Biomedical subjects

L Chang

Publications and source records attributed to L Chang.

At least 253 records · Page 14Linked to original sources

PubMed1996

In vivo 1H MRS choline: correlation with in vitro chemistry/histology.

We correlated the in vivo 1H Magnetic Resonance Spectroscopy (MRS) concentration of the choline peak (CHO) with in vitro chemical measures of choline-containing compounds and a histological grade of cellularity in 18 patients with neoplastic and infectious brain lesions. Gas-chromatography-mass-spectrometry (GCMS) was used to measure the concentrations of free choline (Cho), glycerophosphocholine (GPCho), phosphocholine (PCho) and phosphatidylcholine (PtdCho) from biopsies in the same area where MRS was performed. Cellular density, free Cho, PCho and GPCho were the strongest determinants of 1H MRS CHO while PtdCho was not. Just as the 1H MRS 2.0 peak reflects both the concentration of n-acetyl-l-aspartate and neuronal density, the 1H MRS 3.2 peak reflects the concentration of water-soluble choline-containing compounds and cellular density.

Brain↗

PubMed1996

In vivo proton magnetic resonance spectroscopy of the normal aging human brain.

The effect of age on brain metabolite concentrations was evaluated using localized proton magnetic resonance spectroscopy. This technique allows in vivo measurements of N-acetyl compounds (NA), total creatine (CR), choline-containing compounds (CHO), myo-inositol (MI), glutamate and glutamine (GLX), as well as the percentage of cerebrospinal fluid (CSF) and the brain water content within the brain region studied. Frontal gray matter and frontal white matter brain regions were examined in 36 normal healthy volunteers (19-78 years of age). Using a rigorous absolute quantitation method, with an external reference and atrophy correction, we found relatively stable concentrations of NA, a neuronal marker. In contrast, CR, CHO, MI, and the percentage of CSF increased in the gray matter with age. However, the brain water content decreased significantly with age (r = -0.72; p < 0.0001). No significant age-related changes in metabolite concentrations, CSF or brain water content were observed in the white matter regions. These findings demonstrate that biochemical alterations are associated with aging in the frontal gray matter. There might be an increase in the brain density as indicated by increased metabolite concentrations and decreased brain water content with aging.

Adult↗

PubMed1996

Psychobiologic effects of 3,4-methylenedioxymethamphetamine in humans: methodological considerations and preliminary observations.

3,4-Methylenedioxymethamphetamine (MDMA) is a phenethylamine with potent effects on serotonergic neurotransmission which has been the object of controversy over its potential as a therapeutic adjunct versus its possible risks for causing neurotoxic injury. This paper discusses the background, methodology and preliminary findings of the first FDA approved Phase I study prospectively evaluating the effects of MDMA administration in humans. Six subjects with prior experience with MDMA were administered two different dosages of MDMA and an inactive placebo utilizing a randomized, double-blind methodologic design. Dosages from 0.25 to 1.0 mg/kg, p.o., were administered. All subjects tolerated the procedures without any overt evidence of physical discomfort or psychological distress. MDMA produced a modest increase in heart rate and blood pressure. The threshold dose for the stimulation of ACTH and prolactin appeared to be between 0.5 and 0.75 mg/kg, with the two higher doses clearly stimulating both ACTH and prolactin. Methodology for assessing MDMA's effects on serotonergic neurotransmission is discussed.

Adult↗

PubMed1996

Modification of tyrosine-3 (63) and lysine-6 of Taiwan cobra phospholipase A2 affects its ability to enhance 8-anilinonaphthalene-1-sulfonate fluorescence.

The Tyr-3 (63) and Lys-6 of Naja naja atra phospholipase A2 (PLA2) were modified with p-nitrobenzenesulfonyl fluoride and 4-chloro-3,5-dinitrobenzoate, respectively. Although the ability of the Lys-modified derivative to enhance the ANS fluorescence was lower than that observed with native PLA2, the ANS-binding affinity of the Lys-modified derivative was similar to that of the native enzyme. Modifications on Tyr-3 or/and Tyr-63 of PLA2 resulted in the complete loss of its ability to enhance the ANS fluorescence. Nevertheless, the extent of O-sulfonylation of Tyr residues was not effectively reduced by the addition of ANS. This suggests that Tyr-3 and Tyr-63 interact with the bound ANS in an aromatic ring-stacking manner. Alternatively, the incorporation of a carboxydinitrophenylated group on Lys-6 may notably perturb the nonpolarity of the ANS-binding site.

