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Biomedical subjects

R M Lee

Publications and source records attributed to R M Lee.

At least 91 records · Page 5Linked to original sources
PubMed1990

Increased sympathetic innervation in the cerebral and mesenteric arteries of hypertensive rats.

The density of catecholamine-containing nerve fibers was studied in the cerebral and mesenteric arteries from normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP) in the growing (SHR, WKY) and adult (SHR, SHRSP, WKY) animals. Cerebral arteries from SHR showed an increased adrenergic innervation from day 1. The nerve plexuses reached an adult pattern earlier in SHR than in WKY. The arteries from adult SHR and SHRSP (22 weeks old) showed a markedly higher nerve density than WKY. There was a positive linear correlation between blood pressure and nerve density for four cerebral arteries. The mesenteric arteries were not innervated at birth. However, hyperinnervation of these arteries in the SHR was already present at 10 days of age as compared with WKY. Sympathectomy with anti-nerve growth factor and guanethidine caused a complete disappearance of fluorescent fibers in the mesenteric arteries from SHR and WKY, and in the cerebral arteries of WKY. The same procedure caused only partial denervation of the cerebral arteries from hypertensive animals. We postulate that the increase in nerve density in the cerebral arteries from the hypertensive rats may contribute to the development of arterial hypertrophy in chronic hypertension through the trophic effect of the sympathetic innervation on vascular structure.

Aging↗
PubMed1990

Changes of beta-adrenoceptors in the aortic muscle cells of spontaneously hypertensive rats.

The characteristics of [125I]monoiodocyanopindolol (ICYP) binding to beta-adrenoceptors of cultured aortic smooth muscle cells derived from 4-week-old spontaneously hypertensive rats (SHR) and the Wistar-Kyoto normotensive rats (WKY) were examined. During optimization of the binding assays, we found that the specific binding of ICYP by intact cells was masked by a high level of nonspecific ICYP accumulation in intact cells presumably owing to the lipophilic nature of ICYP. Optimal specific ICYP binding requires that the cells be gently lysed with hypotonic dilution followed by a freeze-and-thaw cycle. Under most experimental conditions tested, the total number of ICYP binding sites in WKY aortic muscle cells was considerably and consistently smaller than that in SHR cells. There was no difference in the Kd values for ICYP binding to SHR and WKY cells. However, when ICYP binding was carried out using crude membrane fractions with well-defined plasma membrane content isolated from aortic muscle strips of adult rats, we found no difference in the number of beta-adrenoceptor sites between SHR and WKY. Morphological evidence indicated that cultured SHR aortic muscle cells contained a greater proportion of larger cells with multinuclear features. These results suggest that an increase in the number of beta-adrenoceptor density per cell in SHR may be associated with cellular hypertrophy of aortic smooth muscle cells. We conclude that under cultured conditions, a higher incidence of polyploid smooth muscle cells in the SHR as compared with WKY was expressed earlier than under in vivo conditions. Therefore, the interpretation of results obtained from cultured cell studies in relation to under in vivo conditions should be exercised with caution.

Animals↗
PubMed1989

Alterations in c-abl gene methylation in cells transformed by phagocyte-generated oxidants.

DNA from 10T1/2 cells transformed by activated neutrophils was analyzed for restriction length polymorphisms (RFLPs) in cellular homologues of retroviral oncogenes, and consistent RFLPs were found in MspI sites of the c-abl gene of all PMN-transformed cell lines. MspI digests probed with c-myc, v-Ki-ras, v-Ha-ras or v-mos showed no RFLPs, and none were observed in EcoRI, PstI, HindIII, BamHI, SmaI, Sau3a, MboI, HhaI, or TaqI digests probed with v-abl. Analysis of HpaII digests supports the conclusion that c-abl RFLPs result from differential methylation of the CCGG HpaII/MspI recognition sequence. MspI RFLPs in the c-abl gene may provide markers for oxidant-related genetic injury.

Animals↗
PubMed1989

Autoradiographic study of smooth muscle cell proliferation in spontaneously hypertensive rats.

