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Biomedical subjects

H M Chang

Publications and source records attributed to H M Chang.

At least 19 recordsLinked to original sources

Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B.

SH3P12/CAP/ponsin, a gene product with a sorbin homology domain and three consecutive SH3 domains in the carboxy-terminus, has been isolated from murine adipocytes and identified as an important adaptor during insulin signaling. Here we describe the cloning, mapping, and expression of the human homologue, termed SORBS1 (sorbin and SH3 domain containing 1). Multiple transcripts of this gene with different mRNA isoforms were observed among different tissues. Here we report 13 alternatively spliced exons, which were ascertained from the full-length cDNA cloned in adipose, liver, and skeletal muscle tissues. Among the major isoforms, the shortest, 2223-bp, open reading frame (ORF) encodes a protein with a predicted molecular weight of 81.5 kDa, while the longest, 3879-bp, ORF encodes a protein of about 142.2 kDa. This gene was mapped to human chromosome 10q23.3-q24.1, which is a candidate region for insulin resistance found in Pima Indians. In human hepatoma Hep3B cells, SORBS1 was partly dissociated from the insulin receptor complex and bound to c-Abl protein upon insulin stimulation. This interaction with c-Abl was through the third SH3 domain and a possible conformational change of SORBS1 induced by insulin. Our data suggest that c-Abl oncoprotein via SORBS1 might play a role in the insulin signaling pathway.

Amino Acid Sequence↗

Quantification of L-ascorbic acid and total ascorbic acid in fruits and spinach by capillary zone electrophoresis.

A standard curve for the quantification of L-ascorbic acid (L-AA) by capillary zone electrophoresis (CZE) was established, and the quantification of ascorbic acid and total ascorbic acid in fruits (lemon, Sunkist, and pineapple) and spinach were performed using D-isoascorbic acid (D-IAA) as an internal standard. The minimum detection limits (MDLs) for L-AA and D-IAA were determined to be 1 and 2 microg/mL, respectively, at 265 nm. Dehydroascorbic acid (DHAA) in fruits and spinach was quantified in the presence of DL-homocysteine. The recoveries for L-AA in these juices were between 95 and 105%.

Ascorbic Acid↗

Correlation of the apparent diffusion coefficient and the creatine level in early ischemic stroke: a comparison of different patterns by magnetic resonance.

It has been reported that reduction of the apparent diffusion coefficient (ADC) after stroke can persist for several days, after which the ADC increases gradually to an abnormally high level. We evaluated ADC values of stroke lesions and compared the results to the cellular density of the lesion by means of the creatine (Cre) level. This two-parameter estimation is of particular relevance in ascertaining the underlying cellular status. Lesion-to-contralateral ADC ratios (ADCn) were obtained based on diffusion-weighted echo-planar and fast spin-echo imaging. Single-voxel localized spectroscopy was used for quantification of cerebral metabolites in infarcted regions. Their levels were also compared to that in homotopic contralateral regions. Fifteen patients with ischemic stroke were examined at times ranging from 18-88 hours following the onset of symptoms. In the stroke lesion, there was a significant correlation between the ADC and the Cre level showing that the higher the cell density the lower the ADC value. For ADCn vs. the lesion Cre concentration and the lesion-to-contralateral Cre ratio (Cre(n)), the strengths of relationship were R2 = 0.70 and 0.58, respectively. It is concluded that ADC is a good reflection of cell density. Greatly lowered ADC values occur within the context of a stable cellularity. ADC and the Cre level have complementary roles in the characterization of stroke lesion with regard to the sequential stage.

Adult↗

Allogeneic bone marrow transplantation for chronic myeloid leukemia: a retrospective study of busulfan-cytoxan versus total body irradiation-cytoxan as preparative regimen in Koreans.

From January 1990 to December 1997, 53 Korean patients with chronic myeloid leukemia (CML) receiving bone marrow transplantation (BMT) from human leucocyte antigen (HLA)-identical sibling donors conditioned with either busulfan and cyclophosphamide (BU/CY regimen) or total body irradiation and cyclophosphamide (TBI/CY regimen) were compared retrospectively. Transplantation-related mortality was 19% in BU/CY and 12% in TBI/CY, and early death (<100 d) occurred in 3 patients conditioned with BU/CY. Grade II-IV acute graft-versus-host disease (GVHD) was 9% of BU/CY and 52% of TBI/CY patients. Overall incidence of chronic GVHD was 50% of BU/CY and 52% of TBI/CY patients. In patients with chronic phase, 5-yr overall survival was 73% in the BU/CY group compared with 87% in the TBI/CY group (p=NS), and overall disease-free survival was 75% in the BU/CY group and 59% in the TBI/CY group (p=NS). So far, with a median follow-up of 45 months, 11 patients have relapsed; three relapses occurred after BU/CY and 8 after TBI/CY. The actuarial 5-yr relapse rate was 15% after BU/CY, 34% after TBI/CY (p=0.46). For patients transplanted in chronic phase within 1 yr after diagnosis, there was a clear trend for a lower relapse rate in the BU/CY group (5-yr relapse rate 0%) compared with the TBI/CY group (5-yr relapse rate 30%). The BU/CY group had similar BMT-related toxicity and similar overall survival and showed a clear trend of low relapse compared with the TBI/CY group. Therefore, BU/CY is an acceptable alternative for patients with CML during HLA-identical sibling allogeneic BMT.

