Normal hypoxanthine and ammonia release from working muscle in partial HPRT deficiency.
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Ammonia↗
Biomedical subjects
M Gross
Publications and source records attributed to M Gross.
The metabolic brain pattern of young subjects given scopolamine.
The effect of an intravenous dose of 0.5 mg of scopolamine on the functional brain activity of normal subjects performing auditory discrimination (CPT) was determined in two independent positron emission tomography studies with [18F] 2-fluoro-deoxyglucose. In the first preliminary study, the most significant effect found was a reduction in the functional activity of the thalamus. In the second "hypothesis-testing" study, an equally prominent effect on thalamic functional activity was seen. Because the second study was performed on a high-resolution scanner with improved methodology, we re-examined scopolamine's effects on those brain regions established as determinants of CPT. Of the regions affected, the reduction in cingulate and the increase in basal ganglia metabolic rates were the most notable. We concluded that scopolamine's effects on the functions of thalamic, cingulate and basal ganglia are the likely causes of scopolamine's well-described attention-altering properties. Alterations in these same brain structures could be responsible for scopolamine's effects on other cognitive functions, e.g., memory. Alternatively, scopolamine's effects on other brain structures such as the hippocampus and frontal cortex could underlie scopolamine's effects on these other cognitive functions. Studies of scopolamine's regional metabolic effects in subjects performing these other cognitive tasks at more than a single dose and at more than one post-drug time are needed to discriminate between these two possibilities.
Acoustic Stimulation↗
Positron emission tomography detects evidence of viability in rest technetium-99m sestamibi defects.
OBJECTIVES: The purpose of this study was to determine the relative value of single-photon emission computed tomographic (SPECT) imaging at rest using technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi) with positron emission tomography for detection of viable myocardium. BACKGROUND: Recent studies comparing positron emission tomography and thallium-201 reinjection with rest technetium-99m sestamibi imaging have suggested that the latter technique underestimates myocardial viability. METHODS: Twenty patients with a previous myocardial infarction underwent rest technetium-99m sestamibi imaging and positron emission tomography using fluorine (F)-18 deoxyglucose and nitrogen (N)-13 ammonia. In each patient, circumferential profile analysis was used to determine technetium-99m sestamibi, F-18 deoxyglucose and N-13 ammonia activity (expressed as percent of peak activity) in nine cardiac segments and in the perfusion defect defined by the area having technetium-99m sestamibi activity < 60%. Technetium-99m sestamibi defects were graded as moderate (50% to 59% of peak activity) and severe (< 50% of peak activity). Estimates of perfusion defect size were compared between technetium-99m sestamibi and N-13 ammonia. RESULTS: Sixteen (53%) of 30 segments with moderate defects and 16 (47%) of 34 segments with severe defects had > or = 60% F-18 deoxyglucose activity considered indicative of viability. Fluorine-18 deoxyglucose evidence of viability was still present in 50% of segments with technetium-99m sestamibi activity < 40%. There was no significant difference in the mean (+/- SD) technetium-99m sestamibi activity in segments with viable (40 +/- 7%) and nonviable segments (49 +/- 7%, p = 0.84). Of the 18 patients who had adequate F-18 deoxyglucose studies, the area of the technetium-99m sestamibi defect was viable in 5 (28%). In 16 patients (80%), perfusion defect size determined by technetium-99m sestamibi exceeded that measured by N-13 ammonia. The difference in defect size between technetium-99m sestamibi and N-13 ammonia was significantly greater in patients with viable (21 +/- 9%) versus nonviable segments (7 +/- 9%, p = 0.007). CONCLUSIONS: Moderate and severe rest technetium-99m sestamibi defects frequently have metabolic evidence of viability. Technetium-99m sestamibi SPECT yields larger perfusion defects than does N-13 ammonia positron emission tomography when the same threshold values are used.
Adult↗
Protein engineering techniques for antibody humanization.
Few proteins have the therapeutic potential of antibodies, which can be developed against a wide variety of targets and genetically or chemically manipulated to further enhance their activities. A number of approaches have been taken in order to render these proteins pharmaceutically useful. Either the amino acid sequence of an antibody can be genetically altered (i.e. reshaped or resurfaced) or the antibody can be conjugated to other proteins or toxins.
