Biomedical subjects
J M Lee
Publications and source records attributed to J M Lee.
Analysis of pulmonary venous flow velocity patterns in hypertensive hearts: its complementary value in the interpretation of mitral flow velocity patterns.
Although the Doppler mitral flow velocity pattern changes in accordance with the degree of left ventricular diastolic dysfunction, it is "normalized" in the presence of heart failure. In this study the pulmonary venous flow velocity pattern was characterized in 43 hypertensive patients with and without heart failure to clarify whether analysis of the pulmonary venous flow velocity pattern provides complementary information in the interpretation of the mitral flow velocity pattern. The mitral flow velocity pattern in 32 hypertensive patients without heart failure was characterized by decreases in the peak early diastolic filling velocity (E) and the ratio of E to peak filling velocity at atrial contraction. The mitral flow velocity pattern was "normalized" in 11 patients with heart failure, with no differences in any mitral flow velocity pattern indexes as compared with 24 normal subjects. The pulmonary venous flow velocity pattern in hypertensive patients without heart failure was characterized by a decreased peak diastolic forward flow velocity (D) and an increased ratio of peak systolic forward flow velocity (S) to D (S/D ratio). In patients with heart failure, D was higher and the S/D ratio was lower compared with hypertensive patients without heart failure (p less than 0.01, p less than 0.01) and normal subjects (p less than 0.01, p less than 0.01). Thus the pulmonary venous flow velocity pattern appeared to be more reliable than the mitral flow velocity pattern in differentiating subgroups of patients with hypertension. Analysis of the pulmonary venous flow velocity pattern in conjunction with the mitral flow velocity pattern provides important and complementary information in the interpretation of the mitral flow velocity pattern in hypertensive patients with and without heart failure.
Conformational changes in mouse MHC class II proteins at acidic pH.
MHC class II molecules bind peptide antigens and present them to T cells. Recent evidence suggests that peptide--MHC class II interaction is regulated by pH. Both peptide binding to and dissociation from MHC class II molecules is enhanced at acidic pH. In this report we use circular dichroism to investigate the possibility that the modulation of peptide association with MHC class II molecules at acidic pH is associated with changes in MHC class II structure. Our results show that a change in the structure of the MHC class II protein A(d) occurs between pH 4 and 5, close to the pH optimum for peptide binding. More drastic changes in A(d) structure occur at lower pH levels, where peptide dissociation is enhanced. The structural changes at pH 4-5 are fully reversible upon neutralization, while changes at pH 3 are not. The pH stability of purified E(d) molecules is somewhat different, with changes observed only at pH less than 4. This may reflect a differential occupancy of the purified molecules with endogenous peptides.
Correlation of structure and viscoelastic properties in the pericardia of four mammalian species.
Although the pericardium is recognized as having important contributions to ventricular function, the relationship between its functional role and structural composition remains poorly understood. Conflicting evidence from low strain rate experiments has shown that differences exist between the mechanical properties of canine, human, and bovine pericardium but with no structural explanation for these differences. This paper examines the pericardia of calves, dogs, pigs, and sheep using a structural/mechanical approach with techniques novel to the pericardial literature. High strain rate mechanical testing for stress-strain response, stress relaxation, and forced vibration response has shown the pericardium to be much more viscoelastic than previously believed under large deformations, but to be quite elastic in small vibrations. The thinner canine and porcine pericardia were found to be significantly stiffer than the thicker bovine and ovine tissues, but equivalently viscoelastic. Biochemical analysis shows these thinner tissues to have significantly higher levels of type III collagen combined with a higher degree of cross-linking. This is the first structural explanation for differences in mechanical properties between the pericardia of different species.
Inverse scattering scheme based on the moment method in the spectral domain, Part I: Theory.
