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Biomedical subjects

D Rose

Publications and source records attributed to D Rose.

At least 109 records · Page 6Linked to original sources

Origin of endothelial cells that line expanded polytetrafluorethylene vascular grafts sodded with cells from microvascularized fat.

PURPOSE: Cell transplantation onto prosthetic vascular grafts remains an attractive technique to reduce the thrombogenicity of polymeric materials. In this study we evaluated whether autologous cells isolated from falciform ligament fat and transplanted onto the lumenal surface of 4 mm expanded polytetrafluorethylene grafts were the same cells present on the surface of these grafts when they were explanted from canine carotid arteries 3 weeks after their implantation. METHODS: The fluorescent dye PKH-26 was used to label transplanted cells to evaluate their fate after implantation of grafts as carotid artery replacements. This fluorescent dye homogeneously labeled all cells in the primary cell isolate. RESULTS: In vitro studies indicated that dye labeling was nontoxic, as evidenced by the normal growth characteristics of fluorescently labeled cells compared with nonlabeled cells. Immunocytochemical analysis of microvascularized fat before cell isolation determined that approximately 90% of the cells stained positive for von Willebrand factor2. At the time of explant, seeded grafts exhibited a nonthrombogenic lumenal cell lining as evidenced by the lack of adherent platelets or fibrin. Cells on the lumenal surface of grafts exhibited PKH-26 fluorescence emission. In addition, these cells expressed von Willebrand factor and actively sequestered DiI-acetylated low-density lipoprotein. CONCLUSIONS: We conclude that sodding of prosthetic grafts with autologous microvascularized fat-derived cells results in the formation of an endothelial cell lining on the lumenal flow surface. These endothelial cells are the same cells placed on the lumenal surface of the graft at the time of initial cell transplantation. Finally, a confluent monolayer forms after high-density cell sodding by the process of cell adherence and spreading, without the need for cell proliferation.

Adipose Tissue↗

[Role of segmental buckling surgery in treatment of stages B and C proliferative vitreoretinopathy detachment. A long-term follow-up].

BACKGROUND: The following questions should be addressed: (1) Is minimal detachment surgery justified in treating detachments with preoperative PVR stage B or C? (2) Can this reattach the retina with stabilization or regression of PVR? MATERIALS AND METHODS: 72 PVR detachments stage B or C (38 C1, 11 C2, 1 C3) were treated by cryopexy, segmental buckling (n = 68) or balloon (n = 4) without drainage or vitrectomy. Reoperation (n = 10) was done without cerclage or vitrectomy. The follow-up of patients alive is 11 to 13 1/2 years and of all patients (31 died) x 7 1/2 years. RESULTS: After the primary operation the retina was reattached in 79%, partially in 15% and detached in 6%. An "early" redetachment (< or = 6 months postoperatively) occurred in 8.3%, no redetachment > 6 months to < 9 years and "late" redetachment (9-13 1/2 years postoperatively) in 2.8%. After reoperation (n = 10) the retina was reattached in 85%, partially in 3%, and detached in 12%. 34 eyes had delayed resorption (2 weeks to 18 months) with a residual concave detachment in area of starfolds and tractions, resulting in dry starfolds or their disappearance after months. Postoperatively there were no rubeosis iridis, no secondary glaucoma and no phthisis bulbi. Subsequent macular pucker developed in 12 eyes, which were not treated by vitreoretinal surgery. Six months postoperatively visual acuity was: 26x 20/60-20/25; 16x 20/200-20/100; 30x < or = 20/400 which was not statistically significant different (p = 0.549) after x 7 1/2 years. CONCLUSION: Primary treatment of a PVR detachment stage B or C1/C2 with cryopexy and segmental buckling and nondrainage seems justified to test for the chance of PVR-regression. The retina was reattached in 8 of 10 patients x 7 1/2 years postoperatively after primary operation without reoperation or vitrectomy and visual acuity was 20/60-20/25 in every third patient, thus implying a lack of late serious complications.