1. The rate of smooth muscle cell proliferation in age-matched 1-4-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was compared using autoradiography. 2. Labelling index, defined as labelled cells/sum of labelled and unlabelled cells x 1000, was obtained from perfusion-fixed superior mesenteric and large mesenteric arteries. 3. In the large mesenteric arteries, the smooth muscle cell labelling indices were similar between the SHR and WKY at all age groups, except at 1 week of age when the smooth muscle labelling index was higher in the SHR. 4. In the superior mesenteric arteries, labelling indices were similar between the rat strains at all age groups. 5. We conclude that, in the SHR, a rapid proliferation of smooth muscle cells in the large mesenteric arteries occurred during the first week of life. This resulted in a higher number of smooth muscle cell layers in the media of muscular arteries. 6. The increased proliferation may play a role in the subsequent development of hypertension in the SHR.

Animals↗
PubMed1989

The management of patients with suspected early postoperative small bowel obstruction.

A 10-year review of 101 patients sustaining an early postoperative small bowel obstruction within 30 days of celiotomy was carried out. Signs, symptoms, lab tests, and x-rays did not indicate which patients required operation. Twenty-three patients were operated on for either failure to resolve their obstruction or because it was feared that ischemic bowel was present. In none of these patients, nor the 78 patients who resolved without reoperation, did dead bowel occur. Early postoperative small bowel obstruction was most often due to adhesions and inflammatory processes. Seven patients died (6.9%), three in the operated and four in the nonoperated group. Because ischemic bowel is very unlikely in patients with early postoperative small bowel obstruction, we advise 10 to 14 days of nasogastric suction initially; after this, improvement is unlikely without reoperation.

Abdomen↗
PubMed1989

Vascular changes associated with deoxycorticosterone-NaCl-induced hypertension.

Rats were injected with deoxycorticosterone (DOC) and salt was added to the drinking water (DOC/NaCl) for 3 weeks. Approximately half of the animals became hypertensive (DOC-H), whereas the remainder showed no increase in blood pressure (DOC-N) compared to age-matched, untreated controls. Morphometric analysis of the alterations in the arteries of the mesenteric bed was carried out in vessels fixed at maximum relaxation. Alterations were observed in the arteries, some of which were related to hypertension, but not to treatment, and some were due to treatment alone. The alterations within the arteries of the mesenteric bed depended in part on the type of artery, i.e. elastic, muscular or arteriolar. An increase in lumen area, in intimal area, and in the area of the media was seen in all types of arteries from DOC-H, but not in either group of normotensive animals. The medial hypertrophy was positively correlated with the increase in blood pressure; and was due to an increase in the number of smooth muscle cell layers in the elastic and muscular arteries, and probably to smooth muscle cell hypertrophy in the arterioles. The adventitial area was increased only in the elastic and muscular arteries. Endothelial injury, degeneration of the basement membrane, loss of heparan sulfate proteoglycan and intimal edema was observed in all the DOC/NaCl-treated animals, but was more severe in those which were also hypertensive. Hypertrophy of the heart and kidneys were observed in both normotensive and hypertensive DOC/NaCl-treated animals. These data indicate that changes in the rat cardiovascular system can be induced by DOC/NaCl treatment in the absence of hypertension, but also that hypertension is associated with specific arterial structural alterations, which vary according to the type of artery.

Animals↗
PubMed1989

Ventilatory support in the management of septic patients.

The use of mechanical ventilation in septic patients with or without ARDS remains under the category of supportive care. It is the task of clinicians to properly manage the ventilated patient and to prevent complications and treat them as soon as possible, if they arise. All clinicians eagerly await the introduction of agents that will either attenuate the inflammatory response in patients with the septic syndrome prior to the development of ARDS or assist in the healing of the acute injury.

Humans↗
PubMed1988

Alterations of elastin and elastase-like activities in aortae of diabetic rats.

