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Biomedical subjects

M M Lee

Publications and source records attributed to M M Lee.

At least 127 records · Page 7Linked to original sources

Effect of low fat-high carbohydrate diets in hypertensive patients with non-insulin-dependent diabetes mellitus.

Effects of variations in dietary fat and carbohydrate content on various aspects of glucose, insulin, and lipoprotein metabolism were evaluated in 11 patients with hypertension, who also had non-insulin-dependent diabetes mellitus (NIDDM). All of these patients were being treated with sulfonylureas, thiazides, and beta-adrenergic receptor antagonists. The comparison diets contained either 40 or 60% of total calories as carbohydrate, with reciprocal changes in fat content from 40 to 20%. The diets were consumed in a random order for 15 days in a crossover experimental design. The ratio of polyunsaturated to saturated fat and total cholesterol intake were held constant in the two diets. Plasma glucose and insulin concentrations were significantly (P less than .001) elevated throughout the day when patients consumed the 60% carbohydrate diet. Fasting plasma total and very-low-density lipoprotein (VLDL) and triglyceride (TG) concentrations increased by 30% (P less than .001) after 15 days on the 60% carbohydrate diet. Total plasma cholesterol concentrations were similar on both diets, as were low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol concentrations.

Analysis of Variance↗

Mullerian inhibiting substance ontogeny and its modulation by follicle-stimulating hormone in the rat testes.

Mullerian Inhibiting Substance (MIS) production in rat testes from the late fetal to the adult period and its modulation by gonadotropins in neonatal testes were studied using immunohistochemistry, northern analysis, and a graded organ culture bioassay for MIS. The intense immunohistochemical staining for MIS seen in fetal and newborn testes began to decrease gradually after the third postnatal day, then decreased dramatically on the fifth postnatal day. MIS immunohistochemical activity was then present at a low level until about the 20th postnatal day, after which it was barely detectable. The testes from rats treated with FSH at birth showed a considerable drop in MIS immunohistochemical activity on the third postnatal day to 29% of control testes, and a less profound decrease on the second and fourth postnatal days to 46% and 61% of control, respectively; thereafter MIS levels were the same in treated and untreated animals. With shorter courses of FSH treatment, immunohistochemical staining showed less depression of MIS on the third day, and no difference by the fourth postnatal day, indicating that the inhibitory effect on testicular MIS production may require continued FSH exposure. Three-day testes that had been treated with FSH for 2-1/2 days had less MIS messenger RNA compared to control testes of the same age, suggesting that the inhibitory effect of FSH on MIS production could be transcriptionally mediated. In contrast LH treatment produced no difference in either messenger RNA expression or immunohistochemical staining for MIS. These findings suggested that FSH may be a modulator of MIS production in neonatal testes.

Aging↗

Onychomycosis.

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Adult↗

A human tRNA gene cluster encoding the major and minor valine tRNAs and a lysine tRNA.

A human genomic DNA clone hybridizing to mammalian valine tRNA(IAC) contained a cluster of three tRNA genes. Two valine tRNA genes with anticodons of AAC and CAC, encoding the major and minor cytoplasmic valine tRNA isoacceptors, respectively, and a lysine tRNA(CUU) gene were identified by Southern blot hybridization and DNA sequence analysis of a 7.1-kb region. At least nine Alu family members were interspersed throughout the 18.5-kb human DNA fragment, with three Alu elements in the intergenic region between the valine tRNA(AAC) gene and the lysine tRNA gene. Each of the five Alu family members in the sequenced region can be categorized into one of the four Alu subfamilies. The coding regions of all three tRNA genes contain characteristic internal split promoter sequences and typical RNA polymerase III termination signals in the 3'-flanking regions. The tRNA genes are accurately transcribed by RNA polymerase III in a HeLa cell extract, since the RNase T1 fingerprints of the mature-sized tRNA transcription products are consistent with the structural genes. The lysine tRNA(CUU) gene was transcribed only slightly more efficiently than the valine tRNA(CAC) gene in the homologous in vitro transcription system. Surprisingly, the valine tRNA(CAC) gene was transcribed about eightfold more efficiently than the valine tRNA(AAC) gene, implicating the presence of a modulatory element in the upstream region flanking the tRNA(CAC) gene.

Base Sequence↗

Alterations in the pulsatile mode of growth hormone release in men and women with insulin-dependent diabetes mellitus.

