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Biomedical subjects

M Wilkinson

Publications and source records attributed to M Wilkinson.

At least 163 records · Page 9Linked to original sources
PubMed1991

Ciliary beat frequency in newborn infants.

The ciliary beat frequencies of 31 newborns and 14 adults were measured in vitro by a photodiode method at body temperature (37 degrees C). The mean (SD) neonatal ciliary beat frequency (12.7 (0.82) Hz) was faster than that in adults (11.1 (0.84) Hz) (p less than 0.01). Increased ciliary beat frequency may be advantageous during the neonatal period.

Adult↗
PubMed1991

Use of biological response modifiers for management of renal cell carcinoma.

The approach to the treatment of patients with metastatic renal cell carcinoma has changed dramatically during the past 5 years. In the past, efforts to treat metastatic renal cell carcinoma were directed at palliation using chemotherapy, hormonal agents, or radiation therapy to control symptoms. Metastatic renal cell cancer was often resistant to these agents. With the advent of biological response modifiers, an entirely different approach is now available. Both recombinant human interferon-alpha (IFA-alpha) and interleukin-2 (IL-2) have significant activity in advanced renal cell carcinoma. Treatment with IFN-alpha can be given as outpatient therapy and provides effective disease control in a substantial minority of cases. Treatment with IL-2-based therapy, although associated with significant acute toxicity, is capable of inducing durable remissions from this otherwise lethal disease.

Carcinoma, Renal Cell↗
PubMed1991

Occurrence of sexual maturation in chronic opiate-treated female rats.

We have investigated the consequences of chronic morphine or fentanyl exposure on the timing of puberty in female Sprague-Dawley rats. The mu-receptor agonists morphine and fentanyl were either added to the drinking water or, in the case of fentanyl, in osmotic mini-pumps. Morphine and fentanyl treatment, beginning at postnatal day 22, delayed the time of the first ovulation/vaginal opening (VO). For example, morphine included in the drinking water (800 mg/l) delayed VO by 5 days. Fentanyl gave similar results but at lower concentrations (30 mg/l). Surprisingly, these treatments delayed but did not prevent VO; i.e. in the face of continued opiate treatment most rats ovulated normally. In contrast, identical doses of morphine blocked oestrous cyclicity in drug-naive adults rats. However, morphine-dependent rats, which have reached VO (and first ovulation) then became briefly acyclic before beginning regular cycles even though opiate treatment was continued. The effects of fentanyl on immature rats were identical with those of morphine, i.e. VO was delayed but ovulation occurred in spite of continued drug treatment. On the other hand, fentanyl did not prevent cyclicity subsequent to VO. Our observation that immature female rats can reach first ovulation despite chronic opiate treatment suggests that some degree of tolerance to opiates may develop. Such a mechanism could operate in normal drug-free rats, via endogenous opioid peptides, in the timing of puberty.

Animals↗
PubMed1990

Expression of c-fos protein by N-methyl-D-aspartic acid in hypothalamus of immature female rats: blockade by MK-801 or neonatal treatment with monosodium glutamate.

Significant NMDA-induced cellular activity in the median eminence-arcuate region of immature female rats was immunocytochemically localized via c-fos protein-like immunoreactivity. The production of this protein was completely prevented by pre-injection of MK-801 or APV, antagonists of the NMDA receptor-coupled ion channel. Treatment of newborn rats with monosodium glutamate (MSG), which destroys glutamate-sensitive neurons, significantly attenuated NMDA-induced c-fos when tested in the peripubertal period. These results implicate NMDA receptors in the expression of c-fos protein-like immunoreactivity in cells of the arcuate nucleus-median eminence of immature female rats.

Aging↗
PubMed1990

Ontogenesis of cell surface mu-opioid ([3H]DAGO) binding sites in rat hypothalamus and ex vivo determination of blood-brain barrier penetration by opioid peptide FK 33-824.

Previous studies have demonstrated that the LH response to naloxone changes during development but the reason(s) for this are unknown. In the present work we have investigated the possibility that variations in cell surface opioid receptor levels (determined in tissue slice/punches) or changes in the ability of opioids to enter the CNS might be responsible. Opioid binding data indicate that both [3H]naloxone and [3H]DAGO-labelled binding sites remain at low levels until 10 days of age after which there is a progressive rise to adult levels at 15 days ([3H]DAGO) and 21 days ([3H]naloxone). Although several peaks and nadirs were observed in this detailed profile of receptor ontogeny, no exact correlation with the time course of LH response to opioid drugs was found. In an adaption of the slice binding assay we are able to quantify drug penetration into the brain (ex vivo binding). Ex vivo binding studies of blood-brain barrier (BBB) ontogeny indicate that there are changes with age in the ability of opioid peptides, injected subcutaneously, to inhibit binding at the mu-receptor. FK 33-824 induced a reduction in [3H]DAGO binding in the mediobasal hypothalamus until 15 days of age. FK in older rats had no effect on [3H]DAGO binding suggesting that formation of the BBB is complete at this age. In contrast, FK injection reduced binding in the median eminence-arcuate nucleus area (outside BBB) until 30 days of age. Surprisingly, this area also became refractory to FK injection after this age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Characterization and functional expression of a rat genomic DNA clone encoding a lymphocyte potassium channel.

