apoptosis in TF-1 and D2 cells. Interestingly, lysophosphatidic acid (LPA) could replace serum to co-operate with PMA in inducing apoptosis via the Rho-dependent pathway. The expression of a constitutively active form of RhoA also increased PMA-induced apoptosis. However, by inhibiting adhesion, most cells underwent PMA-induced apoptosis even in the absence of LPA or serum, indicating that adhesion is required for PMA-induced differentiation. Given that LPA could prevent adhesion for cells maintained in the serum-free medium, here we propose that RhoA has a switching role in determining whether TF-1 and D2 cells undergo differentiation or apoptosis in response to PMA, by modulating cell adhesion.

Apoptosis↗
PubMed2001

Sleep disorders associated with traumatic brain injury.

OBJECTIVES: To investigate the frequency of sleep disorders in traumatic brain injury (TBI) patients with hypersomnia and to discern the relationship between posttraumatic sleep disorders and pretraumatic sleep symptoms. DESIGN: Prospective cohort study using the criterion standard to diagnose sleep disorders in a consecutive sample of TBI patients. SETTING: Academic medical center with level I trauma center, rehabilitative medicine services, and accredited sleep disorders center. PATIENTS: Ten TBI patients with subjective excessive sleepiness. INTERVENTION: Nocturnal polysomnography followed by Multiple Sleep Latency Test. Subjects who had overt sleep apnea on the first nocturnal polysomnography had a second nocturnal polysomnography with titration of nasal continuous positive airway pressure. MAIN OUTCOME MEASURES: Diagnosis of sleep-disordered breathing, narcolepsy, and posttraumatic hypersomnia. RESULTS: A diagnosis of treatable sleep disorder was made in all 10 subjects. Sleep-disordered breathing was found in 7 subjects: overt obstructive sleep apnea (OSA) was diagnosed in 5 subjects, rapid eye movement-related OSA in 1, and upper airway resistance syndrome (UARS) in 1. Narcolepsy was diagnosed in 2 subjects, and the diagnosis of posttraumatic hypersomnia was made in 1 subject. Three subjects had symptoms of hypersomnia before their injury (1 each with narcolepsy, OSA, UARS), and 2 of these were driving a car at the time of injury. CONCLUSION: Treatable sleep disorders appear to be common in the sleepy TBI population, but may be largely undiagnosed and untreated.

Adult↗
PubMed2000

Relative bioavailability of salmon calcitonin given intramuscularly.

BACKGROUND: Salmon calcitonin, a polypeptide hormone, is used in the treatment of osteoporosis, hypercalcemia and Paget's disease. The purpose of this study was to evaluate the pharmacokinetics and relative bioavailability of two salmon calcitonin products, Miacalcic (Novartis Pharmaceuticals, Basle, Switzerland) and Calcinin (Purzer Pharmaceuticals, Taipei, Taiwan). METHODS: This was a randomized, single-dose, crossover study conducted under fasting conditions with a washout period of 1 week between doses. Ten healthy male subjects were enrolled in this study. Each subject received a 100 IU dose (20 micrograms; 50 IU/ampule x 2) of salmon calcitonin intramuscularly (i.m.) followed by collection of blood samples at specified time intervals. Serum salmon calcitonin concentrations were measured using a validated radioimmunoassay method with a detection limit of 15.0 pg/ml. Values for the area under the serum concentration from time zero to last time and infinity curve (AUC0-t and AUC0-infinity), peak concentration (Cmax), time to peak concentration, terminal first order rate constant, terminal half-life, mean residence time, total clearance divided by absolute bioavailability, onset time, maximal effect and duration were compared for each product. RESULTS: The 90% confidence intervals for AUC0-t, AUC0-infinity and Cmax after logarithmic transformation were 93.2% to 113.1%, 97.2% to 114.9% and 84.9% to 108.0%, respectively. CONCLUSIONS: Based on the two one-sided tests procedure, we conclude that Miacalcic and Calcinin are bioequivalent.

Adult↗
PubMed1999

Functional recovery after bilateral pallidotomy for the treatment of early-onset primary generalized dystonia.