Adolescent↗

Interocular transfer of expansion, rotation, and translation motion aftereffects.

The motion aftereffect demonstrates the existence of direction-selective mechanisms in the visual system. However, direction-selective cells exist within many visual areas, including V1 and MT/V5. Can motion aftereffects be generated within each of these areas? In visual cortical areas beyond V1 almost all cells are binocular, whereas a smaller percentage are binocular in V1. The degree of binocularity can be revealed psychophysically by assessing interocular transfer. Interocular transfer of motion aftereffects generated from expanding rotating, and translating dynamic random-dot patterns were therefore compared, since these stimuli should activate cells in higher visual areas selectively. Partial interocular transfer was found that was greater for expansion and rotation than for translation. The results support the involvement of higher visual areas in motion aftereffects to complex animation sequences.

Female↗

CDC44: a putative nucleotide-binding protein required for cell cycle progression that has homology to subunits of replication factor C.

To investigate the means by which a cell regulates the progression of the mitotic cell cycle, we characterized cdc44, a mutation that causes Saccharomyces cerevisiae cells to arrest before mitosis. CDC44 encodes a 96-kDa basic protein with significant homology to a human protein that binds DNA (PO-GA) and to three subunits of human replication factor C (also called activator 1). The hypothesis that Cdc44p is involved in DNA metabolism is supported by the observations that (i) levels of mitotic recombination suggest elevated rates of DNA damage in cdc44 mutants and (ii) the cell cycle arrest observed in cdc44 mutants is alleviated by the DNA damage checkpoint mutations rad9, mec1, and mec2. The predicted amino acid sequence of Cdc44p contains GTPase consensus sites, and mutations in these regions cause a conditional cell cycle arrest. Taken together, these observations suggest that the essential CDC44 gene may encode the large subunit of yeast replication factor C.

Amino Acid Sequence↗

Endothelial cell storage and release of endothelin as a cardioregulatory mechanism.

Coronary vascular endothelial cells release substances into the coronary circulation that modify the contractile system of cardiac myocytes, and cardiac myocytes may release factors that modulate the secretion of cardioregulatory substances by endothelial cells. This regulatory loop is sensitive to the rate of coronary flow and tissue oxygen tension. In the present study, coronary venous effluent from isolated perfused hearts and the contents of the coronary vascular endothelial cells have been collected, the latter by disrupting the cells with coronary perfusion at high pressure. The relative amounts of upregulating and downregulating factors in both collections have been estimated by assaying their effects on the contractility of isolated cardiac trabeculas. The amount of upregulating factor stored in the endothelial cells is sensitive to the rate of coronary flow just before disruption of the cells. The quantity of endothelin in the coronary venous effluent and in the vascular endothelial cell contents was measured by radioimmunoassay and compared with the degree of upregulation of contractility produced by the two types of solutions. Upregulation was never produced in the absence of endothelin. The extent of the increase in contractility that was observed with endothelial cell contents correlated with the concentration of endothelin and was approximately the same as the increase in contractility from similar concentrations of endothelin added to standard Krebs' solution. The amount of the increase in contractility from coronary effluent could be accounted for by the concentration of endothelin in the effluent with the additional presence of some downregulating factor as well. The endothelin antagonist BQ123 inhibited the upregulation from coronary perfusate. It appears that endothelin alone can account for all of the upregulation of contractility produced by the vascular endothelial cells. Coronary flow, probably through shear forces, seems to regulate the production of endothelin possibly from an inactive precursor. Tissue oxygen tension appears to modulate the rate of release of the endothelin from endothelial cells though substances released by cardiac myocytes or other cells in the tissue. The downregulating factor is stored to a much smaller extent.

Animals↗

Renin and renin mRNA in proximal tubules of the rat kidney.

