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Biomedical subjects

B K Lee

Publications and source records attributed to B K Lee.

At least 91 records · Page 5Linked to original sources

Myocardial distribution of cardioplegic solution after retrograde delivery in patients undergoing cardiac surgical procedures.

The myocardial distribution of both antegrade and retrograde cardioplegia for cardiac surgical intervention, after induction of cardioplegia via the aortic root, was directly assessed and compared in 19 patients by means of contrast echocardiography. Two-dimensional transesophageal echocardiographic images of the short axis of the left ventricle at the level of the papillary muscles were obtained after sonicated Renografin-76 microbubbles were injected into an aortic root and/or transatrial coronary sinus catheter during delivery of cardioplegic solution. Segmental distribution of cardioplegic solution was immediately noted in the myocardium at the time of contrast injections. In 11 of 18 patients (61%) cardioplegic solution was dispersed to all left ventricular myocardial segments after antegrade delivery. In 17 of 19 patients (90%) retrogradely delivered cardioplegic solution (after antegrade induction of cardioplegia in 18 of the 19 patients) was dispersed to all the left ventricular myocardial segments, including the septum. In 2 of the patients, initial lack of retrograde distribution of cardioplegic solution was remedied when the coronary sinus catheter was repositioned and contrast cardioplegic solution was reinjected. Imaging of the right ventricle was possible in only 4 of the 19 patients and revealed that after retrograde delivery, cardioplegic solution had been at least partially distributed to the right ventricle as well. We performed off-line videodensitometric analysis in 9 patients after retrograde delivery of cardioplegic solution. Mean peak pixel-intensity ratio of flow from the endocardium to the epicardium in the left ventricular free wall was 1.46 +/- 0.27, and mean peak pixel-intensity ratio of flow from the left to the right intraventricular septal endocardium was 1.39 +/- 0.33 (p < or = 0.05).

Aged↗

Telomere-related markers for the pseudoautosomal region of the mouse genome.

The pseudoautosomal (PA) region of the mammalian genome is the region of the X and Y chromosomes that shares extensive DNA sequence homology and is of special interest because it may play an essential role during male meiosis. We have identified three telomere-related restriction fragments from the PA region of the mouse genome, using an oligonucleotide probe composed of the mammalian telomere consensus sequence TTAGGG. PA assignment of two C57BL/6J-derived fragments was initially suggested by analysis of DNAs from progeny sired by C57BL/6J males carrying the rearranged Y chromosome, Y*: the hybridization intensity of both fragments was concordant with the sex-chromosome complement of the offspring. Further analysis indicated that both fragments were present in female and male F1, mice regardless of the sex of their C57BL/6J parent--a criterion for autosomal or PA linkage. Both fragments were closely linked to each other and located on the X chromosome distal to amelogenin (Amg)--in agreement with X or PA linkage. Confirmation of the PA derivation of these fragments was accomplished by following their segregation in a cross involving XY* males mated to DBA/2J females. A similar experiment identified a third PA-derived restriction fragment of LT/SvEi origin. Identification of PA-derived telomere-related restriction fragments will enable further genetic analysis of this region of the mouse genome.

Animals↗

Geographic origin of the Y chromosomes in "old" inbred strains of mice.

Six distinct Y Chromosomes (Chr) were identified among 39 standard inbred strains of mice with five probes that identified Y Chr-specific restriction fragments on Southern blots. Three Y Chr types, distributed among 31 strains, were of Asian Mus musculus origin. The remaining three Y Chr types, distributed among eight strains, were of M. domesticus origin. The Asian source of the M. musculus Y Chr was confirmed by determining the DNA sequence of 221 bp from an open reading frame within the Sry (sex determining region Y) gene (Gubbay et al., Nature 346: 245-250, 1990) in three inbred strains (C57BL/6J, AKR/J, and SWR/J) and comparing the sequence to the homologous sequences derived from wild caught European and Asian M. musculus males. These data indicate that a minimum of six male mice contributed to the formation of the old inbred strains.

Animals↗

Characterization of the endogenous nonecotropic murine leukemia viruses of NZB/B1NJ and SM/J inbred strains.

We characterized 84 endogenous nonecotropic proviruses of NZB/B1NJ and SM/J inbred strains by examining proviral junction fragment segregation in recombinant inbred (RI) and backcross mice. Forty-five proviruses were shared with other laboratory strains, but 28 were unique to NZB/B1NJ or SM/J. Proviral loci were located on 17 of the 19 mouse autosomes and on both sex chromosomes. These markers will facilitate gene mapping in the NXSM RI set and contribute to the pursuit of a more complete map of the mouse genome.

Animals↗

Thromboelastogram fails to predict postoperative hemorrhage in cardiac patients.

