Biomedical subjects
Publications and source records attributed to D L Brown.
An obese patient with sleep apnea and chronic obstructive pulmonary disease was difficult to sedate and ventilate after tracheostomy. High peak inspiratory pressures and severe patient agitation persisted despite sedation with lorazepam, and threatened security of the tracheostomy. The use of a ketamine infusion sedated the patient and allowed weaning to progress uneventfully.
Two classes of medullospinal units with inhibitory baroreceptor inputs [nucleus paragigantocellularis lateralis (PGCL) units] were recorded in PGCL (conduction velocity 3.1 and 0.67 m/s, respectively). Single-pulse stimulation of PGCL produced two peaks of activation of the lumbar sympathetic chain [sympathetic nerve discharge (SND)] with latencies of 98 and 206 ms. After substracting the delay due to impulse propagation between cord and sympathetic chain (64 ms), a conduction velocity of 2.8 and 0.67 m/s could be estimated for the medullospinal portion of the two sympathoexcitatory pathways stimulated in the PGCL. R wave-triggered activity histograms of PGCL unit discharge and lumbar SND exhibited a similar pattern with one major trough, occurring 108 ms later at the level of the sympathetic chain. It is concluded that PGCL contains two classes of medullospinal neurons with sympathoexcitatory function, the fast-conducting type being predominantly responsible for the cardiac-related rhythm of lumbar SND. Finally, averaging techniques revealed a large respiratory rhythm of lumbar SND in spontaneously breathing rats, but little or no such rhythm could be detected at the level of most PGCL sympathoexcitatory cells.
Previous work had implicated T cells within the stimulating population as having a significant role in the MLR. We now report that depletion of T cells from the stimulators caused a reduction in proliferative response in mixed leukocyte reaction (MLR) by 50% or more. This response could be restored by adding T-enriched cells from the stimulators but not from the responders. During MLR, the T-cells in the stimulating population demonstrated changes characteristic of early activation, namely, increase in RNA synthesis. Stimulator T-cells have been shown to regulate the interleukin 2 (IL 2) production in mixed leukocyte culture (MLC). Depletion of T cells from the stimulators reduced the level of IL 2 in the culture. Addition of IL 2 to the cultures containing T-depleted stimulators reconstituted the proliferative response. Our data suggest that there may be alternative ways of producing IL 2-like growth factors. Depletion of T cells from the stimulators allows the detection of a growth factor which differs from IL 2 in its mode of production. We conclude that optimal proliferation in the MLR requires that the stimulating population contain T cells which regulate the growth factors in the culture.
Milk consumption in 80 households in western Kenya averaged .25 to 1.00 L per family per day. Most of this milk was processed into a milk and tea beverage. Polyphenols, the major determinants of tea flavor and character, form soluble complexes with casein when black tea infusions are mixed with milk. Test diets were prepared from the following treatments: a) casein reference diet; b) milk, no tea leaves; c) milk added after heat treatment; and d) traditional Kenyan-style tea (i.e., milk and tea leaves heated together). Four groups of 10 male 21-day-old Sprague Dawley weanling rats were assembled and assigned to the test diets. Weight gain and protein intake (g/g) during a 28-d test period for the four diets were 1.94, 2.99, 2.93, and 2.77. The least significant difference test showed weight gain for protein intake was greater for rats on the milk-based diet and the diet with milk added after heating than for rats on the traditionally prepared milk and tea drink. Rats did most poorly when assigned to the casein reference diet. Modification of traditional Kenyan tea preparation practices (i.e., adding milk after tea leaves have been removed) might improve the nutritional value of the most popular milk product in western Kenya.
Body composition and D2O dilution kinetics were studied in 15 female goats ranging from 38.0 to 70.1 kg live weight. Infrared spectrophotometric analyses of blood samples drawn during the 4 d following D2O injections were used to estimate D2O space. All does were slaughtered without shrinking and analyzed for dry matter, fat, nitrogen, and ash content. Estimates of D2O space from the late slope of the dilution curve, together with live weight, were used to predict body composition. Conclusions were 1) deuterium oxide space with live body weight accounts for about 90% of the variation in dairy goat empty body fat, empty body nitrogen, and empty body dry matter; 2) less than half the variation in empty body ash is related to live weight and D2O space; and 3) D2O space estimates would be biased by accelerations in water turnover.
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The assembly of cold solubilized microtubules prepared from calf brain and the polymerization of tubulin purified from this material are facilitated by polyamines at physiological concentrations. The number of free amino groups in the polyamine determines the ability of the polyamines to promote microtubule formation. Spermine with four amino groups was the most effective polyamine tested. Spermidine and N'-acetylspermine with 3 amino groups were less effective than spermine but more effective than N8-acetylspermidine and putrescine which contain two free amino groups. Microtubule formation may therefore be controlled by alterations in the nature and amounts of polyamines present.