The elastin content of the aortic muscle and the elastase-like activity of the extracts of aortic muscle were studied in spontaneously diabetic BB rats and in rats made diabetic by a single bolus i.v. injection of alloxan. In both modes of diabetes, the total alkaline-insoluble aortic elastin content was significantly reduced in diabetic rats compared to that in the corresponding control rats. This reduction in aortic elastin was also accompanied by a consistent increase in the elastase-like activities of the aortic extracts prepared from the same tissues. Such a reciprocal relationship between aortic elastin content and elastase-like activity has previously been reported in rats with malignant hypertension. Since the rats used in this study were not hypertensive, the altered elastin metabolism observed in this work is likely to be a manifestation of diabetic disease and may in part account for the vascular changes associated with diabetes mellitus.

Animals↗
PubMed1988

Ultrastructure and morphometric measurements of mesenteric arteries from newborn spontaneously hypertensive rats.

A morphometric and ultrastructural study of superior mesenteric arteries and large mesenteric arteries from newborn spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) was carried out. Morphometric measurements showed that in both vessel types, cross-sectional areas of the lumen and vessel wall components (e.g., media, adventitia) were similar between SHR and WKY. There was also no ultrastructural difference between SHR and WKY in the two types of arteries. We therefore conclude that vascular alterations found in older SHR take place after birth.

Animals↗
PubMed1988

Peptide-containing nerves around blood vessels of stroke-prone spontaneously hypertensive rats.

The distribution and density of nerves containing vasoactive intestinal polypeptide, substance P, and neuropeptide Y around the cerebral and peripheral blood vessels of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied using an indirect immunofluorescence technique. Neonatal sympathectomy of SHRSP with anti-nerve growth factor and guanethidine was also carried out to study the effect of sympathectomy on the distribution of these nerves. Vasoactive intestinal polypeptide nerve density was higher in the veins and superior mesenteric artery of SHRSP than of WKY and lower in the cerebral arteries of SHRSP than of WKY, but no difference was found in the muscular mesenteric arteries. Sympathectomy reduced the density of these nerves in all the peripheral vessels but had little effect on the cerebral arteries. Density of substance P nerves was similar between SHRSP and WKY in the peripheral vessels but higher in the cerebral arteries of WKY than of SHRSP. Sympathectomy reduced the density of these nerves in the peripheral vessels but increased the density in some cerebral arteries of SHRSP. Neuropeptide Y nerve density was higher in the peripheral blood vessels of SHRSP than of WKY, and no difference was found in the cerebral arteries. Sympathectomy almost completely removed these nerves in the peripheral vessels but had no effect on the cerebral arteries. We suggest that some of the differences in nerve density between SHRSP and WKY, especially those in the peripheral blood vessels, may be related to the development of hypertension in the SHRSP.

Animals↗
PubMed1988

Structural and reactivity alterations of the renal vasculature of spontaneously hypertensive rats prior to and during established hypertension.

The renal vasculature of Wistar Kyoto spontaneously hypertensive rats (SHR), prior to (4-5 week) and during established hypertension (21 week) and those of age-matched Wistar Kyoto normotensive rats (WKY) were morphometrically and pharmacologically studied. Under dilated conditions, the vascular resistances (RVR) of the isolated kidneys of young and adult SHR were similar to WKY. Morphometric measurements of renal vasculature indicated that the cross-sectional area of the intima and adventitia and its subcomponents were similar in adult SHR and WKY. With the exception of the preglomerular arterioles, all the renal arteries of adult SHR exhibited elevated cross-sectional quantities of total media, medial smooth muscle cells (SMCs), and extracellular space. Analysis of the SMCs indicated the presence of increased numbers of SMC layers and/or an increase in the SMC volume-to-surface area ratio in arteries sampled from adult SHR. Vascular contraction produced by infusing norepinephrine, BaCl2, angiotensin II, or by stimulating the renal nerves elevated the RVR to a greater degree in adult SHR than in WKY. The sensitivity of the renal vasculature to the various contractile agents was similar in adult SHR and WKY. When compared with WKY, prehypertensive SHR also exhibited increased cross-sectional quantities of arterial media and elevated amplitudes of RVR change in response to norepinephrine and renal nerve stimulation. However, the vascular contractile sensitivity to norepinephrine was reduced. Our results indicate that renovascular wall thickening and the hypercontractile reactivity associated with such a change precedes hypertension in SHR. In prehypertensive SHR, elevations in RVR might be counterbalanced by a decreased norepinephrine sensitivity. An increase in the norepinephrine contractile sensitivity and further vascular thickening with age could elevate the RVR and establish hypertension.