To determine the clinical usefulness of the thromboelastogram in the prediction of postoperative hemorrhage in cardiac patients, we related the results of routine coagulation tests (RCTs) and thromboelastography with the amount of chest tube drainage postoperatively in 101 patients requiring cardiopulmonary bypass. Our data indicated that there was no correlation between RCT results and thromboelastographic variables. No single variable of RCTs and thromboelastography correlated well with the amount of chest tube drainage postoperatively. Before the onset of cardiopulmonary bypass, the most frequent abnormalities detected by thromboelastograms were fibrinolysis and hypocoagulability resulting from factor deficiency. Hypercoagulability detected by thromboelastograms occurred in 13% of patients after cardiopulmonary bypass and usually was not detected by RCTs. The incidence of false-negative thromboelastograms and RCT results in patients who had excessive hemorrhage of unknown cause was 46% and 52%, respectively. The incidence of fibrinolysis as detected by thromboelastograms was similar before and after bypass, but only 2 of the 18 patients with fibrinolysis had excessive hemorrhage postoperatively. Our results indicate that neither RCTs nor thromboelastography predicts the likelihood of excessive hemorrhage in patients after cardiopulmonary bypass. The thromboelastographic results should be interpreted cautiously because of the high rate of unreliable results.

Blood Coagulation Tests↗

Localization of insulin-2 (Ins-2) and the obesity mutant tubby (tub) to distinct regions of mouse chromosome 7.

A DNA mapping panel derived from an interspecific backcross was used to position the mouse insulin-2 locus (Ins-2) on Chromosome 7, near H19 (0/114 recombinants) and Th (1/114 recombinants). Ins-2 is part of a human-mouse conserved linkage group that includes Th, H19, and Igf-2. Analysis of segregation in the F2 generation from the cross C57BL/6J-tub/tub x CAST/Ei demonstrated that Ins-2 and the obesity mutant tubby (tub) are distinct loci, thus eliminating Ins-2 as a candidate gene for tub. These results also refine the estimated genetic distance between tub and Hbb to 2.4 +/- 1.4 cM. The predicted location for a human homolog of tubby is HSA 11p15.

Animals↗

Polyadenylic: polyuridylic acid-induced determinants of host resistance to cytomegalovirus and their potentiation by hyperthermia.

The ability of spleen cells from poly A:poly U-treated mice to inhibit murine cytomegalovirus (MCMV) replication in confluent monolayer cells of secondary mouse embryo fibroblasts (MEFs) cultured at 37 and 40 degrees C was investigated. When spleen cells from BALB/c mice injected 48 h earlier with poly A:poly U were added to MEFs infected 2 h previously with MCMV, 37% less plaques were observed than in cultures containing control cells. Of interest, the poly A:poly U-induced antiviral activity at the elevated temperature (40 degrees C) resulted in a further drop to 61% in MCMV-induced plaques compared to those of the normothermic (37 degrees C) cultures. The antiviral function of spleen cells induced by poly A:poly U was evident in the supernatant fluid when cultured for 48 h at 37 degrees C. MCMV-induced plaques were reduced to 52 and 5% of controls in the plaque assays performed at 37 and 40 degrees C, respectively. Supernatant fluids generated at 40 degrees C, however, inhibited MCMV replication only when incubated at 40 degrees C. No direct inhibitory effect of the supernatant fluids on MCMV was evident; rather, inhibition was effected directly on the MEFs. The NK cell fraction of spleen cells from poly A:poly U-treated mice alone showed only a slight inhibitory effect at 40 degrees C. However, in the presence of the supernatant fluid from poly A:poly U-exposed spleen cells, the antiviral activity of NK cells was significantly increased both at 37 and 40 degrees C. The cellular source of the culture fluid showing poly A:poly U-induced antiviral activity appeared to be in the T-cell population. It was completely neutralized by monoclonal anti-IFN gamma antibody but not by anti-IFN beta, anti-IL4, anti-transforming growth factor, or anti-prostaglandin E2. In conclusion, these data document the ability of spleen cells from poly A:poly U-treated mice to inhibit MCMV replication and this activity is potentiated by hyperthermic conditions. The antiviral function of poly A:poly U-treated spleen cells appeared to be due mainly to the action of IFN gamma produced by T cells. The enhanced antiviral activity by hyperthermia appeared to be related to the action of IFN gamma rather than its production.

Animals↗

Natural killer activity and antibody-dependent cellular cytotoxicity in patients with primary lung cancer.

The NK activity and ADCC of peripheral blood mononuclear cell were examined to evaluate the contribution of ADCC and NK activity to host immune response against lung cancer. The NK activity and ADCC were examined in 58 patients with primary lung cancer and 40 healthy volunteers as normal controls. The NK activity of patients with lung cancer was significantly subnormal, but ADCC was at a normal level. The NK activity was decreased in non-small cell lung cancer (NSCLC), but not in small cell lung cancer (SCLC) compared to normal controls. According to stage, the NK activity in stage II, III-M0 and III-M1 NSCLC showed low levels compared to that of stage I NSCLC, but there was no difference of NK activity in patients with SCLC. The NK activity was not affected by performance status. There was no significant difference of ADCC in patients with lung cancer according to cell type, stage and performance compared with that of normal controls. The NK activity and ADCC were not changed after chemotherapy and operation respectively.

