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Biomedical subjects

R L Hayes

Publications and source records attributed to R L Hayes.

At least 163 records · Page 9Linked to original sources

Activation of pontine cholinergic sites implicated in unconsciousness following cerebral concussion in the cat.

Low levels of cerebral concussion in the cat produce reversible behavioral suppression presumably associated with unconsciousness. This injury is also associated with increased rates of glucose utilization in regions within the dorsomedial pontine tegmentum. Microinjection of carbachol into these regions produced behavioral suppression resembling that following concussion. These data, together with previously published observations on cholinergic responses to brain injury, suggest that concussive unconsciousness may be attributable in part to activation of cholinergic pontine sites.

Animals↗

Intracranial pressure variations associated with activation of the cholinoceptive pontine inhibitory area in the unanesthetized drug-free cat.

Intracranial pressure (ICP) was recorded continuously in chronically prepared, unanesthetized cats in order to investigate the effects on ICP of the cholinergic agonist, carbamylcholine (carbachol), injected by microsyringe needles into the dorsal pontine tegmentum. As reported previously, carbachol microinjections into the medial part of the cholinoceptive pontine inhibitory area (CPIA) located ventromedially to the locus coeruleus produced a comatose state characterized by a profound unresponsiveness to external stimuli, desynchronized electroencephalograms (EEG's), and suppression of postural somatomotor and sympathetic visceromotor functions. Four of six ICP records following carbachol microinjections into the CPIA showed small but significant increases which occurred in association with these carbachol effects. Tracings of ICP increases ranged up to 3.2 mm Hg and were similar in shape to plateau waves. The start and resolution of these carbachol-induced ICP variations were closely associated with the onset and termination of EEG desynchronization and signs of reduced cervical sympathetic tone, but not with changes in systemic arterial blood pressure or arterial pCO2. Temporal associations between ICP increases, desynchronized EEG's, and signs of reduced sympathetic tone were repeatedly confirmed during recovery periods associated both with recurrent comatose states following wakefulness produced by various intensities of external stimulation and with spontaneously occurring states resembling rapid eye movement sleep. The authors infer that carbachol-induced ICP variations may be produced by increased cerebral blood volume in response to accelerated cerebral metabolism and reduced vasoconstrictor tone of cervical sympathetic nerves. The simultaneous occurrence of continuously accelerated cerebral metabolism and reduced cervical sympathetic tone can neither be seen in physiologically normal, awake organisms nor produced by other known experimental manipulations of the central nervous system. Such a paradoxical relationship appears to be a unique consequence of activity within the CPIA. These data suggest that episodic activity within the CPIA may provide at least one endogenous neural basis for plateau waves seen during certain pathological conditions such as disturbed cerebrospinal fluid (CSF) absorption or with reduced equilibrium volume of CSF space.

Animals↗

Myocardial protection: a comparison of cold blood and cold crystalloid cardioplegia.

Two hundred seven consecutive patients were randomized into four groups based on left ventricular end-diastolic pressure and subsequently into groups receiving crystalloid cardioplegia or blood cardioplegia. Hemodynamic data and enzymatic evidence of myocardial ischemia were examined postoperatively. We found slight but significant improvement in the blood cardioplegia group regarding left ventricular stroke work index. Similarly, the levels of creatine kinase and serum glutamic oxaloacetic transaminase were slightly but significantly better with blood cardioplegia. We believe that the technique of blood cardioplegia offers a slight but statistically significant advantage.

Aged↗

Synergistic effect of AMP and fructose 2,6-bisphosphate on the protection of fructose 1,6-bisphosphatase against inactivation by trypsin.

The rate of inactivation of chicken liver fructose 1,6-bisphosphatase by trypsin is reduced if the digestive reaction is conducted in the presence of AMP or fructose 2,6-bisphosphate. The effects of these 2 compounds are synergistic. Although fructose 1,6-bisphosphate does not protect the enzyme against tryptic inactivation, it can enhance the effect of AMP. Selective modification of the AMP allosteric site of fructose 1,6-bisphosphatase with pyridoxal-P and NaBH4 renders the enzyme more resistant to tryptic inactivation, but the modified enzyme is no longer responsive to the protective effect of AMP.

Adenosine Monophosphate↗

An improved method for in situ freezing of cat brain for metabolic studies.

