Search PubMed⌕ Search

Biomedical subjects

K S Thompson

Publications and source records attributed to K S Thompson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Expression of an insulin-responsive glucose transporter (GLUT4) minigene in transgenic mice: effect of exercise and role in glucose homeostasis.

The effects of a GLUT4 mini-transgene (containing 7 kb of 5' flanking and 1 kb of 3' flanking sequence and all exons and introns of the GLUT4 gene as well as a small foreign DNA tag) and of exercise training on expression of GLUT4 and glycemic control in mice were investigated. Transgenic mice harboring the minigene expressed < or = 2-fold the normal level of GLUT4 mRNA and protein in skeletal (gastrocnemius) muscle and adipose tissue. This modest tissue-specific increase in GLUT4 expression led to an unexpectedly rapid blood glucose clearance rate following oral glucose administration. In nontransgenic animals exercise caused a 1.5-fold increase in expression of GLUT4 mRNA and protein as well as a significant improvement of glycemic control. In transgenic animals harboring the minigene exercise increased expression of GLUT4 mRNA and protein derived from the minigene and endogenous gene and led to a further improvement of glycemic control. These findings indicate that the cis-regulatory element(s) controlling exercise-induced expression of the GLUT4 gene is located within the nucleotide sequence encompassed by the GLUT4 minigene. The fact that glycemic control is markedly improved by a relatively low level of expression of GLUT4 caused by the transfected minigene and is further enhanced by exercise in transgenic animals demonstrates that GLUT4 plays a pivotal role in glucose homeostasis in vivo. Of the effectors--i.e., cAMP, insulin, and arachidonic acid--known to down-regulate expression of GLUT4 by 3T3-L1 adipocytes in culture, only the decline in circulating arachidonate level in vivo correlated with up-regulation of GLUT4 caused by exercise.

Animals↗
PubMed1995

Cellular colocalization of diuretic peptides in locusts: a potent control mechanism.

Locust abdominal ganglia are shown to colocalize Locusta-diuretic peptide-, leucokinin I-, and lysine vasopressin-like immunoreactivity in posterior lateral neurosecretory cells. Extracts of abdominal ganglia were partially purified by RP-HPLC then dot immunoassay screened with the same antisera used for immunocytochemistry. Locusta-diuretic peptide-like immunoreactive material coeluted with synthetic Locusta-diuretic peptide, and leucokinin-like immunoreactive material coeluted with locustakinin. Lysine vasopressin-like material eluted in fractions that also showed Locusta-diuretic peptide and leucokinin I immunoreactivity. The diuretic activity of synthetic Locusta-diuretic peptide and locustakinin is demonstrated, and they are shown to act at least additively to promote Malpighian tubule fluid secretion. The immunoreactive neurosecretory cells are assumed to express at least these two peptides, and a model for promoting fluid secretion is proposed.

Abdomen↗
PubMed1995

Analysis of the peptide content of the locust vasopressin-like immunoreactive (VPLI) neurons.

Isolated cell bodies of the locust vasopressin-like immunoreactive (VPLI) neurons, analyzed by HPLC separation and radioimmune assay, contain three arginine vasopressin-like peptides: a previously identified monomer (Fl, Cys-Leu-Ile-Thr-Asn-Cys-Pro-Arg-Gly-NH2) and its antiparallel homodimer (F2), but also the previously unreported parallel homodimer (PDm). VPLI neuron activity significantly reduces the level of cAMP in the CNS. Of the three synthetic peptides, only the monomer (F1, 10(-8) and 10(-6) M) is capable of inhibiting a forskolin-stimulated increase in cAMP in isolated neural membranes. The antiparallel (F2) and parallel dimers (PDm) of this peptide have no effect on this second messenger.

Amino Acid Sequence↗
PubMed1995

Identified octopaminergic neurons provide an arousal mechanism in the locust brain.