Eleven obese men with coexistent obstructive sleep apnea and chronic obstructive pulmonary disease underwent tracheostomy. Nocturnal polysomnography prior to tracheostomy revealed oxyhemoglobin desaturation associated with obstructive apnea. Following surgery, repeated polysomnography was performed to assess the effect of tracheostomy on nocturnal oxygen saturation. Non-apneic desaturation characteristic of that previously described in patients with "type B" chronic obstructive pulmonary disease was noted in six subjects. Oxyhemoglobin saturation in these six fell more than 8 percent below baseline waking and non-rapid-eye-movement (REM) sleep levels. These episodes usually lasted five minutes or longer, occurred almost uniformly during REM sleep, and were acutely ameliorated by low-flow (4 liters per minute) supplemental oxygen. The subjects with REM-associated desaturation did not differ from the subjects without desaturation by preoperative anthropomorphic, blood gas, or pulmonary function criteria. However, subjects with REM-associated desaturation tended to have lower right and left ventricular ejection fractions by pooled gated wall studies. It is concluded that patients with obstructive sleep apnea and chronic obstructive pulmonary disease should be re-evaluated after tracheostomy, since they may be at risk for continued oxyhemoglobin desaturation and progressive right ventricular deterioration despite adequate treatment of their apneic condition.
In characterizing the functional properties of the stimulators in a mixed leukocyte reaction (MLR) we have established that the optimally effective stimulators must themselves be capable of undergoing the early stages of proliferative activation. We treated the stimulators with sublytic doses of a variety of agents (ouabain, ultra-violet radiation, 5-fluorouracil and colchicine), which have been reported to inhibit their stimulating capacity, and then in parallel experiments, we examined the treated cells for their capacity to stimulate allogeneic cells and their ability to respond to Con A. A direct correlation was found between the capacity of mitomycin C-treated splenocytes to stimulate allogeneic cells in an MLR and their ability to undergo changes characteristic of pre-S phase activation, namely, increases in K+ influx and in cell size, in response to Con A. This correlation also existed in the case of metabolically active but immunosuppressed splenocytes from mice undergoing late graft-versus-host (GVH) reaction: these cells did not show increase in potassium influx in response to Con A and their stimulating ability was inhibited. Using fluorescein labelled anti-Thy 1.2 as a marker for T cells in the stimulating population, it was shown that a considerable fraction (up to one third) of the blasts in a mixed leukocyte culture (MLC) originated in the mitomycin C-treated stimulating population. These data are consistent with the hypothesis that induction of maximal proliferation, in MLR, requires that certain of the cells (mainly T cells) of the stimulating population undergo the early stages of activation.
Nuclear structural changes during fertilization and embryogenesis in mice and in sea urchins have been followed by using antibodies against the nuclear lamins A/C and B and against antigens at the periphery of nuclei and chromosomes. Lamins are found on all pronuclei and nuclei during mouse fertilization, but with a diminished intensity on the second polar body nucleus. On sperm in both systems, lamins are reduced and detected only at the acrosomal and centriolar fossae. In sea urchin eggs, lamins are found on both pronuclei. Unlike in other dividing cells, the mitotic chromosomes of sea urchin eggs and embryos retain an association with lamins. The peripheral antibodies delineate each chromosome and nucleus except the mature mouse sperm nucleus. A dramatic change from the expected lamin distribution occurs during early development. In mouse morulae or blastocysts, lamins A/C are no longer recognized, although lamin B remains. In sea urchins both lamins A/C and lamin B, as detected with polyclonal antibodies, are lost after the blastula stage, although a different lamin A/C epitope emerges as recognized by a monoclonal antibody. These results demonstrate that pronucleus formation in both systems involves a new association or exposure of lamins, that the polar body nucleus is largely restricted from the cytoplasmic pool of lamins, and that mitotic chromosomes in the rapidly proliferating sea urchin egg retain associated lamins. They also suggest that changes in the expression or exposure of different lamins are a common feature of embryogenesis.