This report describes the successful treatment of dystonia musculorum deformans with bilateral stereotactic pallidotomy in a 14-year-old girl in whom the dystonia was diagnosed when she was 7 years old. The patient presented with dystonia of the right upper extremity that progressed to generalized dystonia. Preoperatively, she required maximal assistance with all activities of daily living and transfers. She was not a functional ambulator. Postoperatively, she had remarkable functional recovery. At discharge, she was at modified independence level for all basic activities of daily living and required supervision for household ambulation. No postoperative complications were noted. We propose that bilateral stereotactic lysis of globus pallidus interna may be an alternative treatment for dystonia musculorum deformans. The technique of bilateral pallidotomy and theories of its effectiveness are discussed.

Activities of Daily Living↗
PubMed1998

Age-dependent and lobe-specific spontaneous hyperplasia in the brown Norway rat prostate.

We showed previously that exogenously administered testosterone caused age- and lobe-specific overgrowth of the prostate in Brown Norway rats. A common feature observed in testosterone-treated animals was cell hypertrophy in each of the ventral, dorsal, and lateral lobes of both young (6 mo old) and old (24 mo old) rats. By contrast, hyperplasia was seen only in the dorsal and lateral lobes of old rats treated with testosterone. These observations prompted us to examine whether age- and lobe-specific overgrowth might also occur in untreated rats as a consequence of the endogenous hormonal milieu. To this end, blood and prostates were collected from a large number (25-30 rats per group) of 4- to 6-mo-old (young) and 21- to 24-mo-old (old) Brown Norway rats. Both serum testosterone (-45%) and estradiol (-22%) concentrations decreased significantly with age, but the greater magnitude of the decrement in testosterone relative to estradiol led to a reduction in the serum testosterone:estradiol ratio. Paradoxically, although the prostate is androgen dependent, the wet weight, protein, and DNA contents increased significantly with age in the dorsal and lateral lobes of old rats despite the decrease in testosterone level. Histologic examination revealed that the increased weights and DNA contents of the dorsal and lateral lobes in old rats coincided with an increased number of epithelial cells in the distal and intermediate segments of these lobes, indicative of hyperplasia but independent of change in cell size. Taken together, these results show a spontaneous age-related overgrowth of cells in the dorsal and lateral prostatic lobes of old Brown Norway rats despite diminished serum testosterone concentrations. The aging Brown Norway rat, therefore, may be a useful model for studies of some aspects of the pathogenesis underlying spontaneous age-related prostatic hyperplasia.

Aging↗
PubMed1998

Effects of aspirin on arylamine N-acetyltransferase activity in Klebsiella pneumoniae.

This study was designed to assess the effects of aspirin on arylamine N-acetyltransferase (NAT) activities in the bacterium Klebsiella pneumoniae using high performance liquid chromatography to measure the acetylation of 2-aminofluorene (2-AF) with or without aspirin. Cytosols or suspensions of K. pneumoniae with or without specific concentrations of aspirin co-treatment showed different percentages of 2-AF acetylation. The data indicated that there was decreased NAT activity associated with increased levels of aspirin in K. pneumoniae cytosols and in intact bacteria. For the cytosol examination, the apparent values of Km and Vmax decreased 0.59- and 0.58-fold after co-treated with 40 microM aspirin, respectively, for 2-AF. For the intact bacteria examination, the apparent values of Km and Vmax decreased 0.60- and 0.67-fold after co-treated with 40 microM aspirin, respectively, for 2-AF. This report is the first demonstration to show that aspirin can decrease N-acetyltransferase activity in the bacterium K. pneumoniae.

Acetylation↗
PubMed1997

Kinetics of arylamine N-acetyltransferase in tissues from human breast cancer.

