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Biomedical subjects

C Smith

Publications and source records attributed to C Smith.

At least 793 records · Page 44Linked to original sources

Stimulation of DNA replication by growth factor and hormones in Swiss 3T3 cells: comparison of the rate of entry into S phase with in vitro DNA synthesis and DNA polymerase alpha activity.

An approach to the investigation how growth factors and hormones regulate mammalian cell proliferation is to study the activity of enzymes involved in DNA replication. Quiescent cultures of Swiss mouse 3T3 cells were stimulated with prostaglandin F2 alpha, insulin, and/or hydrocortisone for a time at which less than 50% of the cells had initiated DNA synthesis. Such cells were lysed with a Ca++-containing hypotonic buffer and incubated with a nucleotide mixture including [3H]thymidine-triphosphate for 1 hr at 37 degrees C. The amount of radioactive label incorporated into the trichloroacetic acid (TCA)-precipitate and the percentage of labeled nuclei correlated with the in vivo stimulation. Analysis of radioactively and density-labeled DNA in sucrose and CsC gradients indicated that the incorporation of label reflected semiconservative replication. DNA polymerase activities were assayed in supernatants from whole-cell lysates prepared with a hypotonic buffer not containing Ca++. Using various templates, it was shown that the increase in activity of DNA polymerase alpha correlated with the percentage of cells in S phase upon the different stimulation, while DNA polymerase beta activity after various times of stimulation showed that this activity increased only when cells began to enter S phase, regardless of the combination of growth factor and hormones.

Animals↗

Corticosteroid binding globulin, testosterone-estradiol binding globulin, and androgen binding protein belong to protein families distinct from steroid receptors.

The cDNA nucleotide sequences and the deduced amino acid sequences of human corticosteroid binding globulin (hCBG), human testosterone-estradiol binding globulin (hTeBG), and rat androgen binding protein (rABP) were determined. Studies of the steroid binding sites suggest they are toward the carboxy-terminus in hTeBG and rABP and more central in hCBG. hCBG has remarkable sequence homology with members of a superfamily whose functions have diverged; these include thyroxine-binding protein, serine protease inhibitors, egg white proteins, and angiotensinogen. hTeBG and rABP have a 68% amino acid sequence identity. Hybridization studies suggest that hTeBG is probably even more closely related, if not identical, to hABP. The carboxy-terminal sequences of hTeBG and rABP are also similar to that of protein S, a vitamin-K-dependent clotting factor. There were no nucleotide or amino acid sequence homologies between hCBG, hTeBG, or rABP and other steroid binding proteins such as steroid receptors, albumin, alpha-fetoprotein, and vitamin D binding protein. We conclude that the "extracellular steroid binding proteins" and steroid receptors do not appear to have descended from a common ancestor.

Amino Acid Sequence↗

Paradoxical sleep deprivation applied two days after end of training retards learning.

Sprague-Dawley rats (N = 98) were trained in a 2-way shuttle shock avoidance task (50 trials/day for two consecutive days) and then subjected to a paradoxical sleep deprivation (PSD) regime beginning at least 24 hours after the last training session. Results from the various PSD groups indicated that a vulnerable PS window exists from 48-72 hours after the end of the last training session. PSD during this time period produced severe retention deficits. These results suggest the existence of a very long term posttraining PS involvement in the learning/memory process.

Animals↗

Choosing alternative medicine: a comparison of the beliefs of patients visiting a general practitioner and a homoeopath.

This study was concerned with the different health and illness beliefs of patients choosing traditional vs alternative medicine. Two groups of patients, one visiting a GP and the other a homoeopath, were not significantly different in terms of sex, age, education, marital status, religion and income. They were asked to complete a questionnaire measuring such things as their perceived susceptibility to disease and illness; their beliefs concerning their own control over their health; measures of their own mental health; preventive measures in staying healthy; and the perceived efficacy of traditional vs alternative treatment. The major differences between the two groups were the fact that the homoeopathic group were much more critical and sceptical about the efficacy of traditional medicine; they believe that their general health could be improved; and that they tended to have higher psychiatric morbidity. By and large, the two groups did not differ on their beliefs about illness susceptibility or preventive measures. The results suggested that people who choose alternative medicine may do so from disenchantment with, and bad experiences of, traditional medical practitioners, rather than believing that traditional medicine is itself ineffective. Limitations of this particular study are also considered.

