ALBERT

Description: A simple conceptual model is proposed concerning how leaf area efficiency (stemwood growth per unit leaf area) changes with leaf area for trees within a stand. Greater leaf area is generally associated with (i) improved light environment due to greater height and (ii) a lower ratio of photosynthetic to nonphotosynthetic tissue. Greater height and improved light environment result in higher photosynthetic production, which should increase leaf area efficiency. A lower ratio of photosynthetic to nonphotosynthetic tissue suggests that the ratio of respiration to photosynthesis increases, which should decrease leaf area efficiency. In relatively small trees, the influence of increased height (associated with greater leaf area) should more than offset the influence of the increased respiration:photosynthesis ratio; as a result, leaf area efficiency should increase with leaf area. In large trees, further increases in leaf area are associated with minimal increases in height, and leaf area efficiency should decline as the respiration:photosynthesis ratio increases. Predictions from this conceptual model were examined with data from stands of subalpine fir (Abieslasiocarpa (Hook.) Nutt.).

Description: It is commonly assumed that mature forest stands with closed canopies support constant amounts (weight or area) of foliage, independent of stand density. For stand leaf area to be constant, mean leaf area must be plastic with respect to density. We examined the relationship between density and both leaf area index and mean leaf area for two contrasting tree species, lodgepole pine (Pinuscontorta var. latifolia Engelm.) and subalpine fir (Abieslasiocarpa (Hook.) Nutt.). In lodgepole pine, leaf area index tended to be constant over a wide range of absolute and relative densities, but in subalpine fir, leaf area index increased with density. Consistent with these results, mean leaf area of lodgepole pine was more plastic with respect to density than mean leaf area of subalpine fir. The presumption of stable leaf area index independent of stand density, therefore, may not be as general as usually assumed owing to differential responses of mean leaf area to density. Differences in plasticity between the two species were attributed to differences in relative shade tolerance and the effect of shade on competitive interactions at high densities.

Description: Seedlings of 64 open-pollinated slash pine (Pinuselliottii var. elliottii Engelm.) families were grown from seed to 24 weeks of age in raised outdoor boxes under two nitrogen treatments (5 and 50 ppm). Twenty-six shoot characteristics were measured, of which the most promising 12 were evaluated for use in a multitrait selection index to predict parental breeding values of 5- and 15-year field volume growth. Genetic parameters were estimated for each seedling trait and shoot components were analyzed for their contribution to total height increment. Number of stem units was the most important contributor to total height in both nitrogen treatments. Heritabilities were generally higher for all traits in the high-nitrogen regime (h2 = 0.13–0.66). All traits displayed moderate to high genetic stability across both treatments (type B genetic correlations = 0.64–1.32). Total number of stem units (low-nitrogen treatment), free growth stem unit number (low-nitrogen treatment), and caliper (high-nitrogen treatment) exhibited the strongest genophenotypic correlations with 15-year volume (rjm = 0.35–0.39). All possible combinations of two- and three-trait indices were calculated to derive correlations between predicted genetic values and true genetic values (corr (g,ĝ)). Cyclic growth length (high-nitrogen treatment), total height (low-nitrogen treatment), and free growth stem units (low-nitrogen treatment) combined to form the most precise three trait index for predicting 15-year volume growth (corr(g,ĝ) = 0.56). Total number of stem units, total flushes, and total mean stem unit length in the low-nitrogen treatment along with cyclic number of stem units and caliper in the high-nitrogen treatment were also determined to be of potential use in a multitrait selection index based on their heritabilities, juvenile–mature correlations, and performance in two- and three-trait indices.

Description: Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation 〉 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.

Description: Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease 〉 or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.

Description: Idiotypic determinants on neoplastic B cells could provide tumor antigens for vaccination of patients with B-cell tumors. Because this approach requires an individual vaccine for each patient, simple methods for obtaining idiotypic antigen are desirable. Using polymerase chain reaction (PCR) with family-based V-gene and J-region primers, the variable region genes of heavy and light chains (VH and VL) of Ig have been obtained from biopsy material from 13 patients with B-cell tumors. In each case, analysis of random clones derived from the PCR product showed repeated, clonally-related sequences, whereas normal lymphoid tissue generated no repeated sequences. In 3/3 cases, the repeated sequences were found to be the same as those in a tumor-derived hybridoma. Mutational patterns in the V-genes differed among the tumors, with follicular lymphoma tending to be more highly mutated. The individual VH and VL sequences have been assembled with a flexible linker sequence to encode single-chain Fv (scFv). The scFv sequences can be cloned into bacterial expression vectors to produce protein, or into vectors suitable for direct vaccination using naked DNA. In a model system, expressed scFv protein retained all idiotypic determinants defined by a panel of five anti-idiotypic monoclonal antibodies (MoAbs). Similarly, expressed scFv proteins from two patients were shown to react with anti-idiotypic antibodies. This approach allows production of potential vaccines from surgical biopsies within 2 to 3 weeks.