Antibody-Dependent Cell Cytotoxicity↗

Assessment of retrograde cardioplegia distribution using contrast echocardiography.

Retrograde cardioplegia has gained popularity in coronary and noncoronary cardiac operations. We have used contrast echocardiography in the open-chest canine model to compare the distribution of cardioplegia delivered antegrade in the aortic root versus retrograde through the coronary sinus, and to determine the effect of coronary occlusion on that delivery. With no coronary occlusion, antegrade cardioplegia was distributed to the entire left ventricle and septum whereas retrograde cardioplegia was distributed to the left ventricular free wall but had inconsistent delivery to the septum. Acute occlusion of the left circumflex coronary artery resulted in 57.06% +/- 9.52% of the left ventricle not being perfused by antegrade cardioplegia and occlusion of both the left circumflex and anterior descending coronary arteries caused a 65.46% +/- 18.5% reduction in perfusion by antegrade cardioplegia. Acute coronary occlusion had no effect on retrograde cardioplegia distribution. We conclude that retrograde cardioplegia is less homogeneous than antegrade cardioplegia in the intact coronary circulation but that retrograde cardioplegia preserves cardioplegia distal to acutely occluded coronary arteries. Furthermore, contrast echocardiography is a useful method of assessing myocardial perfusion and may have useful clinical applications.

Albumins↗

Mapping anti-müllerian hormone (Amh) and related sequences in the mouse: identification of a new region of homology between MMU10 and HSA19p.

A panel of 78 backcross progeny, BALB/cJ x (BALB/cJ x CAST/Ei)F1, was used to map the gene encoding anti-Müllerian hormone (Amh), also called Müllerian inhibiting substance, to mouse Chromosome 10 (MMU10). This analysis identified a new region of linkage homology between human Chromosome 19p (HSA 19p) and MMU10 and localized an apparent recombinational hot spot in (C57BL/6J x Mus spretus)F1 females [compared with (BALB/cJ x CAST/Ei)F1 males] to the interval between phenylalanine hydroxylase (Pah) and mast cell growth factor (Mgf). In addition, eight unlinked polymorphic sequences, provisionally designated Amh-related sequences (Amh-rs1 through Amh-rs8), were identified by Southern blot analysis using Amh probes. Amh-rs1, -rs2, -rs4, and -rs7 were mapped to MMU1, 13, 12, and 15, respectively, by recombinant inbred (RI) strain and intraspecific backcross analyses. The NXSM RI strain distribution patterns for the four unmapped loci are also presented.

Animals↗

Assessment of myocardial perfusion during CABG surgery with two-dimensional transesophageal contrast echocardiography.

No reliable, quantifiable index of tissue perfusion is currently available to assess the efforts of coronary artery bypass graft (CABG) surgery. We used two-dimensional transesophageal contrast echocardiography with sonicated Renografin-76 microbubbles to determine the distribution of myocardial blood flow during coronary artery bypass graft surgery in 15 patients. Sonicated Renografin-76 contrast agent was injected into the aortic root of all patients after institution of cardiopulmonary bypass and application of the aortic occlusive clamp. Eight patients had contrast agent injected directly into the free proximal end of the vein-CABG anastomosis. All patients again received aortic root injections during reperfusion after anastomosis of the proximal aortovein and distal coronary artery. Echocardiographic images of the left ventricle short axis at the level of the papillary muscles were obtained in real time and analyzed retrospectively from videotape. Injection of contrast provided information about the magnitude and geometric distribution of coronary artery-vein bypass run-off and enabled identification of poorly perfused myocardial regions. When predicted myocardial perfusion patterns, based on preoperative evaluation of epicardial vessel distribution derived from coronary angiography, were compared to actual perfusion patterns assessed with intraoperative echocardiography, contrast regional myocardial perfusion patterns were predicted 84% of the time (71-97%, 95% confidence limit). Regional myocardial perfusion deficits detected after coronary bypass grafting were associated with regional wall motion abnormalities detected after separation from cardiopulmonary bypass. Our technique makes possible on-line visualization of changes in regional blood flow in the heart before, during, and after CABG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The mouse Y* chromosome involves a complex rearrangement, including interstitial positioning of the pseudoautosomal region.