The present study was undertaken to assess the presence of renin enzymatic activity and renin mRNA in proximal tubules of rat kidneys, and to determine the effect of converting enzyme inhibition (CEI) on proximal tubule renin gene expression. Proximal convoluted tubules (PCT), proximal straight tubules (PST), outer medullary collecting ducts (OMCD), and glomeruli (Gloms) were isolated by microdissection. Renin activity was measured in sonicated segments by radioimmunoassay. Renin mRNA levels were assessed using a quantitative PCR. Renin activity in PCT averaged 51 +/- 15 microGU/mm compared to 405 +/- 120 microGU/glomerulus. No measurable renin activity was found in PST and OMCD. Renin activity in both glomeruli and tubules had the same pH optimum, between 7.0 and 7.5. Renin mRNA was consistently detectable in cDNA prepared from PCT and PST, although its abundance per mm tubule was about 1/500th that found in one glomerulus. Renin mRNA was not detectable in OMCD. Tubular renin PCR product identity was confirmed by restriction digestion. CEI administration increased glomerular renin activity and renin mRNA, but not proximal tubular renin. The absence of a stimulatory effect of CEI on proximal tubule renin gene expression suggests the operation of different intracellular signals in control of renin synthesis in the proximal tubule than in the vascular compartment.

Angiotensin-Converting Enzyme Inhibitors↗

The Mayo Clinic experience with the cochlear implant.

The implantation of a cochlear electronic prosthetic device is an acceptable means of improving the communication ability of pre- and postlingually deafened children and adults. A significant number of patients in this series are in the senior citizen age group. It has been beneficial in improving communication ability in selected profoundly deafened individuals. There has been a significant improvement in the cochlear electronic prosthetic device since the initial report of Djourno in 1957.

Adult↗

Recurrence of breast carcinoma following immediate reconstruction: a 13-year review.

To evaluate the effect of immediate reconstruction on the incidence, location, detection, and treatment of recurrent breast cancer, a review of 306 patients operated on according to a standard protocol during the 10-year period 1979 through 1988 was performed. Reconstruction techniques included submuscular implants (207), tissue expanders (84), and musculocutaneous flaps (15). During a minimum follow-up period of 3 years with a mean of 6.4 years, 60 patients (19.6 percent) developed recurrent disease, at a mean interval to recurrence of 31 months. The first locations of recurrences were local (16), regional (11), and systemic (33). Recurrence rates by stage included stage I, 7 patients (5.2 percent); stage II, 45 patients (32.1 percent); and stage III, 8 patients (40 percent). It was not possible to include comparisons with internal control groups of patients in our institution who were not reconstructed or who had delayed reconstructions, thereby preventing conclusions based on such comparisons. Our recurrence data are similar to literature reports of recurrence rates in patients who were not reconstructed after mastectomy. Detection and treatment of recurrences were not inhibited by the reconstructions. When radiation therapy was used in the treatment of local recurrences, the development of symptomatic capsular contracture was recorded in 58 percent of the patients.

Adenocarcinoma↗

Endothelial cells are required for the cAMP regulation of cardiac contractile proteins.

The contractile proteins in mammalian cardiac muscle are regulated by a cAMP-dependent reaction that alters the activity of the actomyosin ATPase. The ATPase activity of cardiac actomyosin has also been shown to depend on factors released by small arteries in the myocardial tissue. Endothelial cells have been implicated in the regulation of the contractile force developed by isolated cardiac tissue. To determine whether endothelial cells are required for the cAMP-dependent regulation of the contractile proteins, the effect of cAMP on the actomyosin ATPase activity was measured in cryostatic sections of isolated, quickly frozen rat ventricular trabeculae. In half of the trabeculae, the endocardial endothelial cells had been damaged by a 1-sec exposure to 0.5% Triton X-100. In trabeculae with intact endothelial cells, cAMP increased actomyosin ATPase activity toward an apparently maximum value. In trabeculae with damaged endothelial cells, cAMP did not change actomyosin ATPase activity. The coronary venous effluent from an isolated heart has already been shown to modify the maximum isometric force developed by an isolated trabecula. The extent to which the force of the isolated trabecula is changed by the coronary venous effluent is closely related to the degree to which cAMP has up-regulated the actomyosin ATPase activity in the isolated heart donating the coronary effluent: the greater the degree of up-regulation of ATPase activity, the greater the increase in force produced by the effluent. These results indicate that endothelial cells are required for the cAMP-dependent regulation of cardiac contractile proteins to function, and these results further suggest that the myocardium autoregulates by modulating the cAMP regulation of contractile proteins with endothelial-derived factors.

