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Biomedical subjects

M Y Kim

Publications and source records attributed to M Y Kim.

104 records · Page 6Linked to original sources

Analyzing doubly censored data with covariates, with application to AIDS.

This paper proposes a method for incorporating covariate information in the analysis of survival data when both the time of the originating event and the failure event can be right- or interval-censored. This method generalizes the one-sample estimation results of De Gruttola and Lagakos (1989, Biometrics 45, 1-11) by allowing the distribution of time between the two events to be a function of covariates under a proportional hazards model. Estimates for the model coefficients, as well as the underlying distributions, are obtained by an iterative fitting procedure based on Turnbull's (1976, Journal of the Royal Statistical Society, Series B 38, 290-295) self-consistency algorithm in combination with the Newton-Raphson algorithm. The method is illustrated with data from a study of hemophiliacs infected with the human immunodeficiency virus.

Acquired Immunodeficiency Syndrome↗

Pulse oximetry and peak flow as indicators of wheezing severity in children and improvement following bronchodilator treatments.

This study examined the changes from the initial peak flows and oxygen saturations (OSAT) of wheezing children at presentation to the emergency department through their treatment in the emergency department. Data was collected prospectively on 785 patients 5 to 20 years of age during an 11-month period from November 1, 1990, to September 30, 1991. Both the initial OSAT and peak flows were correlated with the number of bronchodilator treatments required in the emergency department and with the need for hospitalization. Both the initial OSAT and the peak flows had a limited ability to predict the need for hospitalization. Oxygen saturation appears to be a valid measure of wheezing severity and is more easily obtained in children of all ages. Following bronchodilator treatment, peak flow results in a larger quantitative improvement than OSAT; however, this difference does not appear to have any significant advantage. Aerosolized albuterol and subcutaneous epinephrine resulted in a similar degree of improvement as measured by peak flow and by oxygen saturation, with clinically similar changes in heart rate.

Adolescent↗

Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor alpha and gamma-interferon. Specific role in cell differentiation.

The biochemical signaling mechanisms involved in transducing the effects of tumor necrosis factor alpha (TNF alpha) and gamma-interferon (gamma-IFN) on leukemia cell differentiation are poorly defined. Recent studies established the existence of a sphingomyelin cycle that operates in response to the action of vitamin D3 on HL-60 cells and that may transduce the effects of vitamin D3 on cell differentiation (Okazaki, T., Bell, R., and Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). The effects of TNF alpha and gamma-IFN on sphingomyelin turnover were determined, and the specificity and role of sphingomyelin hydrolysis in HL-60 human promyelocytic leukemia cells with 20% hydrolysis of sphingomyelin at 15 min, 40% hydrolysis at 30-60 min, and return to base line at 2 h. The hydrolyzed sphingomyelin (18 pmol/nmol total phospholipid) was accompanied by the concomitant generation of ceramide (11.2 pmol/nmol total phospholipid). gamma-IFN also caused reversible hydrolysis of sphingomyelin with onset at 1 h and peak effect at 2 h. This sphingomyelin cycle appeared to be specific to the monocytic pathway of HL-60 differentiation, since it was not activated by retinoic acid or dibutyryl cAMP, inducers of granulocytic differentiation, nor with phorbol myristate acetate, an inducer of macrophage-like differentiation. Addition of synthetic ceramide or bacterial sphingomyelinase induced monocytic differentiation of HL-60 cells. Cell-permeable ceramide also caused prompt down-regulation of mRNA for the c-myc protooncogene. The time course of c-myc down-regulation was consistent with the action of ceramide as the mediator of TNF alpha action. These results suggest that sphingomyelin turnover may be an important signaling mechanism transducing the actions of TNF alpha and gamma-IFN with specific function in cell differentiation.

Bucladesine↗

Imipramine binding in depressed patients with psychogenic pain.

Imipramine binding to platelet membranes from depressed patients was analyzed. The patients were divided into two groups: one with depression alone, another with depression and psychogenic pain. The depressed patients with psychogenic pain had lower imipramine binding than the depressed patients without pain.

Blood Platelets↗

Estimating the infectivity of HIV from partner studies.

The main sources of data for estimating infectivity of the human immunodeficiency virus (HIV) come from studies of the susceptible partners of individuals known to be infected with HIV. Estimation of infectivity from these studies is complicated by limitations imposed by the sampling designs. This paper reviews three sampling schemes that have been used in partner studies and, for each, proposes methods for estimating various theoretic models for infectivity. The methods, as well as procedures for checking goodness-of-fit, are illustrated using data from a study by Peterman and colleagues.