Cytological analysis of the mouse Y* chromosome revealed a complex rearrangement involving acquisition of a functional centromere and centromeric heterochromatin and attachment of this chromosomal segment to the distal end of a normal Y* chromosome. This rearrangement positioned the Y* short-arm region at the distal end of the Y* chromosome and the pseudoautosomal region interstitially, just distal to the newly acquired centromere. In addition, the majority of the pseudoautosomal region was inverted. Recombination between the X and the Y* chromosomes generates two new sex chromosomes: (1) a large chromosome comprised of the X chromosome attached at its distal end to all of the Y* chromosome but missing the centromeric region (XY*) and (2) a small chromosome containing the centromeric portion of the Y* chromosome attached to G-band-negative material from the X chromosome (YX). Mice that inherit the XY* chromosome develop as sterile males, whereas mice that inherit the Y*X chromosome develop as fertile females. Recovery of equal numbers of recombinant and nonrecombinant offspring from XY* males supports the hypothesis that recombination between the mammalian X and Y chromosomes is necessary for primary spermatocytes to successfully complete spermatogenesis and form functional sperm.

Animals↗

Surgical treatment of giant cavernous hemangiomas of the liver--analysis of 7 patients.

Seven patients with giant cavernous hemangioma of the liver were treated surgically with success at Pusan Gospel Hospital, Kosin Medical College, Pusan, from 1980 through 1989. They were 3 males and 4 females, and their ages ranged from 6 to 59 years. The tumors were located on the right lobe of the liver in 5 patients and on the left lobe in 2. The lesions were solitary in all patients, and their sizes varied from 4cm to 15cm in diameter. All patients underwent hepatic resection: 1 right hepatic lobectomy and 4 partial resections for tumors on the right lobe, and 1 left lobectomy and 1 left lateral segmentectomy for tumors on the left lobe. There was no surgical death, but 1 patient had a postoperative complication: multiple stress ulcers on the stomach and ileum. The pathologic diagnosis was cavernous hemangioma in all cases. In the long-term follow-up, there was no recurrence of preoperative symptoms in any patient.

Adult↗

Localization of the growth hormone gene to the distal half of mouse chromosome 11.

A DNA fragment size variant for the growth hormone gene, Gh, has been identified among inbred strains of mice. The inbred strains SM/J and CAST/Ei carry the less frequent allele Ghb and 11 other strains carry the Gha allele. Segregation analysis of data from two crosses involving SM/J and NZB/BINJ and a cross involving BALB/cJ and CAST/Ei confirmed the assignment of Gh to mouse chromosome 11 and placed the locus 2.6 +/- 1.8 map units distal to Erba (avian erythroblastosis oncogene A), a position consistent with the assignment of the Gh locus to the q22-q24 region of chromosome 17 on the human map. Segregation analysis also refined the location of Sparc (secreted acidic cysteine-rich glycoprotein) on mouse chromosome 11 to a position 16.7 +/- 4.2 map units proximal to Evi-2 (ecotropic viral integration site 2).

Alleles↗

The NXSM recombinant inbred strains of mice: genetic profile for 58 loci including the Mtv proviral loci.

We report the construction of 17 recombinant inbred (RI) strains of mice derived from the progenitor strains NZB/BINRe and SM/J and the typing of this RI strain set, designated NXSM, for 58 loci distributed on 16 autosomes and the X chromosome. Two backcrosses involving NZB/BINJ and SM/J were constructed to confirm chromosomal assignments and determine gene orders suggested from NXSM RI strain data. From these results we recommend that chromosomal assignments and gene orders suggested from analyses of RI strain sets be confirmed using data obtained by other means. We also typed NZB/BINJ and SM/J for mammary tumor proviral (Mtv) loci. Both strains share three previously described Mtv loci: Mtv-7, Mtv-14 and Mtv-17. In addition, NZB/BINJ contains the previously described Mtv-3 and Mtv-9 loci and two new Mtv proviral loci: Mtv-27 located on chromosome (Chr) 1 and Mtv-28 located on the X chromosome. SM/J contains the previously described loci Mtv-6 and Mtv-8. Four LTR, mink cell focus-forming murine leukemia viral loci were identified and mapped: Ltrm-1 on Chr 12, Ltrm-2 on Chr 16, Ltrm-3 on Chr 5, and Ltrm-4 on Chr 13. The Tgn locus was positioned proximal to the Ly-6 locus on Chr 15.

Animals↗

Segregation patterns of endogenous mouse mammary tumor viruses in five recombinant inbred strain sets.

We identified mouse mammary tumor proviral loci in the AKR/J, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, and SWR/J inbred mouse strains and determined their segregation patterns in the AKXD, AKXL, BXD, BXH, and SWXL recombinant inbred strain sets. Two new Mtv loci, Mtv-29 and Mtv-30, were identified. Mtv-30 was genetically mapped to chromosome 12. Additionally, two previously identified Mtv loci, Mtv-14 and Mtv-23, were genetically mapped to chromosome 4 and chromosome 6, respectively.

Animals↗