Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy.

In both human and murine systems, we have developed an adoptive cellular therapy platform against medulloblastoma and glioblastoma that uses dendritic cells pulsed with a tumor RNA transcriptome to expand polyclonal tumor-reactive T cells against a plurality of antigens within heterogeneous brain tumors. We demonstrate that peripheral TCR Vß repertoire analysis after adoptive cellular therapy reveals that effective response to adoptive cellular therapy is concordant with massive in vivo expansion and persistence of tumor-specific T cell clones within the peripheral blood. In preclinical models of medulloblastoma and glioblastoma, and in a patient with relapsed medulloblastoma receiving adoptive cellular therapy, an early and massive expansion of tumor-reactive lymphocytes, coupled with prolonged persistence in the peripheral blood, is observed during effective therapeutic response to immunotherapy treatment.

Investigation of Feshbach resonances in ultracold 40K spin mixtures.

Magnetically tunable Feshbach resonances are an indispensable tool for experiments with atomic quantum gases. We report on 37 thus far unpublished Feshbach resonances and four further probable Feshbach resonances in spin mixtures of ultracold fermionic 40K with temperatures well below 100 nK. In particular, we locate a broad resonance at B = 389.7G with a magnetic width of 26.7 G. Here 1 G = 10-4 T. Furthermore, by exciting low-energy spin waves, we demonstrate a means to precisely determine the zero crossing of the scattering length for this broad Feshbach resonance. Our findings allow for further tunability in experiments with ultracold 40K quantum gases.

Giant spin oscillations in an ultracold Fermi sea.

Collective behavior in many-body systems is the origin of many fascinating phenomena in nature, ranging from the formation of clouds to magnetic properties of solids. We report on the observation of collective spin dynamics in an ultracold Fermi sea with large spin. As a key result, we observed long-lived and large-amplitude coherent spin oscillations driven by local spin interactions. At ultralow temperatures, Pauli blocking stabilizes the collective behavior, and the Fermi sea behaves as a single entity in spin space. With increasing temperature, we observed a stronger damping associated with particle-hole excitations. Unexpectedly, we found a high-density regime where excited spin configurations are collisionally stabilized. Our results reveal the intriguing interplay between microscopic processes either stimulating or suppressing collective effects in a fermionic many-body system.

Engineering spin waves in a high-spin ultracold Fermi gas.

We report on the detailed study of multicomponent spin waves in an s=3/2 Fermi gas where the high spin leads to novel tensorial degrees of freedom compared to s=1/2 systems. The excitations of a spin-nematic state are investigated from the linear to the nonlinear regime, where the tensorial character is particularly pronounced. By tuning the initial state we engineer the tensorial spin-wave character, such that the magnitude and the sign of the counterflow spin currents are effectively controlled. A comparison of our data with numerical and analytical results shows good agreement.

Intrinsic photoconductivity of ultracold fermions in optical lattices.

We report on the experimental observation of an analog to a persistent alternating photocurrent in an ultracold gas of fermionic atoms in an optical lattice. The dynamics is induced and sustained by an external harmonic confinement. While particles in the excited band exhibit long-lived oscillations with a momentum-dependent frequency, a strikingly different behavior is observed for holes in the lowest band. An initial fast collapse is followed by subsequent periodic revivals. Both observations are fully explained by mapping the system onto a nonlinear pendulum.

Multiband spectroscopy of ultracold fermions: observation of reduced tunneling in attractive Bose-Fermi mixtures.

We perform a detailed experimental study of the band excitations and tunneling properties of ultracold fermions in optical lattices. Employing a novel multiband spectroscopy for fermionic atoms, we can measure the full band structure and tunneling energy with high accuracy. In an attractive Bose-Fermi mixture we observe a significant reduction of the fermionic tunneling energy, which depends on the relative atom numbers. We attribute this to an interaction-induced increase of the lattice depth due to the self-trapping of the atoms.

Diversity in mechanisms of substrate oxidation by cytochrome P450 2D6. Lack of an allosteric role of NADPH-cytochrome P450 reductase in catalytic regioselectivity.

