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Biomedical subjects

M L Ho

Publications and source records attributed to M L Ho.

At least 19 recordsLinked to original sources

Non-adiabatic intramolecular and photodissociation dynamics studied by femtosecond time-resolved photoelectron and coincidence imaging spectroscopy.

Time-resolved photoelectron spectroscopy (TRPES) is emerging as a useful tool for the study of non-adiabatic dynamics in isolated polyatomic molecules and clusters due to its sensitivity to both electronic and vibrational dynamics. A powerful extension of TRPES, coincidence imaging spectroscopy (CIS), based upon femtosecond time-resolved 3D momentum vector imaging of both photoions and photoelectrons in coincidence, is a new technique for the study of complex dissociative processes. Here we show how these spectroscopies can be used to study both non-adiabatic intramolecular and photodissociation dynamics in polyatomic molecules. Intramolecular dynamics in the alpha, beta-enones acrolein, crotonaldehyde and methyl vinyl ketone are studied using both TRPES and laser-induced fluorescence of HCO(X) product yields. The location of the methyl group is seen to have very dramatic effects on the relative electronic relaxation rates and the HCO(X) yield. Applying both TRPES and CIS to the 200 nm and 209 nm photodissociation of the nitric oxide dimer, (NO)2, we observe the fs time-scale evolution of the excited parent neutral via its photoelectron spectrum and the emergence of the NO(A) photofragment including its energy and angular distributions.

Journal Article↗

Brain metabolic changes associated with symptom factor improvement in major depressive disorder.

BACKGROUND: Symptoms of major depressive disorder (MDD) have been linked to regional brain function through imaging studies of symptom provocation in normal control subjects and baseline studies of subjects with MDD. We examined associations between change in depressive symptom factors and change in regional brain metabolism from before to after treatment of MDD. METHODS: Thirty-nine outpatients with MDD underwent 18F-fluorodeoxyglucose positron emission tomography scanning before and after treatment with either paroxetine or interpersonal psychotherapy. Associations were determined between changes in regional brain metabolism and changes in four Hamilton Depression Rating Scale factors (anxiety/somatization [ANX], psychomotor retardation [PR], cognitive disturbance [COGN], and sleep disturbance) and two corresponding Profile of Mood States subscales (tension [TENS] and fatigue [FATIG]). RESULTS: Improvement in ANX, PR, TENS, and FATIG factors was associated with decreasing ventral frontal lobe metabolism. Improvement in ANX and TENS was also associated with decreasing ventral anterior cingulate gyrus (AC) and anterior insula activity, whereas improvement in PR was associated with increasing dorsal AC activity. COGN improvement was associated with increasing dorsolateral prefrontal cortex metabolism. CONCLUSIONS: Brain regions that show significant relationships with symptom provocation in normal control subjects have similar relationships with MDD symptoms as they improve with treatment.

Major Depressive Disorder↗

Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently.

BACKGROUND: The frequent comorbidity of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) suggests a fundamental relationship between them. We sought to determine whether MDD and OCD have unique cerebral metabolic patterns that remain the same when they coexist as when they occur independently. METHODS: [18F]-fluorodeoxyglucose positron emission tomography (PET) brain scans were obtained on 27 subjects with OCD alone, 27 with MDD alone, 17 with concurrent OCD+MDD, and 17 normal control subjects, all in the untreated state. Regional cerebral glucose metabolism was compared between groups. RESULTS: Left hippocampal metabolism was significantly lower in subjects with MDD alone and in subjects with concurrent OCD+MDD than in control subjects or subjects with OCD alone. Hippocampal metabolism was negatively correlated with depression severity across all subjects. Thalamic metabolism was significantly elevated in OCD alone and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower metabolism in thalamus, caudate, and hippocampus than subjects with OCD alone. CONCLUSIONS: Left hippocampal dysfunction was associated with major depressive episodes, regardless of primary diagnosis. Other cerebral metabolic abnormalities found in OCD and MDD occurring separately were not seen when the disorders coexisted. Depressive episodes occurring in OCD patients may be mediated by different basal ganglia-thalamic abnormalities than in primary MDD patients.