N-Acetyltransferase activity and Michaelis-Menten kinetic constants were determined in cancerous and non-cancerous breast tissues from 30 female patients with breast cancer. The results derived from tissue cytosol showed that 12 rapid, ten intermediate and eight slow acetylators based on p-aminobenzoic acid and 2-aminofluorene for substrates. The mean apparent Km values for the monomorphic substrate p-aminobenzoic acid and polymorphic substrate 2-aminofluorene were: 55.0 +/- 18.7, 114.0 +/- 30.0, and 137.0 +/- 37.2 microM; and 62.5 +/- 23.7, 166.0 +/- 67.0, and 239.0 +/- 76.6 microM for the slow, intermediate, and rapid enzymes, respectively. Compared to the enzymes from slow acetylators, the rapid acetylators exhibited mean apparent Vmax values eight- and ten-fold greater for p-aminobenzoic acid and 2-aminofluorene, respectively. A similar trend was obtained from the blood cytosols of cancerous patients and healthy volunteers. N-Acetyltransferase activity of breast cancerous and non-cancerous tissues were 1.5- and 2.2-fold different between rapid and slow acetylator with p-aminobenzoic acid and 2-aminofluorene as substrates, respectively. In breast cancerous tissues, 75% and 70% of the cytosolic N-acetyltransferase activity were inhibited under 2 mM of tamoxifen as substrates of 2-aminofluorene and p-aminobenzoic acid, respectively. Similar results were also found in non-cancerous tissues and blood samples from breast cancer patients and healthy volunteers. The effect of 1 mM tamoxifen on the N-acetyltransferase activity from breast cancerous tissues with positive estrogen receptor was 1.6-fold higher than that of negative estrogen receptor. This is the first demonstration to show that anti-estrogen drug can affect N-acetyltransferase activity in breast cancerous tissues. Therefore, this finding may provide a clue to the use of tamoxifen in prevention of human breast cancer.

4-Aminobenzoic Acid↗
PubMed1997

Bruxism after brain injury: successful treatment with botulinum toxin-A.

Bruxism, the rhythmic grinding of teeth--usually during sleep--is not an infrequent complication of traumatic brain injury. Its prevalence in the general population is 21%, but its incidence after brain injury is unknown. Untreated, bruxism causes masseter hypertrophy, headache, temporomandibular joint destruction, and total dental wear. We report a case of complete resolution of postanoxic bruxism after treatment with botulinum toxin-A (BTX-A). The patient was a 28-year-old man with no history of bruxism who sustained an anoxic brain injury secondary to cardiac arrest of unknown etiology. On admission to our rehabilitation unit 2 months after the injury, the patient presented with severe bruxism and heavy dental wear. The patient was injected with a total of 200 units of BTX-A to each masseter and temporalis. There was total resolution of bruxism 2 days after injection, with no complications. On follow-up 3 months after injection, the patient remained free of bruxism. We propose that botulinum toxin be considered as a treatment for bruxism secondary to anoxic brain injury. Further studies regarding muscle selection and medication dosage are warranted to elucidate the toxin's efficacy in this condition.

Adult↗
PubMed1997

Diversion colitis: a cause of abdominal discomfort in spinal cord injury patients with colostomy.

Diversion colitis is thought to result from nutritional deficiencies secondary to fecal diversion. Symptoms include hemorrhagic purulent rectal discharge, abdominal pain, and tenesmus. 5-Aminosalicylic acid (5-ASA) and N-butyrate enemas have been reported to help this condition non-spinal cord injury (SCI) patients. We report the case of a 49-year-old C6 ASIA B tetraplegic man who had received colostomy because of intractable ileus 10 years earlier. He presented with a 2-week history of rectal pain and bleeding. Abdominal and rectal examination on admission were unremarkable. Colonoscopy showed a partial stricture 70cm proximally to the rectum. The colonic mucosa appeared granular and friable with evidence of linear ulceration. Histopathologic study was consistent with colitis. The patient developed fever, abdominal distention, and extensive retroperitoneal air after endoscopy, suggesting colonic perforation. He was treated with daily 5-ASA suppository and total parenteral nutrition for the presumed diagnosis of diversion colitis, and intravenous antibiotics for perforated colon. After 6 weeks of treatment with 5-ASA, the patient had decreased rectal pain and bleeding. This experience suggests that diversion colitis may be a cause of abdominal discomfort in SCI patients and that 5-ASA may be used in the management of diversion colitis.

Abdominal Pain↗
PubMed1997

Incidence and sequelae of symptomatic venous thromboembolic disease among patients with traumatic brain injury.