Low stringency hybridization screening of a rat genomic DNA library with a previously described cDNA clone encoding a rat voltage-gated potassium channel has resulted in the characterization of a member of the potassium channel family, RGK5. An uninterrupted nucleotide sequence encodes a protein 525 amino acids in length, revealing that the entire coding region resides on a single exon. RGK5 transcripts are present in both mouse thymus and rat brain, as determined by Northern blot analysis. RNA transcribed in vitro from RGK5 genomic DNA directs the expression of functional potassium currents after injection into Xenopus oocytes. The currents are activated by depolarization, being half-activated at -14 mV, and inactivate almost completely during depolarizations of 1 to 2 s. The properties of the currents strongly resemble those of the type n potassium channel present on both immature thymocytes and Th lymphocytes.

Animals↗
PubMed1990

Characterization and agonist regulation of muscarinic ([3H]N-methyl scopolamine) receptors in isolated ventricular myocytes from rat.

Cell surface muscarinic cholinergic receptors have been characterized and quantified for the first time, in intact, isolated adult rat cardiomyocytes. The cells were previously established as functionally fully compatible with cellular responses in intact cardiac tissue. The specific binding of the hydrophilic radioligand, [3H]-NMS, (N-methyl-[3H]-scopolamine methylchloride) was found to be stereo-specific, saturable, reversible and of high affinity. Binding of [3H]-NMS demonstrated appropriate drug specificity and was positively correlated with increasing cell concentrations. Bmax for [3H]-NMS binding to ventricular myocytes, enzymatically dissociated from adult male rats, was 15.8 +/- 1.03 fmol/25 x 10(3) cells (at 4 degrees C) and KD was 0.27 +/- 0.05 nM (n = 14). Binding assays performed at a higher incubation temperature (30 degrees C) yielded a higher Bmax value (22.1 +/- 1.6 fmol/25 x 10(3) cells; n = 11; P less than 0.005 vs. Bmax at 4 degrees C) but an unchanged KD (0.23 +/- 0.06 nM). Pretreatment of myocytes with the muscarinic agonist carbachol (1 mM) at 37 degrees C resulted in a reduction (down-regulation) in specific binding of the hydrophilic ligand [3H]-NMS. The magnitude of this reduction and its rate of recovery were dependent on the time of the exposure to carbachol. Exposures of 30-60 min elicited down-regulated by 35% (Bmax = 14.29 +/- 1.66 changed to 9.5 +/- 1.79 fmol/25 x 10(3) cells, without change in KD P less than 0.01, n = 4). The down-regulation of the muscarinic receptors by carbachol was insensitive to application of bacitracin - an inhibitor of endocytosis. On the other hand preincubation with 10(-9)M atropine, a muscarinic antagonist, hindered the agonist-induced receptor "loss" from the cell surface confirming the muscarinic nature of these receptors. We conclude that our preparation of intact, isolated ventricular cardiomyocytes is ideally suited for the study of cell surface muscarinic receptor regulation under physiological and pathological conditions.

Animals↗
PubMed1990

Testicular carcinoma in patients positive and at risk for human immunodeficiency virus.

Patients with the acquired immunodeficiency syndrome are at increased risk for certain malignancies. Because acquired immunodeficiency syndrome and testicular cancer affect primarily young men, the potential complications that acquired immunodeficiency syndrome might impose raise significant concern. To address this question we performed a retrospective review of all cases of testicular cancer during an 11-year period. Of 140 patients 6 had human immunodeficiency virus infection and 7 were from human immunodeficiency virus risk groups. All cases were either stage I or II disease with seminoma in 8, teratocarcinoma in 3, embryonal cell carcinoma in 1 and teratoma in 1. The clinical presentations of these patients were comparable to those of patients without human immunodeficiency virus risk factors. The majority of the patients received standard therapy, including orchiectomy followed by lymphadenectomy, radiation therapy or chemotherapy depending on stage and pathological subtype. Patients tolerated therapy well with only 1 course of radiation therapy complicated by Pneumocystis carinii pneumonia. All patients achieved complete remission and none died of testicular cancer. Since treatment of these patients may worsen the immunosuppression, surveillance is recommended after orchiectomy for acquired immunodeficiency syndrome patients with stage I disease. However, the majority of patients with human immunodeficiency virus infection should receive standard therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Migraine and menstruation: a pilot study.