Recently, electromagnetic and ultrasonic imaging of inhomogeneous objects by applying the moment-method procedures of forward scattering problems in the reverse sequence have been developed. In this paper, the inverse scattering formulation has been modified to be applicable in the spectral domain. Compared to previous schemes, the suggested formulation illustrates clearly the actual mechanism of the inverse scattering process by explicit separation of the contributions from several variables, such as the measurement location, basis function, and geometry of objects. The ill-posedness inherent in inverse scattering problems was also explained easily in this spectral scheme by the exponentially-decaying behavior of high-frequency spectral components of the scattered field. It implies that enlargement of the discretized cell size is a key factor in regularizing the ill-posedness. In particular, since the singular kernel to be integrated on each cell became regular in the modified scheme, various types of basis functions instead of pulse function were adopted without additional difficulties. This advantage is expected to play an important role in regularizing the noise effect by selecting polynomial basis function on the enlarged cells of discretization in the spectral inverse scattering scheme.
Size of metallic and polyethylene debris particles in failed cemented total hip replacements.
Reports of differing failure rates of total hip prostheses made of various metals prompted us to measure the size of metallic and polyethylene particulate debris around failed cemented arthroplasties. We used an isolation method, in which metallic debris was extracted from the tissues, and a non-isolation method of routine preparation for light and electron microscopy. Specimens were taken from 30 cases in which the femoral component was of titanium alloy (10), cobalt-chrome alloy (10), or stainless steel (10). The mean size of metallic particles with the isolation method was 0.8 to 1.0 microns by 1.5 to 1.8 microns. The non-isolation method gave a significantly smaller mean size of 0.3 to 0.4 microns by 0.6 to 0.7 microns. For each technique the particle sizes of the three metals were similar. The mean size of polyethylene particles was 2 to 4 microns by 8 to 13 microns. They were larger in tissue retrieved from failed titanium-alloy implants than from cobalt-chrome and stainless-steel implants. Our results suggest that factors other than the size of the metal particles, such as the constituents of the alloy, and the amount and speed of generation of debris, may be more important in the failure of hip replacements.
Incidence estimation of genitourinary cancer in Korea.
A nation-wide study was performed to estimate the incidence of bladder, kidney, renal pelvis and ureter, prostate, testicular and other genitourinary cancer among Koreans in Korea using medical records of the inpatients of the beneficiaries of the Korea Medical Insurance Corporation (KMIC) from Jan. 1, 1989 to Dec. 31, 1989. The crude incidence rate of bladder cancer (ICD-9 188) is estimated to be 4.43 and 0.98 per 100,000 in males and females, respectively. Around 1,093 new cases of bladder cancer (895 male and 198 female) are estimated to occur in a year. The adjusted rate for the world population is 7.76 in males and 1.19 in females which is similar to that of Japanese in Osaka and Chinese in Shanghai, but lower than in American whites and blacks. The crude incidence of kidney, renal pelvis and ureteral cancer (ICD-9 189) is estimated to be 1.61 and 0.87 in males and females, respectively. Around 507 new cases of kidney, renal pelvis and ureteral cancer (332 male and 175 female) are estimated to occur in a year. The adjusted rate for the world population is 2.69 in males and 1.04 in females. In the prostate (ICD-9 185), the crude incidence rate of cancer is estimated to be 1.36. Around 274 new cases of prostate cancer are occurring in a year. The adjusted rate for the world population is 2.98 which is similar to the Chinese rate. The incidence of genitourinary cancer continuously increases with age.
Detection of tumor necrosis factor in gingival crevicular fluid.
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beta-Glucocerebrosidase activity in murine epidermis: characterization and localization in relation to differentiation.
