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Biomedical subjects

W Lo

Publications and source records attributed to W Lo.

At least 37 records · Page 2Linked to original sources

Accumulation of biodegradable copolyesters of 3-hydroxy-butyrate and 3-hydroxyvalerate in Alcaligenes eutrophus.

Biodegradable copolyesters of 3-hydroxybutyrate-co-3-hydroxyvalerate (3HB-3HV) were produced by Alcaligenes eutrophus in a two-staged process, namely growth stage and nitrogen-deficient polyester-accumulation stage. When C5 was used as the sole carbon source, the copolyester contained 43 mol % of 3HV. A range of copolyesters with 0-43 mol % of 3HV could be produced by using a medium containing different concentration ratios of butyric acid C4 and C5. Tm of PHB homopolymer was 177.6 degrees C and that of copolyester with highest 3HV mol fraction of 43% was 99.0 degrees C. C5 concentration in the medium could be an effective means to control the polymeric composition and mechanical properties of the copolyesters accumulated in A. eutrophus.

3-Hydroxybutyric Acid↗

Ionotropic glutamate receptors in the retina: moving from molecules to circuits.

The cloning of the glutamate-gated ion channels of the brain revealed an unexpected level of complexity: there are many different genes that encode distinct subunits of the receptor/channel complex and an even larger number of possible receptor subunit combinations. Many--nearly all--of these gene products are expressed in the retina, and the questions that we face today are: how are they used and why are there so many? Answers to these questions will be found at several levels. At the level of transcription, we have learned that different sets of subunits are expressed by different retinal neurons. Little is known about the transcriptional control of these genes, so it remains to be determined whether these patterns of expression reflect the need for different gene products in different retinal neurons or whether these patterns of expression reflect the functional constraints of gene expression. Another level of complexity is caused by alternative splicing, and here we report that at least four and possibly all eight of the different NMDAR1 transcripts are present in the mouse retina. The consequences of this alternative splicing are poorly understood, but antibodies directed against the two different possible C-termini of NMDAR1 label many of the same cell types. It is possible that these different splice variants are combined to generate the channels. While immunohistochemistry provides us with a glimpse of the subunit proteins, much remains to be learned about their half-life within a retinal cell, their intracellular trafficking, their regulation at the synapse, and the proteins associated with their cytoplasmic domains. An approach we have taken towards studying the dynamic properties of receptor subunits has been to fuse them to the cDNA encoding the jellyfish Green Fluorescent Protein. This makes it possible to follow functional subunits in transfected cells over time and to begin to measure the mobility of the protein.

Animals↗

Reactive airways dysfunction syndrome after exposure to dinitrogen tetroxide.

BACKGROUND: Reactive airways dysfunction syndrome (RADS) is characterized by persistent bronchial hyperreactivity and asthmatic symptoms in a previously healthy individual after a single intense exposure to an irritant fume, vapor, or gas. On October 23, 1995, a cloud of dinitrogen tetroxide (N2O4) escaped from a railroad tanker car in Bogalusa, Louisiana, exposing an estimated 4,000 citizens to the gas. METHODS: A sample of 234 patients with respiratory complaints after the spill received a complete history and physical examination, a symptom questionnaire, and pulmonary function tests. Patients whose previously undocumented asthma-like symptoms persisted for 3 months after exposure to N2O4 had methacholine challenge testing. RESULTS: Of the 234 patients evaluated, six met the criteria for a diagnosis of RADS. The distance of these six patients from the source of the leak, their durations of exposure, and initial symptoms were not different from those of the sample patients who did not have RADS. CONCLUSIONS: After evaluation of 234 symptomatic patients who were exposed to N2O4, we diagnosed six cases of RADS. There were no demographic characteristics or initial symptoms that identified patients who were at risk of having this syndrome. We believe we are the first to report cases of RADS due to N2O4 exposure.

Adult↗

Making genes green: creating green fluorescent protein (GFP) fusions with blunt-end PCR products.

The jellyfish green fluorescent protein (GFP) has proven to be a useful tool in protein localization and trafficking studies. Fused to GFP, a protein of interest can be visualized and tracked in vivo through fluorescence microscopy. However, the process of making these fusion proteins is often tedious and painstaking. Here, we describe a simple and quick method for creating GFP fusion proteins using blunt-end PCR product ligation.

