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Biomedical subjects

J B Green

Publications and source records attributed to J B Green.

At least 73 records · Page 4Linked to original sources
PubMed1990

The synthesis and antiallergy activity of 1-(aryloxy)-4-(4-arylpiperazinyl)-2-butanol derivatives.

A series of 1-(aryloxy)-4-(4-arylpiperazinyl)-2-butanol derivatives were prepared and evaluated for antiallergy activity in the passive foot anaphylaxis (PFA) assay in rats. Twenty-seven derivatives had activity equal to or greater than the parent, alpha-(phenoxymethyl)-4-phenyl-1-piperazinepropanol. Six derivatives that possessed greater activity in the PFA than the parent compound were then tested in the guinea pig anaphylaxis (GPA) assay. Five of the derivatives were more potent than the parent (PD50 = 40 mg/kg) in the GPA with alpha-[(4-fluorophenoxy)methyl]-4-(4-fluorophenyl)-1-piperazinepropan ol (PD50 = 3 mg/kg) having the greatest potency.

Animals↗
PubMed1990

Synthesis and antiallergy activity of N-[2-(dimethylamino)ethyl]-4-aryl-1-piperazinecarboxamide derivatives.

A series of N-[2-(dimethylamino)ethyl]-4-aryl-1-piperazinecarboxamides was synthesized and evaluated for antiallergy activity. Several derivatives had activity in the passive foot anaphylaxis (PFA) assay, an IgE-mediated model useful in the detection of compounds possessing antiallergic activity, but no derivative tested had activity at 10 mg/kg in the guinea pig anaphylaxis (GPA) assay. One analogue, N-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)-1-piperazinecarboxamide , had an IC50 = 310 nM for inhibition of tritiated mepyramine binding to H1 histaminic receptors isolated from guinea pig cerebral cortex.

Anaphylaxis↗
PubMed1990

The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF.

Mesoderm in Xenopus and other amphibian embryos is induced by signals from the vegetal hemisphere acting on equatorial or animal hemisphere cells. These signals are diffusible and two classes of candidate signal molecule have been identified: the fibroblast growth factor (FGF) and transforming growth factor beta (TGF-beta) types. In this paper, we compare the effects of cloned Xenopus basic FGF (XbFGF) and electophoretically homogeneous XTC-MIF (a TGF-beta-like factor obtained from a Xenopus cell line) on animal pole explants. We find that they have a similar minimum active concentration (0.1-0.2 ng ml-1) but that, nonetheless, XTC-MIF is at least 40 times more active in inducing muscle. In general, we find that the two factors cause inductions of significantly different characters in terms of tissue type, morphology, gene expression and timing. At low concentrations (0.1-1.0 ng ml-1) both factors induce the differentiation of 'mesenchyme' and 'mesothelium' as well as blood-like cells. These latter cells do not, however, react with an antibody to Xenopus globin. This raised the possibility that the identification of red blood cells in other studies on mesoderm induction might have been mistaken, but combinations of animal pole regions with ventral vegetal pole regions confirmed that genuine erythrocytes are formed. The identity of the blood-like cells formed in response to the inducing factors remains unknown. At higher concentrations XTC-MIF induces neural tissue, notochord, pronephros and substantial and often segmented muscle. By contrast, XbFGF only induces significant amounts of muscle above 24 ng ml-1 and even then this is much less than that induced by XTC-MIF. For both factors an exposure of less than 30 min is effective. Competence of animal pole cells to respond to XbFGF is completely lost by the beginning of gastrulation (stage 10) while competence to XTC-MIF is detectable until somewhat later (stage 11). Since animal pole tissue is known to be able to respond to the natural inducer at least until stage 10, and perhaps until stage 10.5, this suggests that bFGF cannot be the sole inducer of mesoderm in vivo. Taken together, these results are consistent with XTC-MIF being a dorsoanterior inducer and XbFGF a ventroposterior inducer, suggesting that body pattern is established by the interaction of two types of inducing signal. This model is discussed in view of the qualitative and quantitative differences between the factors.

Animals↗
PubMed1990

Carboplatin therapy in advanced endometrial cancer.

A phase II study of the effectiveness and toxicity of carboplatin in the treatment of metastatic or locally advanced endometrial cancer was carried out by the Southwest Oncology Group. Thirty-two patients were registered in the study and 23 were fully evaluable for response and toxicity. Carboplatin was administered in a dose of 400 mg/m2 at 28-day intervals without concomitant hydration if blood counts had recovered sufficiently. There were seven responses (two complete and five partial responses) among the 23 evaluable patients, for an overall response rate of 30%. Four (two of two complete responders and two of five partial responders) of the seven responding patients remain alive at 839+ to 987+ days from the start of therapy. The two complete responders and one of the partial responders had small-volume disease, which may have contributed to their prolonged survival. Myelosuppression was the most prominent toxicity encountered. Seventeen of 27 patients evaluable for toxicity developed platelet counts of less than 75 X 10(3)/muL during therapy, but no hemorrhagic complications were encountered. Leukopenia was less prominent, with only nine of 27 patients developing white blood cell counts of less than 3.0 X 10(3)/microL. No important nephrotoxicity or neurotoxicity was observed. Emesis occurred in ten of 27 patients but was not dose-limiting. No unexpected toxicities were encountered. Carboplatin appears to be an active agent in the treatment of endometrial carcinoma.