Animals↗
PubMed1988

Prenatal and postnatal hydralazine treatment does not prevent renal vessel wall thickening in SHR despite the absence of hypertension.

Previous studies in our laboratory have shown that the renal blood vessels of 21-week-old Wistar-Kyoto spontaneously hypertensive rats exhibited thicker vascular walls than age matched Wistar-Kyoto normotensive rats. Morphometric analysis of the relaxed renovasculature revealed an increase in the cross-sectional area of the media, which in most cases was associated with an increase in the number of smooth muscle cell layers. To test if these structural changes occur in the absence of raised blood pressure, hydralazine was administered to spontaneously hypertensive rats and normotensive controls prior to and during pregnancy (100 ml/l drinking water), and to the newborn males up to 21 weeks of age (16.9 mg/kg/day by gavage until weaning followed by 100 mg/l in the drinking water). Treated animals were compared with untreated rats. Treatment prevented hypertension development in spontaneously hypertensive rats but did not alter the structural changes found in untreated animals with hypertension. At 21 weeks of age, hydralazine-treated spontaneously hypertensive rats had similar wall-to-lumen area ratios, medial cross-sectional areas and numbers of medial smooth muscle layers as untreated hypertensive rats while these parameters were greater in treated and untreated spontaneously hypertensive rats than in either treated or untreated normotensive controls. Withdrawal of hydralazine from 26-week-old spontaneously hypertensive rats that had been treated in utero and postnatally and had normal blood pressures throughout life resulted in the rapid onset of hypertension. Our results show that renal vascular wall thickening in spontaneously hypertensive rats occurs in the absence of high blood pressure and therefore is not a secondary effect of raised blood pressure.

Animals↗
PubMed1988

Airway epithelial damage in premature infants with respiratory failure.

To evaluate the evolution of airway epithelial damage in premature infants developing bronchopulmonary dysplasia (BPD), a detailed quantitative light and electron microscopic evaluation was performed of the major airways in 3 infants who succumbed from respiratory failure. The 3 infants ranged from 24 to 28 wk gestational age and died after 14 h, 10 days, and 6 months of life. The tracheal epithelium was severely damaged with up to half of the epithelium being denuded in each infant. The infants who died after 14 h and after 10 days demonstrated minimal epithelial denudation in more distal bronchial divisions. However, gross and microscopic abnormalities of the ciliated component of the epithelium were common. In the infant with severe established BPD, there was extensive epithelial denudation and ciliary abnormalities out to the fourth bronchial division. The percentage of goblet cells in the total cell population decreased from proximal to distal major airways, with the lowest percentage being seen in the infant with established BPD. These studies demonstrate the respiratory failure and assisted ventilation in the human neonate is associated with severe epithelial damage in the trachea and proximal bronchi. It suggests that the difficulty in clearing airway secretion results from a defect in mucociliary transport system rather than from an increase in airway secretion.

Bronchi↗
PubMed1987

Analysis of drugs from biological fluids using disposable solid phase columns.

The traditional liquid-liquid extraction method for the removal of drug from biological matrix is being superseded by solid phase extraction. This involves the selection of an appropriate sorbent (normal-phase, reversed-phase, ion-exchange etc.), but once this has been achieved the method is quick and simple to operate. Most sample handling losses are avoided so recovery of drug is high and it is easily automated. Disposable columns have several advantages. Samples of 0.05-2.0 ml can be analysed routinely. Several wash stages can be included in a method to provide a specific extraction prior to a quick analysis by high-performance liquid chromatography (HPLC), radioimmunoassay, UV etc. A potential problem is that retention of the drug may involve more than one mechanism. Elution of drug may therefore require a stronger eluting solvent than analytical HPLC systems using the same stationary phase.

Antihypertensive Agents↗
PubMed1987

Structural alterations of blood vessels in hypertensive rats.