Adult↗

Late ulnar neuropathy in the brain-injured adult.

Twenty-five brain-injured adults who were treated for tardy ulnar neuropathy during a 5-year period were studied. Two patients had bilateral involvement. The incidence of late ulnar neuropathy in this population was determined to be 2.5%. The ulnar neuropathy was always on the neurologically impaired side and associated with significant spasticity. Diagnosis was made when intrinsic atrophy was noted in the hand. No patient initiated a subjective complaint. Nerve conduction velocity measurements confirmed impingement of the ulnar nerve in the cubital canal in 16 cases. Twenty-one of the 27 (78%) elbows had moderate to severe heterotopic ossification causing impingement of the ulnar nerve. All patients were treated by anterior transposition of the ulnar nerve. Follow-up averaged 22.7 months. Twenty-three (85%) extremities had complete recovery of ulnar nerve function. Four patients had improved but incomplete recovery of function. Prolonged compression of the nerve led to incomplete recovery.

Adolescent↗

A new intratracheal stent for tracheobronchial reconstruction: experimental and clinical studies.

An intraluminal tracheal stent (ITS) was used experimentally in rabbits and piglets, as well as clinically in infants with tracheal stenosis, to facilitate airway reconstruction. The ITSs were constructed of stainless-steel springs covered with silicone rubber. They were implanted in seven piglets (6 to 8 kg), five rabbits (3 to 5 kg) and three infants. No animals developed severe respiratory distress and all appeared to tolerate the ITS. Postmortem examinations 1 to 8 weeks after surgery showed (1) loss of stent fixation (one pig), (2) increased tracheal secretions, (3) pneumonia (one pig, two rabbits), and (4) focal squamous metaplasia of tracheal mucosa. Stents used to treat three infants (2 to 5 months of age) with complex tracheobronchial stenosis were placed at the time of periosteal tracheoplasty in two. Recurrent stenosis necessitated a second tracheoplasty and stenting in one, and a long tracheostomy tube and balloon dilatations in the other. The third child had endoscopic stent insertion to alleviate severe airway collapse after esophageal tracheoplasty. The child died from progressive respiratory failure after stent dislodgment. Although the stents were well tolerated in animals and they enhanced critical ventilation of all pulmonary lobes in infants after tracheal reconstruction, certain modifications such as alternative methods of fixation, accommodation for tracheal growth, and reduction in tissue reactivity are necessary before further use of the ITS can be advocated.

Animals↗

Intravascular platelet activation in the hemolytic uremic syndrome.

We studied intravascular platelet activation in patients with typical (epidemic) and atypical (sporadic) HUS and found defective aggregation, decreased platelet and increased plasma serotonin in both groups. The findings were present not only on admission during the thrombocytopenic stage of the disease, but persisted for several weeks after recovery of the platelet count. Reduced endothelial PGI2 production was significantly more common in plasma from atypical than typical cases. Plasma from both typical and atypical HUS patients induced aggregation of normal platelets, but this phenomenon was unrelated to both the presence of thrombocytopenia or the stage of the disease. Serum platelet aggregating activity was higher in the atypical HUS patients, and was not associated with immune complexes detectable by polyethylene glycol precipitation. The data indicate that intravascular platelet activation is a feature of both forms of HUS, and may be initiated by different mechanisms in the two subgroups. While abnormal PGI2 synthesis appears to be important in the atypical cases, neither defective PGI2 production nor platelet aggregation by plasma factors adequately accounts for platelet activation in the majority of typical cases.

Adolescent↗

Charybdotoxin block of single Ca2+-activated K+ channels. Effects of channel gating, voltage, and ionic strength.