Anilino Naphthalenesulfonates↗

PubMed1996

Neuroimaging findings in patients with AIDS.

An increasing number of patients are presenting with central nervous system complications of human immunodeficiency virus infection. New imaging technologies such as magnetic resonance imaging, magnetic resonance proton spectroscopy, single-photon emission computed tomography, and positron emission tomography are playing an ever-increasing role in the diagnosis of these complications. As therapeutic modes improve, imaging may assume a growing role in monitoring the responses to therapy among these patients.

AIDS Dementia Complex↗

PubMed1996

Neural basis of confabulation.

We present a case of acute alcohol-induced Korsakoff amnesia. A severe amnestic-confabulatory syndrome characterized the early clinical status. The initial neuropsychological tests demonstrated severe learning deficits plus impaired performance on many, but not all, tests of frontal lobe function. Single-photon emission CT (SPECT) at this stage showed hypoperfusion in the orbital and medical frontal regions and the medial diencephalic area. Four months later, the patient's amnesia remained but there was no confabulation. Repeat neuropsychological tests confirmed an ongoing severe amnesia, but performance on the frontal lobe tests now was normal. Repeat SPECT showed a return to normal perfusion in the frontal brain areas but little improvement in the medial diencephalic region. These findings along with data from the clinical literature suggest that confabulation results from dysfunction of orbital and a medial frontal cortex.

Adult↗

PubMed1996

Evidence for heterogeneous etiologies of adrenal dysfunction in polycystic ovary syndrome.

OBJECTIVE: To examine the hypothesis that, in polycystic ovary syndrome (PCOS), ovarian steroids induce adrenal enzyme dysfunction or adrenal androgen hyperresponsiveness to ACTH. DESIGN: Prospective controlled clinical study. SETTING: Reproductive endocrinology unit of an academic medical center. PATIENTS: Twelve women with PCOS who had adrenal androgen excess were compared with five weight-matched ovulatory women. In half of the women with PCOS, prestudy screening was suggestive of mild 3 beta-hydroxysteroid dehydrogenase (HSD) deficiency. INTERVENTIONS: Basal and adrenal dynamic blood sampling before and after GnRH agonist (GnRH-a) administration for 6 months. MAIN OUTCOME MEASURES: Basal E2 and androgen levels as well as dexamethasone-suppressed, ACTH-stimulated 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone, and androgen levels before and after ovarian suppression. RESULTS: Although none of the subjects with PCOS proved to have mild 3 beta-HSD deficiency, the majority of them (58%) met the criteria for 17,20 lyase hyperactivity before and after GnRH-a therapy. As a group, the remaining subjects with PCOS exhibited an elevated DHEAS response to ACTH before GnRH-a treatment, which may have normalized after GnRH-a treatment. CONCLUSION: Adrenal androgen excess in PCOS may be heterogeneous in etiology, whereas 17,20 lyase hyperactivity appears to be an intrinsic adrenal disorder, adrenal androgen hyperresponsiveness to ACTH may be ovarian induced. Reliance on historical controls may lead to overdiagnosis of mild 3 beta-HSD deficiency.

17-alpha-Hydroxypregnenolone↗

PubMed1996

Fulminant cerebral lymphoma in AIDS.

Three cases of cerebral lymphoma in patients with acquired immunodeficiency syndrome is presented. They are remarkable for their extremely rapid progression, which simulated an infectious processes during trials of antitoxoplasma therapy. Fourteen days of therapy are generally required to assess a negative response. However, earlier biopsies and shorter therapeutic trials may be indicated in these patients.

AIDS-Related Opportunistic Infections↗

PubMed1996

Admission factors can predict the need for ICU monitoring in gallstone pancreatitis.

