Cardiovascular changes following DOCA-NaCl or conditioning in 6-hydroxydopamine-treated rats.
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Biomedical subjects
Publications and source records attributed to R D Smith.
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Destruction of catecholamine-containing fibers in brain at 5 days of age with intracisternal injection of 6-hydroxydopamine reduced body growth, intake of a sucrose solution, and acquisition of an active avoidance response. Further characterization of behavioral deficits indicated that treated animals also showed reduced ingestion of saline solution when injected with desoxycorticosterone and a decreased eating response to insulin. In addition, all of these deficits produced by catecholamine depletion with 6-hydroxydopamine were observed in rats in which brain dopamine was preferentially reduced but not in rats having preferential destruction of noradrenergic fibers, suggesting that dopamine depletion amounts for the observed alterations in developing animals. Although animals treated with 6-hydroxydopamine at 14 days showed reduced intake of a sucrose solution, they did not have reduced growth. Since early malnourishment reduced growth, it seems possible that the reduced growth observed after destruction of dopaminergeic fibers may be related to an acute reduction of food intake which is perpetuated by persistent deficits in ingestive behavior. Evidence implicating malnourishment in other deficits produced by 6-hydroxydopamine could not be obtained.
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This study investigated lifetime and current rates of axis I diagnoses and the personality traits of neuroticism and extraversion in patients receiving complementary medical care in the United Kingdom and United States. Eighty-three patients were interviewed by means of the Structured Clinical Interview for DSM-III-R, and 78 completed the Eysenck Personality Inventory (EPI). Subjects were drawn from the Royal London Homoeopathic Hospital (n = 50) and a holistic family practice in North Carolina (n = 33). High rates of lifetime (68.7%) and current (39.8%) axis I disorders were found, with no substantial differences between the groups, apart from lifetime posttraumatic stress disorder and current social phobia, which were higher in the US sample. The subjects were more introverted but not more neurotic as compared against normative population data with the EPI. The subjects were predominantly older women. We conclude that psychiatrists may need to be aware that patients with depressive or anxiety disorders are likely to seek out complementary treatments for a wide range of medical problems, and should inquire as to use of these in their patients. They may also need to cultivate greater awareness of the health beliefs of such patients.
We examined the effects of picrotoxin and pentylenetetrazol (PTZ) on the responses to motions of ON-OFF directionally selective (DS) ganglion cells of the turtle's retina. These drugs are antagonists of the inhibitory neurotransmitter GABA. For continuous motions, picrotoxin markedly reduced the overall directionality of the cells. In 21% of the cells, directional selectivity was lost regardless of speed and contrast. However, other cells maintained their preferred direction despite saturating concentrations of picrotoxin. And in most cells, loss, maintenance, or even reversal of preferred and null directions could occur as speed and contrast were modulated. In 50% of the cells, reversal of preferred and null directions occurred at some condition of visual stimuli. However, picrotoxin did not tend to alter the preferred-null axis for directional selectivity. For apparent motions, picrotoxin made motion facilitation, which normally occurs exclusively in preferred-direction responses, to become erratic and often occur during null-direction motions. Finally, PTZ had effects similar to picrotoxin but with less potency. The results in this paper indicated that models of directional selectivity based solely on a GABAergic implementation of Barlow and Levick's asymmetric-inhibition model do not apply to the turtle retina. Alternative models may comprise multiple directional mechanisms and/or a symmetric inhibitory one, but not asymmetric facilitation.
In this article, we briefly highlight the use of capillary electrophoresis for sampling, manipulating, and separating extremely small sample sizes. The extraordinary sensitivity that can be obtained by combined capillary electrophoresis-mass spectrometry is then demonstrated using recent results. We briefly describe the ability to detect noncovalently associated complexes (e.g., double-stranded DNA) by electrospray ionization-mass spectrometry, and conclude with recent results that show the potential for using high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry for characterization of biomolecules.
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OBJECTIVES: Unilateral multicystic kidney dysplasia (MCKD) is the second most common urinary tract abnormality diagnosed antenatally. Whilst an isolated unilateral MCKD has a good prognosis, a poor outcome must be expected when MCKD is associated with other complex abnormalities. MATERIAL: Out of 11,176 cases, 693 fetuses were suspected of having urinary tract abnormalities. Urological findings were confirmed in 548 of them. Unilateral cystic kidney was diagnosed prenatally in 85 cases. RESULTS: The study results in a total of 107 cases with proven MCKD. Eighty-five pregnancies with a prenatal diagnosis of MCKD were analysed. The antenatal diagnosis of MCKD was confirmed in 56 cases. Fifty-one children were found to have unilateral MCKD where this had not been explicitly suspected from antenatal scanning. CONCLUSION: Unilateral MCKD is a malformation with an excellent prognosis for child survival and global renal function if encountered in isolation. However, our analysis of live infants and autopsy cases demonstrates a high proportion of severe associated malformations of the urinary tract and other organ systems.
A technique for measuring focal cerebral blood flow (CBF) and brain specific gravity (SG) in gerbils is described; CO2 reactivity and autoregulation were tested. The mean CBF was 29.5 +/- 4.5 ml/100 gm/min and brain SG 1.0500 +/- 0.0004. Unilateral carotid occlusion resulted in a reduction of flow to 12.8 +/- 5.8 ml/100 gm/min in the ipsilateral hemisphere with little change in the contraleteral hemisphere; there was also a decrease in brain SG. One hour after occlusion, brain edema, as judged by decreased SG, developed at CBF less than 20 ml/100 gm/min and reached maximal levels at 7 +/- 2 ml/100 gm/min. The amount of edema appeared to be related chiefly to the residual post-occlusion flow. With bilateral occlusion, CBF was close to zero and there was no change in SG, indicating that in the "no flow" situation, there is no edema.
