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Biomedical subjects

W D Winters

Publications and source records attributed to W D Winters.

At least 55 records · Page 3Linked to original sources
PubMed1989

Synthetic opioids compared with morphine and ketamine: catalepsy, cross-tolerance and interactions in the rat.

Previously it has been shown in rats that both ketamine and morphine induced analgesia and, at larger doses, catalepsy and loss of the righting reflex, all of which were reversed by naloxone at widely different doses. Tolerance developed rapidly to either ketamine or morphine and there was cross-tolerance from ketamine to morphine. However, morphine potentiated the cataleptic effect of ketamine, whether fully-effective doses of morphine were given before ketamine or subeffective doses of both were given concurrently. The present study extends these observations to three specific mu-receptor agonists (sufentanil, fentanyl and alfentanil) and two mu- and kappa-agonist, mu-antagonist opioids (nalbuphine and butorphanol). All five of these opioids potentiated the cataleptic effect of ketamine. Each of the three specific mu agonists showed rapid development of tolerance. Fentanyl and alfentanil showed mutual cross-tolerance with ketamine, but sufentanil did not. This lack of sufentanil-ketamine cross-tolerance may reflect separation of the sites of agonist action and the sites of development of tolerance for the opioids and for ketamine. The potentiating effects of nalbuphine and butorphanol suggest that they potentiate ketamine-induced catalepsy, either by kappa-receptor interactions or by a mu agonist effect. It is suggested that the cataleptic effect of a combination of individually-subeffective doses of ketamine and morphine, rather than ketamine and one of the synthetic opioids, might be of more potential clinical usefulness.

Animals↗
PubMed1989

In vitro immune monitoring of antibody response in dogs given chemoimmunotherapy for lymphoma.

Clinical remission in 30 dogs with lymphoma was induced with a combination of vincristine, L-asparaginase, cyclophosphamide, and doxorubicin HCl, administered sequentially, and then an autochthonous tumor cell vaccine, given intralymphatically, as maintenance therapy. Humoral antibody amounts were monitored in 11 dogs, using a solid-phase bead-type radioimmunoassay. The median survival of the 30 dogs was 13 months from the start of chemotherapy (range, 7 to 25 months; mean, 13.8). The median remission duration was 16 weeks (range, 9 to 98 weeks; mean, 26.8). Correlation between increase in amount of humoral antibody was significant (P = 0.0001 to 0.012), before and after chemoimmunotherapy, in dogs responding to therapy, compared with that in dogs not responding to therapy.

Animals↗
PubMed1988

Effect of radiofrequency radiation on mRNA expression in cultured rodent cells.

Four rodent cell lines were exposed to 2450 MHz microwave radiation at a Specific Absorption Rate (SAR) of 103.5 +/- 4.2 W/kg for varying lengths of time at 37 degrees, 40 degrees, 42 degrees and 45 degrees C. mRNA was extracted from microwave-exposed and sham-exposed cells and dot blotted or Northern blotted to nitrocellulose. Radioisotope labelled DNA probes of oncogenes, heat shock protein or long terminal repeat sequences were hybridized to the mRNA, and the resulting autoradiographs analyzed for differences in levels of mRNA expression between exposed and nonexposed samples. With the cell lines and probes used in this study no significant differences in mRNA expression were observed after microwave exposure.

Animals↗
PubMed1988

Ketamine- and morphine-induced analgesia and catalepsy. I. Tolerance, cross-tolerance, potentiation, residual morphine levels and naloxone action in the rat.