Description: Current intensive chemotherapy for acute nonlymphoblastic leukemia (ANLL) results in a complete remission in the majority of patients. Unfortunately, the duration of remission is short and most of the patients will experience a relapse of their underlying disease. Autologous bone marrow (BM) transplantation is being explored as a treatment modality designed to improve relapse-free survival. We have conducted a phase II trial exploring the combination of busulfan (16 mg/kg) and etoposide (60 mg/kg) in an attempt to improve antitumor efficacy using this novel preparative regimen. To date, 50 patients (48 with ANLL and 2 patients with biphenotypic acute leukemia) have been treated. The first 20 patients received unmanipulated BM; 28 patients subsequently received 4-hydroperoxycyclophosphamide (4–HC) (60 micrograms/mL)-purged bone marrow, and 2 patients with biphenotypic acute leukemia received both 4–HC (60 micrograms/mL) and etoposide (5 micrograms/mL)-purged BM. Thirty-four patients were in first complete remission (CR1), 12 patients in second complete remission (CR2), and 4 patients in relapse. The median time from first complete remission to BM harvest was 3 months (range, 0.8 to 4) compared with median time of 2 months (range, 1.5 to 5.0) for patients in second complete remission. The median time from harvest to transplant was 1 month for both groups (range, 0.4 to 36). A median of 0.7 x 10(8) (range, 0.2 to 1.4) mononuclear cells were infused. Patients achieved an absolute neutrophil count of 〉 or = 500/microL at a median of 26 days (range, 13 to 96), an untransfused platelet count 〉 or = 20,000/microL at a median of 56 days (range, 15 to 278) and a sustained hematocrit 〉 or = 30% at a median of 50 days (range, 19 to 116). Twenty-six patients are alive and in continued CR. Follow-up of the surviving patients ranged from 6 months to 66 months with a median follow-up of 31 months. Patients receiving purged BM have an actuarial disease-free survival of 57% with a relapse rate of 28% compared with patients receiving unpurged BM whose actuarial disease-free survival is 32% with a relapse rate of 62% (P = .06 for relapse rate). The most significant extramedullary toxicities for this regimen are hepatic and cutaneous (including mucositis). The BU/VP-16 regimen is associated with a significant proportion of patients surviving disease free, especially in the group receiving purged BM. Whether this regimen offers a substantial improvement in disease-free survival over currently used regimens will require a prospective randomized study.

Description: Clinical manifestations of arterial and venous thrombosis in a family with protein C deficiency was associated with two mutations in the light chain of protein C: Glu20--〉Ala and Val34--〉Met. Further studies showed that the mutation Glu20--〉Ala which eliminated a gamma- carboxylation site was exclusively responsible for the anticoagulant defect of activated protein C (APC). Membrane-bound human factor Va is inactivated by APC after two sequential cleavages of the heavy chain at Arg506 and Arg306. Human factor Va inactivation by human recombinant APC (rAPC) and a mutant molecule with an alanine instead of a glutamic acid at position 20 (rAPC(gamma 20A)) was investigated in the presence and absence of phospholipid vesicles. During a 2-hour incubation period of the cofactor with either rAPC or rAPC(gamma 20A). In the absence of a membrane surface, factor Va is cleaved quantitatively at Arg506 and retains approximately 60% of its initial cofactor activity. After a 2- hour incubation period with rAPC membrane-bound factor Va has no cofactor activity, whereas in the presence of a membrane surface and rAPC(gamma 20A) factor Va retains 60% of its initial cofactor activity. The completed loss in factor Va cofactor activity upon incubation of the membrane-bound cofactor with phospholipid vesicles and rAPC is associated with cleavages at Arg506 and Arg306, whereas membrane-bound factor Va cleavage at Arg306 by rAPC(gamma 20A) is impaired, resulting in a cofactor that is cleaved at Arg506. Slow cleavage at Arg306 occurs when membrane-bound factor Va is incubated with rAPC(gamma 20A) and only small amounts of fragments of M(r) = 45,000 and 30,000 are noticed. Our data show that the genetic defect which leads to the absence of a gamma-carboxylation site at Glu20 impairs membrane binding of human APC, which in turn is required for cleavage of factor Va at Arg306 and inactivation of the cofactor. The consequence of impaired membrane-dependent cleavage at Arg306 is manifested in vivo by venous and arterial thrombosis.