Acquired Immunodeficiency Syndrome↗

Human deoxycytidine kinase: kinetic mechanism and end product regulation.

The kinetic properties of the monomeric deoxycytidine kinase (EC 2.7.1.74) from leukemic human T-lymphoblasts have been investigated. The results of steady-state initial-rate kinetic analysis and product inhibition studies at pH 7.5 and 37 degrees C indicate that substrate binding follows an ordered sequential pathway, with the magnesium salt of ATP being the first substrate to bind and dCMP the last product to dissociate. At subsaturating substrate concentrations, dCMP produced competitive inhibition against ATP, while against varied deoxycytidine concentrations dCMP exhibited mixed-type inhibition. ADP produced noncompetitive inhibition against either substrate. The limiting Km values for deoxycytidine and MgATP were 0.94 and 30 microM, respectively. The end product inhibitor dCTP exhibited competitive inhibition against varied ATP concentration, with a dissociation constant estimated to be 0.7 microM when extrapolated to zero ATP concentration. dCTP was purely noncompetitive against varied deoxycytidine concentration. On the basis of these kinetic results, and on the strong and specific inhibition by dCTP, it is proposed that this end product functions as a multisubstrate analogue, with its triphosphate group binding to the phosphate donor site of the enzyme and its deoxycytidine moiety overlapping and binding to the deoxynucleoside site in a highly specific manner.

Adenosine Diphosphate↗

Affinity purification of human deoxycytidine kinase: avoidance of structural and kinetic artifacts arising from limited proteolysis.

Homogeneous deoxycytidine kinase has been isolated from leukemic human T-lymphoblasts by affinity chromatography based on a multisubstrate analog, deoxycytidine 5'-adenosine 5"'-P1,P4-tetraphosphate (dCp4A). Chromatography of extract treated with protease inhibitors yielded a monomeric polypeptide, inasmuch as the Mr of the native protein, 59,300, is comparable to the value of 52,000 from sodium dodecyl sulfate polyacrylamide gel electrophoresis. The isoelectric pH was 6.1. But, enzyme isolated without protease inhibitors exhibited two fragments of Mr = 30,000 and 33,000, suggesting that proteolytic cleavage of the parental polypeptide had occurred during affinity chromatography. Both the parental and proteolyzed enzymes phosphorylated deoxyadenosine and deoxyguanosine, as well as deoxycytidine. However, the proteolyzed enzyme had an increased apparent Km for deoxycytidine. In consequence of this, a mixture of the two forms produced bimodal kinetic plots, whereas linear kinetics were displayed by each form alone.

Chromatography, Affinity↗

Kinetics of the efflux of 3H-norepinephrine from rabbit irides.

The pigment cell dependent accumulation of 3H(-)-norepinephrine (1 mumol/l) was studied in rabbit irides. Albino irides served as controls. Neuronal uptake, deamination and O-methylation of 3H(-)-norepinephrine were reduced by desipramine, pargyline and U-0521, respectively. Both albino and pigmented irides accumulated the catecholamine from the incubation medium. At 37.5 degrees C and 120 min of incubation, tissue/medium ratios for pigmented and albino irides were 10.70 and 4.30 ml/g respectively. At 0 degrees C, the accumulation of 3H(-)-norepinephrine in the albino iris was abolished, while the pigmented iris accumulated significant amounts. The tissue/medium ratio was approximately 3 ml/g. When irides were loaded with 1 mumol/l of 3H(-)-norepinephrine for 60 min the drug distributed into four different compartments. Most of the pigment cell dependent binding was associated with compartments III and the "bound fraction". The amount bound in these compartments was 73% of total accumulation. In pigmented irides obtained from reserpine-pretreated rabbits the total binding was reduced to 64% of that in pigmented control irides. The half times for efflux from pigmented iris were 1.2 min, 10.7 min and 94.8 min, respectively, for compartments I, II, and III. Irides were loaded with 3H(-)-norepinephrine in normal physiological salt solution and rates of efflux were studied in Ca2+-free medium. In either albino or pigmented iris, the late efflux declined more slowly compared to that from the control irides. When pigmented irides were loaded with a low concentration of 3H(-)-norepinephrine, the displacement of the labeled amine was equal by each stereoisomer of norepinephrine. Results are discussed in relationship to the pigment cell-dependent uptake of the catecholamine.