The effects of ketamine and morphine on pain perception and catalepsy were compared in rats. Analgesia, as measured by the latency to withdrawal of the tail from a 55 degrees C water bath (tail-flick latency difference, TFLD), was produced by both ketamine and morphine, but at widely different doses, and in each case the effect was reversed by naloxone. Catalepsy, measured by the duration of loss of righting reflex (DLRR) in catatonic animals, was induced by larger doses of both ketamine and morphine and in each case was reduced by a larger dose of naloxone. DLRR and TFLD tolerance developed rapidly and with a similar time course after daily doses of ketamine or morphine. Rats tolerant to the DLRR effect of ketamine showed cross-tolerance to morphine. Rats tolerant to the DLRR effect of morphine did not show cross-tolerance to ketamine when administered the following day; instead, these rats showed potentiation of the ketamine-induced DLRR. The degree of potentiation noted 24 hr after a single or multiple daily doses of 45 mg/kg of morphine is the same as that seen when 2 mg/kg of morphine is given simultaneously with ketamine. The residual brain level of morphine 24 hr after 45 mg/kg is similar to the level 1 hr after a 2-mg/kg dose. The augmented ketamine response in morphine-tolerant rats is postulated to be a result of residual morphine still present in the brain 24 hr after the last DLRR-inducing dose of morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1986

Seasonal and sex influences on ketamine-induced analgesia and catalepsy in the rat; a possible role for melatonin.

Data from this laboratory on ketamine-induced analgesia and catalepsy in rats revealed that factors other than dose modified the difference in the latency of the tail flick response (TFLD), a measure of analgesia, and the duration of the loss of the righting reflex (DLRR), a measure of catalepsy. Untreated female rats showed a longer latency than males in their response to a noxious stimulus at midnight, but not at noon. Females also showed a longer loss of righting reflex response to ketamine than did males, whether at noon or midnight; the loss of righting reflex at night was augmented in both. Although females showed analgesia with administration of ketamine at doses smaller than those which induced catatonia, males showed no analgesia without catatonia and comparable loss of the righting reflex occurred at doses much larger than for females. There was a 3-fold increase in the latency of the tail flick response and loss of righting reflex during the winter, as compared with summer, for females treated with ketamine; males showed a similar variation in the loss of righting reflex. Since analgesia is produced by both melatonin and ketamine, and since ketamine appears to share opiate receptors with an endogenous ligand, beta-endorphin, a role was sought for the pineal and melatonin in the variation of responsiveness to ketamine. Pinealectomized rats failed to show augmentation of the loss of righting reflex induced by ketamine at night and mice showed a seasonal variation in the analgesia induced by melatonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1986

In vitro exposure to electromagnetic fields: changes in tumour cell properties.

Two human colon cancer cell lines, Colo 205 and Colo 320 DM, have been studied for their responses to 60 Hz-generated electromagnetic fields (EMF) using soft agar cloning and monoclonal antibody binding assays to assess exposure-induced changes. Cellular responses have been studied after 24 h continuous exposure of cells concurrently to four experimental conditions; i.e. no EMF (E-M-), magnetic field only (M+, 1.0 G rms), electric field only (E+, 300 mA/m2 rms), and combined electric plus magnetic fields at these intensities (E+M+). Under these conditions, both cell lines demonstrated significantly increased colony formation in soft agar and increased expression of tumor associated antigens after exposure to E+M+ and to M+ as compared to unexposed controls.

Animals↗
PubMed1986

Antigen specific stimulation of immune responses during long-term repeated skin testing with multiple antigens.