Charybdotoxin (CTX), a small, basic protein from scorpion venom, strongly inhibits the conduction of K ions through high-conductance, Ca2+-activated K+ channels. The interaction of CTX with Ca2+-activated K+ channels from rat skeletal muscle plasma membranes was studied by inserting single channels into uncharged planar phospholipid bilayers. CTX blocks K+ conduction by binding to the external side of the channel, with an apparent dissociation constant of approximately 10 nM at physiological ionic strength. The dwell-time distributions of both blocked and unblocked states are single-exponential. The toxin association rate varies linearly with the CTX concentration, and the dissociation rate is independent of it. CTX is competent to block both open and closed channels; the association rate is sevenfold faster for the open channel, while the dissociation rate is the same for both channel conformations. Membrane depolarization enhances the CTX dissociation rate e-fold/28 mV; if the channel's open probability is maintained constant as voltage varies, then the toxin association rate is voltage independent. Increasing the external solution ionic strength from 20 to 300 mM (with K+, Na+, or arginine+) reduces the association rate by two orders of magnitude, with little effect on the dissociation rate. We conclude that CTX binding to the Ca2+-activated K+ channel is a bimolecular process, and that the CTX interaction senses both voltage and the channel's conformational state. We further propose that a region of fixed negative charge exists near the channel's CTX-binding site.

Animals↗

A note on the effects of age and gender on children's social behaviour.

Observations of 40 3-4-year-olds' social behaviour in dyadic play show that total social behaviour towards opposite gender partners increases across this age range, while remaining constant for same gender partners. This finding partially replicates the results of an earlier study (Lloyd & Smith, 1986). In addition, analyses of three subcategories of social behaviour (prosocial, assertive and withdrawal) also yield partial replications. It is suggested that variations in procedure may account for differences between the two studies.

Age Factors↗

DNA hybridisation of cervical scrapes: comparison with cytological findings in Papanicolaou smears.

One hundred and sixty four cervical scrapes were taken over 26 months from 143 women aged 17 to 53 years, using an Ayre spatula. A smear was prepared from each sample for Papanicolaou staining and for cytological examination for evidence of human papillomavirus (HPV) infection. The cells remaining on the spatula were harvested for DNA analysis. These samples were probed for HPV 6, 16, and 18 and the results of DNA hybridisation and cytology were compared. Cytological changes of HPV (anucleate keratinised and keratinised squamous cells, koilocytic change and dyskeratosis, or multinucleation, or both) were detected in 103 (72%) of the samples where HPV DNA was detected; koilocytic changes were present in only 67 (48%). It is concluded that screening for a range of viral changes is a more sensitive method of detecting HPV infection than screening for koilocytic change alone.

Adolescent↗

Leukotriene D4 potentiates the contractile effects of epinephrine and norepinephrine on rat aortic rings.

Previous studies have demonstrated a cooperative interaction between peptido-leukotrienes (LTs) and epinephrine (EPI) relative to induction of platelet aggregation and thromboxane formation. To examine if a similar interaction occurs in arteries, we studied the effects of LTD4 and EPI as well as norepinephrine (NOREPI) on isolated rat aortic rings. LTD4 alone (mean concentration 2 x 10(-7) M) induced contraction in 10 of 15 rings examined (mean peak tension 0.31 +/- 0.27 g/mg of tissue). However, pretreatment of aortic rings with LTD4 (10(-7) M) consistently and significantly enhanced the contractile effects of EPI and NOREPI and lowered the threshold concentration of these agonists required to evoke contraction from 4 x 10(-9) to 3 x 10(-10) M (P less than .05). This enhancement of the sensitivity of aortic rings by LTD4 was not observed when KCl or 5-hydroxytryptamine was used as agonists. Furthermore, the LTD4-induced potentiation of effects of EPI or NOREPI on aortic contraction was blocked by the LT-receptor antagonist FPL-55712, but not by indomethacin. These data suggest a specific cooperative contractile effect of LTD4 and alpha adrenergic agonists on rat aortic rings. This LTD4 potentiation of vascular contraction is mediated through LT-receptor stimulation and not through release of cyclooxygenase metabolites.

Animals↗