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Biomedical subjects

C Kellogg

Publications and source records attributed to C Kellogg.

At least 19 recordsLinked to original sources
PubMed2000

Cisplatin, cytarabine, caffeine, and continuously infused 5-fluorouracil (PACE) in the treatment of advanced pancreatic carcinoma: a phase II study.

Encouraging results using cisplatin, cytarabine, and caffeine for the treatment of pancreatic carcinoma prompted a phase II study using these agents and adding continuous intravenous infusion (CI) 5-fluorouracil (5-FU) (PACE). Patients with advanced pancreatic adenocarcinoma who had not received prior cytotoxic therapy were eligible. Treatment consisted of the following: on day 1, the administration of cisplatin 100 mg/m2 IV, cytarabine 2 g/m2 IV every 12 hours x 2 doses, and caffeine 400 mg/m2 subcutaneously after each cytarabine dose; and on days 3 to 21, 5-FU 250 mg/m2/day given by CI. Cycles were repeated every 28 days. Thirty eligible patients were entered in the study. The median number of cycles received was three. Grade IV neutropenia and thrombocytopenia occurred in 53% and 27% of patients, respectively. Among 30 treated patients, complete remission (CR) was seen in 2 patients and partial remission (PR) in 3 patients, for an overall response rate of 16.7% (95% confidence interval 6.8-32.4%). The median survival was 5.0 months (range: 0.3-32.4 months) and 16.7% and 10% of patients were alive at 1 and 2 years. respectively. Changes in the serum level of CA 19-9 provided an early marker of response which translated in differences in survival. Those with increasing or decreasing/stable levels of CA 19-9 after the first cycle of therapy had median survivals of 1.7 and 8.3 months, respectively (p = 0.0002). Although PACE chemotherapy produced durable responses in pancreatic cancer, the toxicity was substantial. A modification of this regimen with newer, less toxic drugs may provide better results and reduced toxicity. Also, the monitoring of the serum CA 19-9 level may provide a means to assess response and predict survival.

Adenocarcinoma↗
PubMed1997

Coliphage and indigenous phage in Mamala Bay, Oahu, Hawaii.

Public concern over the discharge of primarily treated sewage by two offshore outfalls in Mamala Bay, Oahu, prompted a multidisciplinary study to determine the impact of such activities on the water quality in the bay and at adjacent recreational beaches. As part of this study, we determined the abundance of coliphage as an indicator of fecal pollution along with total viral direct counts and phages infective for Vibrio parahaemoltyicus 16 at stations in Mamala Bay in four quarterly samplings over 13 months. Coliphage (< 1 to 1.2 x 10(3)/liter) were found during each quarterly sampling along an offshore transect to the Sand Island waste treatment facility outfall. The nonpoint coastal stations (Pearl Harbor, Ala Wai Canal, and Ke'ehi Lagoon) had high levels of coliphage during the storm event sampling in February 1994 but much lower levels or none when sampled during dry weather. Coliphage were absent at all samplings at Waikiki Beach and at the control station off Diamond Head. Viral direct counts in eutrophic coastal stations (Pearl Harbor, Ke'ehi Lagoon, Ala Moana Beach, and Ala Wai canal) averaged 10(9)/liter, while counts at offshore stations ranged from 9 x 10(7) to 1 x 10(9) viruses/liter, values similar to those for other marine environments. Vibriophage were found mainly in eutrophic coastal environments (Ala Wai Canal, Pearl Harbor, and Ke'ehi Lagoon) and at the Sand Island Transect stations D1 and D2. The greatest abundance was found during the storm event (February 1994) sampling. These results suggest that the Sand Island outfall influenced the water quality of the immediate surrounding waters but had little effect on the quality of the recreational beaches. Nonpoint discharge sources appeared to be more important in the distribution of fecal indicators in the coastal zone.

Bacteriophages↗
PubMed1995

Occurrence of fecal indicator bacteria in surface waters and the subsurface aquifer in Key Largo, Florida.