Adult↗

Spontaneous acute tumor lysis syndrome with advanced gastric cancer.

Acute tumor lysis syndrome (TLS) occurs frequently in hematologic malignancies such as high-grade lymphomas and acute leukemia, which are rapidly proliferating and chemosensitive tumors. It occurs rarely in solid tumors and has never been reported in gastric adenocarcinoma. Typical biochemical findings of acute tumor lysis syndrome are hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia in patients with a malignancy. Rapid changes of these electrolytes may cause cardiac arrhythmia, seizure, acute renal failure and sudden death. Therefore, as soon as it is detected, it should be taken care of immediately. Until now almost all cases of TLS associated with solid tumor have developed after cytoreductive therapy in chemosensitive tumors. We report here a case of spontaneous acute tumor lysis in a patient of advanced gastric cancer with hepatic metastases and multiple lymphadenopathy. The biochemical finding of TLS improved with the management and tumor burden also showed slight response to the one cycled combination chemotherapy but the patient died of progressive pneumonia.

Acute Disease↗

Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.

BACKGROUND: This randomized controlled trial was to determine whether a combination chemotherapy regimen that contains anthracycline (doxorubicin and cyclophosphamide [AC]) is superior to the conventional cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] combination in premenopausal women with axillary lymph node positive Stage II breast carcinoma. METHODS: Premenopausal women with lymph node positive breast carcinoma were stratified according to age (younger than 35 or 35 years or older) and the number of positive axillary lymph nodes (1-3, 4-9, or >/= 10) and then randomly assigned to receive either doxorubicin 40 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenously (i.v.) every 3 weeks or cyclophosphamide 100 mg/m(2) orally on Days 1 through 14, methotrexate 40 mg/m(2) and 5-fluorouracil 500 mg/m(2) i.v. on Days 1 and 8 every 4 weeks. Both arms were scheduled for six cycles. RESULTS: The median follow-up was 57 months. Eighteen of the 55 AC patients developed recurrence compared with 16 of the 69 CMF patients. The corresponding 5-year recurrence free survival rates were 64% and 78%, respectively (P = 0.12). The site of the first recurrence for AC patients was locoregional in 7%, distant in 22%, and combined in 4%. The corresponding data for the CMF arm were 4%, 16%, and 3%, respectively. Six AC patients died compared with 9 CMF patients. The corresponding 5-year survival rates were 90% and 86%, respectively (P = 0.96). More leukopenia (52%, mostly Grade 1-2) occurred in the CMF arm than in the AC arm (33%, P = 0.001), but no febrile episode was accompanied with leukopenia. CONCLUSIONS: This study showed no difference between AC and CMF with respect to both disease free and overall survival rates in premenopausal women with axillary lymph node positive breast carcinoma.

Adult↗

Melatonin attenuates neuronal NADPH-d/NOS expression in the hypoglossal nucleus of adult rats following peripheral nerve injury.

Oxidative stress and massive production of nitric oxide (NO) have been implicated in the neuropathogenesis following peripheral nerve injury. This study was aimed to ascertain whether melatonin would exert its neuroprotective effect on the lesioned hypoglossal neurons after peripheral axotomy, since it is known to reduce the oxidative damage in a variety of experimental neuropathologies in which NO is involved. Right-sided hypoglossal nerve transection was performed in adult rats following which the animals were given two different doses of melatonin administered intraperitoneally for 3, 7, 14, 21 and 30 successive days. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and neuronal nitric oxide synthase (nNOS) immunohistochemistry were carried out to detect the neuronal NADPH-d/NOS expression in the hypoglossal nucleus (HN). At various time intervals following axotomy, the neurons in the affected HN were induced to express NADPH-d/NOS reactivity on the lesioned side peaking at 14 days. However, the enzyme expression was markedly depressed by melatonin treatment in a dose-dependent manner in terms of frequency of labelled neurons and staining intensity. It is suggested that the suppressive effect of melatonin on NADPH-d/NOS expression may be attributed to its antioxidant properties. Hence, in consideration of therapeutic strategies for reducing the oxidative stress following peripheral nerve injury, melatonin may prove to be beneficial.

