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Biomedical subjects

R Young

Publications and source records attributed to R Young.

At least 271 records · Page 15Linked to original sources

Changes in iron metabolism following surgery.

Studies of iron metabolism were made in 24 patients following surgery under general anaesthesia. No postoperative complications occurred. There was a marked fall in serum iron in all patients on the first postoperative day (P less than 0.001) which remained significantly depressed even at the seventh postoperative day. The total iron binding capacity fell progressively to reach the lowest levels on the third postoperative day, returning to normal levels by the end of the study. Serum ferritin concentration rose significantly in a reciprocal pattern to the changes in serum iron. This study highlights the limitation of iron studies in peripheral blood in postoperative patients.

Adult↗

Behavioral effects of 5-methoxy-N,N-dimethyltryptamine and dose-dependent antagonism by BC-105.

The discriminative effects of 5-methoxy-N,N-dimethyltryptamine (5-OMeDMT) were studied in rats trained to discriminate 1.5 mg/kg or 3.0 mg/kg 5-OMeDMT from saline. A series of antagonist and generalization tests revealed that (1) antagonism of the 5-OMeDMT stimulus response by the presumed serotonin antagonist BC-105 depended on the dose of 5-OMeDMT, (2) the 5-OMeDMT stimulus generalized to LSD, and (3) like 5-OMeDMT, antagonism of the LSD generalization response by BC-105 depended on the dose of LSD. In a second study, with rats responding under a variable-interval (VI) 15-s schedule of reinforcement, doses of 1.0-3.0 mg/kg 5-OMeDMT significantly decreased response rate. Furthermore, the decrease in responding produced by the administration of 1.5 mg/kg (but not by 3.0 mg/kg) 5-OMeDMT was blocked by BC-105. This dose-dependent antagonism was of particular interest since the 1.5 mg/kg and 3.0 mg/kg dose of 5-O-MeDMT had essentially the same effect on responding when given alone. The results of both studies emphasize the importance of 5-OMeDMT dose in antagonism experiments.

Animals↗

Alexander's disease: further light-, and electron-microscopic observations.

The neuropathologic and ophthalmopathologic findings in a 5 3/4-year-old boy with Alexander's disease are reported. Light- and electron-microscopic and immunohistochemical studies revealed that (1) the granular osmiophilic deposits (GOD) in Alexander's disease accumulate mainly in astrocytic processes to form Rosenthal fibers, (2) the Bergmann glia are different in this regard and accumulate the deposits primarily in their perikarya, (3) the Müller cells of retina (which closely resemble astrocytes) do not accumulate GOD, (4) the deposits are also not present in other glial cells and glial-like cells such as pituicytes and pineocytes, (5) the deposits are sparse in the retrobulbar optic nerves, and (6) the peroxidase-antiperoxidase and immunofluorescence studies do not demonstrate glial fibrillary acidic protein (GFAP), albumin, immunoglobulins, or fibrinogen in the astrocytic deposits. The different deposition of GOD in various cytoplasmic regions of astrocytes in different areas of central nervous system (CNS) suggests that astrocyte metabolism may not be uniform throughout the brain. Attention to this point may prove helpful in understanding the pathogenesis of the deposits in Alexander's disease. The absence of immunohistochemically demonstrable plasma proteins and GFAP in the astrocytic GOD indicates that the latter have an origin different from plasma proteins and glial filaments. Alternatively, the deposits may be derived from these proteins, but their antigenicity has since been altered.

Albumins↗

Effect of midbrain stimulus-induced analgesia on immune function in humans.

Electrical stimulation of midbrain structures produces significant and clinically useful analgesia in humans. However, it has been suggested to have immunosuppressive effects in animals. We evaluated immune function in two women who were utilizing implanted midbrain electrodes for pain control. An elevated B cell percentage was observed in one patient after a 72-h control rest period and this was followed by a reproducible fall in B cells after acute stimulation. However, midbrain electrical stimulation did not appear to have any other acute or chronic effects on these persons' immune functions.

Analgesia↗

Comparative carcinogenicity in F344 rats and Syrian golden hamsters of N'-nitrosonornicotine and N'-nitrosonornicotine-1-N-oxide.