The intercellular lipids of the stratum corneum, which are highly enriched in ceramides, are critical for the mammalian epidermal permeability barrier. During the terminal stages of epidermal differentiation, the glucosylceramide content is dramatically reduced, while the content of free ceramides increases. To investigate whether beta-glucocerebrosidase (beta-GlcCer'ase) could be responsible for this change in lipid content, we characterized its activity in murine epidermis, compared enzyme activity to other murine tissues, and localized beta-GlcCer'ase activity within the epidermis. Epidermal extracts demonstrated linear 4-methylumbelliferyl-beta-D-glucose hydrolysis (to 3 h) with protein concentrations between 1 and 250 micrograms/ml. Whole epidermis contained comparable beta-glucosidase activity (9.1 +/- 0.4 nmol/min per mg DNA) to murine brain and liver, and 5-fold higher activity than spleen. Epidermal beta-glucosidase activity was stimulated greater than 15-fold by sodium taurocholate at pH 5.6, and inhibited at acidic pH (3.5-4.0). Bromoconduritol B epoxide (greater than or equal to 1.0 microM), inhibited epidermal enzyme activity by greater than 75%, while activity in brain, liver, and spleen was only inhibited by 6, 17, and 14%, respectively. Moreover, beta-GlcCer'ase mRNA expression in murine epidermis exceeded levels in liver, brain, and spleen. Finally, beta-GlcCer'ase activity was highest in the outer, more differentiated epidermal cell layers including the stratum corneum. In summary, mammalian epidermis contains an usually high percentage (approximately 75%) of beta-glucocerebrosidase activity, and the concentration of activity in the more differentiated cell layers may account for the replacement of glucosylceramide by ceramides in the outer epidermis.
Presuicide attempt communications between parasuicides and consulted caregivers.
A high percentage of parasuicides visit professional caregivers prior to the attempted suicide. The content or outcome of these consultations is unknown. We interviewed hospitalized attempters and the professional caregivers they identified as having been consulted prior to their attempts. About half of these patients directly disclosed suicidal symptoms or intentions, especially to mental health professionals. These professionals more often inquired about suicidal ideations than did nonpsychiatric physicians. However, few caregivers noted suicidal thinking or probed suicidal symptoms. The data suggest that professional caregivers and especially nonpsychiatric physicians should be more sensitive and responsive to the signs and symptoms of suicidality.
Pulmonary venous flow velocity pattern as assessed with transthoracic pulsed Doppler echocardiography in subjects without cardiac disease.
Pulmonary venous flow velocity pattern (PVFVP) was analyzed in 53 subjects (aged 25 to 77 years, mean 47) without cardiovascular disease who underwent transthoracic pulsed Doppler echocardiography. The forward flow velocity pattern was biphasic in 37 of the 53 subjects, with each of the 2 peaks in systole and diastole; flow was triphasic with 2 peaks in systole and the other peak in diastole in the remaining 16 subjects. Peak systolic and diastolic flow velocity ranged from 28 to 84 cm/s and from 27 to 71 cm/s, respectively. Mean systolic flow velocity was significantly greater than mean diastolic flow velocity (53 +/- 12 vs 47 +/- 11 cm/s, p less than 0.01). Systolic flow velocity and the ratio of systolic to diastolic flow velocity increased and diastolic flow velocity decreased with aging (r = 0.52, p less than 0.001, r = 0.70, p less than 0.001 and r = -0.49, p less than 0.001, respectively). Reverse flow occurred during the atrial contraction phase and its velocity (mean 20 cm/s) increased with aging (r = 0.56, p less than 0.001). The parameters of PVFVP were compared with the ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio) measured in the transmitral flow velocity pattern. As E/A ratio increased, systolic flow velocity and systolic/diastolic flow ratio and peak reverse flow velocity decreased (r = -0.40, p less than 0.01, r = -0.67, p less than 0.001 and r = -0.68, p less than 0.001, respectively) and diastolic flow velocity increased (r = 0.58, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Functional mapping of MHC class II polymorphic residues. The alpha-chain controls the specificity for binding an Ad-versus an A k-restricted peptide and the beta-chain region 65-67 controls T cell recognition but not peptide binding.