The purpose was 1) to prospectively determine the prevalence of adverse events necessitating intensive care unit (ICU) monitoring in gallstone pancreatitis (GP) and 2) To identify admission prognostic indicators that predict the need for ICU unit monitoring. Prospective laboratory data, physiologic parameters, and APACHE II scores were gathered on 102 patients with GP over 14 months. Adverse events were defined as cardiac, respiratory, or renal failure, gastrointestinal bleeding, stroke, sepsis, and necrotizing pancreatitis. Patients were divided into Group 1 (no adverse events, n=95) and Group 2 (adverse events, n=7). There were no deaths and 7 (7%) adverse events, including necrotizing pancreatitis (3), cholangitis (2), and cardiac (2). APACHE 11 > or = 5 (P < 0.005), blood urea nitrogen (BUN) > or = 12 mmol/L (P < 0.005), white blood cell count (WBC) > or = 14.5 x 10(9)/L, (P < 0.001), heart rate > or = 100 bpm (P < 0.001), and glucose > or = 150 mg/dL (P < 0.005) were each independent predictors of adverse events. The sensitivity and specificity of these criteria for predicting severe complications requiring ICU care varied from 71 to 86 per cent and 78 to 87 per cent, respectively. The prevalence of adverse events necessitating ICU care in GP patients is low. Glucose, BUN, WBC, heart rate, and APACHE II scores are independent predictors of adverse events necessitating ICU care. Single criteria predicting the need for ICU care on admission are readily available on admission.

Adolescent↗

PubMed1996

Cationic lipids reduce time and dose of c-myc antisense oligodeoxynucleotides required to specifically inhibit Burkitt's lymphoma cell growth.

Burkitt's lymphoma is characterized by a translocation of the c-myc gene with one of the immunoglobulin loci which activates overexpression of the c-myc oncogene. Antisense-oligodeoxynucleotides (AS-ODNs) offer the potential to block specific c-myc gene expression within lymphoma cells, but often exhibit a low efficiency of AS-ODN uptake. In this study, a polycationic lipid reagent, Lipofectamine (LFM), was utilized as a vehicle to increase efficiency of delivery, decrease the time needed to observe an inhibitory effect, and decrease the AS-ODN dose. The objective was to develop a more efficient and rapid in vitro AS-ODN strategy to inhibit proliferation of c-myc-dependent lymphoma cells and to test the specificity of Burkitt's lymphoma cell line-directed AS-ODNs for potential use as molecular purging agents in bone marrow transplantation. Proliferation assays were performed to determine the inhibitory effect of the AS-ODNs on two Burkitt's lymphoma cell lines with different chromosomal translocations, Daudi and ST486, in medium containing 8.5 microM LFM. AS-ODNs at a concentration of 0.36 microM induced a significant decrease in proliferation for both cell lines using the specific AS-ODN for each respective translocation. Within 5 h, Daudi responded to its specific AS-ODN/lipid complexes with a 35% decrease in proliferation, compared to cells which received no treatment or Daudi-specific AS-ODN without LFM (P = 0.0001). Daudi showed an insignificant decrease in proliferation when treated with an AS-ODN specific for the ST486 translocation (4%, P = 0.26). ST486 proliferation was decreased by 52% when treated with the specific antisense for ST486 compared to no treatment or ST486-specific AS-ODN without LFM (P < 0.003). Treatment with the AS-ODN specific for Daudi showed an insignificant 4% decrease (P = 0.42). Controls, including sense ODN for structure, reverse AS-ODN for structure and base composition, and AS-ODN without LFM, did not produce a significant change in cells treated with LFM alone or cells receiving no treatment. Clonogenic assays of both Daudi and ST486 treated with their specific AS-ODNs revealed a 50% inhibition of colony formation after the 5 h incubation as compared to no treatment. Confocal laser scanning microscopy verified that cellular uptake of AS-ODN was enhanced by cationic lipids. Immunoblot analysis showed a 63 +/- 5% and a 50 +/- 3% reduction in intracellular c-myc levels for Daudi and ST486, respectively, when their respective AS-ODNs were administered. Normal bone marrow progenitors were unaffected by the ODN/LFM complexes. These results suggest that the specific c-myc AS-ODN/LFM complexes inhibit c-myc-dependent tumor proliferation at an earlier time and at a lower dose compared to no lipid facilitation. This approach may form the basis for utilizing specific AS-ODN/LFM therapy either alone or in a cocktail of other agents as an ex vivo molecular purging approach to autologous stem cell transplantation in Burkitt's lymphoma.