Aged↗
PubMed1990

Retinol metabolism in rats with low vitamin A status: a compartmental model.

A compartmental model was developed to describe the metabolism of vitamin A in rats with low vitamin A status maintained by a low dietary intake of vitamin A (approximately 2 micrograms retinol equivalents/day). After the IV bolus injection of [3H]retinol in its physiological transport complex, tracer and trace data were obtained from plasma, organs (liver, kidneys, small intestine, eyes, adrenals, testes, lungs, carcass), and tracer data were obtained from urine and feces. The dietary protocol developed for this study resulted in animals having plasma vitamin A levels less than 10 micrograms retinol/dl and total liver vitamin A levels of approximately 1 microgram retinol equivalent. Four compartments were used to model the plasma: one to describe retinol, one to describe the nonphysiological portion of the dose, and two to simulate polar metabolites derived from retinol. The liver required two compartments and a delay, the carcass (small intestine, eyes, adrenals, testes, and lungs, plus remaining carcass) required three compartments, and the kidneys required two. The model predicted a vitamin A utilization rate of 1.65 micrograms retinol equivalents/day with the urine and feces accounting for most of the output. The plasma retinol turnover rate was approximately 20 micrograms retinol equivalents/day; this was 12 times greater than the utilization rate. This indicated that, of the large amount of retinol moving through the plasma each day, less than 10% of this was actually being irreversibly utilized. Similarly, as compared to the whole-body utilization rate, there was a relatively high turnover rate of retinol in the kidneys, carcass, and liver (9.0, 8.2, and 5.8 micrograms retinol equivalents/day, respectively), coupled with a high degree of recycling of vitamin A through these tissues. Of the total vitamin A that entered the liver from all sources including the diet, approximately 86% was mobilized into the plasma. Similarly, of the vitamin A that entered the carcass, approximately 76% was returned to the plasma. All of the retinol that entered the kidneys was modeled as recycling to the plasma. The present studies provide quantitative and descriptive evidence of an efficient metabolism of vitamin A from absorption through turnover and utilization in rats with very low vitamin A status. Furthermore, although their body stores of vitamin A were extremely low, these rats maintained a high level of recycling of vitamin A throughout the body.

Animals↗
PubMed1990

Surgical treatment of epilepsy: three- to six-year follow-up of eleven patients with pharmacologically uncontrolled complex partial seizures.

There are an estimated 100,000 epileptic patients whose response to pharmacologic treatment is unsatisfactory. We report 11 patients with complex partial seizures who were selected for surgical treatment after adequate trials on antiepileptic medication failed. Immediate improvement-no further seizures or reduced frequency of occurrence and severity-was sustained at 3- to 6-year follow-up, and 7 patients were driving, 10 were working, and all were enjoying a better quality of life. Likely candidates for temporal lobectomy or resection of epileptogenic cerebral cortical lesions are those with a single focus of seizure discharge on video-EEG monitoring. If this focus is remote from language or motor areas, and if there is no interference with memory and recall after intracarotid amobarbital injection ipsilateral to the intended surgery, good results can be expected in the majority of such patients. We discuss patient selection and evaluation, and encourage surgical treatment where the indications can be established.

Adolescent↗
PubMed1989

Pyruvate decarboxylase is like acetolactate synthase (ILV2) and not like the pyruvate dehydrogenase E1 subunit.

Protein sequences of pyruvate decarboxylase (PDC) derived from cloned yeast (Saccharomyces cerevisiae) and bacterial (Zymomonas mobilis) genes were compared with each other and with sequence databases. Extensive sequence similarities were found between them and with two others: cytochrome-linked pyruvate oxidase from Escherichia coli and acetolactate synthase (ilvI in E. coli; ILV2 gene in S. cerevisiae). All catalyse decarboxylation of pyruvate using thiamine pyrophosphate (TPP) as cofactor. General overall similarity suggests common ancestry for these enzymes. None of the sequences was similar to the E1 component of pyruvate dehydrogenase from E. coli which also decarboxylates pyruvate with the help of TPP.

Acetolactate Synthase↗
PubMed1989

Dominantly inherited dementia and parkinsonism, with non-Alzheimer amyloid plaques: a new neurogenetic disorder.