1. Habituation is the declining responsiveness of a neural circuit (or behavior) to repetitive stimulation. Dishabituation (or arousal) can be brought about by the sudden presentation of an additional, novel stimulus. A clear example of arousal in the locust is provided by the visual system: the habituated response of the descending contralateral movement detector (DCMD) interneuron to repetitive visual stimuli can be dishabituated by a variety of other visual and tactile stimuli. 2. Application of octopamine to the locust brain and optic lobes dishabituates the DCMD in a manner similar to the effect of visual and tactile stimulation. 3. The locust CNS contains two pairs of octopamine-immunoreactive cells, the protocerebral medulla 4 (PM4) neurons, that could potentially mediate this dishabituation effect; PM4 neurons arborize in the optic lobe, they contain octopamine, and they respond to the same visual and tactile stimuli that dishabituate the DCMD. 4. To investigate whether PM4 activity dishabituates the DCMD, we recorded intracellularly from one of the PM4 neurons while recording extracellularly from the DCMD. When the PM4 neuron is injected with hyperpolarizing current to render it completely inactive, the DCMD exhibits its characteristic habituation to a moving visual stimulus. However, depolarizing the PM4 neuron, to produce action potentials at approximately 20 Hz, significantly increases the number of DCMD action potentials per stimulus. 5. The PM4 neurons may therefore play an important role in dishabituating the DCMD to novel stimuli. This effect is presumably mediated by PM4 neurons releasing endogenous octopamine within the optic lobe.

Animals↗
PubMed1995

Assessing the value of a short-term residential drug treatment program for homeless men.

Cocaine and other substance abuse has been found to be a contributing or primary cause of homelessness in urban men. This project evaluated the effectiveness of the Grant Street Partnership (GSP), a shelter-based treatment program for homeless, cocaine-abusing men, consisting of 90 days of residential treatment and 6 months of aftercare. We tested the hypothesis that the 182 men randomized to the GSP group, as compared to the 112 men randomized to a "usual services" group, would show significantly greater improvement over time in the areas of drug use and residential and economic stability. An 80% response rate was achieved overall for the five follow-up points. Cocaine use, defined as use of cocaine at least once in the prior 30 days, declined from about 90% at baseline for both groups to 11% in the GSP group and 55% in the control group at 21 months. The GSP group was also more likely than the usual services group to have achieved residential stability by the time of the 9 month follow-up. Neither group experienced an improvement over time in employment status.

Adult↗
PubMed1994

Comparative anatomy of serotonin-like immunoreactive neurons in isopods: putative homologues in several species.

It is now commonly accepted that the arthropod nervous system has evolved only once, and so homologies between crustacean and insect nervous systems can be meaningfully sought. To do this, we have examined the distribution of serotonin (5-hydroxytryptamine)-like immunoreactive neurons in the central nervous system (CNS) of four common British isopods. Two species of terrestrial woodlouse, Oniscus asellus and Armadillidium vulgare, the littoral sea slater, Ligia oceanica, and the aquatic water hoglouse, Asellus meridianus, all possess approximately 40 pairs of serotonin-like immunoreactive neurons, distributed throughout the CNS in a very similar pattern. Interspecific homology is clearly suggested. Serotonin-like immunoreactive neurons in the first (T1) and fourth (T4) thoracic ganglia are particularly prominent in each of the four species studied. Whole-mount immunohistochemistry shows that the pair of T1 neurons have large dorsolateral cell bodies and prominent neurites that project medially and then anteriorly, whereas the pair of T4 neurons have ventrolateral cell bodies and neurites that bifurcate to form a thin axon projecting anteriorly to terminate in T3 and a thick medial axon that projects posteriorly into the abdominal neuromeres of the terminal ganglion. Intracellular cobalt staining of these neurons reveals more of their arborizations: the T1 neurons send three processes anteriorly, which arborize in the brain and exist from the CNS via peripheral nerves, whereas the T4 neurons contribute considerably to the extensive pattern of serotonin-like immunoreactive fibres in T3-T6 ganglia. The overall pattern of serotonin-like immunoreactive neurons in the isopods is similar to that in decapod crustacea, and a number of putative homologies can be assigned. It is more difficult to homologize the isopod serotonin-like immunoreactive neurons with those in the insect CNS, but some stained brain and thoracic neurons share common cell body positions and axon trajectories in isopods, decapods, and insects and may therefore be homologous.

