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Biomedical subjects

A Chan

Publications and source records attributed to A Chan.

At least 271 records · Page 15Linked to original sources

Regional localization of 18 human X-linked DNA sequences.

A series of human probes with unique sequences has been isolated from a recombinant phage library constructed with DNA obtained from a human-hamster hybrid cell line. This cell line contained the X chromosome as the only human component. For 18 of these probes, a human X-chromosome origin has been confirmed and they have been regionally assigned by a combination of techniques: dosage studies utilizing DNA from human fibroblasts carrying X-chromosome duplications and deletions; the presence or absence of hybridization to digested DNA from hybrid lines carrying fragments of the X chromosome; and in situ hybridization to metaphase chromosomes. The use of dosage as a means to regionally assign probes significantly improves resolution of the X chromosome.

Animals↗

Hyperprolactinemia: its electrophysiologic and pharmacologic effect on neurons of the ventromedial nucleus of the hypothalamus.

Extracellular action potentials were recorded from 691 neurons in the ventromedial hypothalamus (VMH) of urethane anesthetized female rats under acute and chronic sham-operated and hyperprolactinemic conditions. Hyperprolactinemia was produced by transplanting pituitaries under the kidney capsules. Neuronal excitability was recorded and analyzed during spontaneous, baseline activity and following the iontophoretic application of prolactin, dopamine (DA) and luteinizing hormone-releasing hormone (LH-RH). No statistically significant changes were observed in the spontaneous electrical activity of VMH neurons under the conditions tested. Of the responsive neurons, approximately 90% of the neurons recorded and tested with prolactin displayed an increase in firing activity while DA produced a decrease, independent of the endogenous plasma prolactin levels (basal or elevated). However, the response to LH-RH was modified in the chronic hyperprolactinemic animal. The predominant response of VMH neurons to LH-RH in acute sham-operated and hyperprolactinemic as well as in chronic sham-operated animals was one of inhibition, while in the chronic hyperprolactinemic animal, the application of LH-RH initiated excitation rather than inhibition. These results provide evidence that chronic (long-term) exposure to elevated prolactin levels is a sufficient stimulus to modify the neuronal response pattern of VMH nerve cells to iontophoretically applied LH-RH but not to prolactin nor to DA.

Action Potentials↗

Comparison of the transcriptional properties of the Friend and Moloney retrovirus long terminal repeats: importance of tandem duplications and of the core enhancer sequence.

The effects of sequence differences within the long terminal repeats (LTRs) of various murine retroviruses on transcription are examined by linking genetically engineered recombinant LTRs to the protein coding region of the herpes simplex virus thymidine kinase (TK) gene and assaying TK expression in tissue culture fibroblasts. The Goldberg/Hogness box region and the enhancer region are examined independently. We find that the Friend and Moloney Goldberg/Hogness boxes (TATAAAA and AATAAAA, respectively) give similar results in this assay, whereas differences between the sequences in the enhancer region have a marked effect. Tandem duplications increase the transcription level of the LTR. A single nucleotide transition in the core enhancer sequence has as large an effect on transcription as the presence of a tandem duplication: thymidine in the fifth position of the core enhancer (TCTGTGGTAAG) leads to a much higher transcriptional activity than cytidine. The LTRs have been implicated by others in the oncogenic potential of murine retroviruses, which is perhaps dependent on the transcriptional properties endowed in part by the core enhancer and tandem duplications.

Base Sequence↗

Preliminary characterization of a soluble immunosuppressive molecule from DBA/2 spleen cells using monoclonal antibody immunoadsorbence.

In a previous publication a monoclonal antibody (B16G) which appeared to recognize T suppressor cells and a T-suppressor factor (TsF) in the spleens of DBA/2 mice was described. B16G appears to be directed to a public specificity of DBA/2 TsF and therefore has been shown to inhibit a variety of immunological reactions. The present study involves preliminary characterization of the material with which B16G reacts. It was found that the B16G-reactive protein (putative TsF) could be absorbed and eluted specifically from a B16G immunoadsorbent column. Material eluting from the B16G column reacted with B16G in an ELISA and appeared to run as two or more bands of 40-45 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The eluted material was biologically active (i.e., suppressive) in the standard assay (mixed leukocyte reaction of DBA/2 splenocytes with B10.BR targets), and its suppressive activity was abrogated by the addition of B16G to the mixed leukocyte reaction cultures. Sephadex G-150 chromatography of the B16G-reactive material showed that under these conditions, its native molecular mass was between 80-90 kDa, indicating that it might occur as a dimer under natural conditions.