A family is described in which a dominant form of inheritance, probably autosomal dominant, expresses severe dementia and parkinsonism as the major clinical features. Neuropathological correlates in two autopsied members of this family consisted of extracellular hyaline eosinophilic, congophilic amyloid plaques in decreasing order of frequency in the cerebral cortex, basal ganglia, thalamus, and substantia nigra, and atrophy and gliosis of the basal ganglia and substantia nigra. The extracellular plaques did not stain with antibody raised against the prion protein nor with two separate anti-amyloid A4 antibodies. The combination of dominantly inherited dementia with parkinsonism and extracellular plaques in this distribution that are amyloid and prion protein antibody negative has not been previously reported and thus may represent a new neurological genetic disorder.

Alzheimer Disease↗
PubMed1989

A deletion of the PDC1 gene for pyruvate decarboxylase of yeast causes a different phenotype than previously isolated point mutations.

We deleted most of the pyruvate decarboxylase structural gene PDC1 from the genome of Saccharomyces cerevisiae. Surprisingly, mutants carrying this deletion allele showed a completely different phenotype than previously described point mutations. They were able to ferment glucose and their specific pyruvate decarboxylase activity was only reduced to 45% of the wild type level. Northern blot analysis revealed that a sequence in the yeast genome homologous to PDC1 and formerly designated as a possible pseudogene is expressed and may code for a different but closely related pyruvate decarboxylase. The products of the two PDC genes seem to form hybrid oligomers, however both homooligomers have enzyme activity. Thus, the product of the PDC1 gene is not absolutely necessary for glucose fermentation in yeast.

Blotting, Southern↗
PubMed1989

Acute intermittent porphyria. More than just abdominal pain.

Acute intermittent porphyria is an unusual syndrome that may be very difficult to differentiate from acute intraabdominal processes. Diagnosis requires the documentation of increased urinary porphobilinogen. Failure to perform appropriate tests early in the attack may necessitate diagnostic laparotomy to rule out intraabdominal catastrophies. Once the diagnosis has been made, treatment with intravenous dextrose aborts most acute episodes. Patients should avoid such triggering factors as fasting and certain drugs. Screening of family members is important to identify latent carriers.

Abdomen↗
PubMed1989

Inducing factors and the control of mesodermal pattern in Xenopus laevis.

The mesoderm of Xenopus laevis and other amphibia is formed through an inductive interaction during which cells of the vegetal hemisphere act on cells of the animal hemisphere. Two groups of factors mimic the effects of the vegetal hemisphere. One group consists of members of the fibroblast growth factor (FGF) family, while the other is related to transforming growth factor type beta (TGF-beta). In this paper we discuss the evidence that the FGF family represents 'ventral' mesoderm-inducing signals, and the TGF-beta family 'dorsal' signals. The evidence includes a discussion of the cell types formed in response to each type of factor, the fact that only XTC-MIF (a member of the TGF-beta family) and not bFGF can induce animal pole ectoderm to become Spemann's organizer, and an analysis of the timing of the gastrulation movements induced by the factors.

Animals↗
PubMed1989

Unilateral temporal lobe lesions alter P300 scalp topography.

Event related potentials were recorded from patients with unilateral temporal lobe lesions and healthy volunteers. Subjects were required to silently count on infrequent target tone interspersed among presentations of a non-target tone, with an interval between tones that was relatively long and variable (6-10s). Under these task conditions, the patients were found to have P300 amplitudes that were smaller on the lesioned side relative to the non-lesioned side. This finding is interpreted as evidence that temporal lobe lesions affect the configuration of intracranial sources generating the P300 component of event-related potentials.

Acoustic Stimulation↗
PubMed1988

VP-16 + adriamycin vs. adriamycin alone in advanced adenocarcinoma of the breast, phase II, a randomized trial: a Southwest Oncology Group Study.

One hundred twenty-two patients with advanced adenocarcinoma of the breast were randomized to receive adriamycin (AD) alone or a combination of VP-16 plus lower dose adriamycin (VAD). The patients were stratified to good and poor risk. The starting dose (day 1) of AD was 60 mg/m2 for good risk and 45 mg/m2 for poor risk. The starting dose of the VAD combination for the good-risk patient was VP-16, 75 mg/m2 daily x 5 plus adriamycin 35 mg/m2. The poor-risk dose for VAD was VP-16, 50 mg/m2 daily x 5 plus adriamycin, 30 mg/m2 on day 1. The total dose of AD was 450 mg/m2 on both arms. The patients who were on the VAD arm continued on VP-16 maintenance. Both arms were repeated every 21 days. There were 54 evaluable patients on the adriamycin arm and 52 evaluable patients on the VAD arm. Both arms were similar with regard to age, menopausal status, performance status, and prior hormonal therapy. More hematologic toxicity was seen in the adriamycin arm. Complete responses were observed on both arms, three (5%) with adriamycin and three (5%) with combination. Eleven (19%) and ten (18%) partial responses were observed with the adriamycin and VP-16 plus adriamycin, respectively. AD produced more stable disease than VAD (41% vs. 29%). Complete responses were seen only in the good-risk patients. Time to progression was delayed on the combination arm (P = 0.02). The survival in both arms was similar. The addition of VP-16 to adriamycin does not offer an important clinical advantage.