Venous thromboembolism (VTE) is a potentially life-threatening complication among patients with traumatic brain injury (TBI). However, few reports describe the incidence of this important disease. We reviewed the incidence of symptomatic VTE among 124 consecutive admissions with TBI to a free-standing rehabilitation hospital over an 18-month period. Four patients manifested evidence of VTE within 2 months of injury: two with leg swelling, one with an oedematous arm, and one with respiratory distress. None of the patients with suspected VTE received prophylactic anticoagulant therapy. Diagnosis of VTE was confirmed with venograph in two of the four patients. Although VTE is frequently asymptomatic, the incidence of symptomatic VTE (1.6%) among this series of rehabilitation inpatients with TBI still appears surprisingly low. These results have implications regarding the utility of non-invasive diagnostic screening of asymptomatic VTE and routine anticoagulant prophylaxis of high-risk patients with TBI.

Activities of Daily Living↗
PubMed1997

The Sequence Alerting Server--a new WEB server.

UNLABELLED: A Sequence Alerting Server with a WWW interface is described which informs users with query sequences in database searches about new entries in protein databases related to their query. AVAILABILITY: The server address is http://www.bork.embl-heidelberg.de/alerting/.

Amino Acid Sequence↗
PubMed1997

Evidence for arylamine N-acetyltransferase in Hymenolepis nana.

N-acetyltransferase activities with p-aminobenzoic acid and 2-aminofluorene were determined in Hymenolepis nana, a cestode found in the intestine of the Sprague-Dawley rats. The N-acetyltransferase activity was determined using an acetyl CoA recycling assay and high pressure liquid chromatography. The N-acetyltransferase activities from a number of Hymenolepis nana whole tissue homogenizations were found to be 2.83 +/- 0.31 nmole/min/mg for 2-aminofluorene and 2.07 +/- 0.24 nmole/min/mg for p-aminobenzoic acid. The apparent Km and Vmax were 1.06 +/- 0.38 mM and 8.92 +/- 1.46 nmol/min/mg for 2-aminofluorene, and 2.16 +/- 0.19 mM and 12.68 +/- 2.26 nmol/min/mg for p-aminobenzoic acid. The optimal pH value for the enzyme activity was pH 8.0 for both substrates tested. The optimal temperature for enzyme activity was 37 degrees C for both substrates. The N-acetyltransferase activity was inhibited by iodacetamide. At 0.25 mM iodacetamide the activity was reduced 50% and 1.0 mM iodacetamide inhibited activity more than 90%. Among a series of divalent cations and salts, Fe2+, Ca2+ and Zn2+ were demonstrated to be the most potent inhibi-tors. Among the protease inhibitors, only ethylenediaminetetraacetic acid significantly protected N-acetyltransferase. Iodoacetate, in contrast to other agents, markedly inhibited N-acetyltransferase activity. This is the first demonstration of acetyl CoA:arylamine N-acetyltransferase activity in a cestode and extends the number of phyla in which this activity has been found.

Animals↗
PubMed1996

Evidence for arylamine N-acetyltransferase in the nematode Anisakis simplex.

N-Acetyltransferase activities with p-aminobenzoic acid and 2-aminofluorene were determined in Anisakis simplex, a nematode found in the intestine of the salt water fish Trichiurus lepturus. The N-acetyltransferase activity was determined using an acetyl CoA recycling assay and high pressure liquid chromatography. The N-acetyltransferase activity from a number of Anisakis simplex whole tissue homogenizations was found to be 2.89 +/- 0.52 nmol/min per mg for 2-aminofluorene and 2.54 +/- 0.45 nmol/min per mg for p-aminobenzoic acid. The K(m) and Vmax values obtained were 1.06 +/- 0.69 mM and 9.34 +/- 1.94 nmol/min per mg for 2-aminofluorene, and 2.25 +/- 0.10 mM and 14.44 +/- 0.7 nmol/min per mg for p-aminobenzoic acid. The optimal pH value for the enzyme activity was pH 8.0 for both substrates tested. The optimal temperature for enzyme activity was 37 degrees C for both substrates. The N-acetyltransferase activity was inhibited by iodoacetamide: at 0.25 mM iodoacetamide, activity was reduced 50% and 1.0 mM iodoacetamide inhibits activity more than 90%. Among a series of divalent cations and salts, Cu2+ and Zn2+ were demonstrated to be the most potent inhibitors. This is the first demonstration of acetyl CoA/arylamine N-acetyltransferase activity in a nematode and extends the number of phyla in which this activity has been found.

4-Aminobenzoic Acid↗