Animals↗
PubMed1994

Entropy in biological binding processes: estimation of translational entropy loss.

The loss of translational degrees of freedom makes an important, unfavorable contribution to the free energy of binding. Examination of experimental values suggest that calculation of this entropy using the Sackur-Tetrode equation produces largely overestimated values. Better agreement is obtained using the cratic entropy. Theoretical considerations suggest that the volumes available for the movement of a ligand in solution and in a complex are rather similar, suggesting also that the cratic entropy provides the best estimate of the loss of translational entropy.

Angiotensin II↗
PubMed1994

Localization of Locusta-DP in locust CNS and hemolymph satisfies initial hormonal criteria.

Locusta-diuretic peptide (Locusta-DP) is a potent stimulant of fluid secretion and cyclic AMP production by locust Malpighian tubules. In this study, a polyclonal antiserum raised to the C-terminus of Locusta-DP reveals a wide distribution of immunoreactive cell bodies and processes throughout the CNS, and endings in two important neurohemal release sites: the corpora cardiaca and the perivisceral organs. HPLC fractionation of CNS, neurohemal structures, and hemolymph reveals immunoreactive material that coelutes with synthetic Locusta-DP and stimulates cyclic AMP production by locust tubules. The identity of the immunoreactive and biologically active material is confirmed as authentic Locusta-DP by mass spectrometry.

Animals↗
PubMed1994

The difficult doctor-patient relationship: somatization, personality and psychopathology.

The difficult doctor-patient relationship and "difficult patients" have been the subject of considerable anecdotal study. Reliable methods for identification of difficult patients have not been available for the empirical study of their prevalence and characteristics. We developed the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ), composed of 30 Likert items, completed by physicians after encounters with patients. Adult patients and their providers in an academic, municipal hospital clinic participated in the instrument development (n = 92), reliability (n = 224), and assessment of patient characteristics phases (n = 113) of the study. The DDPRQ was shown to be a reliable, practical instrument. Factor analysis revealed 5 dimensions with face validity. The DDPRQ classified 10.3-20.6% of patient encounters as "difficult" depending on the sample. Demographic characteristics, provider characteristics and most medical diagnoses were not associated with DDPRQ score. In contrast, difficult patients were characterized by psychosomatic symptoms, at least mild personality disorder, and Axis I (major) psychopathology, and most had more than one of these characteristics. The need to identify and understand these components of difficult patient behavior and to include the doctor-patient relationship in strategies for managing the difficult patient is discussed.

Adult↗
PubMed1993

Cyclic AMP-induced transcriptional repression of the insulin-responsive glucose transporter (GLUT4) gene: identification of a promoter region required for down-regulation of transcription.

The mechanism(s) by which cyclic AMP represses transcription of the GLUT4 gene was investigated. 3T3-L1 preadipocytes were stably transfected with a series of 5' deletion mutants of the mouse GLUT4 gene promoter fused to the bacterial CAT gene and then were induced to differentiate into adipocytes. A method based on reverse transcription/polymerase chain reaction (PCR) amplification was developed and optimized to quantitate expression of CAT mRNA transcripts. Treatment with 8-bromo-cAMP down-regulated the level of CAT mRNA in adipocytes transfected with the -7000/CAT, -785/CAT and -469/CAT constructs, but not the -78/CAT construct. Thus, the regulatory element(s) which mediates transcriptional repression by cAMP resides in the proximal promoter of the GLUT4 gene between positions -469 and -78. Since down-regulation of GLUT4 mRNA is unaffected by inhibitors of protein synthesis, cAMP (and insulin) may activate phosphorylation or dephosphorylation of an existing transcription factor that interacts with the GLUT4 proximal promoter.

3T3 Cells↗
PubMed1993

Molecular analysis of spontaneous nephrotropic anti-laminin antibodies in an autoimmune MRL-lpr/lpr mouse.

