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Biomedical subjects

M Wilkinson

Publications and source records attributed to M Wilkinson.

At least 199 records · Page 11Linked to original sources
PubMed1988

Development of phorbol ester (protein kinase C) binding sites in cat visual cortex.

Tritiated phorbol-12,13-dibutyrate [( 3H]PDBu), a phorbol ester, was utilized to autoradiographically localize protein kinase C (PKC) in the cat visual cortex. Thin, slide-mounted sections of adult cat brain were used to characterize binding of [3H]PDBu. This was found to be saturable, reversible, and more readily displaced by phorbol ester than by synthetic diacylglycerols. Binding sites displayed a tissue concentration of 20 pmol/mg protein, and a dissociation constant of 8.0 nM. [3H]PDBu was slow to associate with its receptor, requiring 9.5 h to reach equilibrium. Autoradiograph revealed that PKC is heterogeneously distributed in the cat brain, and displays a laminar-specific pattern in the visual cortex. This laminar distribution undergoes marked changes during the first two months of postnatal life. In the visual cortex of neonatal kittens, [3H]PDBu binding is confined to layers I and V. Layer III acquires high levels of binding by postnatal day 15, layer II by 28 days, and layer VI becomes labelled by 40 days of age. Adult animals exhibit high levels of binding in all laminae except layer IV. Age-dependent changes in PKC's laminar distribution do not seem to be correlated with specific anatomical, neurochemical, or behavioural events during development. PKC appears to be associated with cell bodies or processes intrinsic to the visual cortex, and is probably not located on the terminals of cortical afferents.

Aging↗
PubMed1988

HLA-D region alpha-chain monoclonal antibodies: cross-reaction between an anti-DP alpha-chain antibody and smooth muscle.

Two monoclonal antibodies, Tal 3C3 and Tal 1B5, raised against purified plasma membrane extract of the Bristol 8 B lymphoblastoid cell line and previously shown to recognize epitopes on denatured HLA-D alpha-chains revealed several differences in staining patterns when screened by immunocytochemical techniques on pre-fixed paraffin-embedded sections of human tissues. Although Tal 3C3 staining was weaker and more restricted than Tal 1B5 on immunoregulatory cells expected to express class II antigens, this monoclonal antibody showed additional strong activity on normal smooth muscle. Biochemical studies show that whereas Tal 1B5 reacts with DR alpha-chains, Tal 3C3 predominantly defines DP alpha-chain subunits and a high molecular weight (200-250 kD) actin binding protein known as filamin. In view of several recent reports that the cellular distribution of class II antigens may be more widespread than hitherto thought and may be expressed by cells not normally involved in specific immune functions, these findings emphasize that unexpected monoclonal antibody reactions must be interpreted with caution. It is clearly important to include both immunohistological tissue section and biochemical studies in the initial screening procedures for monoclonal antibodies in order to distinguish between specific target antigen activity and cross-reactions with unrelated molecules.

Antibodies, Monoclonal↗
PubMed1988

Effects of ovariectomy and estradiol replacement on naloxone induced LH secretion in the female rabbit.

The effects of an opioid antagonist, naloxone, on the secretion of gonadotrophins were investigated in the long term ovariectomized rabbit. In the intact and acutely ovariectomized rabbit (2 days p.o.) naloxone at 10 mg/kg induced an increase of 260-300% in LH secretion at 40 min post-injection. From days 33-66 post-surgery naloxone at 10 mg/kg caused significant elevations in LH release even when animals were treated with estradiol benzoate 24 h previously. By contrast, treatment with oestradiol benzoate 3 h before naloxone abolished the LH increase. An LH surge could be elicited in these rabbits with GnRH treatment. These studies indicated that long term ovariectomy in the female rabbit does not completely remove the opioid control of GnRH release and that the LH response to naloxone is influenced by circulating estradiol levels.

Animals↗
PubMed1988

Sodium channel toxins veratrine and veratridine modify opioid and muscarinic but not beta-adrenergic binding sites in brain slices.

We have examined the influence of the sodium channel toxins veratrine and veratridine on mu-opioid ([3H]-DAGO), muscarinic ([3H] NMS) and beta-adrenergic ([3H] CGP) receptors in rat brain slices. These drugs reduce opioid and muscarinic binding while leaving beta-receptors unaffected. Veratrine is inhibitory at 0 degree or at 30 degrees C whereas veratridine is without effect at 0 degree C. These data suggest that some factor contained in the mixture of drugs (veratrine) can block opioid and muscarinic receptors independently of depolarization. Veratridine does not affect muscarinic receptors at ice temperature. Similar observations were made in thin sections of cat brain at 0 degree C. The concentrations of the toxins which cause 50% inhibition of binding are well within the range (5 x 10(-5) M-10(-4) M) routinely used for depolarization experiments. We suggest that caution be used in the interpretation of results obtained from veratrum alkaloid-induced depolarizations. It would not be surprising if the binding of other ligands to their receptors was also affected.