N'-Nitrosonornicotine (NNN) or N'-nitrosonornicotine-1-N-oxide (NNN-1-N-oxide), one of its metabolites, was added to the drinking water (0.012% for 36 weeks) of groups of male and female F344 rats or to the drinking water (0.016% for 31 weeks) of groups of male and female Syrian golden hamsters. All rats treated with NNN had died after 12 months but 50% of those treated with NNN-1-N-oxide survived for 22 months. NNN induced esophageal tumors in 23/24 rats and nasal cavity tumors in 21/24 rats. NNN-1-N-oxide induced esophageal tumors in 10/24 rats and nasal cavity tumors in 18/24 rats. There was no difference in survival rates among hamsters treated with either NNN or NNN-1-N-oxide. NNN induced tracheal tumors in 2/20 hamsters and nasal cavity tumors in 4/20 hamsters. NNN-1-N-oxide did not induce respiratory tract tumors in hamsters. These results demonstrate that NNN-1-N-oxide is less carcinogenic than NNN in F344 rats and Syrian golden hamsters.

Animals↗

S gene product: identification and membrane localization of a lysis control protein.

The product of the bacteriophage S gene has been previously shown to be required for an essential step in triggering host cell lysis. By using two different protein labeling systems, maxicells and UV-irradiated infected cells, we identified the S gene product as an 8,500-molecular-weight polypeptide associated with the cell envelope. The apparent molecular weight is significantly less than the 11,500 predicted from the S gene sequence. We were unable to confirm two previous identifications of S gene products, an acidic 15,000-molecular-weight polypeptide found by two-dimensional gel electrophoresis of infected cells and a 5,500-molecular-weight polypeptide in purified phage particles.

Bacteriolysis↗

DEET (N,N-diethyltoluamide) does not affect sperm number, viability and head morphology in male rats treated dermally.

DEET (N,N-Diethyltoluamide) was applied dermally to groups of 80 Sprague Dawley rats 5 days/week for 9 weeks (63 days), at three dose levels, (100, 300, and 1000 mg/kg). The undiluted material was applied with micropipettes to shaved patches. There was no run off and the material wet out onto the skin. Dose levels were calculated based on mean weights and adjusted weekly by reweighing half the animals in each group and calculating a mean body weight. Animals were scheduled for kill at three times; days 36-37, 65-66 and 95-96 after initiation of treatment. Data collected at each kill included sperm count, viability as assessed by ATP levels and morphology; testes histopathology (control and high-dose groups only) and body and organ weights (liver, kidneys and testes). DEET, when applied dermally, did not alter sperm count, sperm morphology, sperm viability, body weight or food consumption at any dose level tested.

Adenosine Triphosphate↗

Prophylactic cefoxitin in cesarean section.

The effectiveness of prophylactic cefoxitin in preventing postcesarean section infection was studied in a high risk population. One hundred women were evaluated, and on a random double-blind basis 50 received placebo and 50 received cefoxitin. There were three doses of drug given intravenously, either placebo or 1 gram of cefoxitin at the time of cord clamping and again four and eight hours later. Those receiving cefoxitin had significantly less postoperative infections, fewer had bacteremia and there was less postoperative fever as measured by the fever index. The patient with the most protracted infection in this study received cefoxitin. Problems with the use of systemic antibiotic prophylaxis in preventing postcesarean section infection are discussed. Cefoxitin is an effective agent to use in patients undergoing cesarean section who are at high risk for infection.

Adult↗

Comparative discriminative stimulus effects of 5-methoxy-N,N-dimethyltryptamine and LSD.

Rats were trained to discriminate injections of either 5-OMe DMT (1.5 mg/kg) or LSD (0.096 mg/kg) from saline in a two-lever drug discrimination task. After stable discrimination performances were attained (greater than 85%) in each group, dose-response generalizations between the two groups of animals were examined. The results revealed that the 5-OMe DMT-stimulus response generalized to LSD and that the LSD-stimulus response generalized to 5-OMe DMT. Furthermore, both the 5-OMe DMT-stimulus and the LSD-stimulus could be significantly attenuated by the serotonin antagonist BC-105. However, the pattern of the dose-related antagonism by BC-105 was different between the drug stimuli. It was concluded that while the discriminative stimulus effects of 5-OMe DMT and LSD may be mediated via a common serotonergic system, the receptor interaction of these agents within that pharmacological system may be somewhat different.