Animals↗
[Computer-assisted rehabilitation of auditory perception after cochlear implants and hearing aid management].
A newly developed computer-aided rehabilitation programme simplifies the training of auditory perception after cochlear implant or hearing-aid fitting. The programme is interactive, hierarchically structured, applicable without any computer knowledge and adjustable to individual requirements of each patient. There are two versions of the programme, one for clinical and one for home use. A transfer option provides simple data exchange of results and new training exercises via floppy disk. The present experience shows that, with this programme, auditory perception is improved more rapidly than with traditional therapy and that the patients are strongly motivated and concentrated over a long period in order "to beat the computer". The home version is appreciated for making possible schedule-free training without inconvenient and time-consuming trips to the therapist.
Auditory Perception↗
[Secondary ambulatory voice prosthesis implantation with the argon laser using local anesthesia].
An alternative technique for secondary tracheo-esophageal puncture and voice prosthesis implantation in topical anesthesia on an outpatient basis was developed. With argon laser beam passed through a glass fibre in the instrument channel of a flexible endoscope a secondary puncture of the tracheo-esophageal wall is obtained. A voice prosthesis is fitted subsequently, so that the whole operation is performed in one session in about 30 minutes. We generally administer 7.5 mg Midazolam orally for light sedation; antibiotics are not required. This method expands the possibility of voice prosthesis fitting in patients who are not considered or willing to have general anesthesia for various reasons. In 33 cases we did not see any complication. In two cases the tracheal wall was too tight due to radiation therapy, so that an operation had to be performed later on in general anesthesia. In one case technical problems led to an operation in local anesthesia in two steps. In all cases the patients did not complain of any considerable discomfort.
Ambulatory Surgical Procedures↗
Immunomodulating actions of carotenoids: enhancement of in vivo and in vitro antibody production to T-dependent antigens.
Previously, we demonstrated an enhancement of in vitro antibody (Ab) production in response to T-dependent antigens (TD-Ag) by astaxanthin, a carotenoid without vitamin A activity. The effects of beta-carotene, a carotenoid with vitamin A activity, and lutein, another carotenoid without vitamin A activity, on in vitro Ab production were examined with spleen cells from young and old B6 mice. In addition, the in vivo effects of lutein, astaxanthin, and beta-carotene on Ab production were studied in young and old B6 mice. Lutein, but not beta-carotene, enhanced in vitro Ab production in response to TD-Ags. The depletion of T-helper cells prevented the enhancement of Ab production by lutein and astaxanthin. In vivo Ab production in response to TD-Ag was significantly enhanced by lutein, astaxanthin, and beta-carotene. The numbers of immunoglobulin M- and G-secreting cells also increased in vivo with the administration of these carotenoids when mice were primed with TD-Ags. Antibody production in response to TD-Ags in vivo and in vitro was significantly lower in old than in young B6 mice. Astaxanthin supplements partially restored decreased in vivo Ab production in response to TD-Ags in old B6 mice. Lutein and beta-carotene also enhanced in vivo Ab production in response to TD-Ags in old B6 mice, although to a lesser extent than did astaxanthin. However, none of the carotenoids had an effect on in vivo or in vitro Ab production in response to T-independent antigen. These results indicate significant immunomodulating actions of carotenoids for humoral immune responses to TD-Ags and suggest that carotenoid supplementation may be beneficial in restoring humoral immune responses in older animals.
Adjuvants, Immunologic↗
New method for detection of C34-T mutation in the AMPD1 gene causing myoadenylate deaminase deficiency.
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AMP Deaminase↗
Expression of the gastric H+/K(+)-ATPase and histidine decarboxylase during omeprazole treatment.