MHC proteins are polymorphic cell surface glycoproteins involved in the binding of peptide Ag and their presentation to T lymphocytes. The polymorphic amino acids of MHC proteins are primarily located in the N-terminal domains and are thought to influence T cell recognition both by influencing the binding of peptide Ag and by direct contact with the T cell receptor. In order to determine the relative importance of individual polymorphic amino acids in Ag presentation, a number of groups have taken the approach of interchanging polymorphic amino acids between different alleles of MHC protein in an attempt to define which of the polymorphisms influence peptide binding and which influence T cell recognition by direct contact with the TCR. The peptide OVA323-339 has been previously shown to bind to the MHC class II protein Ad and to have a much lower affinity for Ak, whereas the peptide hen egg lysozyme 46-61 binds well to Ak and poorly to Ad. In the present report, we have analyzed the ability of purified wild-type MHC class II proteins as well as the ability of three different hybrid molecules between Ad and Ak to bind and present these peptides. We find that the alpha-chain of the MHC class II protein plays a critical role in the binding of HEL46-61 and confers the specificity for binding OVA323-339, regardless of which beta-chain is present. We also find that the beta-chain region 65-67 does not control the specificity of peptide binding to the MHC protein, but is important in T cell responses to preformed MHC-peptide complexes, suggesting a role for this region in contacting the TCR.
Muscimol injections into the median raphe nucleus increase serum ACTH and corticosterone concentrations via a nonserotonergic mechanism.
Midbrain raphe serotonin (5-HT) neurons can influence the pituitary-adrenal axis. The midbrain raphe nuclei also contain a number of non-5-HT neurons, including gamma-aminobutyric acid (GABA) interneurons which can modulate 5-HT neuronal activity. We investigated the effects of intraraphe injections of the GABAA agonist, muscimol, on serum adrenocorticotropin hormone (ACTH) and corticosterone concentrations. Rats were infused with muscimol (0, 25, 50, and 100 ng in 0.5 microliters saline) into the median raphe nucleus (MR). The animals were killed 30 min later, and trunk blood was collected for measurement of serum concentrations of ACTH and corticosterone by radioimmunoassay. Muscimol dose dependently increased plasma concentrations of these two pituitary-adrenal hormones. In order to determine the role of MR 5-HT neurons in these effects, separate groups of implanted animals were infused with either the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) or ascorbic acid vehicle into the MR. Two weeks later, the animals were infused with muscimol (100 ng in 0.5 microliters) and sacrificed as above. Treatment with 5,7-DHT, which markedly reduced hippocampal concentrations of 5-HT (-83%) and 5-HIAA (-73%), did not block intra-MR muscimol-induced elevations in ACTH and corticosterone. Thus, 5-HT neurons within the MR apparently do not mediate the increased activity of the pituitary-adrenal axis produced by stimulation of MR GABAA receptors.
Regulation of NGF gene expression in CNS glia by cell-cell contact.
Nerve growth factor (NGF) gene expression in central nervous system (CNS) glia appears to be associated with active glial growth. To study the underlying molecular mechanisms, we examined the effects of a number of growth-related factors on NGF mRNA expression in glial cultures. Our results suggest that glial membrane interaction, as a consequence of growth, actively inhibits NGF gene expression in CNS glia.
Behavioral sensitization to cocaine is not associated with changes in serotonin (5-HT) fiber immunoreactivity in rat forebrain.
We investigated whether cocaine-induced behavioral sensitization is associated with changes in serotonin (5-HT) immunoreactivity. Male Sprague-Dawley rats were injected with either cocaine (15 mg/kg, IP) or saline twice daily for seven days. Their behavior was observed and rated for locomotor activation and stereotypy. One day after the final injection, the brains were processed for 5-HT immunohistochemistry. The intensity of 5-HT immunoreactive staining of 5-HT axons and terminal varicosities was blindly rated in cocaine-sensitized rats and found not to differ from saline-treated rats. The results support the hypothesis that unlike some amphetamine derivatives, repeated cocaine administration which results in behavioral sensitization is not neurotoxic to 5-HT axons and terminals in the forebrain.
Septal choline acetyltransferase immunoreactive neurons: dose-dependent effects of AF64A.