Adult↗

PubMed1995

Ipomeanol analogs as chemopreventive agents: effect on the in vitro metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific, powerful, organospecific lung carcinogen. 4-Ipomeanol (IPO) is an investigational chemotherapeutic drug with specific toxicity towards the lung. We hypothesized that non-toxic analogs of IPO could be competitive inhibitors of the metabolic activation of NNK. We had shown previously that 4-hydroxy-1-phenyl-1-pentanone (HPP) and 7-hydroxy-1-phenyl-1-octanone (4-HPO) are effectively inhibiting the lung tumor activity of NNK in A/J mice. In these extended studies we have synthesized 11 new analogs of HPP and tested them for their in vitro activities as inhibitors of the metabolism of NNK. The present study demonstrated that the lipophilicity in the molecule is playing an important role for the inhibition of NNK metabolism with pulmonary and hepatic microsomes of A/J mice.

Animals↗

PubMed1995

T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years.

In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.

Adenosine Deaminase↗

PubMed1995

Sulfated oligosaccharides promote hepatocyte growth factor association and govern its mitogenic activity.

Hepatocyte growth factor (HGF) is a potent mitogen, motogen, and morphogen for various epithelial cell types. The pleiotropic effects of HGF are mediated by its binding to a specific high affinity receptor, c-Met. In addition, HGF binds to heparan sulfate proteoglycans on cell surfaces and within the extracellular matrix. Incubation of HGF with 0.1, 1.0, and 10 micrograms/ml of heparin, heparan sulfate, or dextran sulfate resulted in a concentration-dependent increase in mitogenic potency in a primary rat hepatocyte bioassay, whereas sodium sulfate or fucoidan did not. Although co-incubation of HGF with sulfated compounds that enhanced HGF-dependent mitogenesis did not alter the binding isotherm of HGF for the c-Met receptor in a solid phase assay, an increase in autophosphorylation of the c-Met receptor in intact A549 cells was observed upon their addition. A series of chemically sulfated malto-oligosaccharides varying in unit size and charge was tested in the bioassay in order to provide additional insights into the nature of the HGF-heparin interaction. While sulfated di-, tri-, tetra-, and pentasaccharides did not significantly potentiate HGF-dependent mitogenesis, larger oligosaccharides such as the sulfated hexa-, hepta-, or a sulfated oligosaccharide mixture containing decasaccharides resulted in an approximate 2-, 4-, and 7-fold enhancement, respectively. We observed a correlation between the sulfated oligosaccharide preparations that enhanced mitogenic potency and those that promoted HGF oligomerization in vitro, as measured by gel filtration and analytical ultracentrifugation. These findings indicate that heparin-like molecules can stabilize HGF oligomers, which may facilitate c-Met receptor dimerization and activation.

Animals↗

PubMed1995

Binding of thyroxine to pig transthyretin, its cDNA structure, and other properties.

Thyroxine binding to proteins in pig plasma during electrophoresis was observed in the albumin, but not in the prealbumin and post-albumin regions. Transthyretin could be identified in medium from in vitro pig choroid plexus incubations by size and number of subunits and a very high rate of synthesis and secretion. Its electrophoretic mobility was intermediate between that of thyroxine-binding globulin and albumin. It bound thyroxine, retinol-binding protein, anti-(rat transthyretin) antibodies and behaved similarly to transthyretins from other vertebrate species when plasma was extracted with phenol. Inhibition experiments with the synthetic flavonoid F 21388, analysing the binding of thyroxine, suggested that transthyretin is not a major thyroxine carrier in the bloodstream of pigs. Cloning and sequencing of transthyretin cDNA from both choroid plexus and liver showed that the same transthyretin mRNA is expressed in pig choroid plexus and liver. The amino acid sequence derived from the nucleotide sequence revealed that pig transthyretin differs from the transthyretins of all other studied vertebrate species by an unusual C-terminal extension consisting of the amino acids glycine, alanine and leucine. This extension results from the mutation of a stop codon into a codon for glycine. The unusual C-terminal extensions do not seem to interfere with the access of thyroxine to its binding site in the central channel of transthyretin.