The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion time-series analysis. Compared to those in age-matched controls, integrated 24-h concentrations of GH were 2- to 3.5-fold higher in diabetic men (P = 0.002) and women (P = 0.0005). Both men and women with DM had over 50% more GH pulses per 24 h than their non-DM counterparts. In addition, maximal GH pulse amplitude was markedly elevated in the men and women with DM (P = 0.0019 and 0.0189, respectively). That the increase in maximal pulse amplitude was accounted for by greater baseline levels was documented by a higher interpulse valley mean GH concentration in the diabetics compared to the controls (P = 0.0437 and 0.0056, men and women, respectively) and the absence of any difference in incremental pulse amplitude for either sex (P greater than 0.05). DM men had larger GH pulse areas (P = 0.039) than control men, apparently accounted for by greater pulse width (P = 0.0037). Pulse areas in DM and non-DM women were indistinguishable. Time-series analysis revealed that the 24-h (circadian) rhythms of serum GH concentrations exhibited significantly increased amplitudes in the diabetic group as a whole (compared to the controls, P = 0.011). However, the times of maximal GH concentrations (acrophases) were not significantly different. As a group, serum insulin-like growth factor-I was lower in DM vs. non-DM individuals (P = 0.0014), although when separated by sex this difference did not reach statistical significance in women (P = 0.317). The present data confirm the higher circulating levels of GH previously reported to occur in individuals with poorly controlled DM. The altered frequency of GH pulses together with enhanced interpulse GH concentrations and an amplified circadian GH rhythm are compatible with hypothalamic dysfunction associated with dysregulation of somatostatin and/or GHRH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Serum adrenal steroid concentrations in premature infants.

To evaluate serum adrenal steroid concentrations in preterm infants, 17-hydroxyprogesterone (17-OHP), 17-hydroxypregnenolone, 11-deoxycortisol, cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione, 18-hydroxycorticosterone, and aldosterone values were determined in 9 sick and 13 healthy premature infants. Serum steroid concentrations were compared to previously reported data from healthy full-term infants. 17-OHP, 11-deoxycortisol, and aldosterone values were higher in sick preterm infants than in healthy preterm infants. Compared to healthy full-term infants, the premature infants-had significantly higher 17-hydroxypregnenolone, 17-OHP, and DHEA sulfate concentrations. Cortisol values were not different between the sick and healthy preterm infants and were similar to full-term values. Aldosterone values were also similar between the premature and the full-term infants. The findings of elevated steroid precursors in preterm infants and low cortisol levels in stressed sick preterm infants may indicate a relative immaturity of adrenal enzyme activity and inadequate adrenal reserve for stress.

17-alpha-Hydroxypregnenolone↗

Red cells slide as they form doublets and deform in rouleaux.

Mammalian erythrocyte aggregation increases when the levels of plasma proteins favoring aggregation rise. Red cell aggregate formation has been attributed to noncovalent bonding of adjacent erythrocyte plasma membranes by these proteins and similar macromolecules. The proposed membrane to membrane noncovalent bonds would keep each membrane from sliding during aggregate formation because the bonds responsible for maintaining cell-cell contact would need to be disrupted. Because past studies of doublet formation suggested that the membranes might slide during contact expansion, we embedded latex particles in the membranes of individual human red cells and recorded doublet formation on video tape. The cells were suspended in a buffer that contained polyvinylpyrrolidone at a concentration sufficient to cause a moderately elevated sedimentation rate. The latex particles remained stable in position relative to each host cell during doublet formation, indicating that sliding was involved. We also stretched individual rouleaux using a glass rod and observed that latex particles attached to red cells whose contact area was reduced by the motion maintained their position during their return to a normal shape. These studies show that erythrocyte aggregate formation is accomplished by membrane sliding and that aggregate shape change and disruption during blood flow commonly involve sliding. The sliding motion argues that the attraction between red cell membranes generated by an array of elongated macromolecules involves a delocalized rather than a noncovalently coordinated adhesion.

Erythrocyte Aggregation↗

The role of arterial endothelial cell mitosis in macromolecular permeability.