Animals↗

[Highly restricted detachment surgery without puncture: long-term results on the topic of postoperative "residual detachment" and late re-detachment].

BACKGROUND: Detachment surgery without drainage, a surgery limited to area of break, implies minimization of procedure and complications. In a 1st study (1970-1977) 1,000 consecutive detachments were treated with favorable results (primary reattachment in 83%, after reoperation in 91%, follow-up 4 months-7 1/2 years). A prospective 2nd study (8/1979-1/1980) followed to answer the questions: (1) Differential diagnosis between postoperative "residual detachments" and surgical failure. (2) Is rate of "late" redetachment after minimal segmental buckling greater than after cerclage? PATIENTS AND METHODS: Prospective study of 107 detachments operated 8/1979-1/1980 with follow-up of 11-11 1/2 years. Detachments: 21 eyes with aphakia, 1 with pseudophakia, 16 with PVR stage C1/C2. TREATMENT: cryopexy and segmental buckling or balloon in area of break without drainage, no vitrectomy, no cerclage. Orientation of buckles: 76 radials, 20 circumferentials, 11 radials with circumferentials. RESULTS: After 1 operation retina was reattached in 99 eyes (92.6%), after reoperation of primary failure (confined to original or to previously undetected break) the retina reattached in 104 eyes (97%). Types of postoperative "residual detachments" after non-drainage: (1) convex residual detachment (delayed absorption) or (2) concave residual detachment (traction), both of them with no hole (to observe) and (3) convex residual rhegmatogenous detachment (to reoperate). Longterm results (follow-up 11 years) of 104 reattached retinas: "early" redetachment (2-4 months postoperatively) in 6 eyes or 5.6% because of PVR and "late" redetachment (3 to 7 years postoperatively) in 7 eyes or 6.5% because of new breaks. After reoperation reattachment in 99 eyes (92.6%); only 1 of 107 eyes had 2 reoperations. Reasons for final failure: PVR (3.7%), no hole found (2.8%), massive choroidals (0.9%). CONCLUSION: After detachment surgery without drainage there can be: (1) convex or (2) concave "residual" detachment and (3) rhegmatogenous residual detachment with new contour (reoperation needed). Favorable longterm results after minimal surgery (6.5% "late" redetachment during 11 years postoperatively) and use of minimal surgery as reoperation (50% a balloon) for reattaching the retina do not support the necessity of a prophylactic cerclage as primary operation, even not as reoperation per se. A simple alternative to a surgical prophylaxis represents a so-called "passive" prophylaxis consisting in explaining the visual field to the patient and asking him to test it regularly.

Adolescent↗

Intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus.

We retrospectively reviewed the charts of 96 patients infected with human immunodeficiency virus (HIV) who received intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia (PCP). These patients, all of whom had either a history of PCP or a CD4 lymphocyte count of < or = 0.2 x 10(9)/L, were intolerant of sulfa drugs, neutropenic, or intolerant of aerosolized treatment. Intramuscular pentamidine was given monthly by the Z-track technique at a dosage of 300 mg (4 mg/kg if the patient weighed < 50 kg). During a total of 350 months of primary prophylaxis in 47 patients and 426 months of secondary prophylaxis in 49 patients, only three cases of PCP occurred. More than 73% of the patients were receiving zidovudine concomitantly. Adverse reactions to intramuscular pentamidine included two episodes of hypotension, three of sterile abscess, two of glucose intolerance, and one of asymptomatic hypoglycemia. The administration of intramuscular pentamidine by the Z-track technique for PCP prophylaxis appears to be highly effective and minimally toxic.

AIDS-Related Opportunistic Infections↗

Meiosis-specific arrest revealed in DNA topoisomerase II mutants.