Sewage waste disposal facilities in the Florida Keys include septic tanks and individual package plants in place of municipal collection facilities in most locations. In Key Largo, both facilities discharge into the extremely porous Key Largo limestone. To determine whether there was potential contamination of the subsurface aquifer and nearby coastal surface waters by such waste disposal practices, we examined the presence of microbial indicators commonly found in sewage (fecal coliforms, Clostridium perfringens, and enterococci) and aquatic microbial parameters (viral direct counts, bacterial direct counts, chlorophyll a, and marine vibriophage) in injection well effluent, monitoring wells that followed a transect from onshore to offshore, and surface waters above these wells in two separate locations in Key Largo in August 1993 and March 1994. Effluent and waters from onshore shallow monitoring wells (1.8- to 3.7-m depth) contained two or all three of the fecal indicators in all three samples taken, whereas deeper wells (10.7- to 12.2-m depth) at these same sites contained few or none. The presence of fecal indicators was found in two of five nearshore wells (i.e., those that were < or = 1.8 miles [< or = 2.9 km] from shore), whereas offshore wells (> or = 2.1 to 5.7 miles [< or = 3.4 to 9.2 km] from shore) showed little sign of contamination. Indicators were also found in surface waters in a canal in Key Largo and in offshore surface waters in March but not in August. Collectively, these results suggest that fecal contamination of the shallow onshore aquifer, parts of the nearshore aquifer, and certain surface waters has occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Clostridium perfringens↗
PubMed1991

Evidence for a contribution of paramagnetic ions to water proton spin-lattice relaxation in normal and malignant mouse tissues.

Paramagnetic ions complexed to proteins may lose, retain, or enhance solvent paramagnetic relaxation (SPR) relative to free solution. We measured T1 and T2 of three mouse cancers, their normal counterparts, and six additional tissues. Long T1 of cancers was not caused by necrosis or by different contents of water, fat, or blood. Dissociable (TCA-extractable) and nondissociable (ashed) Mn, Cu, and Fe were measured by AA. Cancers had less Mn, Cu, and Fe than did normal counterparts. All 12 tissues had inverse correlations between T1 and dissociable Mn and Cu. For Mn alone to account for reduced T1, the extent to which SPR of the Mn-protein complexes would be enhanced is by factors of 0.6 to 13, below the maximum observed in Mn-enzymes. Different amounts of paramagnetic ion-protein complexes may account for part of the differences in T1 of water protons in different tissues, and the longer T1 of cancer cell water may be caused in part by reduced amounts of such complexes.

Animals↗
PubMed1991

Neonatal exposure to therapeutic caffeine alters the ontogeny of adenosine A1 receptors in brain of rats.

Caffeine is a methylxanthine, commonly used in the premature neonate to treat apnea of prematurity. It is efficacious and appears to have few short-term side effects. An animal model, designed to mimic the developmental period in brain and level and duration of exposure in humans, was used to investigate possible long-term effects of early developmental exposure to caffeine on the ontogeny of the adenosine receptor to which caffeine binds. Specific binding at the adenosine A1 receptor, in five distinct regions of the brain was determined in rats, 14-90 days old, as a function of early postnatal exposure to caffeine, over days 2-6. In cortex, cerebellum and hippocampus but not in the brain stem or hypothalamus, there was an increase in specific binding, following neonatal exposure to caffeine, compared to specific binding in control animals. Kinetic analysis of binding to the A1 site in cortical tissue suggests that this increase was due to an increased maximum binding density (Bmax); binding affinity (Kd) did not change. Thus, limited exposure to caffeine, in the early neonatal period, may result in up-regulation of the adenosine A1 receptor that persists to young adulthood in the rat.

Animals↗
PubMed1991

Potentiation of acoustic startle behavior in the rat (Rattus norvegicus) at the onset of darkness.