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Nuclear matrix structure closely resembles the organization of nonchromatin components of nuclei in situ. However, reports on the extent to which nuclear components are reorganized during matrix isolation have produced conflicting results, and the reality of an in situ nuclear matrix is still in question. We have prepared nuclear matrices by processing cells still attached to the growth substrate through the extraction steps, thus avoiding mechanical disruption due to homogenization and centrifugation. Furthermore, the extensive residual cytoskeleton seems to keep the residual nuclei "stretched out" so that they retain many features of intact nuclei. Indirect immunofluorescence staining was used to compare the distribution of nuclear antigens in intact nuclei with their organization in nuclear matrices, as well as at each stage of nuclear matrix preparation. We have applied monoclonal antibodies P1, I1, PI1, and PI2, which had been generated against isolated matrices, as well as autoimmune sera detecting lamins, perichromin, and centromere antigens. Chromatin and RNA extraction was monitored with Hoechst 33258, ethidium bromide, and antihistone. The lamins, PI1, and, to a great extent, PI2 and centromere antigens were little affected by the extraction. The data suggest furthermore that PI1 is a fundamental nuclear matrix component and may serve in integrating peripheral and internal nuclear functions. P1 and perichromin were extensively redistributed after chromatin extraction, supporting a role for these antigens in spatial ordering of chromatin. I1 was progressively extracted at each stage of nuclear matrix preparation and was artifactually associated with matrices which had not been digested with RNase. This study demonstrates unequivocally that the organization of many nuclear matrix components in final preparations reflects their organization in situ. It does indicate, however, that some components retained in matrices are extensively redistributed during nuclear matrix preparation and that their role in nuclear organization must be evaluated in consequence.
In urethane-anesthetized rats, electrophysiological recordings of spontaneously active neurons in the vasopressor area of the rostral ventrolateral medulla were analyzed for participation in cardiovascular regulation. A total of 138 units were found which were inhibited by transient increases in mean arterial pressure elicited by intravenous injection of norepinephrine, aortic occlusion, or electrical stimulation of the hypothalamus, with 100% inhibition occurring at 148 mm Hg. Histograms of postsystolic activity showed that these units had pulse-synchronous rhythms which grew more prominent as arterial pressure increased. Furthermore, electrical stimulation of the superior laryngeal nerve, which elicited a vasodepressor response, strongly inhibited these units. Thus, these neurons were termed negatively correlated cardiovascular units. At least half of these cells project to or through the thoracic spinal cord. In addition, arterial pressure sensitivity is conveyed through carotid sinus and aortic arch afferents. Approximately half of the cardiovascular units are also excited by hypothalamic stimulation. Finally, analysis of neighboring cells showed that it is possible to distinguish between cardiovascular and respiratory units. These data are consistent with the concept of a medullary center which supports tonic sympathetic vasomotor tone and which mediates baroreceptor reflexes, as well as vascular responses of the defense reaction.
Narcotic anesthesia is commonly used for patients with depressed myocardial function. Post-thoracotomy analgesia is increasingly provided by epidural narcotic analgesia. Combination of the two techniques may have resulted in respiratory depression and death in a 66-year-old ischemic heart disease patient following thoracotomy.
When diets containing 33 and 18 ppm monensin sodium were fed for ad libitum intake to dairy goats, milk fat content was reduced by 15 and 5%. Milk protein content was increased 10% when 33 ppm sodium monensin was fed with diet at restricted intake. Milk yield was not affected. Both ad libitum and restricted consumption of diet containing 33 ppm monensin sodium reduced ratios of ruminal acetate:propionate. These resulted from increased propionate concentration with ad libitum consumption and from reduced acetate with restricted feeding. Diets containing 18 ppm monensin sodium resulted in slightly higher concentrations of both propionate and acetate. Monensin sodium did not reduce feed intake significantly.
We have used immunofluorescence staining with antibodies to tubulin and electron microscopy to examine the effects of microtubule assembly-promoting drug taxol on the organization of microtubules in unstimulated and in mitogen stimulated mouse splenic lymphocytes. A 4-h exposure to 10 microM taxol of unstimulated or stimulated cells results in an extensive reorganization of the microtubule system to form one to a few large bundles of microtubules which extend from the centrosome. Concomitantly, the centrosome is displaced from the normal position near the nucleus to a position near the plasma membrane. The Golgi apparatus is not disrupted by this treatment and also appears to be displaced in association with the centrosome. We then examined the capacity of lymphocytes with taxol-reorganized microtubules to respond to stimulation by the mitogen concanavalin A. The taxol-induced reorganization of microtubules has no effect on the increase in cell size (blastogenesis), the changes in structure of the nucleus and cytoplasm, or on the DNA replication that occurs in response to mitogen. The stimulated cells, however, do not proliferate and appear to accumulate in mitosis with the appearance of multiple asters. We conclude that all of the major events of mitogenic stimulation up to the first mitosis can occur in the presence of a highly reorganized microtubule system. Our results suggest that taxol will be a useful drug in determining those lymphocyte functions that are dependent on the presence of normal microtubule organization.
The porcine heart is an excellent physiological and anatomical experimental model because of its close similarity to the human heart. However, the pig is difficult to use in chronic experiments because of its propensity to develop malignant hyperthermia (MH). We have employed a technique which greatly reduces the incidence of MH in the chronic pig model, making its use feasible for a variety of experimental protocols.