The present experiments were performed on twelve male Wistar rats to study the quantitative, topographic correlation between transendothelial permeability of Evans Blue-albumin (EBA) conjugate and endothelial cell replication at the single-cell level. En face preparations of the thoracic aorta were examined by fluorescence microscopy. We found a high degree of correlation between endothelial cell mitosis and EBA leaky spots. Although endothelial cell mitosis is very rare in occurrence, nearly all junctions around the dividing cells were leaky (99%), in contrast to only 0.03% of the non-mitotic cells. In addition, electron microscopic observations showed that the junction around a dividing endothelial cell is leaky, whereas that around a dying cell is not. With the aid of our theoretical model, we were able to analyze the dynamics of macromolecular passage through leaky endothelial junctions. The duration of endothelial cell mitosis was estimated to be 67 min, which constituted 0.01% of the duration of the total cell cycle. The time-dependent change in junctional geometry during endothelial cell turnover leads to an inverse relationship between macromolecular size and duration of junctional leakage. For albumin the duration of leakiness across aortic endothelial cell is approximately 3.7 hr. The present findings lend support to our hypothesis that transiently open junctions surrounding the dividing endothelial cells provide the major pathway through which macromolecules enter the subendothelial space to result in lipid accumulation.

Animals↗

Coronary perfusion during acute myocardial infarction with a combined therapy of coronary angioplasty and high-dose intravenous streptokinase.

Two hundred and sixteen patients with acute myocardial infarction were treated with immediate infusion of high-dose (1.5 million units) intravenous streptokinase followed by emergency coronary angioplasty. The infarct lesion was crossed and dilated in 99% and persistent coronary perfusion after the procedure was achieved in 90% (including 3% with significant residual stenosis). Total in-hospital mortality was 12%. Multivariable analysis showed a higher hospital mortality with cardiogenic shock (41% vs 5% without shock), older age, lower left ventricular ejection fraction, and female sex. Final patency of the infarct-related vessel was determined by follow-up in-hospital cardiac catheterization. Coronary reocclusion occurred in 11% (symptomatic in 7%, treated with emergency angioplasty or bypass surgery; silent in 4%, treated medically). Of the surviving patients with successful initial establishment of infarct vessel patency, 94% were discharged from the hospital with an open infarct artery or a bypass graft to the infarct vessel. There was significant improvement in both ejection fraction (44% to 49%; p less than .0001) and regional wall motion in the infarct zone (-3.0 SD to -2.4 SD; p less than .0001) among patients with persistent coronary perfusion and insignificant residual stenosis at the time of the follow-up cardiac catheterization. Thus, a treatment strategy for acute myocardial infarction that includes immediate administration of streptokinase followed by emergency coronary angioplasty, and coronary bypass surgery when necessary, results in a high rate of early and sustained patency of the infarct-related vessel.

Angioplasty, Balloon↗

Developing red cell flow orientation shown by changes in blood reflectivity.

The rate of onset of erythrocyte flow orientation at normal concentration has not previously been established. Reflectivity of blood and resuspended non-aggregated red cells at normal (41%) and elevated (60%) hematocrit has been used to examine this process. Video recordings were made before, during, and after shearing by bob motion in a cylinder-in-cylinder viscometer at shear rates ranging from 4 to 100 inverse seconds. Unaggregated erythrocytes in PBS, already more reflective than blood before shearing, became even more reflective during shearing even at the lowest shear rate studied. The time required for the increased reflectivity to stabilize was observed to be inversely proportional to shear rate for both blood and resuspended red cells. Reflection became constant after a total shear strain (bob shear rate x time) from 4 to 10 at all shear rates studied. Onset of increased reflection expressed in total shear strain units (an index of overall bob movement) was independent of shear rate in the absence of aggregation. When red cells were studied in native plasma, reflectivity increased as much as 30% during shearing, but always remained below unaggregated red cell reflectivity for the same hematocrit and shear rate. Greater reflectivity of unaggregated red cells persisted after cessation of shearing, while blood's reflectivity dropped progressively over several seconds to its pre-shearing value. The geometry chosen for study and insensitivity to light source composition indicate that specular reflection by red cells near the cup's inner surface is responsible for the increased light return during flow. Maximal rate of rise in reflectivity at all shear rates studied was observed to coincide with blood's previously reported transient shear stress overshoot and to correspond with an overall bob motion that would rotate suspended particles approximately 45 degrees. The close relation of both reflectivity increase and shear stress overshoot to such modest overall bob movement indicates that an efficient flow-mediated rotation of either individual or aggregated erythrocytes from initially random positions toward an orientation in the shear plane characterizes flow onset.