Amino Acid Sequence↗

PubMed1995

Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease.

In this clinical study the cerebrospinal fluid (CSF) level of a novel form of the beta-amyloid peptide (A beta) extending to position 42 (A beta 42) was determined in patients with Alzheimer's disease (AD) as well as controls. In addition to measurement of CSF A beta 42 levels, total A beta peptides, microtubule-associated protein tau, and apolipoprotein E (ApoE) genotype were also assessed. It is interesting that CSF A beta 42 levels were found to be significantly lower in AD patients relative to controls, whereas total A beta levels were not. A beta 42 has recently been shown to preferentially deposit in the brain tissue of patients with AD, suggesting that diminished clearance may account for its reduction in CSF. As previously reported, tau levels were increased in AD patients; however, neither A beta 42 nor tau levels were apparently influenced by the ApoE genotype.

Aged↗

PubMed1995

The neuropathology of parkinsonism: an overview.

The neuropathology of parkinsonism is reviewed as it occurs in primary (idiopathic) and secondary extrapyramidal syndromes. Present understanding of the significance of Lewy bodies in Parkinson's disease, diffuse Lewy body disease, and Lewy body variant of Alzheimer's disease is emphasized. The neuropathology produced by a variety of secondary causes is also considered to demonstrate the diverse lesions that can result in parkinsonism.

Alzheimer Disease↗

PubMed1995

Conditions that may determine blood vessel phenotype in tissues grafted to brain.

The hypothesis, that a blood vessel's phenotype is determined by the tissue it vascularizes and not by the vessel's source, does not hold for tissue beyond a certain period of development. In mature skeletal muscle grafted to choroid plexus of adult and 2-week-old rats, some vessels were choroidal or fenestrated (FV) rather than, according to the hypothesis, continuous (CV), like those of muscle. In E14 fetal muscle placed on the choroid plexus, approximately 80% of the grafts' capillaries were CV, like those of muscle. Most choroidal FV that entered the grafts were apparently changed to CV. By E16, about 70% of the graft vessels remained as FV rather than being converted. Thus, FV were changed to CV by a hypothetical conversion factor made, apparently, by E14 grafts but not by E16 grafts. In grafts from [3H]thymidine-labeled donors, an appreciable number of CV in E14 grafts were identified as intrinsic to the muscle. When hosts were labeled to verify the origin of FV in their nonlabeled donor grafts, only a few FV, to date, were tagged. The FV must have come from host choroid plexus, the only available source of graft FV. Vascular endothelial growth factor (VEGF) might convert CV into FV, yet VEGF and the mRNA for its receptor were present in choroid plexus but not in the grafts. Therefore, VEGF is not a conversion factor. The purported factor that changes FV to CV may be expressed in E14 muscle grafts but diminishes by fetal age E16 and beyond.

Animals↗

PubMed1995

Penetration of solutes, viruses, and cells across the blood-brain barrier.

The aspects presented here of how solutes, viruses and cells are able to cross the BBB indicate that there must be an active interaction of endothelium with viruses and immune system cells before they can penetrate the brain and spinal cord. The axoplasmic pathway taken by lectin-solute conjugates is similar but not identical to that followed by viral particles during their retrograde or anterograde transit through the axoplasm. Both the conjugates and virus are transferred to other neurons transsynaptically but the receptor mediated transfer utilized by viruses is far more specific. Cranial nerves are involved in both the entry and egress of antigens into and out of the brain. Antigen, generated within the CNS, may be able to escape from the brain to lymphoid tissue by passing into the fluid around a cranial nerve, thence via the lymph into lymph nodes to initiate an immune response involving the CNS.

Animals↗