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J Moon

Publications and source records attributed to J Moon.

80 records · Page 5Linked to original sources
PubMedDate not supplied

Expanded use of multivisceral transplantation for small children with concurrent liver and intestinal failure.

Fifty-five children with liver and intestinal failure have been transplanted at our center under daclizumab induction therapy since 1998. Of those, 19 received five multiviceral transplantation (MVT), 12 liver-intestine-pancreas transplants, and 2 noncomposite liver and intestine transplants (NCLIT) before 2001 (group 1). During this period, MVT was only used in children with gastric dysmotility. After 2001, we expanded the use of MVT. Therefore, 36 children in this period (group 2) received MVT except for two who received NCLIT. Median age was 1.08 in group 1 and 1.06 in group 2. Median recipient weight was 8.2 kg in group 1 and 7.5 kg in group 2. Six-month, 1-, and 2-year patient survivals were 54%, 37%, and 32% in group 1 and 94%, 91%, and 71% in group 2 (P = .00037). A statistically significant difference was observed in freedom from rejection between the two groups with group 2 being favorable (P = .0019). A statistically significant difference was observed in freedom from rejection between the two groups with group 2 being favorable (P = .0019) Four died of rejection in group 1 (21%); none died of rejection in group 2. There have been two esophago-gastrostomy strictures (one in each group) and a serious reflux of this anastomosis (group 2). Strictures were treated with balloon dilatation, and the reflux was surgically corrected. In 24 recent cases, gastro-gastric anastomosis was used in MVT with no complications to date. No pancreatic rejection was seen. Small children tolerated MVT with improved survival rates and reduced rates of rejection. Use of MVT may be considered as an alternative to liver-intestine-pancreas transplant.

Antibodies, Monoclonal↗
PubMedDate not supplied

Analysis of rejection episodes in over 100 pediatric intestinal transplant recipients.

Rejection after intestinal transplant is a significant source of morbidity and mortality. We analyzed number of rejections, severity, and duration of episodes in pediatric recipients of intestinal transplants. One hundred eighteen intestinal transplants were performed: intestine (n = 27), liver-intestine (n = 27), modified multivisceral (n = 7), and multivisceral (n = 57). A total of 186 rejections were classified: mild (n = 89), moderate (n = 70), severe (n = 27). Duration of episodes doubled for each increasing step in severity. Treatment of mild rejection was with steroids, moderate rejection was treated with OKT3, severe rejection required OKT3 and organ removal. Most rejections occurred during the first month posttransplant, with the incidence of all rejections declining after 6 months posttransplant. Intestine and liver-intestine recipients had significantly higher probability of developing severe rejections, as compared to MVT. In summary, recipients of MVT seemed to be protected from rejection as compared to intestine or liver-intestine recipients.

Adolescent↗
PubMedDate not supplied

Renal dysfunction following adult intestinal transplant under tacrolimus-based immunosuppression.

We analyzed data from the records of 24 adult patients who survived more than 2 years after intestinal transplantation performed between 1995 and 2002 under tacrolimus-based immunosuppression. Ages ranged from 19.3 to 59.2 years old (median 32.1 years). Tacrolimus cumulative level was defined as a sum of weekly average tacrolimus level over time. Kidney function was evaluated by the 6-month average serum creatinine level. Estimated creatinine clearance was calculated with the Cockcroft-Gault formula. Student's t test was used for analysis. Primary diseases were mesenteric thrombosis (n = 7), trauma (n = 4), Crohn's (n = 3), Gardner's (n = 5), and others (n = 7). Procedures were isolated intestinal transplant (n = 10), liver and intestine (n = 1), multivisceral transplant (n = 9), or modified multivisceral transplant (n = 4). Cumulative tacrolimus levels ranged between 1161 and 8623 ng*day/mL (median 4132 ng*day/mL) at 0 to 12 months. Pretransplant kidney function as mean creatinine clearance was 114 mL/min per 1.73 m(2) (n = 24). Creatinine clearance decreased to a mean of 49.6 mL/min per 1.73 m(2) (43.5% of pretransplant) at 2 years (P < .0001). The average creatinine clearance at 18 to 24 months in each patient with a cumulative tacrolimus level <4500 ng*day/mL was 63% +/- 25% of preoperative creatinine clearance. In patients with a cumulative tacrolimus level >4500 ng*day/mL, it was 34% +/- 17%. Cumulative tacrolimus level >4500 ng ng*day/mL was significantly associated with a decreased creatinine clearance at 2 years (P = .006). Renal function decreased significantly after intestinal transplantation in adults. Cumulative tacrolimus level in the first year affected renal function at 2 years.