In Experiment 1 (N = 8), a 20-ms light pulse, given at various times before a noise burst, inhibited reflex expression with a single trough at a lead time of 70 ms, whereas a dark pulse facilitated the reflex with two peaks at 40 and 160 ms. In Experiment 2 (N = 18) facilitation by dark onset had a single peak, and inhibition by light onset a single trough; thus, the double peak of the dark pulse may result because inhibition from light onset at the end of the dark pulse was briefly impressed on the facilitatory effect of dark onset. In Experiment 3 (N = 12), diazepam (2.5 mg/kg, but not 1 mg/kg) eliminated dark facilitation but not light inhibition. These diazepam data reveal a basic similarity, perhaps identity, of the mechanisms responsible for the effect of dark onset and those producing reflex facilitation by Pavlovian fear conditioning and prolonged background noise, because all are moderated by a GABAergic system.

Animals↗
PubMed1990

Early developmental exposure to benzodiazepine ligands alters brain 31P-NMR spectra in young adult rats.

Alterations in brain high energy phosphate compounds, using 31P-NMR (nuclear magnetic resonance) spectroscopy, were measured in vivo in young adult (3-4 months) rats following prenatal exposure to ligands acting specifically at benzodiazepine (BDZ) binding sites. The exposure induced a decrease in intracellular pH that indicated a predominant interaction of the drugs in utero with central-type BDZ receptor sites. Late gestational exposure to BDZ ligands also induced changes in brain phosphocreatine (PCr) utilization. Exposure to the lowest dose of DZ (1.0 mg/kg) but not the higher dose (2.5 mg/kg) induced a significant change in PCr utilization. Exposure to the central-type BDZ receptor antagonist RO15-1788 alone clearly altered PCr utilization in adult offspring, and DZ (2.5 mg/kg) when administered concurrently was not able to prevent this effect. Though exposure to a peripheral-type ligand (PK11195) had no effect by itself, it converted the effect of the high dose of DZ to that of the low dose. Together, these results indicate an interaction during development between the central and peripheral-type BDZ binding sites on organization and/or regulation of cellular energy metabolism. Normalized ATP levels were not changed by any prenatal treatment indicating adequate buffering of intracellular ATP by phosphocreatine. The dopaminergic antagonist haloperidol did not alter intracellular pH or any index of phosphate metabolism indicating a selective receptor mediated role for BDZ ligands in influences on the long term organization of intracellular phosphate metabolism.

Animals↗
PubMed1990

Cografts of adrenal medulla with C6 glioma cells in rats with 6-hydroxydopamine-induced lesions.

Amitotic [3H]thymidine-labeled C6 glioma cells, which are known to produce neurotrophic factor(s), were grafted alone and with adrenal chromaffin cells in an attempt to improve chromaffin cell survival and phenotypic differentiation. Long-Evans rats with unilateral 6-hydroxydopamine-induced lesions of the nigrostriatal pathway were divided into four groups: (1) those receiving adrenal medullary cells co-transplanted with C6 glioma cells; (2) those receiving adrenal medullary graft alone; (3) those receiving C6 glioma grafts alone; and (4) those serving as a vehicle control group. All rats were killed one month after transplantation. Immunohistochemical, neurochemical, and autoradiographic methods were used to identify and characterize the grafted cells. Tyrosine hydroxylase-immunoreactive cells were found in all animals that received grafts of the adrenal medulla alone or of adrenal medulla co-transplanted with C6 glioma cells. The cograft recipients had more tyrosine hydroxylase-immunoreactive cells than the hosts receiving just adrenal chromaffin cells (P less than 0.05). Additionally, more grafted chromaffin cells formed processes in the former group. All three tissue recipient groups (adrenal medullary, C6 glioma cell, and cografted animals) had a significant reduction (P less than 0.05) in ipsilateral rotations after amphetamine (0.5 mg/kg i.p.) injections as compared to the control vehicle recipient group. Moreover, the reduction in rotation was more marked in the cografted hosts than in the other two implanted groups (P less than 0.05). Significantly higher dopamine levels were found in the transplant sites of both cograft and adrenal medullary graft recipients than in sham grafted control animals.