Erythrocytes↗

Time-dependent effects of endotoxin on the ultrastructure of aortic endothelium.

The aortic endothelium from control and Escherichia coli (E. coli) endotoxin-treated rats and rabbits was examined by transmission and scanning electron microscopy. Following the intravenous injection of endotoxin, the animals were sacrificed at intervals ranging from 1 min to 4 hr. As early as 1 min after endotoxin, there was a widening of the subendothelial space (SES) and an increase in tortuosity of the internal elastic lamina (IEL). At 5 min, the tortuosity of the IEL increased to a peak value, and the SES showed an increase in the amount of smooth muscle cells (SMC). Initial endothelial damage occurred 5 min after endotoxin: SEM showed some spindle-shaped endothelial cells starting to peel from the underlying SES, and TEM showed some endothelial cells protruding or arching into the lumen. The new findings in this study are that endotoxin injection a) has a very rapid (less than 15 min) effect on rat and rabbit aortic endothelium, including localized endothelial injuries in the intima, and b) induces ultrastructural alterations also in the SES, IEL and portions of the tunica media. These effects were largely reversed within 1 hr after endotoxin administration, thus indicating that the endothelium and other components of the arterial wall can recover with great speeds.

Animals↗

Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases.

Quantitative frequencies of clinical abnormalities in xeroderma pigmentosum were estimated by abstracting published descriptions of 830 patients in 297 articles obtained from a survey of the medical literature from 1874 to 1982. The median patient age was 12 years with nearly equal numbers of male and female patients. Cutaneous symptoms (sun sensitivity or freckling) had a median age of onset of between 1 and 2 years. Forty-five percent of the patients described had basal cell carcinoma or squamous cell carcinoma of the skin. The median age of first nonmelanoma skin cancer among patients with xeroderma pigmentosum was 8 years, more than 50 years less than that among patients with skin cancer in the United States. Melanomas were reported in 5% of patients. Ninety-seven percent of the reported basal and squamous cell carcinomas and 65% of the melanomas in patients with xeroderma pigmentosum occurred on the face, head, or neck. Seventy percent probability of survival was attained at age 40 years, a 28-year reduction in comparison with the US general population. Ocular abnormalities were reported in 40% of the patients described and were restricted to tissues exposed to ultraviolet radiation (lid, conjunctiva, and cornea) and included ectropion, corneal opacity leading to blindness, and neoplasms. Neurologic abnormalities were found in 18% of the cases reported, consisting of progressive mental deterioration, hyporeflexia or areflexia, and progressive deafness in some patients in association with dwarfism and immature sexual development. There was scant information concerning the efficacy of any therapeutic regimen.

DNA Repair↗

Fetal microcirculation of abnormal human placenta. I. Scanning electron microscopy of placental vascular casts from small for gestational age fetus.

The latex injection-corrosion cast technique coupled with scanning electron microscopy was applied to the study of small for gestational age placentas. The main ultrastructural changes observed in the fetal vasculature of small for gestational age placentas were less branching of arteries and veins, capillaries with variable diameters, and many capillary bud projections; also numerous "H"-shaped anastomoses were present in the capillary network. The corrosion/cast technique approach enabled us to visualize the three-dimensional distribution of arteries, veins, and capillary network as well as the ultrastructural alterations among the various-sized vessels in the abnormal placenta. Light microscopic examination of these placentas revealed numerous syncytial knots and fibrinoid deposits pressing on arteriolar and capillary vessels at different locations. We suggest that the numerous capillary buds and anastomoses are characteristics of neovascularization and may be a compensatory phenomenon of the capillary network. This information could shed new light on alterations of physiologic functions of the pathologic placenta.

Adult↗

Fetal microcirculation of abnormal human placenta. II. Scanning electron microscopy of placental vascular casts from fetus with severe erythroblastosis fetalis.

The latex injection-corrosion cast technique coupled with scanning electron microscopy was applied to the study of severe Rh sensitization of the placenta. The main observed ultrastructural changes in fetal vasculature in this type of placenta were very similar to those of the small for gestational age placenta; large-sized vessels exhibited less branching than those of the normal placenta, and the capillary network showed numerous vascular buds and "H"-shaped anastomoses. In addition, in Rh-sensitized placentas, the capillary network was remarkably sparse, and the cast also revealed smooth-surfaced veins with distinct U shapes undulating through the placental stroma. These U-shaped veins may be the result of umbilical flow impedance with subsequent umbilical venous hypertension, which stretches the veins into undulating form.