Base Sequence↗

A profile of six community-based HIV prevention programs targeting Asian and Pacific Islander Americans.

Based on a framework (i.e., research and evaluation, prevention and services, and advocacy and policy), the goal of this article is to profile six community-based HIV prevention programs targeting Asian and Pacific Islander (API) Americans, especially among men who have sex with men. These six programs were chosen based on one or more of the following three criteria: (a) epidemiological profiles of AIDS cases among Asian and Pacific Islander Americans, (b) ethnic diversity, and (b) community development among Asian and Pacific Islander Americans in the fight against HIV. The six programs are (a) the Kokua Kalih Valley Health Center, Honolulu; (b) the Asian and Pacific Islander Wellness Center, San Francisco; (c) the Asian Pacific AIDS Intervention Team, Los Angeles; (d) the Asian and Pacific Islander Coalition on HIV and AIDS, New York City; (e) the AIDS Services in Asian Communities, Philadelphia; and (f) the Massachusetts Asian AIDS Prevention Project, Boston. The present analysis reveals that five programs have their roots in the gay or bisexual communities. Two programs have existed for about 3 years (the epidemic is going into its 17th year). Major financial support for the six programs are federal, state, or county sources; private support is generally minimal. All six programs offer a wide range of culturally competent and linguistically appropriate prevention activities and services (including two national projects) targeting a diverse API population. However, gaps in services exist in the younger programs. In addition to a paucity of epidemiological, surveillance, and empirical data, most reported that barriers fall into one or two interrelated categories: (a) structural (e.g., lack of governmental or private funding) or (b) cultural (e.g., denial of risk, homophobia, fear of confidentiality). These findings suggest that HIV prevention activities and services for Asian and Pacific Islander Americans should be based on empirical and cultural data, and that API Americans should become more actively involved in social and political activities. Asian and Pacific Islander American agencies are challenged to integrate HIV with other health and social issues pertinent to the communities.

Asian↗

Modulation of plasminogen activator inhibitor-1 in vivo: a new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition.

We examined the potential of in vivo linkage of plasminogen activator inhibitor-1 (PAI-1) and angiotensin II (Ang II) in the setting of endothelial injury and sclerosis following radiation injury in the rat. PAI-1 is a major physiological inhibitor of the plasminogen activator (PA)/plasmin system, a key regulator of fibrinolysis and extracellular matrix (ECM) turnover. PAI-1 mRNA expression in the kidney was markedly increased (9-fold) at 12 weeks after irradiation (P < 1.001 vs. normal control). In situ hybridization revealed significant association of PAI-1 expression with sites of glomerular injury (signal intensity in injured vs. intact glomeruli, P < 0.001). Angiotensin converting enzyme inhibitors (ACEI, captopril or enalapril) or angiotensin II receptor antagonist (AIIRA, L158,809) markedly reduced glomerular lesions (thrombosis, mesangiolysis, and sclerosis; sclerosis index, 0 to 4+ scale, 0.49 +/- 0.20 in untreated vs. 0.05 +/- 0.02, 0.02 +/- 0.01, 0.04 +/- 0.02 in captopril, enalapril and AIIRA, respectively, all P < 0.01 vs untreated). Further, ACEI and AIIRA markedly attenuated increased PAI-1 mRNA expression in the irradiated kidney (36, 19 and 20% expression, respectively, for captopril, enalapril and AIIRA, compared to untreated irradiated kidney, P < 0.05, < 0.01, < 0.01). This effect was selective in that neither tissue-type nor urokinase-type PA mRNA expression was affected by these interventions. Thus, we speculate that inhibition of the renin-angiotensin system may ameliorate injury following radiation by accelerating fibrinolysis and ECM degradation, at least in part, via suppression of PAI-1 expression. In summary, inhibition of Ang II, in addition to its known effects on vascular sclerosis, may also by its novel effect to inhibit PAI-1, lessen fibrosis following endothelial/thrombotic injury.

Angiotensin II↗

Alterations in the light transmission through single lens fibers during calcium-mediated disintegrative globulization.