This study introduces a new method for rapid freezing of the cat brain. The method employed a Styrofoam box which was fitted around the head of the animal. Liquid nitrogen was poured into the box until the head was submerged. Temperature changes in three brain sites (ventral hypothalamus, the fourth ventricle, and the corpus callosum) and levels of labile carbohydrate metabolites (glycogen, glucose, ATP, P-creatine, and lactate) in five brain regions (cortex, thalamus, midbrain, cerebellum, and pons) frozen by the box method were compared with those frozen by a conventional cup method in which liquid nitrogen was poured into a hollow Styrofoam cup placed on top of the skull. The box method shortened the time of arrival of the freezing front and improved the freezing rate. The time required to bring the tissue to -20 degrees C was shortened, from 20 min at the ventral hypothalamus and 10-12 min at the fourth ventricle with the cup method, to less than 5 min at both sites with the box technique. Continued perfusion of brainstem prior to freezing was demonstrated. Levels of metabolites frozen by either method were similar. Lactate levels in any of the five brain regions studied by either method were not elevated, indicating no ischemic change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of naloxone on systemic and cerebral responses to experimental concussive brain injury in cats.

This study examined the effects of bolus injections of naloxone hydrochloride, a specific narcotic antagonist, on systemic cardiovascular function, intracranial and cerebral perfusion pressures, blood gas status, and cortical encephalograms (EEG's) in 38 cats after two different grades of experimental brain injury. Naloxone had no prolonged effects on uninjured control animals. However, as compared to a saline-injected control group, naloxone significantly reversed the hypotension and reduction in pulse pressure seen after higher grades of injury. These changes persisted for at least 60 minutes after injection and were accompanied by increased intracranial and perfusion pressures. More severely injured hypotensive cats injected with naloxone also had higher values of arterial pO2 and pH, lower pCO2, as well as higher EEG amplitudes. In less severely injured normotensive cats, naloxone produced greater effects on cardiovascular variables and intracranial pressure when injected 15 minutes rather than 45 minutes after injury. These data suggest that endogenous opiates may contribute to some instances of hypotension seen after concussive brain injury. Levels of endogenous opiates may also increase transiently even with lesser degrees of injury not associated with hypotension. The possible clinical application of narcotic antagonists to the treatment of head injury is discussed.

Animals↗

Pretreatment with minor histocompatibility antigens prevents the development of functional CTL helper cell activity.

We have been studying the regulation of allogeneic cytotoxic cells (CTL) in vivo. CBA/J (H-2k, mls d) responder mice are unable to develop CTL after an allogeneic footpad immunization if they are pretreated i.p. with spleen cells from either C3H/HeN (H-2k, mls c) or B10.BR (H-2k, mls b) mice. These mouse strain combinations are H-2 compatible but differ at the Mls and other minor histocompatibility loci. We reported that this state of CTL unresponsiveness is specific and that the allogeneic cells used for footpad immunization and the pretreatment strain must share both minor antigens and part of the MHC. In this paper, we describe some of the characteristic features of this CTL unresponsiveness. The CBA host plays an active role and appears to down-regulate its subsequent response against minor antigens after the initial pretreatment. This statement is based on the following: 1) The inhibition of in vivo CTL generation can be achieved by injecting F1 or irradiated C3H cells, i.e., under conditions where GVHD was not a factor; and 2) the state of unresponsiveness is abolished by host treatment with cyclophosphamide. In addition, we demonstrate that the lack of CTL development in pretreated responder animals is the result of impaired helper cell activity. Draining LNC from unresponsive mice can become functionally cytolytic if cultured in a Con A-activated spleen cell supernatant. However, normal CTL responses were not restored after adult thymectomy or splenectomy. Thus, the state of CTL inhibition that is induced by the minor antigen pretreatment is the result of a host-mediated regulatory circuit.

Animals↗

ECG findings in geriatric depressives given trazodone, placebo, or imipramine.

ECG effects were evaluated in 60 depressed geriatric patients in a drug-free baseline state and weekly during treatment with trazodone, placebo, or imipramine. Eighteen patients underwent crossover from placebo or imipramine to trazodone. Imipramine increased heart rate and was associated with more isolated ECG complications. Trazodone and placebo did not increase heart rate and had no other significant ECG effects.