Animals↗

Rapid separation of lysozyme from chicken egg white by reductants and thermal treatment.

Reductants (0.1-2.0% ascorbic acid, cysteine, or cystine and 0.04-1. 0% beta-mercaptoethanol) were added to 5-fold diluted, salted duck egg whites (commercially and laboratory prepared) and fresh egg whites (chicken and duck), and subsequently the mixtures were heated at 70 degrees C for 1-10 min. The maximal recovery and purification fold of lysozyme obtained from fresh chicken egg whites added with 1. 0% ascorbic acid were 78% and 2.4, respectively. Storage tests showed that the obtained lyophilized lysozyme powder after dialysis was stable when refrigerated at 4 degrees C for 3 months.

Animals↗

Epimeric separation of L-ascorbic acid and D-isoascorbic acid by capillary zone electrophoresis.

Capillary zone electrophoresis (CZE) was used for separation of L-ascorbic acid (L-AA) and D-isoascorbic acid (D-IAA) in a model system. The effects of borate buffer concentration (0.05-0.25 M) and pH (pH 7.5-9.0) on migration time, resolution (Rs), and theoretical plates (N) were investigated. The migration times of L-AA and D-IAA increased with the increasing pH of carrier electrolyte (0.2 borate buffer), and the resolutions (Rs) of L-AA and D-IAA were calculated to be 12.98 at pH 9.0. Concentrations of borate buffer (pH 9.0) increased the Rs values of L-AA and D-IAA, and buffer concentrations >0.1 M were found to be effective for separation of L-AA and D-IAA. Methanol in the carrier electrolyte was also influential in improving the separation of L-AA and D-IAA, which increased with the increasing concentrations (0-10%) of methanol. The optimal separation conditions for L-AA and D-IAA were as follows: carrier electrolyte, 0.2 M borate buffer (pH 9.0); applied voltage, 25 kV, with an uncoated fused silica capillary, 75 microm (i.d.) x 57 cm.

Ascorbic Acid↗

Isolation of immunoglobulin from egg yolk by anionic polysaccharides.

Isolation conditions of immunoglobulin in egg yolk (IgY) were optimized by the addition of various levels of Na-alginate (Alg), lambda-carrageenan (lambda-Cg), Na-carboxymethyl cellulose (CMC), and pectin (PC) to 6-fold diluted yolk. The mixtures were then reacted at pH 4.0-6.0 for 30 min. The optimal isolation conditions of IgY for Alg, lambda-Cg, and CMC were at the 0.1% level and at pH 5.0, while those for PC were at the 0.15% level and at the same pH. The remaining lipid and remaining protein in the supernatants thus obtained was 0.5-3.8% and 10-17%, respectively, and more than 90% of lipoproteins were precipitated. The IgY recovery was determined to be 33-74% by means of single radial immunodiffusion method when IgY was isolated under the optimal conditions. PC showed the best recovery of IgY, while lambda-Cg provided the least. The interactions between polysaccharides and lipoproteins were mainly ionic bonds, hydrophobic interactions, and hydrogen bonds as determined by the addition (0-2.0 M) of NaSCN or urea to the polysaccharide-lipoprotein precipitates.

Alginates↗

Ultrastructural localisation of NADPH-d/nNOS expression in the superior cervical ganglion of the hamster.

This study examined NADPH-d and nNOS expression in the SCG of hamsters. By light microscopy, numerous NADPH-d/NOS positive processes were widely distributed in the ganglion. Ultrastructurally, the NADPH-d reaction product was associated with the membranous organelles of neuronal soma, dendrites, myelinated fibres, small granular cells, and axon profiles bearing agranular vesicles. The NOS immunoreaction product, on the other hand, was localised in the cytoplasm of principal neurons and dendrites. Some of the NADPH-d/NOS labelled processes formed junctional contacts including synapses or zonulae adherentia. Compared with the neurons, the nonneuronal cells in the ganglion, namely, macrophages, satellite cells and endothelial cells were labelled by NADPH-d but devoid of nNOS immunoreaction product. The results suggest that the NADPH-d/NOS positive fibres in the SCG originate not only from the projecting fibres of the lateral horns of thoracic spinal cord, but also from the principal neurons and small granular cells; some may represent visceral afferent fibres. Electron microscopic morphometry has shown that about 67% of the principal neurons contain NADPH-d reaction product, and that the majority were small to medium sized neurons based on cross-sectional areas in image analysis. On the basis of the present morphological study, it is concluded NO is produced by some local neurons and possibly some nonneuronal cells in the SCG as well as some fibres of extrinsic origin. In this connection, NO may serve either as a neurotransmitter or neuromodulator.