Adult↗

An instrument to evaluate the time dependent flow properties of blood at moderate shear rates.

The rheology of blood is characterized by shear thinning, viscoelasticity, and thixotropy. Its rheological evaluation is usually accomplished using a torque balance technique during rotational viscometry. Because a stable torque balance does not develop instantly, studies of thixotropy and viscoelasticity of blood have usually been carried out only at low shear rate where their development is slow enough to be monitored accurately. The torque balance technique may be converted from static to dynamic by incorporating the rate of change of sensing system angular momentum. We have modified our Couette viscometer, adding a computer-controlled stepping motor and a second digital voltmeter. The latter is used to determine the angular position of the sensing system every 25 or 50 msec. The new approach allows rapid observation of the development and disappearance of shear stress, enabling us to examine the transient behavior of blood at moderate shear rate (1 to 100 inverse seconds). The transient flow behavior of blood at moderate shear rate is most easily compared directly with the behavior of Newtonian fluids. We present information about the response of our system using a torque balance observation rate of 20 per second. Blood's viscoelasticity is observed to fall substantially as shear rate rises, while its thixotropic transient excess stress rises steadily with increasing shear rate.

Blood Flow Velocity↗

Kinetics of adhesive interaction in vitro of human erythrocytes in plasma.

The initial step in rouleaux formation, the stacking of two red blood cells, is mechanically a process of three stages, compression, sliding, and creeping. Although this has been thoroughly described for cells in synthetic polymer solutions the present work was undertaken to analyze the process for cells in normal plasma, in order to lay the basis for comparison for ongoing studies of blood from patients with blood disorders. For each experiment a small amount of blood was diluted in its own plasma. A drop from the suspension was then placed on a coverslip, the coverslip covered with paraffin oil in a chamber, and the chamber quickly placed on the stage of an inverted microscope for observation and cinemicroscopy. Twenty-four doublet formations in blood plasma from five subjects were analyzed. After two cells make rim to rim contact, they move closer together by deformation of the contiguous rims to a straight line boundary (compression). Then one of the cells moves up over the other and begins the process of registration which previous work has established as a sliding interaction. The peak sliding velocity (on average 0.35 micron/sec) occurs near halfway to complete overlap. Sliding almost completely stopped just before full overlap, which was achieved very slowly (creeping). The several forces involved during sliding were identified, the force balance was examined, and from the variation of the velocity of sliding it was concluded that the medium between the touching membranes exhibits shear-rate-dependent viscosity.

Cell Adhesion↗

DNA repair protects against cutaneous and internal neoplasia: evidence from xeroderma pigmentosum.

Xeroderma pigmentosum (XP), is a rare, autosomal recessive disease with sun sensitivity and multiple neoplasms in association with reduced DNA repair. As a reflection of the clinical consequences of deficient DNA repair, XP serves as a model for determining the effects of proficient DNA repair. To estimate the risk of developing neoplasms in XP, we abstracted reports of 726 XP patients (from 41 countries) published from 1874 to 1982. Despite limitations of a literature survey, the XP patients under age 20 years had an estimated 2000-fold increase in frequency of basal cell and squamous cell carcinoma of the skin, of cutaneous melanoma, of cancer of the anterior eye, and of cancer of the anterior tongue, in comparison to the general population. These sites are all potentially exposed to u.v. radiation, a strong carcinogen which produces DNA damage that is poorly repaired by XP cells. XP patients under age 20 years also had an estimated 12-fold increase in occurrence of neoplasms in sites not exposed to u.v. radiation. Among the XP patients under age 40 years with internal cancer, there was a disproportionate representation of malignant neoplasms of the brain (especially sarcomas), and oral cavity (excluding tongue) compared to US whites under age 40 years. These internal neoplasms may be related to exposure to chemical environmental carcinogens that cause DNA damage which, like u.v.-induced damage, is poorly repaired by XP cells. These reports provide no evidence of an increase in XP of common lethal neoplasms such as lymphomas, or female genital tract or endocrine system cancers. These findings suggest that DNA repair plays a role in protection against u.v.-induced neoplasia and in protection against some internal neoplasms in the general population.

Adolescent↗