The gastric proton pump H+/K(+)-ATPase in the parietal cell is central to acid secretion into the stomach. We performed the following experiment to examine the pattern of expression of the alpha- and beta-subunits of the H+/K(+)-ATPase at the transcriptional level during 7 days' application of the proton pump inhibitor omeprazole, in relation to the expression of gastrin and histamine, two stimuli of gastric acid secretion. Serum gastrin concentrations and mRNA levels of antral gastrin, fundic histidine decarboxylase (HDC) and H+/K(+)-ATPase alpha- and beta-subunits were determined after 8 h, 1, 3 and 7 days. Omeprazole treatment rapidly caused an increase in the serum gastrin concentration and the antral gastrin mRNA level after 3 days. HDC mRNA expression showed a steady increase with a 5-fold induction after 1 week. However, mRNA levels of the alpha- and beta-subunits of the H+/K(+)-ATPase were unchanged during the course of omeprazole treatment. These results suggest that omeprazole inhibition of the gastric proton pump does not result in feedback activation of H+/K(+)-ATPase gene expression despite adaptive changes of the endocrine stomach.
Animals↗
A new method for tracheoesophageal puncture under topical anesthesia.
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Anesthesia, Local↗
"Drugs and AIDS--reaching for help": a videotape on AIDS and drug abuse prevention for criminal justice populations.
This article describes the development of a videotape targeted at persons under supervision of the criminal justice system. The videotape seeks to encourage those who use illicit drugs to enter drug treatment and to motivate those at risk for exposure to human immunodeficiency virus (HIV) to alter behaviors that may transmit infection. The criminal justice system presents an important opportunity to deliver such messages, particularly to a large population of persons briefly detained in a jail or lockup and released without subsequent incarceration. Evidence suggests that, even in this audience, knowledge of how to prevent exposure to HIV is widespread, yet those at risk often fail to take appropriate precautions: motivating behavior change demands more than imparting information. In order to shape this videotape, we analyzed the target audience and developed a drama-based approach that applies the framework of social learning theory, the health belief model, and principles of social marketing. This article describes the integration of that theoretical framework into the production process, content, and strategy of the videotape.
Acquired Immunodeficiency Syndrome↗
Characterization of mammalian Gs-alpha proteins expressed in yeast.
The guanine nucleotide regulatory protein, GS, mediates transmembrane signaling by coupling membrane receptors to the stimulation of adenylyl cyclase activity. The full length coding sequences for the M(r) = 42-45,000, short form (S), and M(r) = 46-52,000, long form (L), of the alpha-subunits of rat GS were placed in yeast expression vectors under the regulatory control of the copper-inducible CUP1 promoter and transformed into Saccharomyces cerevisiae. In the presence of 100 microM CuSO4, the transformed yeast expressed GS-alpha mRNAs and proteins. In reconstitution experiments, rat GS-alpha(S and L), solubilized from yeast membranes with 1% cholate, conferred NaF-, (-)isoproterenol-, and guanine nucleotide-dependent sensitivity to adenylyl cyclase catalytic units in S49 lymphoma cyc- cell membranes, which are devoid of endogenous GS-alpha. GS-alpha (S) demonstrated twice the activity of GS-alpha(L) in reconstitution assays of fluoride-stimulated adenylyl cyclase activity. Comparison of GS-alpha (S) expressed in yeast with GS purified from rabbit liver or human erythrocytes showed that the crude recombinant protein was fully competent in reconstituting NaF-stimulated adenylyl cyclase activity, but was only 2-5% as potent as purified GS. Addition of bovine brain beta gamma subunits during reconstitution enhanced all parameters of adenylyl cyclase activity for GS-alpha(S and L) obtained from yeast. In contrast, transducin beta gamma only enhanced agonist-stimulated adenylyl cyclase activity for GS-alpha (S and L) following reconstitution. These results demonstrate that the expression of functional mammalian GS-alpha subunits in yeast may be useful for their biochemical characterization.
Adenylyl Cyclases↗
Safety, immunogenicity, and efficacy of a malaria sporozoite vaccine administered with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane as adjuvant.
A Plasmodium falciparum circumsporozoite protein (PfCSP) recombinant fusion protein, R32NS1(81), formulated with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane (Detox) was administered to 12 volunteers. One volunteer had malaise and self-limited painful induration at the injection site after the second dose and declined further immunization. The other 11 volunteers tolerated the three doses of 1,230 micrograms of vaccine, but most complained of sore arms; in five cases the pain or malaise was severe enough to interfere with work or sleep. Two weeks after the third dose of vaccine, four of the 11 immunized volunteers had > or = 14 micrograms/ml of antibodies to the repeat region of the PfCSP in their serum. Two of these four volunteers did not develop P. falciparum parasitemia when challenged by the bite of five mosquitoes carrying P. falciparum sporozoites. The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia. These data are consistent with other studies, and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans. The challenge is to improve the immunogenicity of PfCSP-based vaccines, and to develop methods for including PfCSP peptides as components of multitarget malaria vaccines.