Adult↗
PubMedDate not supplied

HIV protease (HIV PR) inhibitor structure-activity-selectivity, and active site molecular modeling of high affinity Leu [CH(OH)CH2]Val modified viral and nonviral substrate analogs.

This report details the structure-activity relationships of the HIV gag substrate analog Val-Ser-Gln-Asn-Leu psi[CH(OH)CH2]Val-Ile-Val (U-85548E), an inhibitor exhibiting subnanomolar affinity towards HIV type-1 aspartic proteinase (HIV-1 PR). Our data show that the P1-P2' tripeptidyl sequence provides the minimal chemical determinant for HIV-1 PR binding. We describe the structure-activity properties of Leu psi[CH(OH)CH2]Val substitution in other peptidyl ligands of nonviral substrate origin (e.g., angiotensinogen, insulin and pepstatin). Furthermore, the aspartic proteinase selectivities of a few key compounds are summarized relative to evaluation against human renin, human pepsin, and the fungal enzyme, rhizopuspepsin. These studies have led to the rational design of nanomolar potent inhibitors of both HIV-1 and HIV-2 PR. Finally, a 2.5 A resolution X-ray crystallographic structure of U-85548E complexed to synthetic HIV-1 PR dimer (Jaskolski et al., Biochemistry 30, 1600 [1991]) provided a 3-D picture of the inhibitor bound to the enzyme active site, and we performed computer-assisted molecular modeling studies to explore the possible binding modes of the above series of Leu psi[CH(OH)CH2]Val substituted HIV-1 PR inhibitors.

Amino Acid Sequence↗
PubMedDate not supplied

Vanadium as a modulator of cellular regulatory cascades and oncogene expression.

Vanadium, a trace metal in the environment and in biological systems, influences the behavior of enzymes, mimics and regulates growth factor activity, is a potential mutagenic and carcinogenic agent, and regulates gene expression. The diverse biological actions of vanadium result from its capacity to function as an oxyanion, oxycation, or prooxidant. Vanadium is found in water, rocks, and soils in low concentration and in relatively high concentrations in coal and oil deposits. Vanadium compounds at much higher concentrations than are typically ingested are being considered in the treatment of diabetes mellitus. The actions of insulin and vanadium on the insulin receptor are similar, but the mechanisms are not identical. Vanadium modulates growth-factor-mediated signal transduction pathways. Vanadium promotes cell transformation and diminishes cell adhesion. Consistent with its mitogenic action and its capacity to mimic mitogenic growth factors, vanadium stimulates expression of protooncogenes. In particular, oxygen-derived active species are involved in the expression of the jun protooncogene in the presence of vanadium. The unique cellular activity of vanadium makes it a tool of unparalleled potential for studying mechanisms of cell growth, differentiation, and metabolism.

Animals↗
PubMedDate not supplied

Among a range of transition metals and ligands vanadium.desferroxamine excels in accelerating reactivity of ferrocytochrome c toward molecular oxygen.

Despite early knowledge of the requirement for metals in the reactions of ferrocytochrome c with oxygen, the relative effectiveness of metals and the factors that modulate effectiveness remain unknown. We have compared the catalytic power of five metals and report the effects of pH and ligand on their effectiveness as catalysts. Catalysis by metal ions was greatest at higher pH, where the rate of aerobic oxidation was lowest. Iron (Fe2+), copper (Cu2+), vanadium(V) (V(V)), manganese (Mn2+), and aluminum (Al3+) were tested in combination with EDTA, ADP, histidine, or desferrioxamine (Des) at pH 2.6, 3.2, and 4.0. At pH 2.6, only vanadium(V) increased the initial rate of the oxidation of ferrocytochrome c (by 6.2-fold). At pH 4.0, however, all the metals markedly stimulated the oxidation of cytochrome c. The order of effectiveness was V(V).Des >> Cu.ADP2+ > Fe.EDTA2+ > Mn.Des2+ > Al.EDTA3+ (where the stated ligand represents the most stimulating one for a given metal). At pH 3.2 the metal complexes had intermediate effects, with vanadium again being the most effective. The preeminence of vanadium among the metals is novel. Where the heme crevice is closed (pH 4), transition metal ions mediated almost all of the reduction of oxygen, while at the lowest pH (2.6) transition metal ions were largely unnecessary. Vanadium(V) was the most active of the metals at all values of pH and the only metal to accelerate the oxidation of ferrocytochrome c at pH 2.6. Understanding of the range of biological actions of vanadium will not be complete without a knowledge of its redox reactivity within the components of biological systems.

Adenosine Diphosphate↗
PubMedDate not supplied

Easing the pain.

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Bandages↗