Adrenal Medulla↗
PubMed1989

The relationship of benzodiazepine binding sites to the norepinephrine projection in the hypothalamus of the adult rat.

The relationship of benzodiazepine binding sites to noradrenergic terminals in different brain regions of adult rats was evaluated. The in vitro addition of 10(-5) M diazepam (DZ) significantly reduced the depolarization-induced release of [3H]norepinephrine (NE) in the hypothalamus, while no effect was observed in the cerebellum, suggesting that DZ may act directly on NE terminals in the hypothalamus. The action of DZ in the hypothalamus was blocked either by co-incubation with the benzodiazepine (BZ) antagonist RO 15-1788 (a neutral ligand for BZ binding sites) or with the GABA antagonist, bicuculline. Analysis of BZ binding heterogeneity, using the triazolopyridazine CL 218,872 as displacing agent, indicated that binding heterogeneity exists in both the cortex and hypothalamus, whereas the cerebellum has a more homogeneous binding site population. Binding site heterogeneity does not appear to explain the selective effect of DZ on hypothalamic noradrenergic terminals. Systemic injection of the neurotoxin 6-hydroxyDOPA decreased NE levels significantly in the cerebellum, cortex and hypothalamus. Only in the hypothalamus, however, did the decrease in NE levels correlate in magnitude with the decrease in BZ receptor binding. A large proportion of BZ receptors may be located presynaptically on the hypothalamic NE terminals. The location of these BZ binding sites may contribute to the unique response to DZ observed in the hypothalamus following either in vitro or in utero exposure.

Animals↗
PubMed1983

Development of benzodiazepine binding subtypes in three regions of rat brain.

An examination of the development of benzodiazepine binding of the high and low affinity triazolopyridizine (TPZ) type was undertaken in rat cortex, hippocampus and cerebellum. Various concentrations of a typical triazolopyridizine, CL-218-872, were used to displace [3H]flunitrazepam from synaptosomal fractions from rats of postnatal ages day 0, 7, 14, 21, 35 and 70. In contrast to the cortex and cerebellum, hippocampus displays high affinity TPZ binding at birth, prior to the periods of dendritic elaboration and synaptogenesis, suggesting that adult proportions of high and low affinity sites are maintained throughout postnatal development. Delayed postnatal development of high affinity TPZ sites is observed in the cerebellum, similar to the postnatal development previously observed in the cortex.

Aging↗
PubMed1983

Prenatal diazepam exposure: effects on auditory temporal resolution in rats.

The maturation of temporal acuity in the auditory system of the rat was evaluated following prenatal exposure to diazepam (DZ; 0, 2.5, 10 mg/kg to the dam on each of the last 8 days of gestation). Acuity was defined by the effectiveness of brief silent periods in white noise (gaps) as in inhibitors of an immediately subject acoustic startle reflex. In uninjected control rats the gaps became effective at 25-28 days of age, and onset was delayed in prenatally exposed animals according to dose. No DZ was present in the rat offspring at animals in adulthood (0, 0.5, 1.5, 4.5 mg/kg). These injections reduced the inhibitory effect of the gap on startle behavior in all animals, but less so in those previously exposed to DZ in utero. The threshold of temporal acuity in the rat approximates that found in humans and the function matures at the same relative rate in the two species. Further, administration of DZ in the adult human has the same effect on temporal acuity in the auditory system as it does in the adult rat. There are presently no data available on the effects on human auditory development of exposure to DZ in utero. The data we present have the importance of temporal acuity in the perception of speech and, thus, in the maturation of language ability.

Animals↗
PubMed1982

Inhibition of tryptophan hydroxylase: neurochemical action of catecholamide seizure-inducing agent.