Aged↗

Soluble factors in tolerance and contact sensitivity to 2,4-dinitrofluorobenzene in mice. IV. Characterization of migration inhibition factor-producing lymphocytes and genetic requirements for activation.

The production of migration inhibition factor (MIF) in vitro by lymph node cells from mice with contact sensitivity to 2,4-dinitrofluorobenzene (DNFB) was investigated. MIF activity of cell-free culture supernatants was measured using a micro, indirect "hanging-drop" assay system. We found that DNFB-sensitized lymph node cells are stimulated to produce MIF by co-culture with DNP-labeled spleen cells or splenic adherent cells. The stimulation was quantitatively antigen-specific, as co-culture with TNP-spleen cells or TNP-splenic adherent cells induced only low levels of MIF activity. Pretreating the immune lymph node cells with different antisera plus complement, before addition of DNP-spleen cells, showed that MIF production is dependent on Ia- T cells. Additional experiments showed that in order for the T cells to be stimulated, homology at the I-A subregion of the major histocompatibility complex between the T cells and DNP-spleen cells is required. Collectively, these results correlate with our previous finding that transfer of contact sensitivity is mediated by Ia- T cells and indicate that both tests, i.e., transfer in vivo and MIF production in vitro, are measuring effector functions of the same T cell subset.

Animals↗

The induction of alloreactive cytotoxic responses in vivo are inhibited by pretreatment with M is-disparate cells.

Alloreactive cytotoxic cells (CTL) are subject to regulation. These experiments were designed to study the in vivo down-regulation of CTL. Mice injected with allogeneic lymphoid cells (responders) develop CTL that are assayed in vitro by their ability to lyse 51Cr-labeled target cells of an appropriate H-2 haplotype. However, if CBA/J responder mice (H-2k, mls d) are pretreated with spleen cells from C3H/HeN mice, which are H-2 compatible (H-2k) but Mis- and minor antigen-disparate (mis c), there is virtually complete inhibition of the ability to develop CTL against A/J cells (H-2a, mls c) in vivo. In a similar manner, pretreatment of CBA/J responders with B10.BR (H-2k, mls b) cells resulted in the inhibition of the CTL response against B10.A(4R) (H-2h4, mls b). The state of CTL responsiveness appears to be H-2 restricted and requires that the allogeneic cells used for immunization share minor histocompatibility antigens with the strain of mouse selected for pretreatment.

Animals↗

Studies of the vivo uptake of Ga-67 by an experimental abscess: concise communication.

The blocking of Ga -67 plasma protein-binding sites-by administration of scandium citrate, ferric citrate, and a colloidal hydrous ferric oxide preparation-reduced the uptake of Ga-67 in normal soft tissues and also that in the viable portion of an experimental abscess. On the other hand, enhancement of Ga-67 plasma protein binding by administration of rabbit apotransferrin increased Ga-67 uptake in both abscess and normal soft tissues. These results indicate that the pathways of Ga-67 from blood into inflammatory processes and normal soft tissues may be similar. However, when Ga-67 plasma protein binding was increased by inducing anemia, a markedly decreased Ga-67 uptake in the abscess resulted, whereas uptake in normal soft tissue was still elevated. It is possible that the discrepancy between the effects of apotransferrin and anemia on abscess-tissue uptake of Ga-67 resulted from a secondary effect produced by anemia, i.e., a decrease in the macrophage population in the abscess. Taken as a whole, the results obtained suggest that Ga-67 leaves the blood and enters inflammatory lesions by pathways that are probably quite different from those in a soft-tissue tumor, and that the routes for abscesses may be similar to those occurring in normal soft tissues.

Abscess↗

A new method for labeling microspheres with 68Ga.

We have developed a simple, highly efficient, and rapid technique for labeling a commercially available human serum albumin microsphere preparation with 68Ga for use in positron tomography. An isotonic acetate buffer system is use. Maximum 68Ga labeling is obtained at pH 4.8 (approximately 97%) but deviations from that pH (e.g., 0.5 of a pH unit) produce only minor decreases in binding efficiency. The preparation is stable on standing over a period of 4 h, and in vivo studies in the rat and dog show it to be specific for the lungs. Little change occurs in the tissue distribution of 68Ga over a period of approximately 1 h.

Animals↗