Animals↗

Striatocapsular haemorrhage.

Haemorrhages in the striatocapsular area, or striatocapsular haemorrhages (SCHs), have been regarded as a single entity, although the area is composed of several functionally discrete structures that receive blood supply from different arteries. We analysed the morphological and clinical presentations of 215 cases of SCHs according to a new classification method we have designed on the basis of arterial territories. SCHs were divided into six types: (i) anterior type (Heubner's artery); (ii) middle type (medial lenticulostriate artery); (iii) posteromedial type (anterior choroidal artery); (iv) posterolateral type (posteromedial branches of lateral lenticulostriate artery); (v) lateral type (most lateral branches of lateral lenticulostriate artery); and (vi) massive type. The anterior type (11%) formed small caudate haematomas, always ruptured into the lateral ventricle, causing severe headache, and mild contralateral hemiparesis developed occasionally. The outcome was excellent. The middle type (7%) involved the globus pallidus and medial putamen, frequently causing contralateral hemiparesis and transient conjugate eye deviation to the lesion side. About 50% of the patients recovered to normal. The posteromedial type (4%) formed very small haematomas in the posterior limb of the internal capsule and presented with mild dysarthria, contralateral hemiparesis and sensory deficit, with excellent outcome in general. The posterolateral type (33%) affected the posterior half of the putamen and posterior limb of the internal capsule and presented with impaired consciousness and contralateral hemiparesis with either language dysfunction or contralateral neglect. The outcome was fair to poor but there were no deaths. The lateral type (21%) formed large elliptical haematomas between the putamen and insular cortex. Contralateral hemiparesis with language dysfunction or contralateral neglect developed frequently but resolved over several weeks. The clinical outcome was relatively excellent except when the haematoma size was very large. The massive type (24%) formed huge haematomas affecting the entire striatocapsular area. Marked sensorimotor deficits and impaired consciousness, ocular movement dysfunctions including the 'wrong-way' eyes were observed quite frequently. The outcome was very poor with a case fatality rate of 81%. The clinico-radiological presentations suggested its origin was the same as the posterolateral type.

Adult↗

Spinocerebellar ataxia in Singapore: predictive features of a positive DNA test?

Significant differences in frequency of the different spinocerebellar ataxia (SCA) subtypes have been described to occur in different populations. A 'blunderbuss' diagnostic DNA testing approach would entail unnecessary healthcare cost. In this study, we determine the prevalence of SCA subtypes and predictive features of a positive DNA test in consecutive clinically diagnosed SCA cases in Singapore. Twenty-one consecutive patients from 14 families were evaluated over a 3-year period. Thirteen patients (61.9%) from 6 families had a positive DNA test. Eleven of these (all ethnic Chinese) had SCA 3 (abnormal CAG size ranged from 61 to 71), and 2 ethnic Malays had SCA 2 (abnormal CAG size of 39). Clinical features which were highly predictive of a positive DNA SCA test in our population included presence of a positive family history, chorea and dystonia, muscle and tongue fasciculations, gaze-evoked nystagmus, and hypertonia. Our study draws attention to the observation that knowledge of relatively specific features of the most common SCA subtype in a local population can greatly enhance the practical accuracy of the choice of which SCA DNA test to order.

Adult↗

Multiple connexin expression in regenerating arterial endothelial gap junctions.

Endothelial cells form gap junctions that, according to vessel type, may be composed of up to 3 types of connexin, connexin37, connexin40, and connexin43. Although changes in connexin expression have been linked to growth and injury in cultured endothelial cells, information on connexin expression in regenerating endothelium in situ is lacking. We investigated gap junction distribution and expression of all 3 endothelial connexins during healing in rat carotid artery after denudation injury. En face viewing of the vascular luminal surface by means of immunoconfocal microscopy was used to examine the spatial and temporal expression pattern of the endothelial connexins. Gap junction spots labeled by specific antisera against connexin37, connexin40, and connexin43 were quantified 7, 14, and 28 days after injury, and the relations among the connexins were examined by using colocalization analysis. Complementary electron microscopy was also conducted. After injury, the regenerating endothelium initially expressed small, sparse gap junctions, the numbers of which progressively increased to values equivalent to those of controls. Although connexin40 gap-junctional spot size and area returned to uninjured levels by 28 days after injury, connexin37 and connexin43 spot size and area exceeded those of the uninjured artery (P<0.05). Double-label analysis showed that even though colocalization of connexins to the same gap-junctional spot is a common feature, the extent of colocalization was time dependent (>80% in the intact artery at postinjury day 28 and <70% at postinjury days 7 and 14, P<0.01). We conclude that distinct alterations in expression of the 3 connexins are associated with regeneration of the arterial endothelium in situ, implying different intercellular communication requirements during the various phases of the healing process.