Adult↗

Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings.

BACKGROUND: In functional brain imaging studies of major depressive disorder (MDD), regional abnormalities have been most commonly found in prefrontal cortex, anterior cingulate gyrus, and temporal lobe. We examined baseline regional metabolic abnormalities and metabolic changes from pretreatment to posttreatment in subjects with MDD. We also performed a preliminary comparison of regional changes with 2 distinct forms of treatment (paroxetine and interpersonal psychotherapy). METHODS: Twenty-four subjects with unipolar MDD and 16 normal control subjects underwent resting F 18 ((18)F) fluorodeoxyglucose positron emission tomography scanning before and after 12 weeks. Between scans, subjects with MDD were treated with either paroxetine or interpersonal psychotherapy (based on patient preference), while controls underwent no treatment. RESULTS: At baseline, subjects with MDD had higher normalized metabolism than controls in the prefrontal cortex (and caudate and thalamus), and lower metabolism in the temporal lobe. With treatment, subjects with MDD had metabolic changes in the direction of normalization in these regions. After treatment, paroxetine-treated subjects had a greater mean decrease in Hamilton Depression Rating Scale score (61.4%) than did subjects treated with interpersonal psychotherapy (38.0%), but both subgroups showed decreases in normalized prefrontal cortex (paroxetine-treated bilaterally and interpersonal psychotherapy-treated on the right) and left anterior cingulate gyrus metabolism, and increases in normalized left temporal lobe metabolism. CONCLUSIONS: Subjects with MDD had regional brain metabolic abnormalities at baseline that tended to normalize with treatment. Regional metabolic changes appeared similar with the 2 forms of treatment. These results should be interpreted with caution because of study limitations (small sample size, lack of random assignment to treatment groups, and differential treatment response between treatment subgroups).

Adult↗

Sexually dimorphic effect of glutamate treatment on cell cycle arrestment of astrocytes from the preoptic area of neonatal rats.

Neurotoxicological studies have indicated that L-glutamate exhibits more pronounced effects on the preoptic area (POA) neurons of male rats than on those of females in the neonatal period. However, no information has previously been available as to whether or not such sexual dimorphism also exists for the effects of glutamate on astrocytes from POA. The present paper reports the differential effects of L-glutamate on astrocytes isolated from POA of neonatal male and female rats. The proliferation of astrocytes was measured by methods of cell count and cell cycle analysis. In addition, the activity of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) was assayed to understand its role in the glutamate-induced disturbance of the cell cycle progression of astrocytes. The results revealed that L-glutamate, at doses of 0.5 and 1.0 mM, inhibited the proliferation of astrocytes derived from male rats more severely than those derived from females. The L-glutamate treatment blocked the cell cycle progression and caused an accumulation of cells in the S phase. The activity of CaM kinase II declined more markedly in astrocytes derived from male rats than in those from females after glutamate treatment. These findings suggest that the proliferation of astrocytes derived from POA of neonatal rats can be inhibited in a sexually dimorphic manner by L-glutamate, possibly through blocking the cell cycle progression and partially related to the inactivation of the CaM kinase II.

Aging↗

Molecular fingerprinting of Mycobacterium tuberculosis strains isolated in Vietnam using IS6110 as probe.

SETTING: Northern and Southern areas of Vietnam. OBJECTIVE: To study the correlation between DNA fingerprinting of 168 Mycobacterium tuberculosis strains isolated from patients with a particular historical past (political separation of Vietnam for 20 years) and data about geographical origin, drug susceptibility, HIV infection and BCG vaccination status. METHODS: Comparison of restriction fragment length polymorphism (RFLP) patterns produced by Southern hybridization of Pvull-digested chromosomal DNA. RESULTS: The number of IS6110 copies for the 168 strains ranges from 0 to 23. Strains originating from the North or the South differ strongly with respect to the number of copies of IS6110. Indeed, the strains originating from the north have predominantly from 3 to 14 IS6110 copies while the southern strains have predominantly from 15 to 23 IS6110 copies. Furthermore, strains isolated in the North are dispersed into 6 groups whereas 80% of the strains isolated in the South form a single group. Moreover, the prevalence of drug resistance is higher in strains isolated in the South than in the North. No noticeable correlation is observed between RFLP patterns, drug susceptibility, or HIV infection. CONCLUSION: The IS6110 fingerprints of 168 M. tuberculosis strains isolated in Vietnam showed a high range of polymorphism. Only a few strains have been found with no IS6110 (1.8%). The differences between the strains from the North and South, having more than six IS6110, suggests that they derived from ancestral strains that would be distinguishable by the number of IS6110 and their transposition sites throughout the genome. The genomic structure of the population of strains from South Vietnam resembles that of the Beijing strain population. This could account for a similar evolution of M. tuberculosis due to a selection by BCG-induced immunity in the two populations.