To explore the genetic relationship between anti-laminin and anti-DNA autoantibodies (autoAb), VH gene and gene family expression were determined among autoAb derived from an individual 6-mo-old MRL-lpr/lpr mouse. Whereas 85% of the anti-DNA Ig were identified by one of two VH family probes, 7183 and VHJ558, none of the anti-laminin antibodies (Ab) examined were recognized by these probes. Subsequent V region sequence analysis of three of the anti-laminin Ab revealed that they in fact utilized a J558 VH gene (VH50). Furthermore, FR2 and CDR2 oligonucleotide probes complementary to VH50 recognized multiple anti-laminin Ab by Northern blot analysis; the FR2 probe recognized two control anti-DNA Ab, but neither probe recognized anti-DNA Ab from the same mouse. Polymerase chain reaction amplification of MRL-lpr/lpr genomic liver DNA using primers generated from VH50 and Vk50 sequences indicated that all three anti-laminin Ig have a single replacement mutation in both their VH and Vk genes. Search of the nucleic acid databases revealed that both germline VH and Vk genes are expressed unmutated by murine lupus anti-dsDNA autoAb, previously sequenced in other laboratories. Sequence comparisons suggest that differences in anti-DNA and anti-laminin reactivity may be dependent upon somatically generated differences in the CDR3 regions of the H and L chains. The results indicate that lupus anti-laminin Ab can arise from distinct B cell populations but express the same unmutated germline V region genes as lupus anti-dsDNA autoAb. They further raise the possibility that these distinct B cell populations may be activated and expanded either: independently, by distinct Ig receptor ligands such as the Ag, laminin and DNA; or simultaneously, by a common ligand such as an anti-Id recognizing a common V region epitope.

Amino Acid Sequence↗
PubMed1993

Carbohydrate regulation of the rat L-type pyruvate kinase gene requires two nuclear factors: LF-A1 and a member of the c-myc family.

Transcription of the L-type pyruvate kinase (L-PK) gene is induced in response to increased carbohydrate metabolism in the liver. We have demonstrated previously that a segment of the 5'-flanking region of the L-PK gene between -183 and -96 is necessary and sufficient for the glucose response in primary hepatocytes. To explore the protein factors that are involved in carbohydrate regulation, we have performed mutational analyses and in vitro binding studies of this segment. Sequences critical for the glucose response were mapped from -171 to -124. This segment contains the consensus binding sites for two nuclear transcription factors: LF-A1 and MLTF. Both factors are capable of binding to the corresponding L-PK sites in vitro. Mutational and functional analyses indicated that LF-A1 is indeed involved in glucose induction of the L-PK gene. The PK MLTF-like site consists of two imperfect CACGTG motifs, the core binding site for a family of transcription factors related to c-myc. Unexpectedly, mutations in either motif that resulted in defective glucose stimulation retained in vitro binding to MLTF. Furthermore, an authentic MLTF binding site from the adenovirus major late promoter was not functionally interchangeable with the natural sequence. These data indicate that binding of MLTF, in presence of LF-A1, is not capable of supporting the glucose response. Conversion of either imperfect motif to CACGTG within the context of the mutations disrupting the opposite site restored the response to elevated glucose. Thus, the factor that recognizes the PK MLTF-like site and participates in mediating the carbohydrate response of the L-PK gene appears to be a member of the c-myc family distinct from MLTF.

Animals↗
PubMed1993

Thermodynamic characterization of the structural stability of the coiled-coil region of the bZIP transcription factor GCN4.

The thermal stability of a 56 amino acid fragment of GCN4 has been studied by high-sensitivity differential scanning calorimetry and circular dichroism spectroscopy. This fragment contains the leucine zipper and part of the basic region. The thermal unfolding of GCN4-56 is a reversible process and can be well represented by a reaction of the form N2<-->2U, indicating that the unfolding of the leucine zipper is a two-state process in which the helices are only stable when they are in the coiled-coil conformation. As expected, the transition temperature is concentration dependent. At pH 7.06 and a protein concentration of 5 x 10(-4) M the transition temperature is close to 70 degrees C while at 5 x 10(-6) M it is close to 50 degrees C. The enthalpy change for unfolding is 31.5 kcal mol-1 at 70 degrees C. Since the isolated helices are unstable, interactions at the interface between the two helices play a key role in the stabilization of the native dimer. These interactions primarily involve the burial of apolar surface from the solvent (hydrophobic effect) and electrostatic interactions. Structural thermodynamic calculations have permitted a dissection of the magnitude of the various contributions to the total Gibbs free energy of stabilization.