Cytochrome P450 (P450) 2D6 was first identified as the polymorphic human debrisoquine hydroxylase and subsequently shown to catalyze the oxidation of a variety of drugs containing a basic nitrogen. Differences in the regioselectivity of oxidation products formed in systems containing NADPH-P450 reductase/NADPH and the model oxidant cumene hydroperoxide have been proposed by others to be due to an allosteric influence of the reductase on P450 2D6 (Modi, S., Gilham, D. E., Sutcliffe, M. J., Lian, L.-Y., Primrose, W. U., Wolf, C. R., and Roberts, G. C. K. (1997) Biochemistry 36, 4461-4470). We examined the differences in the formation of oxidation products of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, metoprolol, and bufuralol between reductase-, cumene hydroperoxide-, and iodosylbenzene-supported systems. Catalytic regioselectivity was not influenced by the presence of the reductase in any of the systems supported by model oxidants, ruling out allosteric influences. The presence of the reductase had little effect on the affinity of P450 2D6 for any of these three substrates. The addition of the reaction remnants of the model oxidants (cumyl alcohol and iodobenzene) to the reductase-supported system did not affect reaction patterns, arguing against steric influences of these products on catalytic regioselectivity. Label from H(2)18O was quantitatively incorporated into 1'-hydroxybufuralol in the iodosylbenzene- but not in the reductase- or cumene hydroperoxide-supported reactions. We conclude that the P450 systems utilizing NADPH-P450 reductase, cumene hydroperoxide, and iodosylbenzene use similar but distinct chemical mechanisms. These differences are the basis for the variable product distributions, not an allosteric influence of the reductase.

Multi-center clinical comparison of combination anorganic bovine-derived hydroxyapatite matrix (ABM)/cell binding peptide (P-15) and ABM in human periodontal osseous defects. 6-month results.

BACKGROUND: Intraosseous periodontal defects present a particular treatment problem. New bone replacement grafts offer promise for improved results. METHODS: The role of a synthetic cell-binding peptide (P-15), combined with anorganic [corrected] bovine-derived hydroxyapatite bone matrix (ABM), was compared to ABM alone in human periodontal osseous defects in a controlled, monitored, multi-center trial. Following appropriate initial preparation procedures, flap surgery with defect and root debridement was performed. Two osseous defects per patient were treated randomly with each procedure after surgical preparation. Appropriate periodontal maintenance schedules were followed, and at 6 to 7 months, re-entry flap surgery was performed for documentation and finalization of treatment. RESULTS: T test and Mann-Whitney U analyses of patient mean values from 33 patients revealed that the combination ABM/P-15 grafts demonstrated significantly better mean defect fill of 2.9 +/- 1.2 mm (72.9%) versus a mean defect fill of 2.2 +/- 1.4 mm (50.67%) for defects treated with ABM (P<0.05). Other hard tissue findings showed similar clinically superior results with the use of ABM/P-15. Relative defect fill results showed 81% positive (50% to 100% defect fill) responses with ABM/P-15 and 67% positive responses with ABM. There were 3.5 times as many optimal results (> or = 90% defect fill) with ABM/P-15 and twice as many failures (minimal response) with ABM. Soft tissue findings showed no significant differences between treatments. CONCLUSIONS: These results suggest that the use of the P-15 synthetic cell-binding peptide combined with ABM yields better clinical results than the ABM alone in intrabony periodontal defects.

Fatigue properties of hydroxyapatite-coated dental implants after exposure to a periodontal pathogen.

We studied the fatigue properties of rods (4 mm diameter) of hydroxyapatite-coated, titanium alloy implant material after it was exposed to a periodontal pathogen, Actinobacillus actinomycetemcomitans (Aa). We varied the crystallinity of the hydroxyapatite (HA) coating in these rods to the levels of, 60.5%, 52.8%, and 47.8%. Each rod was first inoculated with Aa in the log phase of its growth cycle. After 48 h, we counted the adhered cells. We measured the dissolution of HA coating due to bacterial exposure alone by determining the calcium and phosphate concentrations in the bacterial growth media. Once the adherent bacteria were removed from these rods, we subjected them to 5 million cycles of fatigue testing after immersion in Lactated Ringer's solution. We then determined the calcium and phosphate concentrations in the fatigue media. We found additional coating loss after fatiguing of the samples. This coating loss was a cumulative effect of bacterial exposure and fatigue loading of the hydroxyapatite-coated dental implant alloy. The lower crystallinity sample showed a higher loss of coating within the range of crystallinity studied here. The HA coating in implants during clinical use may undergo such changes, because they are exposed to the same bacteria.