Animals↗

Age-related alteration of gap junction distribution and connexin expression in rat aortic endothelium.

We investigated endothelial gap junctions and their three component connexins, connexin37 (Cx37), Cx40, and Cx43, during growth and senescence in rat aorta by en face immunoconfocal microscopy and electron microscopy. Gap junction spots labeled by specific antisera against Cx37, Cx40, and Cx43 were quantified at 1 day, 7 days, 28 days, 16 months, and > or =20 months of age, and the relationship between the connexins was examined by co-localization analysis. At birth, all three connexins were abundantly expressed; the number and total area of connexin spots then declined within 1 week (p<0.05 for each connexin). From 1 week, each connexin showed a distinct temporal expression pattern. Whereas Cx43 signal decreased progressively, Cx37 signal fluctuated in a downward trend. By contrast, Cx40 maintained an abundant level until > or =20 months of age (> or =20 months vs. 28 days, p<0.05 for number and total connexin signal area). These patterns were associated with changes in endothelial cell morphology. Double-label analysis showed that the extent of co-localization of connexins to the same gap junctional spot was age-dependent [>70% at birth and 28 days old; <70% at later stages (p<0.05)]. We conclude that expression of the three connexins in aortic endothelium is age-related, implying specific intercellular communication requirements during different stages after birth.

Aging↗

The effect of breast- and bottle-feeding on oxygen saturation and body temperature in preterm infants.

From July 1997 to June 1998, 25 preterm infants (birth weight < 1800 g) were included in a prospective study to compare the clinical effects of breast- and bottle-feeding. Oxygen saturation, heart rate, respiratory rate, and body temperature were recorded every minute for 20 minutes during feeding periods. Eighty pairs of breast- and bottle-feeding sessions were observed at the chronological age of 9.3 +/- 4.3 (range = 2.1-25.3) weeks. Oxygen saturation and body temperature of the preterm infants were significantly higher when they were directly breastfed. There were 2 episodes of apnea (breath pause more than 20 seconds) and 20 episodes of oxygen desaturation (PaO2 < 90%) during bottle-feeding and none during breastfeeding. We conclude that breastfeeding is a more physiological feeding method for the preterm infant and bottle-feeding may be more stressful.

Apnea↗

Bilateral intracranial vertebral artery disease in the New England Medical Center, Posterior Circulation Registry.

BACKGROUND: Previous studies of patients with bilateral intracranial vertebral artery (ICVA) disease were selective and retrospective. METHODS: We studied risk factors, vascular lesions, symptoms, signs, and outcomes in patients with bilateral ICVA disease among 430 patients in the New England Medical Center Posterior Circulation Registry. RESULTS: Forty-two patients had bilateral ICVA occlusive disease (18 had bilateral stenosis; 16, unilateral occlusion and contralateral stenosis; and 8, bilateral occlusion). The most common risk factors were hypertension (32/42 [76%]) and hyperlipidemia (22/42 [52%]). Sixteen patients (38%) had transient ischemic attacks (TIAs) only; 18 (43%), TIAs before stroke. Occlusive vascular disease also involved the basilar artery in 29 patients (69%), the extracranial vertebral arteries in 18 (43%), and the internal carotid arteries in 11 (26%). Only 6 patients had no other major vascular lesion. Cerebellar symptoms were common. Among 30 patients with infarction, 21 (70%) had proximal intracranial territory involvement, and 15 (50%) had distal territory involvement. The location of occlusive lesions in relation to posterior inferior cerebellar artery origins did not significantly influence prognosis. During follow-up, 31 patients had no symptoms or slight disability, 2 had progression, and 7 died. Among 7 patients with poor outcome, 6 also had basilar artery stenosis or occlusion and 5 had proximal and distal intracranial territory infarcts. CONCLUSIONS: Most patients with bilateral ICVA occlusive disease have hypertension, other major occlusive lesions, and TIAs before stroke. Short- and long-term outcomes are usually favorable, but patients with bilateral ICVA and basilar artery-occlusive lesions often have poor outcomes.

Academic Medical Centers↗