Amino Acid Sequence↗
PubMed1993

Morphology of the vasopressin-like immunoreactive (VPLI) neurons in many species of grasshopper.

It has previously been shown that the pair of vasopressin-like immunoreactive (VPLI) neurons of the locust, Locusta migratoria, have cell bodies on the ventral midline of the suboesophageal ganglion and extensive arborisations in all ganglia of the central nervous system. In the present study, we have stained vasopressin-like immunoreactive neurons in 16 additional species of grasshopper, and consistently find this pair of extensive neurons: we assume these to be interspecies homologues. However, the anatomy of these neurons falls into two morphological types: the first, typified by Schistocerca gregaria, has most of its processes distributed in dorsal and lateral neuropil of all ganglia; the second, typified by Locusta migratoria, is equally extensive in its arborisation, but the distribution of branches is shifted peripherally into the optic lobes and the proximal portions of peripheral nerves. It has been suggested that the peripheral fibres in Locusta migratoria are neurohaemal organs for the release of a vasopressin-like diuretic peptide. Our sample of 17 Acridoid species has deliberately selected animals from very different habitats, but our extensive survey of VPLI anatomy shows that peripheral fibres are only present in species from the subfamily Oedipodinae (of which Locusta migratoria is a member) and that no peripheral fibres are present in any of the species from the 4 other subfamilies of the Acridoidea that we have examined. The presence of peripheral fibres is therefore determined by phylogeny and not by habitat. The absence of peripheral VPLI fibres in most grasshopper species examined in this study probably means that the release of putative diuretic hormone from VPLI to control water homeostasis cannot be a conserved function of this ubiquitous neuron. In contrast, the extensive central arborisations and rare antigenicity, which are highly conserved features of the VPLI neuron in all those grasshoppers we have examined, suggests that any conserved role is more likely to be central. A central role for the VPLI neuron has yet to be determined.

Animals↗
PubMed1993

Merkel cell tumor of the head and neck. Five new cases with literature review.

Merkel cell carcinoma (MCC) of the skin is an uncommon, but highly aggressive neoplasm with a marked propensity for local and distant metastasis. Despite the fact that more than half of the 600 cases of MCC reported in the literature involved primary sites in the head and neck, MCC has rarely been discussed in otolaryngology publications. We present five new cases of MCC of the head and neck and summarize 89 additional cases from the literature in which detailed treatment and survival data were given. Our findings again emphasize the difficulty in making the initial histopathologic diagnosis of MCC and demonstrate the necessity of early diagnosis and multimodality treatment.

Adult↗
PubMed1993

Re-inventing progressive community psychiatry: the use of history.

Over the last half-century progressives in community psychiatry have challenged the social order while addressing the needs of persons with psychiatric disorders. Recently, however, their vision and energy has faltered. A re-evaluation of the progressive position is essential, beginning with a review of its historical experience. Unfortunately, modern psychiatry has become increasingly ahistorical. Those histories that do exist reveal little about the experiences of progressive practice and tend to attack it from the right or from the left. There is a tremendous need to synthesize new socially-oriented histories of the progressive movement in community psychiatry.

Community Mental Health Services↗
PubMed1993

Community psychiatry training for general psychiatry residents: results of a national survey.

Through its residency training committee, the American Association of Community Psychiatrists (AACP) surveyed residency training programs throughout the country with the goal of discovering what training is currently in place to prepare psychiatrists for work in "community" or "public" settings which serve traditionally underserved populations. The authors summarize the results of the survey and offer suggestions for further steps needed to improve residency training curricula and to address the need for well qualified psychiatrists to choose careers in community psychiatry.

Career Choice↗