OBJECTIVE: To define the term "menstrual" migraine and to determine the prevalence of "menstrual" migraine in women attending the City of London Migraine Clinic. DESIGN: Women attending the clinic were asked to keep a record of their migraine attacks and menstrual periods for at least 3 complete menstrual cycles. RESULTS: Fifty-five women completed the study. "Menstrual" migraine was defined as "migraine attacks which occur regularly on or between days -2 to +3 of the menstrual cycle and at no other time". Using this criterion, 4 (7.2%) of the women in our population had "menstrual" migraine. All 4 women had migraine without aura. A further 19 (34.5%) had an increased number of attacks at the time of menstruation in addition to attacks at other times of the cycle. Eighteen (32.7%) had attacks occurring throughout the cycle but with no increase in number at the time of menstruation. Fourteen (25.5%) had no attacks within the defined period during the 3 cycles studied. DISCUSSION: A small percentage of women have attacks only occurring at the time of menstruation, which can be defined as true "menstrual" migraine. This group is most likely to respond to hormonal treatment. The group of 34.5% who have an increased number of attacks at the time of menstruation in addition to attacks at other times of the month could be defined as having "menstrually related" migraine and might well respond to hormonal therapy. The 32.7% who have attacks throughout the menstrual cycle without an increase at menstruation are unlikely to respond to hormonal therapy. The 25.5% who do not have attacks related to menstruation almost certainly will not respond to hormonal therapy.

Adolescent↗
PubMed1990

The effect of exercise on circulating immunoreactive calcitonin in men.

Moderate-duration exercise increases serum catecholamine and serum calcium levels and might as a result be also expected to increase the levels of circulating serum immunoreactive human calcitonin (HCT). To explore this possibility, HCT was studied during and after moderate duration symptom-limited dynamic exercise in 13 healthy males, mean age 28 +/- 6.9 (SD) years. The mean duration of exercise using the Bruce treadmill protocol was 14.1 +/- 2.2 (SD) minutes. The mean heart rate (HR) peaked at 185 +/- 6 (SD) bpm which was 96.1% of the predicted maximal HR for age. Values for HCT, uncorrected for changes in plasma volume, showed a minimal decrease in the recovery phase, whilst HCT corrected for changes in plasma volume did not alter during exercise or recovery. The serum parathyroid hormone (PTH) also did not change. At peak exercise, uncorrected but not corrected values for plasma noradrenaline, adrenaline and dopamine had increased significantly. Corrected plasma total calcium increased during recovery. In summary, dynamic weight-bearing moderate-duration exercise did not elevate HCT in healthy males.

Adult↗
PubMed1990

Glial and neuronal differentiation in the human fetal brain 9-23 weeks of gestation.

Nineteen human fetal brains ranging from 9-23 weeks of gestation were examined immunocytochemically for evidence of glial and neuronal differentiation. Radial glia were positive for vimentin and glial fibrillary acidic protein (GFAP) throughout the age range. S100-positive cells which were presumed to be astrocytes were present from 9 weeks; they were always more widespread in the cerebrum and the brainstem than GFAP-positive mature astrocytes, which could be detected with certainty only at 14 weeks. Carbonic anhydrase II (CA II)-positive oligodendrocytes were present in the brainstem in small numbers from 17 weeks. Neuronal fibre tracts in the cerebrum were positive for 160 kD phosphorylated neurofilament protein (BF10) from 9 weeks, but negative for 200 kD phosphorylated neurofilament protein (RT97) and for 70 and 200 kD non-phosphorylated neurofilament protein (NFP) whereas most tracts in the brainstem were positive for BF10 from 9 weeks and positive for the other neurofilament proteins from 14 weeks. Corticospinal tracts differed in remaining negative for neurofilament proteins other than BF10, which showed positive reaction throughout. Perikarya of differentiated neurons in all areas of the brain were neurofilament-negative but neuron specific enolase (NSE)-positive. Germinal eminence cells were focally vimentin-positive from 15 weeks, focally GFAP-positive from 17 weeks, and negative for all NFP and for NSE. The value of a short fixation time and pretreatment with trypsin in the immunocytochemical demonstration of GFAP is stressed.

Brain↗
PubMed1990

Analgesic use: a study of treatments used by patients for migraine prior to attending the City of London Migraine Clinic.

Eighty-three unselected patients attending the City of London Migraine Clinic for the first time were asked about their drug intake and use of alternative treatment. Thirty-one of those questioned took regular daily doses of medication. Fifteen were taking a combination of drugs bought 'over the counter' (OTC) and drugs prescribed by their GP; eleven took OTC drugs only; and 5 took prescription drugs only. It was noticeable that those taking drugs prescribed both by the GP and obtainable over the counter were more likely than the other groups to be taking several drugs rather than a single type. Thirty five of the 83 (42.2%) had tried alternative treatments for their attacks.

Complementary Therapies↗
PubMed1990

Histidine-stimulated acid secretion in the conscious rat is mediated by amino acid uptake system N.

The characteristics of sodium-dependent, histidine-stimulated gastric acid secretion were studied in the conscious gastric-fistulated rat. Intragastric L-histidine, but not glutamine, asparagine, glutamic acid or glycine, stimulated acid secretion. The histidine-stimulated acid secretion was inhibited by the presence of glutamine or asparagine, but not by glutamic acid or glycine. The substitution of lithium for sodium in the gastric perfusate was tolerated. Together with previous data, the results indicate that an N-like amino acid uptake system mediates histidine-stimulated acid secretion in the conscious rat.

Amino Acids↗