BCG Vaccine↗

Effects of nonsteroidal anti-inflammatory drugs and prostaglandins on osteoblastic functions.

It has been reported that nonsteroidal anti-inflammatory drugs (NSAIDs) suppress bone repair and bone remodeling but only mildly inhibit bone mineralization at the earlier stage of the repair process. We proposed that the proliferation and/or the earlier stage of differentiation of osteoblasts may be affected by NSAIDs. This study was designed to investigate whether NSAIDs affect the proliferation and/or differentiation of osteoblasts and whether these effects are prostaglandin (PG) mediated. The effects of PGE1 and PGE2, indomethacin, and ketorolac on thymidine incorporation, cell count, intracellular alkaline phosphatase (ALP) activity, and Type I collagen content in osteoblast-enriched cultures derived from fetal calvaria were evaluated. The results showed that both PGs and NSAIDs inhibited DNA synthesis and cell mitosis in a time- and concentration-dependent manner. However, intracellular ALP activity and Type I collagen content were stimulated at an earlier stage of differentiation in osteoblasts. These results suggested that (i) the inhibitory effect of ketorolac on osteoblastic proliferation contributes to its suppressive effects on bone repair and remodeling in vivo; (ii) PGEs and NSAIDs may be involved in matrix maturation and biologic bone mineralization in the earlier stage of osteoblast differentiation; and (iii) the effects of ketorolac and indomethacin on cell proliferation and differentiation may not be through the inhibition of the synthesis of PGE1 or PGE2.

Alkaline Phosphatase↗

Characteristics of primary osteoblast culture derived from rat fetal calvaria.

Primary osteoblast cultures, which reflect more phenotypic properties of normal osteoblasts than osteoblastic cell lines, can be used as an experimental tool for investigating the osteoblastic functions in vitro. Primary osteoblast cultures were obtained from the parietal bones of calvaria of fetal rats in this study. Differential characteristics of osteoblasts in our culture system were examined and fibroblast cultures were also tested for comparison. We tested the alkaline phosphatase (ALP) and von Kossa stains on osteoblast and fibroblast cultures to examine the expression of ALP and the subsequent matrix mineralization occurred at 2 and 3 weeks after cell confluence respectively. The results showed that osteoblast cultures revealed obvious positive stains of ALP and von Kossa, while fibroblast cultures revealed negative stains, suggesting the osteoblast culture system used in this study reflects the typical phenotypes of primary osteoblasts but not fibroblasts. We tested the ALP activities following various doses of PGE2 or ketorolac treatments in primary osteoblast and fibroblast cultures. The results showed that PGE2 and ketorolac stimulated intracellular ALP activities of osteoblasts in dose dependent fashions, while very low ALP activities were detected in either the control or agents treated cultures of fibroblast. These results suggest that PGE2 may be involved in osteoblastic differentiation and the stimulatory effect of ketorolac on osteoblastic ALP activity may not be PGE2 mediated. The responses of osteoblasts to both agents can be as the characteristics of primary osteoblast derived from rat calvaria.

Alkaline Phosphatase↗

Low total body bone mineral content and high bone resorption in Korean winter-born versus summer-born newborn infants.