Human histologic and histomorphometric analysis comparing OsteoGraf/N with PepGen P-15 in the maxillary sinus elevation procedure: a case report.

The use of the anorganic bovine bone mineral OsteoGraf/N combined with demineralized freeze-dried bone allograft has received widespread use in sinus elevations. This composite graft material has proven to be suitable, predictable, and successful for the placement and integration of endosseous implants in the edentulous, atrophic maxilla. In this case study, the current materials and accepted methodology were compared with the latest tissue-engineered bone replacement graft material, PepGen P-15. PepGen P-15 is a combination of OsteoGraf/N and a synthetic peptide (P-15) that mimics the cell-binding domain of Type-I collagen responsible for cell migration, differentiation, and proliferation. The radiographic, histologic, and histomorphometric evaluations of the sinus grafted with PepGen P-15 showed enhanced bone formation within a shorter time interval compared with the composite graft material of OsteoGraf/N and demineralized freeze-dried bone allograft.

Multi-center clinical evaluation of combination anorganic bovine-derived hydroxyapatite matrix (ABM)/cell binding peptide (P-15) as a bone replacement graft material in human periodontal osseous defects. 6-month results.

A synthetic cell-binding peptide (P-15) combined with anorganic bovine-derived hydroxyapatite bone matrix (ABM) was compared to demineralized freeze-dried bone allograft (DFDBA) and open flap debridement (DEBR) in human periodontal osseous defects in a controlled, monitored, multi-center trial. Following appropriate initial preparation procedures, flap surgery with defect and root debridement was performed. Three osseous defects per patient were treated randomly with one of three procedures after surgical preparation. Appropriate periodontal maintenance schedules were followed, and at 6 to 7 months re-entry flap surgery was performed for documentation and finalization of treatment. Analysis of variation (ANOVA) and t test analyses of patient mean values from 31 patients revealed that the combination ABM/P-15 grafts demonstrated significantly better mean defect fill of 2.8 +/- 1.2 mm (72.3%) versus a mean defect fill of 2.0 +/- 1.4 mm (51.4%) for defects treated with DFDBA (P <0.05) and a mean defect fill of 1.5 +/- 1.3 mm (40.3%) (P <0.05) for defects treated with DEBR. Other hard tissue findings showed similar clinically superior results with the use of ABM/P-15. Relative defect fill results showed 87% positive (50% to 100% defect fill) responses with ABM/P-15, 58% positive responses with DFDBA, and 41% positive responses with DEBR. There were 8 to 9 times more failures (minimal response) with DFDBA and DEBR (26% to 29% frequency) than with ABM/P-15. Soft tissue findings showed no significant differences among treatments except for greater clinical attachment level gain with ABM/P-15 compared to DEBR. These results suggest that the use of the P-15 synthetic cell-binding peptide combined with ABM yields better clinical results than either DFDBA or DEBR. Further studies are needed to determine the relative roles of the ABM and/or the P-15 in these improved results.

Long-term retrospective studies on hydroxyapatite coated endosteal and subperiosteal implants.

This article reports a long-term retrospective study on hydroxyapatite-coated implants, which covers more than 6 years of clinical use. The authors discuss not only cylinder implants, but blade and subperiosteal implants as well. This study reveals that, for the time covered, a definite clinical advantage exists to coating implants with hydroxyapatite.

Immediate implantation after extraction of a horizontally fractured maxillary lateral incisor.

When indicated, osseointegrated implant prosthetics may be placed immediately following atraumatic tooth extraction. This article describes the delicate and precise surgical and prosthetic disciplines for an immediate extraction and implant case.