Adenocarcinoma↗
PubMed1988

The structure and regulation of phosphoglucose isomerase in Saccharomyces cerevisiae.

We have cloned and sequenced the PGI1 gene, encoding phosphoglucose isomerase (E.C.5.3.1.9), from Saccharomyces cerevisiae. The nucleotide sequence predicts subunits of 554 amino acids with a molecular weight of 61,230. Both the size and amino acid composition correlate well with measurements from purified protein. We have compared the PGI1 protein with the predicted sequence for pig muscle PGI. In spite of some evolutionary divergence the proteins are very similar and there are some highly conserved regions, two of which have been implicated in the active site. It has been suggested that PGI exists in two or more isozyme forms in S. cerevisiae and analogy with ADR2/ADC1 suggests that such PGI isozymes might also be differentially regulated during glycolytic/gluconeogenic growth. We have used accurate quantitation of PGI1 mRNA and gene fusions of PGI1 to the lacZ gene of Escherichia coli to show that PGI1 transcription is regulated neither between glycolytic and gluconeogenic growth nor between exponential and stationary phase. The complete lack of PGI activity in PGI1 deletion mutants and of differential regulation suggests that the isozymes of PGI might result merely from processing of the PGI1 gene product.

Amino Acid Sequence↗
PubMed1988

Changes in hepatic parenchymal and nonparenchymal cell vitamin A content during vitamin A depletion in the rat.

Levels of total, unesterified and esterified retinol were determined in liver, liver parenchymal cells (PC) and liver nonparenchymal cells (NPC) during vitamin A depletion in rats. Liver vitamin A levels decreased from 113 to 4 micrograms over a 97-d experimental period; plasma retinol concentrations did not change significantly during this time. Initially, greater than 90% of hepatic vitamin A was in the esterified form and most (93%) was localized in NPC. During vitamin A depletion, there were significant declines in retinyl ester content of both PC and NPC, but unesterified retinol levels were not significantly affected. Plasma retinol concentrations were significantly correlated with unesterified retinol mass in PC and NPC, but not with retinyl ester mass. Although 94% of the liver's negative vitamin A balance was due to changes in NPC retinyl ester levels, the fractional rate of retinyl ester loss from PC and NPC was almost identical. Since unesterified retinol levels in plasma, PC and NPC appeared to be conserved even when liver retinyl ester stores were virtually depleted, and since the retinol utilization rate was apparently not decreasing during this stage of vitamin A depletion, these data support the hypotheses that homeostatic mechanisms controlling the three pools of unesterified retinol are linked, and that vitamin A utilization rate is maintained as long as unesterified retinol levels in plasma, PC and NPC are normal.

Animals↗
PubMed1988

Use of compartmental analysis to describe effects of dietary fat saturation and load on plasma triglyceride dynamics in the rat.

Model-based compartmental analysis was used to interpret data on temporal changes in plasma triglyceride (TG) response to a chronic infusion of chylomicrons (CM) in the rat. Male rats were fed purified diets which varied in fat load [L = 10% (w/w), H = 30%] and P/S ratio (P = 4.6, S = 0.2). Lymph CM isolated from donor rats which were absorbing the P or S fat were infused into recipients for 8 h on 3 consecutive days: on d 1 and 3, CM infusion rate reflected the fat content of the previous diet and on d 2, the other load; the infusion replaced dietary fat. Serial plasma samples from each period were analyzed for TG concentration; TG distribution in plasma lipoproteins and liver lipids was measured after d 3. To describe observed group average data, a compartmental model was developed using the Simulation, Analysis and Modeling computer program. Two compartments were needed in plasma (CM vs nonCM TG); each had 2 outputs: removal of TG-fatty acids by lipoprotein lipase (LPL) and uptake of remnant lipoproteins by the liver. After a delay in the liver, there were 3 fates for TG-derived fatty acids: oxidation, retention, or secretion in very low density lipoproteins. Simulation of changes in the rate constant for total CM TG turnover indicated that the basal level of LPL rose rapidly and dramatically in response to TG infusion; the rise was higher for H vs L. After 3-5 h, apparent LPL activity decreased. Simulation of the rate of CM TG turnover indicated that the turnover rate rose immediately after infusion began to levels higher than the infusion rate, and then came into a slight negative balance. Although the observed data could be qualitatively described based on current understanding of TG metabolism, application of model-based compartmental analysis generated testable hypotheses about quantitative aspects of the system dynamics.

Animals↗