Seasonal differences in newborn total body bone mineral content (TBBMC) have not been studied, particularly in relation to alterations in vitamin D status in winter. In vitamin D deficiency bone resorption may be high and bone mineralization low. Bone resorption may be assessed by serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP) measures. Because vitamin D supplements throughout pregnancy are uncommon in Korea, we hypothesized that in Korean winter newborns, TBBMC is low and serum ICTP high from high bone resorption and low 25-hydroxyvitamin D (25-OHD) compared with those in summer newborns. Seventy-one Korean term infants were studied prospectively in summer (July through September, n = 37) versus winter (January through March, n = 34); TBBMC was measured before 3 days of age by dual-energy x-ray absorptiometry. Significant seasonal differences were found: winter newborns had 6% lower TBBMC (least squares means +/- SD; 86.7 +/- 7.7 gm vs 93.9 +/- 7.8 gm, p = 0.0002), lower cord serum 25-OHD (10.7 +/- 8 nm vs 30 +/- 15 nm, p = 0.0001) and 1,25-dihydroxyvitamin D, and higher ICTP (96.4 +/- 20.3 microg/L vs 74.8 +/- 24 microg/L, p = 0.0002) and calcium than summer newborns. TBBMC correlated with serum 25-OHD (r = 0.243, p = 0.047) and inversely with ICTP (r = -0.333, p = 0.008). We suggest that in Korea low maternal vitamin D status in winter results in marked reduction in newborn TBBMC.

Absorptiometry, Photon↗

Gallbladder volume and contractility in term and preterm neonates: normal values and clinical applications in ultrasonography.

The aim of this study was to establish the normal values and evaluate associated factors of gallbladder volume and contractility in term and preterm neonates by using ultrasonography. Sonographic measurement of gallbladder volume was performed by using the ellipsoid method in 50 preterm and 46 term infants. We collected data soon after delivery and at 6-h fasting, and at 3-h and 6-h fasting following regular milk feeding. Serial postprandial changes of gallbladder volume and contractility were collected at 15-min intervals for one hour. Gallbladder contraction index (C.I.) was determined as percentage decrement of postprandial size from initial size. Fasting gallbladder volume was larger in term group (p < 0.05). Term neonates more readily showed significant contraction (C.I. > 50%; p < 0.05). In preterm infants significant contraction was clearly observed at postconceptional age > 31 weeks or body weight > 1300 g. The presence of hepatobiliary diseases might be detected by evaluating serial changes of gallbladder volume and contractility under ultrasonography in the neonatal stage.

Gallbladder↗

Effects of ketorolac on bone repair: A radiographic study in modeled demineralized bone matrix grafted rabbits.

The effects of ketorolac on bone repair were studied radiographically. The effects of methylprednisolone were also compared. Demineralized bone matrix was grafted into the fractured gap of rabbit's ulna as an experimental bone repair model. The rabbits received ketorolac 2 or 4 mg/kg body weight daily for 6 weeks after transplantation. Serial radiographic studies were performed 2, 4, and 6 weeks after transplantation. Mineralization of grafts and bone union were evaluated as the parameters of bone repair. Comparing the bone repair among groups at individual time points, ketorolac-treated groups showed no statistical differences as compared with the control group in either mineralization or bone union, whereas methylprednisolone significantly suppressed both parameters. However, comparing the mineralization during the healing process in each group, the control group and the group treated with ketorolac 2 mg/kg showed a significant increase during the period from the 2nd to the 4th week of medication, whereas both the group treated with ketorolac 4 mg/kg and the methylprednisolone-treated group showed no significant increase during this period. This poor mineralization of grafted bone in repair process affected by ketorolac suggests that 4 mg/kg of ketorolac might delay the endochondral ossification process during the period from the 2nd to the 4th week of fracture healing.

Animals↗

Effects of elution [correction of eution] conditions on the separation of calpastatin, mu- and m-calpain on DEAE-Sephacel chromatography.

A rapid stepwise measurement for the activities of calpastatin and mu- and m-calpains was developed by using 2-stage elution at pH 8.5 and then 7.0. The activities of calpastatin, mu-calpain and m-calpain can be rapidly assayed following the separation on DEAE-Sephacel chromatography by a 2 stage elution with 90 mM NaCl (pH 8.5), and then by 200 and 300 mM NaCl in elution buffer (pH 7.0). No significant differences in the recovery of these proteinases and inhibitor was observed between stepwise gradient and linear gradient methods.