Delayed-type hypersensitivity (DTH) skin testing as an assay of immune competence is a widely used technique. Accordingly, clinical situations frequently occur which require that skin tests be performed many times on the same patient. In the present investigation, in vivo and in vitro immune responses were studied over a 7-month period in 22 normal human volunteers, each of whom were skin tested 6 times at monthly intervals with multiple antigens. Patterns of responses to the 7 specific skin test antigens observed during repeated skin testing in vivo indicated non-significant, but detectable, declines in skin test reactivity to tetanus, diphtheria and streptococcus antigens and increases in reactivity to trichophyton, tuberculin, candida and proteus antigens. In vitro lymphocyte transformation assays (LTAs) of cell-mediated immune (CMI) activities revealed that repeated skin testing, e.g., 3-5 serial skin tests, induced significantly increased levels of CMI reactions with 3 of the 4 skin test antigens used as challenge antigens. Since no significant changes in in vitro CMI responses were detected using 3 control "non-skin test" antigens, the effects observed were confirmed to be antigen specific. Increased IgG antibody responses were detected for only the toxoid antigens during the skin testing period. For the group of 22 normal volunteers, positive statistical correlations were not observed between any individual skin test antigen and the immune reactions assayed specifically for that antigen, including DTH responses and levels of circulating antigen-specific antibodies. Short term differences were detected between tetanus, diphtheria and streptococcus antigens in their LTA response patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Transferrin binding to two human colon carcinoma cell lines: characterization and effect of 60-Hz electromagnetic fields.

125I-Labeled human transferrin was used to study the binding of transferrin to Colo 320 DM and Colo 205 human cell lines derived from adenocarcinomas of the colon. Although transferrin uptake was greater in both cases at 37 degrees than at 4 degrees it was found that slightly greater than two-thirds of the transferrin associated with the cells at 37 degrees was not bound to surface receptors but rather had been internalized by the cells. Subsequent analysis of true surface binding at 4 degrees by Scatchard analysis allowed determination of the number of transferrin receptors as well as association constants for the interaction. The number of transferrin receptors per cell was found to be inversely related to the cell density of the cultures from which cells were removed for study. Association constants were unaffected by cell density, with average values of 1.2 and 5.4 X 10(8) M-1 obtained for Colo 320 DM and Colo 205, respectively. Additionally, maximum theoretical numbers of receptors of 1.05 X 10(5)/cell for Colo 320 DM and 1.39 X 10(5)/cell for Colo 205 were determined. Furthermore, exposure of Colo 205 cells to three different experimental situations, i.e., 60 Hz-generated electric field only (E+, 300 mA/m2rms), magnetic field only (M+, 1.0 gauss rms), and combined electric + magnetic fields at these intensities (E+M+), altered the expression of transferrin receptors as compared to a concurrently run unexposed control population of cells (E-M-). In three separate experiments the number of transferrin receptors quantitated on both M+ and E+M+ cells was independent of cell culture density and was close to or exceeded the maximum theoretical number of receptors determined for this cell line. In contrast, E+ cells expressed fewer transferrin receptors than was predicted on the basis of cell culture density.

Adenocarcinoma↗
PubMed1986

Changes in non-specific immune responses induced by repeated delayed-type hypersensitivity skin testing with multiple antigens.

Delayed-type hypersensitivity (DTH) responses following in vivo multiple-antigen skin testing in healthy individuals have been well described as indicators of immune responsiveness. In contrast, little information is available about how repeated in vivo multiple antigen skin testing could effect major non-specific parameters of immune responses. In a prospective study of 22 healthy adult volunteers, DTH skin tests were performed 6 times at 4-week intervals over a 28-week course. Prior to each skin test, blood specimens were collected and evaluated by in vitro assays of non-specific parameters related to humoral and cell-mediated immune (CMI) responses. Sustained effects of repeated skin tests in the volunteers included decreased numbers of circulating polymorphonuclear leukocytes (PMNLs), increased serum IgM levels and decreased DTH responses in those individuals originally designated as high DTH responders. Increased lymphocyte transformation with PHA was transiently observed in the study group at 4-12 weeks into the study. In contrast, numbers of T, B and total lymphocytes, levels of IgG, IgA, and circulating immune complexes, and serum blocking activity did not change. This study suggests that few alterations in non-specific immune parameters may be expected to occur in normal, adult individuals as a result of repeated multiple-antigen skin tests.

Adolescent↗
PubMed1985

Effects of 6-methoxy-2-benzoxazolinone on the pineal melatonin generating system.