Vascular changes in the mesenteric arteries were examined in three animals models for human essential hypertension. These models are: spontaneously hypertensive rats, which develop hypertension with age; Dahl model of genetic, salt-dependent hypertensive rats; and deoxycorticosterone-salt hypertensive rats. Morphometric measurements of the arterial wall components (e.g., endothelium, media) were carried out in the elastic arteries, muscular arteries, and arteriolar vessels from the mesenteric bed. The observed changes were correlated with the stages of hypertension development and the effect of antihypertension therapy, including sympathectomy. Specific emphasis was made to determine whether the changes observed were primary in nature, and related to the causes of hypertension, or they were secondary adaptive changes. A comparison of the three models showed that common changes in the intima, media, and adventitia were present in the three models. Alterations in the endothelium (e.g., enlargement of subendothelial space, necrotic changes), adventitia (collagen increase), and hypertrophy of the smooth muscle cells are secondary adaptive changes, because these changes occur subsequent to the development of hypertension, and antihypertensive therapy also prevent these changes from taking place. In contrast, hyperplasia of the smooth muscle cells is a primary change, because it occurs prior to the onset of hypertension. Functionally, alteration in the media is probably the most important change, because it can cause hyperreactivity of the arteries in response to stimulation. Damage to the endothelial cells may play a role in the maintenance of hypertension during the later phase. Alteration in adventitia is a passive change, which does not appear to have a major role in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Structural and functional consequence of neonatal sympathectomy on the blood vessels of spontaneously hypertensive rats.

Neonatal sympathectomy of spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) was performed by a combined treatment with antiserum to nerve growth factor and guanethidine during the first 4 weeks after birth. The development of hypertension was completely prevented in the treated SHR: at 28 to 30 weeks of age, systolic blood pressure of treated SHR was 139 +/- 2 mm Hg as compared with 195 +/- 8 mm Hg in untreated SHR. The extent of sympathectomy was verified by histofluorescence. Fluorescence histochemistry for catecholamine-containing nerves showed a complete absence of adrenergic nerves in the mesenteric arteries of treated rats. A supersensitivity to norepinephrine was exhibited by mesenteric arteries, anococcygeus muscle, and tail arteries from the treated SHR and WKY. In the mesenteric vascular bed, maximal response to norepinephrine was significantly reduced by sympathectomy. Sympathectomy also abolished the responses (e.g., generation of excitatory junctional potentials) of tail arteries to electrical stimulation of perivascular nerves. Morphometric measurements of three categories of mesenteric arteries showed that sympathectomy had no effect on the hypertrophic change of smooth muscle cells in the conducting vessels, but it prevented the hyperplastic changes of the muscle cells from reactive, muscular arteries and small resistance vessels. These results suggest that one of the primary roles of the overactive sympathetic nervous system in the development of hypertension in SHR is manifested through its trophic effect on the arteries of SHR. This trophic effect appears to cause a hyperplastic change in the smooth muscle cells in the reactive and resistance vessels, thereby contributing to the development of hypertension in older SHR.

Animals↗
PubMed1987

Assessment of postmortem respiratory ciliary motility and ultrastructure.

Acquired and congenital abnormalities in the mucociliary transport system result in respiratory dysfunction and clinical disease. Although upper and lower respiratory epithelium can be analyzed premortem, it is uncertain whether postmortem analyses provide a valid indicator of the premortem status of the ciliary apparatus. To address this question, we studied nasal ciliary motility and ultrastructure from 2 patients 16 h after death. After placement of the epithelial samples in Krebs-Henseleit solution and warming to body temperature, normal ciliary motility and frequency were observed in both samples. The specimen then could be stored within the solution at 4 degrees C for subsequent reanalysis on later days for as long as 60 h after collection with no deterioration in ciliary motility, as assessed by video motion analysis. Quantitative assessment of the ciliary ultrastructure did not reveal any abnormality in microtubular arrangements, and good tissue preservation was seen. These studies demonstrate that postmortem collection of nasal epithelium samples can provide a valid assessment of premortem ciliary structure and function.

Aged↗