Buffers↗

Trial on timing of introduction to solids and food type on infant growth.

OBJECTIVE: The optimal time and choice of solid foods to introduce to an infant's diet is unknown. The aim of this randomized trial was to determine whether early versus late introduction of solid foods and commercially prepared versus parent's choice of solid foods affects growth or body composition in the first year. METHODS: White infants (n = 165) were recruited before 3 months of age and were randomized to receive: 1) commercially prepared solid foods (commercial) from 3 to 12 months, 2) commercially prepared solid foods from 6 to 12 months, 3) parent's choice of solid foods (choice) from 3 to 12 months, or 4) parent's choice of solid foods from 6 to 12 months. Anthropometrics and body composition, using dual energy x-ray absorptiometry, were determined at 3, 6, and 12 months. Three-day diet diaries were completed at 3, 6, 9, and 12 months. RESULTS: There were no differences in growth or body composition between infants in early versus late introduction groups or commercial versus choice groups at any age. The total energy intake was not different among infants in the early compared with the late group at any age. Infants in the commercial group consumed less protein calories at 9 months (80 +/- 3 kcal/d vs 88 +/- 3 kcal/d) and 12 months 101 +/- 5 kcal/d vs 148 +/- 5 kcal/d), less fat calories at 12 months (263 +/- 10 kcal/d vs 343 +/- 10 kcal/d), and less total calories at 12 months (884 +/- 24 kcal/d vs 1022 +/- 25 kcal/d) compared with the choice group. CONCLUSION: The early introduction of solid foods to an infant's diet does not alter growth or body composition during the first year of life and results in a displacement of energy intake from formula. Infants consuming commercially prepared foods have a decreased caloric intake from protein and fat; however, despite this difference, there is no effect on growth or body composition.

Age Factors↗

Vocal fundamental frequency measures as a reflection of tumor response to chemotherapy in patients with advanced laryngeal cancer.

The fundamental frequency (F0) characteristics of 19 male patients with advanced laryngeal cancer, treated with cisplatin-based chemotherapy as part of a Larynx Preservation Protocol (LPP), were measured before each of three cycles of chemotherapy received before definitive radiotherapy (RT). In these select patients, for whom chemotherapy resulted in > or = 50% decrease in the tumor bulk, it was found that mean F0 was essentially unaffected by the disease and did not change over the course of chemotherapy, although the cycle of their treatment could be differentiated by both speaking F0 variability (pitch sigma) and F0 perturbation (jitter). Although these measures failed to distinguish between those patients showing a complete response (CR) (no measurable disease) versus a partial (PR) (residual) tumor response at the primary disease site, the significant changes observed in both groups indicate that frequency variation measures could prove valuable in the documentation of tumor response to nonsurgical therapeutic intervention if the voice is directly affected. Additional assessment of 15 age- and disease-matched patients who showed minimal or no primary response to the chemotherapy showed no significant change in any of the frequency measures after one chemotherapy cycle, suggesting that vocal improvement seen in the successful chemotherapy patients was not due to postbiopsy healing or other systemic influence unassociated with tumor reduction.

Carcinoma, Squamous Cell↗

Expression of vascular endothelial growth factor in synovial fibroblasts is induced by hypoxia and interleukin 1beta.

OBJECTIVE: To study the mechanism by which hypoxia and inflammatory cytokines mediate angiogenesis in the rheumatoid pannus through their effects on the fibroblast-like type B synoviocyte, the major cell type of normal synovia. METHODS: Fibroblasts were prepared from synovial tissue of healthy and diseased individuals, and cultured in the presence of various stimuli. The expression of vascular endothelial growth factor (VEGF) was assessed by ELISA and reverse transcription polymerase chain reaction. RESULTS: Unlike normal fibroblasts, synovial fibroblasts from rheumatoid arthritis (RA) and osteoarthritis constitutively secreted significant levels of VEGF, which is known to act directly on endothelial cells. VEGF secretion was further inducible by both hypoxia and interleukin 1beta (IL-1beta) and these increases were additive. In contrast, tumor necrosis factor alpha was unable to induce VEGF expression. CONCLUSION: Under hypoxia or IL-1 stimulation, conditions common to the inflamed synovium, type B synoviocytes secrete increased levels of VEGF, which is likely to act on nearby endothelia, promoting angiogenesis. The constitutive expression of VEGF in rheumatoid synovial fibroblasts may reflect an altered phenotype involved in the pathology of RA.