H13/04, an audiogenic seizure-inducing catecholamide, has previously been demonstrated to decrease the accumulation of 5-hydroxytryptophan (5-HTP), while increasing the accumulation of dihydroxyphenylalanine (DOPA) after aromatic acid decarboxylase inhibition in vivo. The present study examined the effect of H13/04 on intracellular storage, release, and metabolism of serotonin (5-HT) and noradrenaline (NA) in vitro in order to differentiate between the primary effects of the drug and possible secondary effects due to neurotransmitter interaction. H13/04 had not effect on NA synthesis by brain minces from C57BL/6 mice, but did have a marked effect on [P3H]5HT synthesis from [3H]tryptophan in mouse brain minces. H13/04 was subsequently shown to competitively inhibit tryptophan hydroxylase. The data presented in this study indicate that the primary action of H13/04 on biogenic amines is to decrease the synthesis rate of 5-HT by competitive inhibition of tryptophan hydroxylase. The lack of any effect on NA in vitro is consistent with the hypothesis that the primary biochemical action of the drug is on the 5-HT system and that the action on NA in vivo is an indirect effect possibly secondary to the inhibition of 5-HT synthesis.

Acoustic Stimulation↗
PubMed1980

Prenatal exposure to diazepam alters behavioral development in rats.

Characteristic potentiation of rat locomotion responses and acoustic startle reflexes that normally appear in the third postnatal week was absent in rats exposed to diazepam during the third week of gestation. Loss of these behaviors suggests a long-term effect that may result from changes in cellular development. Tissue undergoing neuronal differentation may be especially sensitive to drugs that act on the central nervous system, and the period in which differentiation occurs is perhaps critical for the induction of changes that are later expressed as altered behavior.

Animals↗
PubMed1979

Development of muscarinic cholinergic receptors in inbred strains of mice: identification of receptor heterogeneity and relation to audiogenic seizure susceptibility.

The concentrations and biochemical properties of muscarinic acetylcholine receptors in the brains of two highly inbred strains of mice, DBA/2J and C57BL/6J, have been studied using [3H]quinuclidinyl benzilate (QNB), a potent and specific receptor antagonist. As is the case with rat brain, murine muscarinic receptors exist in at least two forms, which differ in their affinities for receptor agonists but which have the same high affinity for receptor antagonists. Carbamylcholine binding to mouse neural membranes can be resolved into two components with KDs of 5.2 times 10(-7) and 7.9 times 10(-5) M. There is a regional heterogeneity of brain receptors with respect to their distribution between these high and low agonist affinity forms. Brain stem and hypothalamus receptors display binding properties that would be expected if over 60% of their receptors were in the high affinity state, while only 30-40% of cortex, striatum and thalamus receptors appear to be in the high affinity form. Hippocampal receptors display the least amount of high agonist affinity character. Saturation curves and Scatchard plots of QNB binding at 2, 14, 21 and 42 days postnatal age in both strains indicate no differences or changes in the affinity or nature of the binding with age. Significant increases in QNB binding per mg membrane protein were observed between 14 and 42 days in the cortex, hippocampus, striatum, thalamus and hypothalamus, but not in the midbrain-pons-medulla region. In the hippocampus the DBA mice had significantly more QNB binding. In the hypothalamus decreases with age in total binding were noted in DBA, while slight increases were noted in C57. Compared to C57, hippocampal receptors in DBA displayed lower agonist affinity at 14 and 21 days, a trait which was not apparent when DBA had outgrown their audiogenic seizure sensitivity at 42 days. The differences in receptor density and agonist state distribution between the two strains may be related to audiogenic seizure sensitivity.

Acoustic Stimulation↗
PubMed1976

Audiogenic seizures: relation to age and mechanisms of monoamine neurotransmission.