Animals↗

Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line.

We report the isolation and characterization of 19 classes of nonrearranging T cell-specific cDNA clones and two cDNA clones encoding the alpha and beta chains of the T-cell antigen receptor from a human T-cell line, Jurkat. Results indicate that the human alpha-chain gene, like its beta-chain counterpart, undergoes somatic rearrangement in T cells. In addition, it shows sequence homology to its beta-chain counterpart and immunoglobulin, indicating that the human alpha chain is also a member of the immunoglobulin supergene family. Sequence comparison suggests that the alpha chain also may be composed of variable (V), diversity (D), joining (J), and constant (C) region gene segments. The protein deduced from the cDNA sequence has a molecular weight of 29,995 and possesses six potential N-glycosylation sites. The availability of alpha- and beta-chain genes of the T-cell receptor from the same T-cell line provides tools to study their possible roles in recognition of antigens and major histocompatibility complex products by the human T-cell receptor.

Amino Acid Sequence↗

Hormonal modulation of the responsiveness of midbrain central gray neurons to LH-RH.

The spontaneous firing rate of midbrain central gray (MCG) neurons and the effect of iontophoretically applied prolactin and luteinizing hormone releasing hormone (LH-RH) on the electrical activity of these neurons was studied in untreated and estrogen-progesterone-treated ovariectomized female rats. The spontaneous firing rate of MCG neurons as well as the neuronal membrane responsiveness to iontophoretically applied prolactin was unaffected by the presence or absence of ovarian hormones. In both treated and untreated rats, the majority of neurons were not responsive to prolactin. On the other hand, the responsiveness of MCG neurons to iontophoretically applied LH-RH was influenced by hormonal treatment. A significantly larger number of MCG neurons were inhibited by LH-RH in hormone-treated animals than in untreated rats. The present work provides evidence at the electrophysiological level that ovarian hormones do not affect the firing rate of MCG neurons but do modulate the responsiveness of MCG neurons to LH-RH.

Action Potentials↗

Sensitivity of hyperthermia-treated human cells to killing by ultraviolet or gamma radiation.

Human xeroderma pigmentosum (XP) or Fanconi anemia (FA) fibroblasts displayed shouldered 45 degrees C heat survival curves not significantly different from normal fibroblasts, a result similar to that previously found for ataxia telangiectasia (AT) cells, indicating heat resistance is not linked to either uv or low-LET ionizing radiation resistance. Hyperthermia (45 degrees C) sensitized normal and XP fibroblasts to killing by gamma radiation but failed to sensitize the cells to the lethal effects of 254 nm uv radiation. Thermal inhibition of repair of ionizing radiation lesions but not uv-induced lesions appears to contribute synergistically to cell death. The thermal enhancement ratio (TER) for the synergistic interaction of hyperthermia (45 degrees C, 30 min) and gamma radiation was significantly lower in one FA and two strains (TER = 1.7-1.8) than that reported previously for three normal strains (TER = 2.5-3.0). These XP and FA strains may be more gamma sensitive than normal human fibroblasts. Since hyperthermia treatment only slightly increases the gamma-radiation sensitivity of ataxia telangiectasia (AT) fibroblasts compared to normal strains, it is possible that the degree of thermal enhancement attainable reflects the genetically inherent ionizing radiation repair capacity of the cells. The data indicate that both repair inhibition and particular lesion types are required for lethal synergism between heat and radiation. We therefore postulate that the transient thermal inhibition of repair results in the conversion of gamma-induced lesions to irrepairable lethal damage, while uv-type damage can remain unaltered during this period.

Cell Survival↗

Urticaria and angio-oedema.