Animals↗

Alpha-adrenoreceptor-related dissociation constants and intrinsic efficacies of stereoisomers of epinephrine.

THe alpha-adrenoreceptor-related dissociation constant and intrinsic efficacy of the stereoisomers of epinephrine were determined on the rabbit aortic strip. (-)-Epinephrine showed higher affinity than (+)-epinephrine or the desoxy analogue epinine. Efficacy of (+)-epinephrine relative to (-)-epinephrine was low (relative efficacy, er = 0.44). Epinephrine had about the same affinity and efficacy as (+)-epinephrine. When the alpha-adrenoreceptors were protected against dibenamine by an equimolar concentration of the isomers, (-)-epinephrine was found to be more effective than (+)-epinephrine or epinine. These results suggest that the stereoisomers of catecholamines differ not only in affinity but also in intrinsic efficacy.

Animals↗

Ileal obstruction caused by idiopathic sclerosing encapsulating peritonitis.

A 26-year-old woman presented with epigastric pain, vomiting, and a palpable mass in the right lower abdomen. Ultrasonography showed a high echogenic mass associated with a small amount of ascites in the right lower abdomen. Computed tomography demonstrated entrapped ileal loops within a thin-walled fibrous capsule. A thin fibrous sac encasing the terminal ileum was detected on laparotomy and confirmed as idiopathic sclerosing encapsulating peritonitis.

Adult↗

Issues in deep space radiation protection.

The exposures in deep space are largely from the Galactic Cosmic Rays (GCR) for which there is as yet little biological experience. Mounting evidence indicates that conventional linear energy transfer (LET) defined protection quantities (quality factors) may not be appropriate for GCR ions. The available biological data indicates that aluminum alloy structures may generate inherently unhealthy internal spacecraft environments in the thickness range for space applications. Methods for optimization of spacecraft shielding and the associated role of materials selection are discussed. One material which may prove to be an important radiation protection material is hydrogenated carbon nanofibers.

Aluminum↗

Atypical pulmonary metastases: spectrum of radiologic findings.

Typical radiologic findings of a pulmonary metastasis include multiple round variable-sized nodules and diffuse thickening of interstitium. In daily practice, however, atypical radiologic features of metastases are often encountered that make distinction of metastases from other nonmalignant pulmonary diseases difficult. A detailed knowledge of the atypical radiologic features of a pulmonary metastasis with a good understanding of the histopathologic background is essential for correct diagnosis. Squamous cell carcinoma is regarded as the most common cell type of a cavitating metastasis, but metastatic nodules from adenocarcinomas and sarcomas also cavitate occasionally. Calcification can occur in a metastatic sarcoma or adenocarcinoma, which makes differentiation from a benign granuloma or hamartoma difficult. Peritumoral hemorrhage results in areas of nodular attenuation surrounded by a halo of ground-glass opacity. Pneumothorax commonly occurs in metastases from an osteosarcoma. Air-space consolidation is often seen in cases of metastases from gastrointestinal tract malignancies. Even though tumor emboli in pulmonary arteries can be seen at computed tomography, diagnosis is difficult because they are located in small or medium arteries. A common radiologic appearance of an endobronchial metastasis is an atelectasis. In cases of an endobronchial or a solitary pulmonary metastasis, differentiation between bronchogenic carcinoma and metastasis is difficult. Dilated vascular structures within the mass can be seen in metastatic sarcomas. A sterilized metastasis after chemotherapy is radiologically indistinguishable from a residual viable tumor. Benign tumors such as uterine leiomyomas and giant cell tumors of the bone rarely metastasize to the lung.

Calcinosis↗

Foreign bodies in the chest: how come they are seen in adults?

The radiologic and clinical findings of foreign bodies in the chest of children are well recognized. Foreign bodies in adults are infrequent, however, and the radiologic findings of these unusual circumstances have rarely been described. We classified various thoracic foreign bodies into three types according to their cause: Type I, Aspiration, Type II, Trauma or Accident; Type III, Iatrogenic. This pictorial essay will illustrate the radiologic findings and consequences of thoracic foreign bodies in adults, which have rarely been described in the radiologic literature. The clinical significance of thoracic foreign bodies will be also be discussed.

Accidents↗