PubMed Health⌕ Search

Biomedical subjects

P Killian

Publications and source records attributed to P Killian.

13 recordsLinked to original sources

Cold water swim stress- and delta-2 opioid-induced analgesia are modulated by spinal gamma-aminobutyric acidA receptors.

Cold water swim stress for 3 min at 5 degrees C produces antinociception in the tail-flick test in mice by activation of delta opioid receptors in the brain. Also, the inhibition of the tail-flick reflex produced by i.c.v. administration of delta opioid receptor agonists is known to be mediated by spinal gamma-aminobutyric acid (GABA) receptors. The purpose of this investigation was to determine if the cold water swim stress-induced antinociceptive response is mediated by GABA receptors in the spinal cord. First, i.c.v. administration of the delta-2 receptor antagonist, naltriben, but not the delta-1 receptor antagonist, 7-benzylidenenaltrexone, antagonized the cold water swim stress-induced antinociception in ICR mice and confirmed the role of delta-2 receptors in this response. Next, the involvement of spinal GABAA receptors was shown through intrathecal administration of GABAA receptor antagonists, picrotoxin and bicuculline, which inhibited the cold water swim stress-induced antinociceptive response. Thus, the antinociception produced through activation of the delta-2 receptor in the brain by cold water swim stress involved a descending pathway mediated by spinal GABAA receptors. This descending pathway appeared to be the same as that activated by i.c.v. administration of delta-2 opioid agonists in the brain.

Analgesia↗

Endocrine complications of AIDS and drug addiction.

The endocrine and metabolic consequences of illicit drug use and HIV disease are extensive and profound. Both narcotic drug use and AIDS have the capacity to cause clinically significant multiglandular derangements. Admittedly, we were not able to focus as much attention on the less frequently occurring disturbances of calcium, phosphorus, or folate metabolism in HIV disease. Similarly, we reported very little information about the endocrinologic significance of the use of classes of narcotics other than opiates and to a far lesser extent cocaine. Even with these limitations, the spectrum of drug abuse and HIV-related endocrine manifestations discussed previously is quite diverse. Given the pervasive effects of drug abuse on other organ systems, it is not surprising to find expanding interest in the endocrine consequences of narcotic drug use. In fact, the use of these drugs is responsible, in part, for the past and continuing interest in identifying receptors for these agents and similarly structured endogenous ligands. As these investigations proceed, we must appreciate the limitations in translating basic and clinical scientific findings to the clinical setting. Much of the current research does not study street-relevant narcotic doses, does not use research designs involving polydrug use, and does not involve the processes or routes of drug administration used by active narcotic addicts. There is a critical need for more research methods with animal models and clinical study settings that more adequately mimic drug use outside of the laboratory. Our ability to develop appropriate psychopharmaceutical agents to respond to the different faces of drug abuse in the United States will depend on continued progress in the area of neuroendocrinology. With respect to the consequences of HIV disease, the clinical findings of elevated hormonal levels in some endocrine systems are amazing given what one would expect if one postulated direct or indirect destruction by HIV or the opportunistic complications that accompany AIDS. In unraveling this puzzle, careful attention must be given to evaluating the degree to which the clinical or biochemical consequences are due to a direct HIV effect, to an effect of a complicating infection or neoplasm, or to an AIDS-related therapeutic intervention. More work is needed also in obtaining histopathologic information to correlate with the biochemical and clinical derangement. In summary, there is a wealth of information demonstrating a wide spectrum of endocrine/metabolic consequences of drug abuse and AIDS. Still, just as many questions remain unanswered. While the exact biologic mechanisms are unclear, many of the biochemical aberrations have clinical relevance.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗

Epitopes within the HLA-B5,B35 cross-reacting group.

The HLA-B5,B35 cross-reacting group is a large and serologically complex antigen family which includes the World Health Organization-recognized specificities HLA-B5,B51,Bw52,B35,Bw53,B18,Bw70,Bw71, and Bw72. In addition, several variants of antigens in this cross-reacting group have been described in the past but have not yet gained official recognition. A genetic basis for the complexity and the protein and molecular bases of this highly cross-reactive and polymorphic cross-reacting group have yet to be established. The potential contributions of shared amino acid sequences, the occurrence of multiple epitopes on a single HLA-B molecule, and the presence of new HLA-C antigens have been difficult to resolve. To address this issue, we have carefully examined the serologic reactions of more than 900 allo- and monoclonal antibodies (Tenth International Workshop, Third Asia-Oceanic Workshop, and local reagents) versus lymphocytes from 92 individuals of diverse ethnic origin (North American Caucasians, North American blacks, Amerindians, Middle Eastern Caucasians), 84 of whom were informative for the HLA-B5,B35 cross-reacting group and related antigens. Our results demonstrate that the HLA-B5,B35 gene products share different combinations of distinct epitopes. We have constructed a model for the evolution of this cross-reacting group by assigning polarity to distinct diversification steps utilizing principles of maximum parsimony.

Antibodies, Monoclonal↗

Pseudotumor cerebri, empty sella syndrome, and adrenal adenoma.

Benign intracranial hypertension (BIH) and empty sella syndrome occurred in a patient with Cushing syndrome resulting from adrenal adenoma, removal of which was followed by return of cerebrospinal fluid pressure to normal. This case does not clarify the pathophysiology of BIH, but it does raise questions about the treatment of BIH with corticosteroids, which are of unproved efficacy and may sometimes cause the same clinical syndrome.

Adenoma↗

Ouabain hypoglycemia: insulin mediation.

The fall in blood sugar occurring during infusion of ouabain (1 microgram per kilogram per minute for a 60-minute period) in dogs is accompanied by an increased uptake of glucose and potassium by the liver. Concurrently, plasma insulin in the portal blood increases significantly. This increase appears to be a result of increased insulin secretion caused by ouabain.

Animals↗

Acute rheumatic fever and rheumatic heart disease on the Navajo reservation, 1962-77.

The occurrence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) among Navajos was ascertained for the period from 1962 through 1977 by means of hospital discharge diagnoses and patients' charts. The annualized attack rate for ARF was 12.4 per 100,000 population, with no clear evidence of an overall secular trend. The proportion of recurrences (19.6 percent) and clinical features were similar to those reported elsewhere, but no seasonal variation in attack rates was noted. Between 1962-71 and 1972-77, the age of RHD patients increased, suggesting few newly diagnosed cases and the aging of known patients. A streptococcal disease control program was instituted in many Navajo elementary schools before 1975. In the program, throat cultures were performed routinely for some asymptomatic children and for all symptomatic children. During the subsequent 3 years, ARF rates declined from 13.5 to 8.2 per 100,000 in areas covered by the program, while in the noncovered areas the rates showed little change-9.5 to 10.1 per 100,000.

Acute Disease↗