6-Methoxy-2-benzoxazolinone (6-MBOA) at concentrations greater than 20 microM stimulates serotonin N-acetyltransferase (NAT) activity of rat pineal glands in 48-hr organ culture as well as of glands freshly cultured, indicating that 6-MBOA acts postsynaptically. The effects of 6-MBOA on NAT activity can be blocked by propranolol but not by prazosin, suggesting that 6-MBOA acts on the beta receptor. At the doses used 6-MBOA stimulation does not block or enhance NAT stimulation by norepinephrine, but is additive with vasoactive intestinal polypeptide which stimulates NAT activity at a site different than the beta receptor. This study demonstrates that 6-MBOA stimulates rather than inhibits melatonin biosynthesis and does not prevent stimulation of melatonin synthesis by norepinephrine. The progonadal association with eating plants containing 6-MBOA in the Montane vole may be due to over stimulation of melatonin receptor sites. Other possible explanations include an extrapineal action such as a blockade of melatonin receptors in the central nervous system, a blockade of receptors on the gonads or to a direct action of this agent on the gonads.

Acetyltransferases↗
PubMed1985

Retardation of embryogenesis by extremely low frequency 60 Hz electromagnetic fields.

Fertilized Medaka fish eggs were used to determine if electromagnetic fields, designed to simulate those beneath a high voltage power line, have biological effects on vertebrate embryo development. The newly fertilized eggs were exposed to a 60 Hz electrical field of 300 mA/m2 current density, a 60 Hz magnetic field of 1.0 gauss RMS, or to the combined electric plus magnetic fields for 48 hours. No gross abnormalities were observed in any of the embryos as they developed, but significant development delays were seen in those embryos exposed to either the magnetic or to the combined electromagnetic fields; delays were not seen in the embryos exposed to the electrical field. Thus, a 60 Hz magnetic field like that encountered in a man made powerline environment was shown to retard development of fish embryos.

Animals↗
PubMed1984

Humoral immune responses to adenoviruses, herpes virus type 1, and Candida albicans in sera of dental patients with oral neoplastic and periodontal diseases.

Levels of immunoglobulin class-specific antibodies as determined by solid phase radioimmunoassays to herpes simplex virus type 1 (HSV-1), human adenovirus types 5, 21, and 31 and to Candida albicans in sera from untreated healthy dental patients were not significantly different from levels of these antibodies in sera from untreated dental patients with benign oral tumors, oral carcinoma, or periodontal disease. These results show that higher levels of immunoglobulin class-specific antibodies to HSV-1, the three adenoviruses, or Candida albicans are not a consistent finding in sera from patients with oral cancer when comparisons are made with healthy patients and patients with other oral diseases.

Adenoviruses, Human↗
PubMed1984

Effects of amine pretreatment on ketamine catatonia in pinealectomized or hypophysectomized animals.

The present studies were designed to clarify the role of catecholamines and pineal idolamines on ketamine-induced catatonia in the intact, pinealectomized or hypophysectomized chick and rat. In the pinealectomized chick, pretreatment with dopamine increased the duration of catatonia (DOC) after ketamine, but pretreatment with norepinephrine did not. The pineal indolamines exhibited mixed actions. Serotonin and N-acetyl serotonin which augmented ketamine DOC, did not do so in the absence of the pineal gland, whereas melatonin potentiated the ketamine DOC in both the intact and pinealectomized chick. Ketamine was more potent in the hypophysectomized chick and the circadian rhythm noted in the intact chick was absent; furthermore, melatonin did not augment the ketamine DOC whereas dopamine continued to do so. This study did not demonstrate a species difference regarding the role of the amines on the pineal in spite of the immature blood-brain barrier in the young chick and the intact barrier in the rat. In addition, these data indicate a direct role of the pituitary in the augmentation of ketamine DOC induced by melatonin. Furthermore, dopamine appeared to act on systems more closely involved with the induction of ketamine catatonia rather than directly on the pituitary.

Amines↗
PubMed1983

Cortical kindled seizures: modification by excitant and depressant drugs.