Urticaria and angio-oedema are a symptom complex covering a wide range of clinical disorders. Specific types are now well described, and it appears that many cases of idiopathic chronic urticaria which make up the vast majority of patients referred for assessment are due to intolerance to natural salicylates, preservatives and colouring agents. There is, therefore, an urgent need for legislation to enforce the clear identification of these chemicals in processed food and drugs.

Angioedema↗

Hormonal and chemical modulation of ventromedial hypothalamic neurons responsive to vaginocervical stimulation.

Neurons of the ventromedial hypothalamus (VMH) in female rats were electrophysiologically recorded via multibarrelled glass micropipettes and tested for responsiveness to vaginocervical stimulation as well as to a variety of other peripheral stimuli. A small percentage of VMH neurons were found to be specifically responsive to vaginocervical stimulation (type I response) in the ovariectomized animal. Priming the rats with estrogen (E) and progesterone (P) significantly increased the percentage of neurons responding specifically to vaginocervical stimulation but had no effect on the percentage of nonspecifically responding (type II) and nonresponding (type III) neurons. Pharmacological testing of all three types of VMH neurons was accomplished by iontophoretic application of luteinizing hormone releasing hormone (LHRH), prolactin (PRL), and dopamine (DA) to the cell membrane. PRL excited the majority of neurons tested and DA inhibited the majority of tested units regardless of the hormonal condition of the animal or the response elicited by vaginocervical and peripheral stimulation, LHRH, however, produced changes in firing rate which were related to the type of response evoked by vaginocervical stimulation. In E-P-primed animals, neurons which were specifically or nonspecifically affected by vaginocervical stimulation responded to LHRH in a similar manner whereas a different LHRH response profile was obtained in those neurons which were not effected by vaginocervical stimulation. The results indicate that an afferent pathway from the vaginocervix to the VMH exists, that E-P priming in some manner increases the probability that a VMH neuron will respond specifically to vaginocervical probing, and that the effect of LHRH is different in neurons responding to vaginocervical stimulation than in nonresponding neurons.

Animals↗

The effects of hyperthermia and ionizing radiation in normal and ataxia telangiectasia human fibroblast lines.

The effects of 45 degrees C hyperthermia and gamma radiation have been studied in three normal human fibroblast lines (GM38, GM730, WI38) and compared to the effects in two lines derived from patients with the hereditary disease ataxia telangiectasia (AT3BI, AT5BI). All lines, both normal and gamma-sensitive AT, showed a similar resistance to killing by heat alone, suggesting that the defect responsible for the increased radiation sensitivity in AT lines does not confer increased heat sensitivity. Shouldered survival curves were obtained in each case indicating the ability to accumulate sublethal heat damage. All normal and AT cell lines exhibited increased resistance to the lethal effects of heat in response to a thermal stress, indicating that the defect that causes radiosensitivity in AT cell lines does not prevent the induction of thermotolerance. Heat (45 degrees C, 30 min) was shown to increase the sensitivity of the normal cell lines to killing by gamma radiation. The thermal enhancement ratios obtained ranged from about 2.5 to 3.0. The same heat treatment, however, produced very little increase in the radiation sensitivity of the AT cells. Thermal enhancement ratios of about 1.2 were obtained in these lines. We hypothesize that, in normal cells, this heat treatment inactivates the process which is already defective in AT lines, and that this process may be required for the proper rejoining of double-strand breaks produced during the repair of other radiation-induced lesions.

Acclimatization↗

Von Recklinghausen's disease associated with gastrointestinal carcinoid tumors.

The occurrence of both gastrointestinal carcinoid and von Recklinghausen's disease in the same patient is uncommon. There seems to be a predilection for ampullary carcinoids in these patients. This article reports the sixth case, including a review of the literature and a brief discussion of the implications of this finding. A carcinoid tumor should be suspected in any patient with von Recklinghausen's disease presenting with gastrointestinal bleeding, obstruction, abdominal pain, and particularly obstructive jaundice.

Ampulla of Vater↗

Construction of a simple spike counter for analysis of electrophysiological recording data.

