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Biomedical subjects

B Schulman

Publications and source records attributed to B Schulman.

15 recordsLinked to original sources

A splice variant of Skp2 is retained in the cytoplasm and fails to direct cyclin D1 ubiquitination in the uterine cancer cell line SK-UT.

Cyclin D1 is an important regulator of the transition from G1 into S phase of the cell cycle. The level to which cyclin D1 accumulates is tightly regulated. One mechanism contributing to the control of cyclin D1 levels is the regulation of its ubiquitination. SK-UT-1B cells are deficient in the degradation of D-type cyclins. We show here that p27, a substrate of the SCF(Skp2) ubiquitin ligase complex, is coordinately stabilized in SK-UT-1B cells. Further, we show that expression of Skp2 in SK-UT-1B cells rescues the cyclin D1 and p27 degradation defect observed in this cell line. These results therefore indicate that the SCF(Skp2) ubiquitin ligase complex affects the ubiquitination of cyclin D1. In addition, we show that SK-UT-1B cells express a novel splice variant of Skp2 that localizes to the cytoplasm and that cyclin D1 ubiquitination takes place in the nucleus. We propose that the translocation of Skp2 into the nucleus is required for the ubiquitination of cyclin D1 and that the absence of the SCF(Skp2) complex in the nucleus of SK-UT-1B cells is the mechanism underlying the ubiquitination defect observed in this cell line. Finally, our data indicates that differential splicing of F-box proteins may represent an additional level of regulation of the F-box mediated ubiquitination pathway.

Alternative Splicing↗

Organ donation in three major American cities with large Latino and black populations.

It has been suggested that areas with large inner-city Black and Latino populations have worse organ donation rates than those with large suburban and rural White populations. Yet data are sparse. We studied family refusal rates (FRRs) to cadaver organ donation between 1/84 and 5/87 in three United States city-areas (New York, Los Angeles, and Miami) with large Black and distinct Latino populations. Blacks are at least 18% and Latinos at least 25% of the combined general population of the three cities, totaling over three and four million people, respectively. In addition, Blacks and Latinos represent 42% of cadaver transplant recipients, 49% of patients on waiting lists, and 57% of the patients on dialysis in the three cities. Combining the data from the three cities, Black (45%) and Latino (43%) FRRs were similar (P = .78), and each was significantly higher than that in the White population (17%) (P less than 0.0001). The overall refusal rate in NYC (42%) was significantly higher (P less than .0001) than in LA (26%) or Miami (21%), and LA's refusal rate was significantly higher than Miami (P = .03). The refusal rates for the White (31%) and Black (55%) populations in NYC were each significantly higher than their respective populations in LA (14% and 33%) or Miami (11% and 36%) (P less than .05). Although Miami Latinos had a lower FRR (35%) than Latinos in NYC (46%) or LA (45%), the difference was not statistically significant (P = .19 and P = .20, respectively). In the three cities combined, 515 of a possible 1772 medically and legally eligible organ donors were lost during the 40 months studied due to families' refusal of consent. This represents approximately 1000 transplantable kidneys and large numbers of extrarenal organs. Further studies are needed to elucidate the reasons for differences in donation rate among groups and regions in the United States.

Black or African American↗

Organ allocation.

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Altruism↗

Pretreatment of cadaver donors with methylprednisolone in human renal allografts.

Fifty cadaveric kidney donors were randomly allocated to two groups. Group 1 received 5 grams of intravenously administered methylprednisolone two to four hours prior to organ harvesting after the pronouncement of brain death. Group 2, which served as the control group, received no pretreatment. Of 100 kidneys harvested, 16 were discarded for various reasons, and 84 were transplanted and were available for evaluation, 40 from the pretreatment group and 44 from the control group. The transplant centers using these kidneys were unaware of the status of the kidney they received, that is, whether it was from a pretreated or a control group. The two groups of kidneys, pretreated and control, did not differ according to the length of warm or cold ischemia time or presence of preformed cytotoxic antibodies. The difference in graft failure between the two groups at three months was insignificant, even when the two groups were compared according to the method of preservation used.

Antibody Formation↗

Professional advisory committee: a new initiative in governance.

In her article, the author describes the establishment of a professional advisory committee by the board of trustees of the Sisters of Charity of Ottawa Health Service. This new initiative gives the organization's professional disciplines a direct voice on the board and embraces a spirit of openness.

Catholicism↗

Urgent priority transplantation: when should it be done?

The success of heart transplantation has created longer waiting lists of candidates, some of whom require transplantation urgently. Decisions must be made regarding which patients require urgent transplantation and how many donor hearts should be committed to urgent transplantation. To determine whether some patients who are considered refractory to medical therapy may be stabilized for elective transplantation, 40 patients transferred for urgent transplantation underwent intensive vasodilator and diuretic therapy, and outcomes were determined. To examine the impact of urgent transplantation on survival, we then determined the survival for urgent priority candidates in the western region. Discharge of the patients who were receiving oral dosages of vasodilators and diuretics was possible for 32 of 40 patients (80%), with a 6-month actuarial survival of 75% on medical therapy, despite an initial ejection fraction of 0.15 +/- 0.04, a cardiac index of 1.9 +/- 0.6 L/min/m2, and a pulmonary wedge pressure of 30 +/- 8 mm Hg. Of 11 patients discharged to await regular priority transplantation, one died suddenly, one died postoperatively, and the others went home 14 +/- 4 days after transplantation. The eight patients unable to be discharged after transfer had lower initial mean arterial pressures and serum sodium levels. Of 59 urgent priority patients from the five western region programs, 50 patients underwent transplantation after 33 +/- 41 days. Subsequent 1-month survival was 88% and overall survival 80%, compared with 97% and 90% in 137 regular priority patients, with a 4.5 times greater risk of early mortality in the urgent group (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Emergencies↗