Two experiments were performed. In the first, the cholinotoxin, AF64A (0.5, 1.0 or 1.5 nmol/ventricle), or vehicle (3.0 microliters) was injected (ICV) bilaterally into male rats (n = 23). Choline acetyltransferase (ChAT) immunoreactive (IR) perikarya in the four subgroups of the septal complex were visualized by immunocytochemistry (PAP method) 28 days postinjection, and counted using a microprojector (x40). The 0.5 nmol/ventricle dose of AF64A significantly reduced (31%) the number of ChAT-IR cell bodies in the intermediate subgroup (rostral extension of the nucleus basalis/substantia innominata). Higher doses did not produce additional reductions. The highest dose (1.5 nmol/ventricle) of AF64A resulted in significant decreases in ChAT-IR cell bodies in the dorsal (51%) and midline (35%) subgroups (medial septum), but did not affect the number of ventral subgroup (diagonal band of Broca) ChAT-IR neurons. In the second experiment, electrolytic lesions were placed in the corpus callosum, cingulum and overlying cingulate gyrus, in order to simulate the nonselective damage seen following the 1.5 nmol/ventricle dose of AF64A. In comparison to the surgical controls (n = 3), the electrolytic lesions (n = 6) failed to significantly affect the number of ChAT-IR perikarya in any of the septal subdivisions. Thus the distinct subgroups of septal ChAT-IR neurons are differentially sensitive to the toxic effects of ICV administered AF64A: intermediate much greater than dorsal greater than midline much greater than ventral subgroup.
Adjuvant effect of human growth hormone with an inactivated flavivirus vaccine.
Vaccines made by inactivating pathogenic microorganisms have been dramatically successful in controlling diseases in humans and animals. Despite their successes, they have a major disadvantage in that several inoculations are required for them to be effective. To overcome this problem, a commercial inactivated vaccine preparation against tickborne encephalitis was combined with human growth hormone (HGH). This formulation produced complete protection in a murine model with only one dose of vaccine, apparently by binding hormone and antigen to an insoluble matrix containing aluminium hydroxide. Thus it is postulated that when virus-specific lymphocytes are attracted to the site of injection, the hormone is at a high local concentration and stimulates the clonal expansion of antigen-specific T cells. The development of genetically engineered HGH now gives unlimited supplies of hormone, potentially resulting in an increase in efficacy of a wide variety of vaccines, especially those needing prolonged immunization schedules such as those being developed to combat human immunodeficiency virus infection.
Effects of coronary angioplasty on left ventricular diastolic filling in patients with old myocardial infarction: a study with pulsed Doppler echocardiography.
To examine the effects of percutaneous transluminal coronary angioplasty (PTCA) on left ventricular diastolic filling in patients with an old myocardial infarction, transmitral flow velocity pattern was measured using pulsed Doppler echocardiography before and after PTCA for the peak early diastolic filling velocity (E) and the ratio of the early diastolic filling to peak atrial filling velocities (E/A ratio) in 73 patients with coronary artery disease. These patients were classified into three groups: 34 patients without previous myocardial infarction (no MI group), 16 patients with an old myocardial infarction in whom a non-infarct-related vessel was reperfused by PTCA (MI-1 group), and 23 patients with an old myocardial infarction in whom the infarct-related vessel was reperfused by PCTA (MI-2 group). The degree of improvement in left ventricular diastolic filling was calculated using the values before PTCA as controls. The % increases in E and E/A ratio were 20 +/- 15 and 25 +/- 19%, respectively, in the no MI group and 27 +/- 20 and 18 +/- 16%, respectively, in the MI-1 group and there was no significant difference between these groups. The % increases in E and E/A ratio in the MI-2 group were 7 +/- 19 and 6 +/- 17%, respectively, and were significantly (P less than 0.05) less than those in the no MI and MI-1 groups. An increase in E, E/A ratio or both by 20% or more was observed in 21 of the 34 (62%) patients of the no MI group, in 10 of the 16 (63%) patients of the MI-1 group and in six of the 23 (26%) patients of the MI-2 group. Thus, reperfusion of a non-infarct-related vessel in patients with an old myocardial infarction improves left ventricular diastolic filling to the same degree and with the same frequency as in patients without myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)