Although the processes of mitosis and meiosis are similar, there is evidence for fundamental regulatory differences between the two. To examine these differences, we have compared the meiotic phenotype of DNA topoisomerase II mutants with their previously described mitotic phenotype (C. Holm, T. Goto, J. Wang, and D. Botstein, Cell 41:553-563, 1985). top2 mutants in meiosis show no defects in the latest detectable stages of recombination, yet they arrest prior to spindle establishment at meiosis I. Fluorescence and electron microscopy reveal that top2 mutants exhibit wild-type levels of meiotic chromosome condensation and form morphologically normal synaptonemal complex but are delayed in the exit from pachytene. Arrested cells retain viability and form colonies if transferred to mitotic medium. Our results suggest that the top2 meiotic arrest is regulatory in nature. This arrest may have evolved to ensure the resolution of fortuitous tangles between nonhomologous chromosomes.

Chromosomes, Fungal↗

Cardiac endothelial cells modulate contractility of rat heart in response to oxygen tension and coronary flow.

The aim of this study was to determine if endothelial cells in the heart release substances into the coronary perfusion medium that modify the contractility of myocardial cells. To assay the effects on the contractility of cardiac muscle of fluid that has passed through the coronary vasculature, a new method has been developed based on the cascade principle used to study vascular smooth muscle function. The coronary venous effluent from an isolated perfused working heart was collected periodically, and after reoxygenation it was used as the bathing medium for trabeculae isolated from the endocardial surface of another heart. The coronary venous effluent changed the contraction of the isolated trabeculae. The amplitude and the direction of the change depended on the degree of oxygen saturation of the coronary effluent before it was reoxygenated and the rate of coronary flow at the time the effluent was collected. The response of the trabecula to the coronary effluent was substantially altered by damaging the endocardial endothelium with a 1-second exposure to 0.5% Triton X-100 in Krebs' solution. It was completely eliminated by damaging endothelial cells in both the perfused heart producing the effluent and the trabecula on which the effluent was assayed. Therefore, endothelial cells are required for the presence of cardioactive substances in the coronary effluent. The production of a labile endothelium-derived upregulating (positively inotropic) factor and a more stable endothelium-derived downregulating (negatively inotropic) factor has been demonstrated and appears to account for all of the changes in myocardial contractility produced by the coronary effluent. Neither of the endothelium-derived substances demonstrated in the isolated perfused heart is nitric oxide or endothelin. The concentration of the endothelium-derived upregulating factor is sensitive to oxygen tension, whereas the concentration of the endothelium-derived downregulating factor is sensitive to the rate of coronary flow but not oxygen tension. The coronary effluent appears to contain substances that stimulate secretion by the endothelial cells (preendothelial factors) as well as substances that have been produced by the endothelial cells (endothelial factors). The results indicate that during the passage of perfusion medium through the coronary vasculature upregulating and downregulating factors are added to the perfusate in relative concentrations that depend at least in part on local tissue PO2 and the rate of coronary flow. In the intact heart, this mechanism could operate to maintain balance between energy supply and work performed.

Animals↗

The Sukhumi primate monkey model for viral lymphomogenesis: high incidence of lymphomas with presence of STLV-I and EBV-like virus.