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The use of willingness to pay (WTP) in valuing the benefits of health care programs is increasing. Although such values have been derived using open-ended, bidding, or payment-card techniques, recently discrete-choice questionnaires have been advocated, particularly following the report of the National Oceanographic and Atmospheric Administration concerning the validity of using WTP to estimate environmental benefits. It is argued that discrete-choice questions offer a more realistic market, and will therefore lead to more valid responses and yield higher response rates through reduced mental demands. The author reviews these issues in a critical assessment of discrete-choice questions.
Angiotensin II (Ang II) receptors of the AT1 subtype are coupled to heterotrimeric G nucleotide-binding proteins, G(q/11), to activate phospholipase C-beta isoforms with production of inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol. The resultant release of intracellular Ca2+ and increased Ca2+ influx are major determinants of several acute cellular responses initiated by Ang II, including secretion of aldosterone from the adrenal cortex and smooth muscle contraction. However, cellular events related to more prolonged effects of Ang II, such as hypertrophic and hyperplastic responses, are triggered by intracellular signaling cascades that are less dependent on Ca2+ signals. The Ang II-induced activation of Raf-1 kinase, p42 MAP-kinase and c-fos expression in response to Ang II in adrenal glomerulosa cells does not require Ca2+ influx. Moreover, the dose-response relationships for Raf-1 activation, MAP-kinase activation and mitogenesis show significantly higher sensitivity to Ang II than the InsP3, Ca2+-release and aldosterone secretory responses. The sensitivities of both Raf-1 kinase and MAP-kinase stimulation by Ang II to the inhibitors of phosphoinositide kinases, wortmannin and LY 294002, suggest that inositol phospholipids may play a role in these activation events unrelated to their role in Ca2+ signaling. To investigate the changes of various inositides after stimulation at the single cell level, fluorescent probes were developed in which pleckstrin homology domains with distinct binding specificities to inositol phospholipids were fused to the green fluorescent protein and expressed in NIH 3T3 cells. The use of these probes revealed heterogeneity of the inositol lipid pools and their complex relationship to Ca2+ signals. The use of these tools will help to further clarify the complex role of these lipids in initiating Ca2+-dependent and -independent signaling responses.
Sixty-one large dogs (weighing 22.7 kg or more) with cranial cruciate ligament ruptures (CCLRs) were treated with either fibular head transpositions (FHTs; n = 22 stifles), lateral fabellar sutures (LFSs; n = 39 stifles), or conservatively (CT; n = 11 stifles) with rest and aspirin. Based on owner evaluation, dogs treated with FHTs or CT did not perform as well as dogs treated with LFSs (p less than 0.05). There was no difference in owner evaluation scores for the dogs treated with FHTs or CT. Thirty dogs were reevaluated by investigators. No differences between treatment groups regarding age, sex, or time until diagnosis were noted. No differences in scores for lameness, stifle instability, or forceplate analysis among the treatment groups were observed. Degenerative joint disease progressed or remained severe regardless of treatment, based upon radiographic evidence.
The efficacy and tolerability of losartan 100 mg/hydrochlorothiazide (HCTZ) 25 mg and enalapril 10 mg/HCTZ 25 mg were compared in a double-blind, randomized trial in hypertensive patients inadequately controlled and experiencing side effects on prior therapy. Patients with moderate or severe hypertension, currently treated with at least two single-agent drugs (excluding angiotensin-converting enzyme inhibitors), with a sitting diastolic blood pressure (DBP) above 90 mm Hg, and at least one undesirable drug-related symptom were randomized to once-daily treatment with one of the combinations for 12 weeks. Losartan/HCTZ lowered sitting DBP from the prior therapy baseline by 13.7 mm Hg and sitting systolic blood pressure 19.3 mm Hg; similar reductions occurred with enalapril/HCTZ. Trough sitting DBP was reduced to normal levels (< 90 mm Hg) in 63% of patients switched to the losartan combination and in 58% of those treated with the enalapril combination. Each combination was associated with improved tolerability compared with prior therapy, although fewer patients reported each of 24 undesirable symptoms after 12 weeks of losartan/HCTZ. The improvement from prior therapy in the occurrence of cough was significantly greater with losartan/HCTZ (P = .005). Enalapril/HCTZ, but not losartan/HCTZ, increased serum uric acid levels at week 12. In conclusion, the combination of losartan 100 mg/HCTZ 25 mg offers a beneficial therapeutic option for patients with a history of moderate to severe hypertension whose blood pressure is not adequately controlled or who exhibit side effects while on two or more single-agent antihypertensive drugs. In this population, the switch from prior antihypertensive therapies to once daily losartan 100 mg/HCTZ 25 mg improves blood pressure control and reduces side effects.
The X-ray structure of the periplasmic glucose/galactose receptor (binding protein) of Salmonella typhimurium has been solved by the method of multiple isomorphous replacement and refined to a resolution of 2.4 A with an R-factor of 15.8%. The protein consists of two highly-similar structural domains with a bound sugar molecule trapped between. A combined sequence/structural approach is used to compare the structure of this protein to a similar arabinose receptor. The new sequence alignment obtained is used to analyze a number of features conserved for structural and functional reasons. This information allowed the prediction of similar features within the sequence of the analogous ribose receptor. Some of the consequences of the structures for chemotaxis and transport are discussed.