Animals↗

Hallucinogens as discriminative stimuli: a comparison of 4-OMe DMT and 5-OMe DMT with their methythio counterparts.

Rats, trained to discriminate 1.5 mg/kg of the hallucinogenic agent 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a two-lever drug discrimination task, were challenged with various doses of the 4-methoxy, 4-methylthio and 5-methylthio derivatives of DMT. The 5-OMe DMT cue was found to generalize to all three of these agents; the order of potency is 5-OMe greater than 5-SMe greater than 4-OMe greater than 4-SMe DMT.

Animals↗

Intraperitoneal preloads of water, but not isotonic saline, suppress schedule-induced polydipsia in rats.

In Experiment 1, 10 ml intraperitoneal preloads of water completely suppressed the acquisition of schedule-induced polydipsia in four of six rats. Preloads of 10 ml of isotonic saline retarded the acquisition of polydipsia slightly, but there were no significant differences in asymptotic levels of water intake between Saline Preload and Sham Preload groups. Experiments 2 and 3 demonstrated that established polydipsia was suppressed by about 10 ml when 10 ml water preloads were given; whereas, 10 ml saline preloads had no significant effect on established polydipsia. These results demonstrate that schedule-induced polydipsia is sensitive to internal states of water balance.

Animals↗

Comparison of behavioral properties of di- and tri-methoxyphenylisopropylamines.

Prominent among the class of hallucinogenic phenylisopropylamines is the 2,5-dimethoxy substitution pattern; this pattern has long been recognized as being an important feature of the more potent agents within this class. The purpose of this present study was to explore the behavioral properties of a series of methoxylated phenylisopropylamines in order to determine the effect of other substitution patterns and the relative importance of individual methoxy groups. Rats, trained to discriminate the hallucinogenic agent 2,5-dimethoxy-4-methyl-phenylisopropylamine (DOM) from saline in a two-lever drug discrimination task, were challenged with a series of di- and trimethoxyphenylisopropylamines (i.e., DMA and TMA derivatives). DOM-stimulus generalization was found to occur with 2,4-DMA but not with 2,3-DMA, 2.6-DMA, or 3,5-DMA; generalization also occurred with 2,3,4-TMA, 2,3,5-TMA, 2,4,6-TMA and 3,4,5-TMA. The 2,4-dimethoxy pattern also emerges as an important feature among the more active agents.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

Discriminative stimulus properties of DOM and several molecular modifications.

Rats trained to discriminate racemic 2,5-dimethoxy-4-methylphenylisopropylamine, (+/-)-DOM (1.0 mg/kg), from saline in a two-lever drug discrimination task were challenged with the optimal isomers of DOM as well as with several related agents which represent minor molecular modifications of the DOM structure. Generalization of the (+/-)-DOM stimulus was found to occur to R(-)-DOM, S(+)-DOM, (+/-)-2,5-dimethoxyphenylisopropylamine (2,5-DMA), R(-)-2,-5-DMA, and the 2-demethyl derivative of (+/-)-DOM. The 3-methyl positional isomer of (+/-)-DOM was found to produce only 34% DOM-appropriate responding at the highest dose tested while administration of S(+)-2,5-DMA and the 5-demethyl derivative of (+/-)-DOM resulted in disruption of behavior.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

A comparison of the behavioral effects of DOM homologs.

Twenty-four rats, trained to discriminate 1.0 mg/kg of (+/-)-DOM, i.e. (+/-)-2,5-dimethoxy-4-methylphenylisopropylamine, from saline under a VI-15 schedule of reinforcement, were challenged with a series of DOM homologs. The agents examined included the 4-ethyl (DOET), -propyl (DOPR), -butyl (DOBU), -tertiary butyl (DOTB) and -amyl (DOAM) derivatives as well as the R(-)- and S(+)-isomers of DOET. The (+/-)-DOM stimulus was found to generalize to all of the agents, except DOTB and DOAM, where only partial generalization occurred. The results suggest that the stimulus properties produced by the latter two compounds may differ from those of the remainder of the series. Furthermore, the ED50 values obtained, for those compounds to which the DOM-stimulus generalized, correlated significantly (r2 = 0.94) with the human hallucinogenic potencies of these agents.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