T-cell leukemia virus-like proviral sequences (STLV-I) as well as EBV-like sequences were detected in PBLs and tissues of non-human primates (Papio hamadryas baboons, Green monkeys and Macaca arctoides; Sukhumi Primate Center/Georgia) by PCR. Surprisingly, two different types of STLV-I within Papio hamadryas baboons were found. One of its represents the baboon prototype STLV-I-Su described earlier, present in lymphomatous baboons from the "high-lymphoma stock", which shows about 83% homology to HTLV-I and 85% to STLV-I in the env and tax genes. The inter-individual variability within this subtype is very low (about 1% in the tax gene). The second subtype was mainly found in asymptomatic animals from the control colony and showed in the env gene 95% homology to HTLV-I, but only 82% to the prototype baboon sequence. The presence of two subtypes within the Sukhumi baboon population might be interesting in respect to the inoculation experiments with human leukemic blood and to possible interspecies transmissions. The nature of the Herpes Papio-virus was elucidated as EBV-like and the homology to the human EBV was > 90% in the polymerase gene. The homologies between different monkey species were between 92 and 96% and also here two subtypes within the baboons were detected. This is the first direct demonstration by sequencing that the Herpes Papio virus is closely related to EBV. For further studies of this animal model, rabbits were inoculated with cells originated from lymphomatous baboons and macaques. The rabbits developed generalized lymphomas lethal within 1-2 months. EBV-like and STLV-I-like sequences could be detected by PCR and sequencing showed 99-100% identity to the inoculum, indicating in fact the transmission from monkey to rabbit. These animal models seem to be very suitable for the elucidation of the pathogenesis of human HTLV-I associated T-cell leukemia/lymphoma and might be further on used for therapeutical and preventative studies.

Animals↗

The sneeze: maturation of the reflex in kittens.

This is the first study to compare the influence of nasal afferent stimulation on inspiratory and expiratory muscle activity during sneezing, in kittens and adult cats. In kittens, we demonstrate that nasal afferent stimulation does not reinforce inspiratory activity prior to the expiratory thrust as it normally does in adult cats. These stimulations evoke an active expiration similar to but weaker than the expiratory thrusts observed under the same conditions during sneezing in adult cats. Sneezing can be elicited from three weeks of life. Among the different hypotheses discussed, the most likely explanation appears to be the immaturity of medullary respiratory connections.

Aging↗

A comparative HRP study of the neuronal supply to the inferior and superior nasal meatus in the cat.

Neurons supplying the nasal mucosa in the cat were retrogradely labelled with horseradish peroxidase. Sensory trigeminal neurons to the inferior and superior nasal meati are somatotopically organized, according to the ophthalmic or maxillary origin of the afferents studied. Whatever their relative location, the cell bodies from nasal afferents were, on average, smaller than the overall cell population in the ganglion, in keeping with the high proportion of nasal receptors innervated by thin fibers. Postganglionic neurons from parasympathetic origin could be labelled in the sphenopalatine ganglion. These neurons probably supply mucosal secretory glands. They are in the same size range as the bulk of neurons in the same ganglia.

Animals↗

Adjuvant dietary fat intake reduction in postmenopausal breast cancer patient management. The Women's Intervention Nutrition Study (WINS).

Management of localized breast cancer now commonly involves a breast-sparing approach combined with systemic adjuvant therapy resulting in improved cosmetic results and patient survival. Reducing dietary fat intake represents a conceptually new approach to further improve outcome of patients with resected breast cancer. The rationale supporting evaluation of dietary fat reduction in the management of patients with localized breast cancer is based on: (1) epidemiologic observations (along with biochemical and hormonal correlates) of major differences in stage-by-stage survival of patients with localized breast cancer comparing outcome in countries with low fat (Japan) versus high fat (U.S.A.) dietary intakes; (2) relationships between dietary fat intake and factors prognostic of clinical outcome in patients with established breast cancer; (3) effects of weight gain (especially that associated with adjuvant chemotherapy) on breast cancer clinical outcome; (4) in vivo animal studies demonstrating adverse influence of increased dietary fat intake (especially linoleic acid) on growth and metastatic spread of mammary cancer; (5) direct adverse effects of increased linoleic acid on human breast cancer growth in vitro; (6) plausible mechanisms which could mediate the effects of dietary fat intake reduction on breast cancer growth and metastatic spread; (7) demonstration of adherence to dietary fat reduction regimens in ongoing clinical feasibility studies including those involving postmenopausal patients with resected breast cancer; and (8) favorable sample size requirements for definitive assessment of dietary fat intake reduction influence on breast cancer growth and metastases (using as endpoints relapse-free survival and overall survival) in postmenopausal breast cancer patients with localized disease.

Animals↗