Animals↗
PubMed1988

Sensory deafferentation fails to modify muscarinic receptor binding in raccoon somatosensory cortex.

The characteristics and distribution of muscarinic acetylcholine (mACh) receptor binding in primary somatosensory (SI) cortex and the caudate nucleus of raccoons were studied using [3H]-QNB, a muscarinic antagonist. The binding characteristics were similar to reported values in rat and cat. Autoradiographs produced from tissue sections labeled with [3H]-QNB showed the distribution of mACh receptors in the forebrain of the raccoon. [3H]-QNB binding was highest in cerebral cortex, neostriatum and hippocampus. Within SI cortex, binding was high in layers I-III and VI and relatively low in layers IV and V. Autoradiographs obtained from animals that had undergone peripheral deafferentation of part of the forepaw revealed no changes in [3H]-QNB binding in the affected cortical region during the time that physiological reorganization is known to occur.

Afferent Pathways↗
PubMed1988

Effects of the noradrenergic neurotoxin DSP4 on growth and the gonadal steroid- and PMSG-induced release of LH in the prepubertal female rat.

We have examined the effect of DSP4 treatment on PMSG-induced ovulation. A marked attenuation of the stimulatory effects of PMSG (7.5 I.U.) by DSP4 was evidenced by the significantly lower number of corpora lutea present in the ovaries of those animals which ovulated compared to controls. In addition, ovarian weight was lower in the DSP4 group. In a further experiment, we examined the effect of DSP4 on the induction of an LH surge by progesterone (P) in estradiol benzoate (EB) primed rats. DSP4 administration 2 hours prior to P eliminated the LH surge seen in controls. In view of our previous observations that DSP4 can interact with opioid receptors, we attempted to block its inhibitory effect on PMSG and EB/P stimulations. Coinjection of naloxone, an opioid antagonist, only partially prevented the influence of DSP4. It seems likely, therefore, that opioid receptors are not involved in the inhibitory effects of DSP4 described here. In further experiments, we studied the effects of DSP4 on spontaneous sexual maturation in female rats. DSP4 was administered (50 mg/kg, IP) on either day 5, day 23, day 29, or both day 24 and day 26 of life. Growth was inhibited and vaginal opening (VO) was significantly delayed in all except the day 29 group. However, VO occurred at the same body weight as the controls. By the end of the experiment, hypothalamic noradrenaline levels were not significantly different between control and DSP4-treated animals. The lack of an effect of DSP4 on the progression to puberty may be due to sufficient recovery of the central noradrenergic systems during the time course of the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Forearm mineral content in normal men: relationship to weight, height and plasma testosterone concentrations.

We measured forearm bone mineral content by single photon absorptiometry together with height, weight and the plasma concentrations of testosterone, free testosterone and sex steroid binding globulin in 66 normal Caucasian males aged 29-46 years. Multiple regression analysis suggests that bone mineral content in either the dominant or the nondominant arm is correlated with weight and sex steroid binding globulin (p less than 0.05 for both parameters). The partial negative correlation of bone mineral content (corrected for weight and sex steroid binding globulin) with plasma testosterone failed to reach statistical significance (p = 0.07). The parsimonious regression equation which best explained the bone mineral content measurements in the nondominant forearm in these men was bone mineral content = 29.1-0.374 (plasma testosterone) + 0.383 (weight) + 0.220 (sex steroid binding globulin) with an R2 value of 29.7%. A similar equation was generated for the dominant arm.

Adult↗
PubMed1988

Nimodipine in migraine prophylaxis.

Nimodipine is a compound that is thought to block the influx of calcium through channels in vascular smooth muscle. This paper describes a double-blind parallel-group comparison of 40 mg nimodipine three times a day and placebo. Sixty-eight patients received treatment after a run-in period of 2 months, and of these, 57 completed 8 weeks or more of the trial. All but five of these completed the full 6-month trial. The nimodipine and placebo groups showed no significant differences in the frequency of attacks, severity or duration of headache, or gastrointestinal or other symptoms.