Adjuvants, Immunologic↗
Creating an agenda for research and evaluation: HIV service delivery, the Ryan White CARE Act, and beyond.
HRSA, AHCPR and NCAP convened a working meeting in November 1992, to discuss creation of a national agenda for research and evaluation on HIV service delivery systems that are cost-effective, responsive to the needs of the diverse populations affected by the epidemic, and reflective of the lessons learned so far. In this article, the interests and goals of the conveners are described, the meeting's process and outcomes are discussed, and the nine key study areas that were identified and chosen by the meeting participants are presented. It is hoped that this article will stimulate further interest among private and public funders and among the research community in fostering the implementation of HIV service delivery-related research and evaluation studies. If this is accomplished, decision-makers will be better enabled to make informed and responsive policy decisions.
Delivery of Health Care↗
Migraine. Identifying and removing barriers to care.
The high levels of pain and disability associated with undiagnosed migraine or inadequate treatment of migraine offer a potential target for healthcare intervention. Both the individual patient and society are affected by decisions regarding which migraine sufferers are most in need of medical care. Pain is the most important symptom for the individual patient, but disability may be the most important consequence of migraine for an increasingly cost-conscious society. These two perspectives are the components of a migraine severity or impact measure being developed to define migraine sufferers most in need of care. The criteria for developing screening programs provide a context for evaluating healthcare interventions for migraine. Barriers to effective care occur on at least three levels: many people with migraine do not consult doctors; consulters may not receive the correct diagnosis; and even when the correct diagnosis is made, many migraineurs do not receive effective treatment. Screening and impact measures may help both to improve diagnosis and to determine which migraineurs are most in need of care. Public and physician education, screening, and impact measures might circumvent many of the barriers to effective care for people with migraine.
Health Services Accessibility↗
Kinetics of assembly and dissociation of the mitochondrial creatine kinase octamer. A fluorescence study.
The dissociation of octameric mitochondrial creatine kinase (Mi-CK) into dimers induced by the transition-state analogue complex (TSAC) mixture (creatine+Mg(2+)+ADP+NO3-) is accompanied by a large (25.2%) decrease in Trp fluorescence. This effect is caused by a Trp residue situated at the dimer-dimer interface within the octamer, which becomes susceptible to solvent quenching upon octamer dissociation. Octamer formation, induced by adding excess EDTA to TSAC-dissociated Mi-CK, involves a transient tetrameric species, whereas the dissociation reaction proceeds in a one-step, all-or-none fashion. From fluorescence spectroscopic investigations of the octamer formation and dissociation reactions, a first-order dissociation rate constant of 0.19 min-1 and a bimolecular association rate constant of 318 M-1 s-1 at 30 degrees C were obtained. The octamers formed after EDTA addition can be dissociated again by lowering the temperature to 4 degrees C, indicating a substantial hydrophobic contribution to the interactions stabilizing the octamer.
Animals↗
Pressure-induced dissociation of ribosomes and elongation cycle intermediates. Stabilizing conditions and identification of the most sensitive functional state.
Pressure-induced dissociation of ribosomes has been considered a major reason for the inhibition of protein biosynthesis and, hence, bacterial growth at high hydrostatic pressure [Jaenicke, R. (1981) Annu. Rev. Biophys. Bioeng. 10, 1-67]. We reexamined the issue, using a buffer system with polyamines that has been optimized to reproduce in-vivo-like performance of protein biosynthesis in vitro. By slightly modifying this buffer, we were able to find conditions that stabilize functional ribosomal complexes against the dissociating effect of pressure up to 100 MPa and uncharged tight couples up to 60 MPa. Approaching the physiological conditions by reducing the Mg2+ concentration down to 4 mM, one finds a significant destabilization of the post-translocational complex, which represents the most pressure-sensitive intermediate of the elongation cycle and is possibly the limiting factor for the pressure-induced block of protein biosynthesis and bacterial growth.
Buffers↗