Mice with a genetically determined susceptibility to audiogenic seizures were utilized to analyze the ontogeny of central monoamine neurotransmission in relation to a behavior with age-specific properties. Levels of noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) were measured in forebrain and hindbrain regions at 14, 21, 28, and 42 days postnatal age in genetically sensitive or resistant strains of mice. An in vivo estimate of tyrosine and tryptophan hydroxylase activity was obtained at the same ages by following the accumulation of 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) respectively, after the administration of a centrally effective L-amino acid decarboxylase inhibitor (R04-4602, 800 mg/kg). At 14 days, there was a faster rate of accumulation of DOPA in both the forebrain and hindbrain of the sensitive mice compared to mice of the nonsensitive strain. At 21 days, the age of maximal sensitivity in the sensitive mice, the levels of NA were significantly lower in both regions of the sensitive mice, but the accumulation of DOPA was similar between strains at this age. There was also a slightly lower level of 5-HT in the forebrain of sensitive mice at 21 days accompanied by a slower rate of accumulation of 5-HTP in this region. In the hindbrain of the sensitive animals however, the rate of accumulation of 5-HTP was faster than in the sensitive strain. At 28 days, some impairment in mechanisms within NA-containing neurons in the sensitive mice was still apparent (including lower NA levels). At 42 days, there were no differences in amine levels, however, the levels of accumulated DOPA and 5-HTP were significantly lower in the sensitive strain. The results suggest that in the sensitive mice, developmental differences in mechanisms of monoamine storage and/or synthesis may exist which could contribute to deficient amounts of physiologically releaseable transmitter.

5-Hydroxytryptophan↗
PubMed1976

Central action of a catechol-amide seizure-inducing agent: opposing effect on tyrosine and tryptophan hydroxylase activity in vivo.

The audiogenic seizure-inducing drug H13/04 was found to elicit opposing effects on the in vivo accumulation of 5-HTP (5-hydroxytryptophan) and DOPA (3,4-dihydroxyphenylalanine) in the brain following inhibition of L-amino acid decarboxylase. In strains of mice that normally do not exhibit audiogenic seizures, H13/04 retarded the accumulation of 5-HTP in the telencephalon, diencephalon and brainstem and enhanced the accumulation DOPA in the diencephalon and brainstem. The duration of the biochemical action of H13/04-correlated with the duration of the behavioral effect. When H13/04 is administered to strains of mice with a genetically-determined susceptibility to audiogenic seizures, but at an age when they are developing resistance to seizures, H13/04 does not alter the incidence of sound-induced seizures. The effect on the accumulation of 5-HTP and DOPA was similar to that noted in the genetically-resistant strain; a retardation of the accumulation of 5-HTP in the telencephalon and brainstem and an enhancement of DOPA accumulation in the brainstem. Since the rate of accumulation of 5-HTP and DOPA is a measure of the in vivo rates of tryptophan and tyrosine hydroxylase, respectively, the results may reflect changes in neural activity with consequent effects on the synthesizing enzymes. These results emphasize the usefulness of the drug in analyzing central mechanisms underlying audiogenic seizure activity and in studying functional properties and interactions of the central catechol-and indoleamine systems.

Amides↗
PubMed1975

In vivo rates of tyrosine and tryptophan hydroxylation in regions of rat brain at four times during the light-dark cycle.

The in vivo rates of tyrosine and tryptophan hydroxylation were studied in three regions of young adult rat brains at 4 times the light-dard cycle. The procedure utilized was to analyze the accumulation of Dopa and 5-HTP after injection of a centrally effective L-amino acid decarboxylase inhibitor, NSD 1015. Monoamine levels were also determined in all control animals and some treated animals. The reate of tyrosine dydrosylation in the telencephalon was significantly higher 7 hrs after dard onset than at the other three times tested. Smaller variations in tyrosine and tryptophan hydroxylation rates as a function of time of day were also observed. 5-HT levels were significantly higher during the light phase than the dark in the telencephalon with the same trend occurring in the diencephalon and brainstem. NA was stable in the telencephalon but reached lower levels in the light and higher levels in the dark in the other two regions. In the telencephalon DA reached high levels early in the light and in the dark phases, showing a biphasic variation. Of particular interest was the apparent lack of carrelation between cyclic changes in the monoamine levels and the changes in hydroxylation rates. Rates of hydroxylation can be considered indicative of rates of monoamine synthesis. This observation is discussed in relation to feedback and other mechanisms regulating synthesis and release of monoamines.

Amino Acids↗