PURPOSE: The purpose of this study was to examine changes in the light transmission through single cortical fibers isolated from the rat lens during the process of disintegrative globulization. METHODS: Single cortical fibers were isolated from adult rat lens by treatment with trypsin in a solution containing 10 mM HEPES, 10 mM EDTA, and 280 mM sucrose (pH 7.4, 300 to 310 mOsm) HEPES-EDTA-sucrose (HES) solution. The isolated fibers were illuminated by a white light source, and the light transmission through the fibers was collected by a charge-coupled device camera and quantified by digital image analysis. In some experiments, thin sections of fixed lens cells were examined using transmission electron microscopy. RESULTS: Enzymatic dissociation of the lens yielded elongated fibers, which, in the presence of Ringer's solution (containing 2 mM Ca2+), underwent disintegrative globulization. Measurements of light transmission through elongated fibers suspended in HES solution showed maximal transmission at the center of the fiber. Exposure of the cortical fibers to Ringer's solution led to biphasic changes in the intensity of the transmitted light. Within 5 to 10 minutes of exposure to Ringer's solution, a general decrease in the light transmission across the long axis of the fiber was observed. Extended superfusion led to a local, apparent increase in light transmission corresponding to the formation of membrane blebs and globules. Images of disingerated globules focused above their equator showed bright halos with dark central zones. In electron micrographs, the single fibers showed uniform electron density. No significant inhomogeneities or precipitation of intracellular crystallins was observed in globules generated from fiber cells exposed to Ringer's solution; in addition, no high molecular weight protein aggregates were found in the globules. CONCLUSIONS: Exposure to calcium alters the light-transmitting properties of isolated cortical fibers. The initial decrease in the average light transmittance of the fiber appears to be secondary to cell swelling and may relate to protein-based opacification. An apparent increase in light transmission through calcium-generated globules is likely because of the Becke line generated by a mismatch between the refractive index of the medium and the globule cytoplasm and accentuated by the transition from rod-shaped to spheroidal morphology.

Animals↗

Gabapentin associated with aggressive behavior in pediatric patients with seizures.

Gabapentin (GBP) is a new antiepileptic drug (AED) approved for adjunctive treatment of complex partial seizures with or without seizures secondarily generalization in adults. We report 2 children who received GBP for intractable seizures and who developed intolerable aggressive behavior requiring dose reduction or drug discontinuation. Behavioral changes should be recognized as a possible side effect of GBP, especially in mentally retarded children.

Acetates↗

Epidemiology of influenza A virus infection in patients with acute or chronic leukemia.

Influenza infection is a significant cause of morbidity and mortality in immunocompromised hosts, but its importance in adult cancer patients is largely undescribed. We therefore conducted a prospective study of the incidence and clinical features of influenza infection in patients with acute or chronic leukemia. The cohort, which consisted of all adult leukemia patients undergoing remission-induction chemotherapy during the 1991-1992 influenza epidemic, was followed prospectively for development of signs and symptoms of acute infection of the upper or lower respiratory tract. Of these 294 patients, 111 received chemotherapy as inpatients and 183 as outpatients. Throat swabs and nasal washes for viral culture were obtained from all symptomatic patients, who were then followed until all signs and symptoms resolved. Symptoms of respiratory tract infection developed in 37 leukemia patients (13%). Among these, influenza (A/Beijing/ H3N2) caused 3 (21%) of the 14 infections that developed during hospitalization but only 1 (4%) of the 23 that developed in the community (P = 0.14). Influenza patients presented with fever, rhinorrhea, nasal congestion, headache, and myalgia; those with other infections presented with signs and symptoms of lower respiratory tract infection (productive cough, rales, or rhonchi). Development of pneumonia was common in influenza patients, 1 of whom died from secondary fungal and gram-negative pneumonia. Influenza A virus infections accounted for a substantial portion of acute respiratory infections among adult leukemia patients during a community epidemic. Most infections appeared to be nosocomial and the most likely sources were visitors or hospital personnel. Immunization of household contacts and hospital staff may reduce the risk of influenza infection and its pulmonary complications in leukemia patients.

Acute Disease↗

Influenza A virus infections among hospitalized adult bone marrow transplant recipients.