Adolescent↗
PubMed1988

Opioidergic control of luteinizing hormone release in the female rabbit: influence of ovariectomy and steroid replacement on pulsatile secretion.

The influence of ovariectomy and steroid replacement on naloxone-induced changes in pulsatile secretion of luteinizing hormone (LH) in the female rabbit was examined. Blood samples were taken every 5 min through an indwelling catheter in the rabbit ear artery, and plasma was stored until assayed for LH by established radioimmunoassay procedures. In the intact animal, saline injection had no effect on LH secretion. Although naloxone (10 mg/kg) caused a 7-fold increase in mean LH pulse amplitude by 30 min after injection, this increase was not statistically significant because 5 of 11 animals did not respond. In animals ovariectomized 48 h previously, naloxone significantly increased LH concentration by 194% at 23 min after injection. When long-term ovariectomized rabbits were treated with estradiol benzoate and then were given naloxone, no significant increase in LH was observed, although many animals did respond. Treatment of long-term ovariectomized rabbits with 1 microgram estradiol benzoate and 100 micrograms progesterone or 1 mg testosterone propionate on Days 1 and 3 and naloxone on Day 4 resulted in a significant increase in LH 19-24 min later. Although there was an increase in pulse amplitude, no change was detected in pulse frequency after naloxone. These data suggest that the hypothesis of steroid-opioid coupling in the control of LH secretion is not applicable to the female rabbit.

Animals↗
PubMed1988

Opioidergic control of luteinizing hormone secretion in the female rabbit: influence of age on the response to naloxone.

To examine the role of opioid neurons on luteinizing hormone (LH) secretion in the female rabbit, we determined LH release at timed intervals after naloxone administration to rabbits aged 25-150 days. The LH response to naloxone (10 mg/kg) was not significantly elevated until day 43 when LH rose 76-113% above basal levels at 40-80 min. In 56-day-old females the corresponding increase was 160% at 15 min and in 65- to 67-day-olds it was 154%. From 70 to 80 days of age the LH response was blunted and no significant elevations could be elicited. By contrast, naloxone-induced LH increases were again evident when rabbits were older than 100 days. At all ages no significant change in FSH concentrations was observed. In the adult females, naloxone at 2.5, 5, and 10 mg/kg caused increases in LH secretion which occasionally were high enough to induce ovulation as exemplified by elevated serum progesterone 4 days later. These data suggest that opioid peptides may be involved in the prepubertal rise in LH and in the normal inhibition of adult secretion in the female rabbit.

Aging↗
PubMed1988

Cardiac effects produced by long-term stimulation of thoracic autonomic ganglia or nerves: implications for interneuronal interactions within the thoracic autonomic nervous system.

Electrical stimulation of an acutely decentralized stellate or middle cervical ganglion or cardiopulmonary nerve augments cardiac chronotropism or inotropism; as the stimulation continues there is a gradual reduction of this augmentation following the peak response, i.e., an inhibition of augmentation. The amount of this inhibition was found to be dependent upon the region of the heart investigated and the neural structure stimulated. The cardiac parameters which were augmented the most displayed the greatest inhibition. Maximum augmentation or inhibition occurred, in most instances, when 5-20 Hz stimuli were used. Inhibition of augmentation was overcome when the stimulation frequency was subsequently increased or following the administration of nicotine or tyramine, indicating that the inhibition was not primarily due to the lack of availability of noradrenaline in the nerve terminals of the efferent postganglionic sympathetic neurons. Furthermore, as infusions of isoproterenol or noradrenaline during the period of inhibition could still augment cardiac responses, whereas during the early peak responses they did not, the inhibition of augmentation does not appear to be due primarily to down regulation of cardiac myocyte beta-adrenergic receptors. The inhibition was modified by hexamethonium but not by phentolamine or atropine. Inhibition occurred when all ipsilateral cardiopulmonary nerves connected with acutely decentralized middle cervical and stellate ganglia were stimulated, whereas significant inhibition did not occur when these nerves were stimulated after they had been disconnected from the ipsilateral decentralized ganglia. Taken together these data indicate that the inhibition of cardiac augmentation which occurs during relatively long-term stimulation of intrathoracic sympathetic neural elements is due in large part to nicotinic cholinergic synaptic mechanisms that lie primarily in the major thoracic autonomic ganglia. They also indicate that long-term stimulation in intrathoracic sympathetic neural elements with frequencies as low as 2 Hz may augment the heart as much as higher stimulation frequencies, depending upon the structure stimulated and the cardiovascular parameter monitored.

Adrenergic beta-Antagonists↗