The effects of several excitant-convulsants, cataleptic anesthetics, and gamma-acetylenic gamma-aminobutyric acid (GABA) were tested on seizures kindled by repetitive electrical stimulation of the motor cortex in the rat. A dose response was determined for each drug. For most of the drugs, the doses tested ranged from those causing some signs of behavioral excitation to those inducing epileptoid activity. None of the excitant-convulsants, including strychnine, physostigmine, amphetamine, bicuculline, or pentylenetetrazol, increased the afterdischarge duration (AD) or behavioral response (BR) of the partially developed (PD-KCS) or generalized fully developed (KCS) kindled cortical seizures. Whereas pentylenetetrazol had no effect on the PD-KCS, it has been previously shown to increase significantly the AD and BR of the developing or partially developed amygdaloid kindled seizures. Lidocaine, gamma-butyrolactone, gamma-acetylenic GABA, phencyclidine, and ketamine inhibited the AD of the KCS by greater than or equal to 80%. Lidocaine, phencyclidine, and ketamine decreased whereas gamma-butyrolactone and gamma-acetylenic GABA increased the AD of the PD-KCS. The ability of gamma-butyrolactone and gamma-acetylenic GABA to potentiate the PD-KCS while inhibiting the KCS presents a paradox not readily explained. Our results combined with previous reports of the effects of gamma-butyrolactone and gamma-acetylenic GABA on amygdaloid kindled seizures indicate that the KCS is more susceptible to GABAnergic and cataleptic inhibition than is the fully developed amygdaloid kindled seizures. The differences between the response of cortical kindled and that of amygdaloid kindled seizures to some of the drugs tested may indicate differences in the physiological and biochemical mechanisms involved in producing these seizures.

Anesthetics↗
PubMed1983

New techniques for detecting tumor markers: a prospective.

The search continues for biomarkers in body fluids that can identify the presence of otherwise undetectable tumors. Presently tumor biomarkers can be useful in monitoring neoplastic disease during and after therapy, although their role in early diagnosis is less certain. The value of each tumor biomarker in each clinical situation can be estimated by its concentration in biofluids, the sensitivity of the detection techniques, and the specificity of its in vivo and in vitro activities. A wide range of new multidisciplinary biotechnologies applied to tumor biomarkers promises additional and improved assays for highly sensitive and specific detections of human neoplasia. These new assays will have the potential for making accurate estimations of initial tumor burden, micrometastasis, and residual and occult tumor cells remaining after surgery.

Breast Neoplasms↗
PubMed1983

Detection of common antigens in primary and recurrent human meningiomas by radioimmunoassays and other serologic tests.

Antibodies in sera from 72 patients with untreated intracranial tumors, 60 patients with non-neural untreated tumors, and 30 normal donors were measured by immunodiffusion (ID), complement-fixation (CF), double-antibody precipitation radioimmunoassay (DAPRIA), and solid-phase bead-type radioimmunoassay (SBRIA) techniques using partially purified preparations of a reference meningioma-associated antigen (MAA), newly prepared MAAs derived from primary and recurrent tumors, and antigens from normal neural tissues. SBRIA tests were markedly more specific and sensitive than ID, CF, or DAPRIA in detecting MAA antibody. SBRIA tests also detected antibody reactive with common MAAs derived from primary and recurrent meningiomas in sera from meningioma patients prior to and following tumor excision. Checkerboard-type tests using dilutions of MAA versus sera from 20 meningioma patients and 20 age- (+/- 5 years) and sex-matched normal donors showed that antibody responses by the meningioma patients to MAA could be separated from those to other broad-reacting tumor and normal cell antigens, and from those of the matched normal donors. Sera from meningioma patients contained antibodies reactive with normal fetal, but not adult, neural antigens; thus suggesting a need for careful definition of control normal antigens used in serological testing.

Antibodies, Neoplasm↗