Although influenza virus continues to cause annual epidemics of respiratory diseases, surprisingly little is known about the frequency and clinical course of influenza among adult patients with cancer. During the 1991-92 influenza epidemic in Houston, Texas, we followed all adult BMT recipients hospitalized at M.D. Anderson Cancer Center. None of these 68 patients had received prophylaxis for influenza. Influenza virus type A was isolated from 8 (29%) of 28 BMT recipients with an acute respiratory illness. Five of these infections were acquired in the hospital. All 8 patients presented with an upper respiratory tract illness. In 6 patients, the infection was complicated by pneumonia. The frequency of influenza was similar among autologous (5 of 18) and allogeneic (3 of 10) BMT recipients. The risk of developing pneumonia was not related to the type of transplant or to the engraftment status. All patients received broad-spectrum antibiotics. The 2 patients who did not develop pneumonia also received amantadine. The mortality with pneumonia was 17%. During community outbreaks, influenza is a frequent cause of acute respiratory illness among hospitalized adult BMT recipients and is frequently complicated by pneumonia. Studies are needed to define the optimal means of preventing and treating influenza in BMT recipients.

Adult↗

Antibody response to a two-dose influenza vaccine regimen in adult lymphoma patients on chemotherapy.

A study was conducted to determine if a two-dose regimen of influenza vaccine would enhance the immunologic response of 41 patients with lymphoma receiving chemotherapy. Hemagglutinin-inhibiting antibody responses to influenza A/H1N1, A/H3N2 and B virus occurred in 32%, 24% and 20% of patients following one dose, and in 49%, 41% and 46% of patients following two doses, respectively. Responses to one or more vaccine components occurred in 42% of patients after one dose and in 71% after two doses. Fifty percent of the patients who did not respond after one dose responded after two doses. A two-dose regimen of influenza immunization may significantly enhance the response rate of cancer patients receiving chemotherapy.

Adult↗

Use of imipenem in the treatment of pulmonary nocardiosis.

A case of pulmonary nocardiosis with empyema in a 55-year-old man with macroglobulinemic lymphoma is presented. Treatment with imipenem followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) resolved his symptoms and cleared the roentgenographic abnormalities. This case illustrates the clinical potential of imipenem against Nocardia.

Drug Therapy, Combination↗

Magnetic resonance angiography: analysis of vascular lesions of the temporal bone and skull base.

Contrast-enhanced, high resolution, computed tomography (CT), along with gadolinium-enhanced magnetic resonance imaging (MRI), provide the skull-base surgeon with essential information for diagnosis and surgical planning. Evaluation of skull-base vasculature has traditionally been performed with angiography. Four-vessel angiography is an invasive procedure that subjects the patient to the potential risks of vascular injury, stroke, renal damage, anaphylaxis, and radiation. The development of gradient-recall echo pulse sequence in MRI provides a means to evaluate the vasculature with a noninvasive, low-risk technique. We review the experience of the House Ear Clinic with magnetic resonance angiography (MRA) in evaluating cranial-base abnormalities including paragangliomas, aberrant vessels, and dural sinus thrombosis. Based on a review of 25 cases, we conclude that MRA is a useful procedure for evaluation of major arteries, veins, and dural sinuses. The technique has been less helpful in defining small vessel detail such as feeding blood supply and tumor staining.

Carotid Arteries↗

Novel Tay-Sachs disease mutations from China.

We describe three HEXA mutations associated with infantile Tay-Sachs disease (TSD) in three unrelated nonconsanguineous Chinese families. Novel mutations were found in two of these families. The third is a previously reported mutation (G-->A transition at nt 1444) (Nakano et al., 1988). Direct sequencing of PCR products identified a novel insertion of an A after nt 547 in family 1. This change generates an early termination codon 6 bp downstream from the insertion site. Allele-specific oligonucleotide hybridization confirmed homozygosity in the proband. Single strand conformational polymorphism analysis and direct sequencing of amplified exon 13 revealed a T-->C transition at nt 1453 with the corresponding amino acid substitution W485R in the second family. This mutation creates an Fnu4HI restriction site. The proband is homozygous for this allele. When the site-specific mutagenized alpha cDNA carrying the T-->C transition at nt 1453 was expressed in COS 1 cells hexosaminidase S activity was not detectable above background. A G-->A transition at nt 1444 (exon 13) corresponding to the E482K substitution was found in the third family. This mutation occurs at a CpG dinucleotide. It has been reported in an Italian TSD proband and causes defective intracellular transport of the alpha-subunit from the rough endoplasmic reticulum to the Golgi apparatus.

Animals↗