Alternative Splicing↗

Production of biologically active human RelA (p65) in baculovirus-infected insect cells.

A recombinant baculovirus was constructed to express a cDNA encoding RelA (p65), a member of the NF-kappa B/Rel family of proteins. Infection of Spodoptera frugiderda insect cells with the recombinant baculovirus resulted in the production of the biologically active protein as measured by immunoblotting using RelA-specific antisera and by electrophoretic mobility shift assays. The recombinant protein bound specifically to an oligonucleotide containing the NF-kappa B consensus motif but not to that containing the unrelated Oct-1 consensus motif. Thus insect cell-derived RelA possess properties similar to the native protein and may be used in physical, biochemical, and pharmacological studies.

Animals↗

Evidence for multiple satellite cell populations and a non-myogenic cell type that is regulated differently in regenerating and growing skeletal muscle.

We have performed studies to determine if different populations of satellite cells provide nuclei to growing and regenerating skeletal muscle fibers. Satellite cells were isolated from regenerating or growing anterior tibialis muscles, and their phenotypic properties were compared in vitro. Isolates from regenerating muscle contained 31% satellite cells, and those from control muscle contained 66% satellite cells, as determined by their expression of desmin. Among the desmin-positive satellite cells present from each preparation, two distinct populations of satellite cells were evident. Approximately 28% of satellite cell colonies were composed of only large cells, contained less than 50 cells/colony, and were designated as type 1 colonies. The remainder of satellite cell colonies isolated from either regenerating or control muscles were primarily composed of small cells, contained from 60 to 150 cells/colony, and were designated as type 2 colonies. Despite dramatic differences in the ratio of myogenic to non-myogenic cell types, satellite cells from regenerating and control muscles formed myotubes and expressed myosin heavy chain at similar levels. Treatment of regenerating cultures with dexamethasone resulted in a 16% increase in the number of desmin-positive colonies and dramatically decreased the proliferation of non-myogenic cells. These results suggest that at least two distinct populations of satellite cells can be isolated from regenerating and control skeletal muscles, and that non-myogenic cells are differentially regulated in regenerating versus non-regenerating environments.

Animals↗

Changing epidemiology of triplet pregnancy: etiology and outcome over twelve years.

Neonates of 34 triplet pregnancies were admitted to our neonatal unit over a twelve-year period (1983 to 1995), with an incidence of 1 out of 812 deliveries. Thirty (88%) of the pregnancies were the result of ovulation induction and artificial fertilization: artificial insemination from husband (n = 3), in vitro fertilization (n = 9), and gamete intra-fallopian transfer (n = 6). All except one had antenatal sonographic diagnosis, 79% in the first trimester. The most common pregnancy-related complication was preterm labor (56%). Twenty-seven (79%) were delivered by cesarean section. There were 101 live births (one stillborn). Mean gestation age was 33.6 +/- 2.94 weeks, mean birthweight 1809 +/- 485 g, with 7 extremely low birthweight (< 1000 g [6.8%]). Neonatal complications included respiratory distress syndrome (12%), intraventricular hemorrhage (8.8%), retinopathy of prematurity (8%), sepsis (3%), severe asphyxia (3%), and omphalopagus conjoined twins (1%). The perinatal and neonatal mortality was 49 per 1000 and 59 per 1000, respectively. The introduction of advanced artificial fertilization techniques and ovulation induction agents resulted in a major increase in multifetal gestations. Early prenatal diagnosis, judicious prolongation of gestation, and planned delivery by cesarean section combined with major improvement in neonatal care by experienced neonatologists has improved survival of triplet neonates.

Adult↗