A method for constructing a simple spike counter from a conventional calculator by taking advantage of the "adding display to memory" function [(M+) key] is described. The modification involves connecting the (M+) key to a dissecting pin and to a metallic notebook binder which is taped on to a transparent plastic sheet. The plastic sheet can then be placed on top of a polygraph record. After entering "1" into the calculator, a spike can be counted by making a single contact between the pin and the metal fastener. The total number of spikes counted can be displayed on the calculator by pressing the key for memory recall. The spike counter described herein is suitable for counting extracellular action potentials recorded on chart paper as well as other biological signals such as the rate of contraction of muscle.

Animals↗

Postoperative wound infections: a study of bacteriology and pathogenesis.

Of 200 patients, 6.5% were skin carriers of Staphylococcus aureus and 3.5% became skin carriers after admission. Development of skin carrier state was associated with a long preoperative hospital stay. A second study of 275 cases showed that skin carriers of S. aureus had a significantly higher subsequent staph wound infection rate than non-carriers, but nose and/or throat carriers of S. aureus did not. Peroperative wound contamination was a significant factor in the subsequent development of wound infection. In clean surgery the infection rate was 5.9%. Both wound contamination and infection was due to gram positive organisms, usually S. aureus. When the gastrointestinal or biliary tract had been opened, the infection rate was 28%, the usual contaminating and infecting organisms were enteric and only occasionally S. aureus. There is a need for improved methods of minimizing peroperative wound contamination.

Bacteriological Techniques↗

The use of directional Doppler ultrasound in the assessment of saphenofemoral incompetence.

The prevalence of saphenofemoral incompetence in a series of 105 consecutive patients undergoing saphenofemoral ligation as part of an operation for primary varicose veins was determined using a directional continuous-wave Doppler ultrasonic device. Saphenofemoral incompetence was correctly predicted in 97% of limbs. Using conventional clinical methods, incompetence was correctly predicted in 82% of limbs. This difference was highly significant (P less than 0.01 McNemar). It is concluded that a directional Doppler ultrasonic assessment is a useful aid in the pre-operative determination of saphenofemoral incompetence.

Adult↗

Action of prolactin, dopamine and LHRH on ventromedial hypothalamic neurons as a function of ovarian hormones.

The effect of iontophoretically-applied prolactin, dopamine, LHRH and LHRH-antagonist analog on the electrical activity of neurons (n = 192) located in the ventromedial nucleus of the hypothalamus (VMH) was studied in untreated and hormone-treated ovariectomized female rats (n = 63). The spontaneous electrical activity of VMH neurons was unaffected by the presence or absence of the ovarian hormones. Neuropharmacological studies indicate that the iontophoretic deposition of prolactin and dopamine produced opposing results, in that prolactin increased the electrical activity of the majority of the VMH neurons tested while dopamine decreased their activity. Finally, the application of LHRH and LHRH-antagonist analog to VMH neurons resulted in a marked suppression of their electrical activity that was even more pronounced in the presence of ovarian hormones. The present work provides evidence at the electrophysiological level of hormonal influences on the responsiveness of VMH neurons to LHRH and its antagonist analog, and demonstrates a relationship between the responsiveness of VMH neurons to prolactin and dopamine.

Animals↗

The use of common carotid waveform analysis in the diagnosis of carotid occlusive disease.

Duplex scanning with spectral analysis of the pulsed Doppler signal are currently used to detect and classify disease at the carotid bifurcation. Although the sensitivity of the test exceeds 90%, the method has a lower specificity which ranges between 8 and 50%. The poor specificity is due to the difficulty in distinguishing flow disturbances normally present at the carotid bifurcation from those produced by minimal amount of disease. In order to improve the ability of the method to predict normalcy, new features measured from the low common carotid waveform are evaluated on 150 sides. The difference of frequency from the systolic peak (a) to the point of first zero slope after peak systole (b) was used to define the ratio (a-b)/a. A ratio greater than 0.5 was associated with 76% of the normal sides and only 7% of the diseased sides. A ratio below 0.5 was associated with 83% of the diseased sides. This ratio, when used alone, can improve the specificity of the method to 76%.

Angiography↗