A macroscopic approach for stress-driven anisotropic growth in bioengineered soft tissues.

The simulation of growth processes within soft biological tissues is of utmost importance for many applications in the medical sector. Within this contribution, we propose a new macroscopic approach for modelling stress-driven volumetric growth occurring in soft tissues. Instead of using the standard approach of a-priori defining the structure of the growth tensor, we postulate the existence of a general growth potential. Such a potential describes all eligible homeostatic stress states that can ultimately be reached as a result of the growth process. Making use of well-established methods from visco-plasticity, the evolution of the growth-related right Cauchy-Green tensor is subsequently defined as a time-dependent associative evolution law with respect to the introduced potential. This approach naturally leads to a formulation that is able to cover both, isotropic and anisotropic growth-related changes in geometry. It furthermore allows the model to flexibly adapt to changing boundary and loading conditions. Besides the theoretical development, we also describe the algorithmic implementation and furthermore compare the newly derived model with a standard formulation of isotropic growth.

First Direct Measurement of (12)C((12)C,n)(23)Mg at Stellar Energies.

Neutrons produced by the carbon fusion reaction (12)C((12)C,n)(23)Mg play an important role in stellar nucleosynthesis. However, past studies have shown large discrepancies between experimental data and theory, leading to an uncertain cross section extrapolation at astrophysical energies. We present the first direct measurement that extends deep into the astrophysical energy range along with a new and improved extrapolation technique based on experimental data from the mirror reaction (12)C((12)C,p)(23)Na. The new reaction rate has been determined with a well-defined uncertainty that exceeds the precision required by astrophysics models. Using our constrained rate, we find that (12)C((12)C,n)(23)Mg is crucial to the production of Na and Al in pop-III pair instability supernovae. It also plays a nonnegligible role in the production of weak s-process elements, as well as in the production of the important galactic γ-ray emitter (60)Fe.

Near-barrier fusion of the 8B + 58Ni proton-halo system.

Fusion cross sections were measured for the exotic proton-halo nucleus 8B incident on a 58Ni target at several energies near the Coulomb barrier. This is the first experiment to report on the fusion of a proton-halo nucleus. The resulting excitation function shows a striking enhancement with respect to expectations for normal projectiles. Evidence is presented that the sum of the fusion and breakup yields saturates the total reaction cross section.

Doppler shift as a tool for studies of isobaric analog states of neutron-rich nuclei: application to 7He.

We have developed a new technique to study exotic neutron-rich nuclei via their isobaric analog states (IAS). We populate high-isospin states in resonant reactions of radioactive ion beams with protons. Characteristic gamma rays emitted from excited decay products were used to identify the population of the IAS. We show that information on the differential and total cross section for formation of the IAS can be extracted from the energy spectrum of the Doppler-shifted gamma rays. This technique was applied to the study of T=3/2 states in 7Li, which are analogs of states in 7He. The analog of the 7He ground state was clearly observed, whereas the presence of the analog of a narrow 1/2(-) state at 0.6 MeV excitation in 7He reported by M. Meister et al. [Phys. Rev. Lett. 88, 102501 (2002)] was excluded at the 90% confidence level. Evidence is presented for a broad 1/2(-) state at a higher excitation energy in 7He.

Analog states of 7He observed via the 6He(p,n) reaction.

Isobaric analog states of 7He have been investigated by a novel technique involving the observation of the resonant yield of neutrons from the 6He(p,n) reaction in coincidence with gamma rays from the decay of the (0(+),T=1) state in 6Li. The gamma rays provide a clean signature for the isospin-conserving neutron decay of the low-lying isobaric analog resonances. It is conclusively shown that the analog of the recently observed low-lying spin-orbit partner of the 7He ground state does not exist. Evidence is presented that this state lies at much higher energies, in agreement with microscopic calculations.

Revalidation of the isobaric multiplet mass equation.

We have determined the energy of the J(pi) = 1/2(+), T = 3/2 resonance in 32S(p,p) to be E(p) = 3374.7+/-0.8 keV. This disagrees with the previously accepted value of E(p) = 3370+/-1 keV by Abbondanno et al. [Nuovo Cimento 70A, 391 (1970)] and solves a problem raised by recent observations of unexpected deviations from the isobaric multiplet mass equation. This resonance is also important in calibrating the beta-delayed proton spectra from 33Ar and 32Ar, and our findings may modify previous conclusions.

Population studies of the human V kappa A18 gene polymorphism in Caucasians, blacks and Eskimos. New functional alleles and evidence for evolutionary selection of a more restricted antibody repertoire.

Immunoglobulin gene polymorphisms are interesting because they reflect differences in the available antibody repertoire which may affect the susceptibility to specific infections. Until recently, the human V kappa gene, A18, was known as a nonfunctional gene only. In this study, we cloned and sequenced four apparently functional alleles and determined the gene frequencies in three well-defined populations: Danish Caucasians, eastern Greenland Eskimos and Mozambican blacks. The A18b allele that was recently described in Native American Navajos by Atkinson et al. was found in all three populations with gene frequencies of 8%, 45% and 23% in Caucasians, Eskimos and blacks, respectively. Conversely, the frequencies of the nonfunctional A18a allele were 92%, 55% and 57%. Further, three new A18 alleles, c, d, and e were found exclusively in blacks, among whom they had an total frequency of 19%. These data indicate that both the A18a and A18b alleles originated before the diversification of Africans and non-Africans 90,000 years ago, whereas the A18c, A18d and A18e alleles may have a more recent origin. The functionality of the A18b allele was documented by the demonstration of properly rearranged and somatically hypermutated A18b messenger RNA present in the blood lymphocytes of individuals carrying this allele. The expression clearly exceeded that of a known functional V gene, A2, indicating that functional A18 alleles contribute significantly to the available antibody repertoire. In this context, it is surprising that the functional A18b allele apparently has been negatively selected in the Caucasian population, among whom 85% completely lack a functional gene.

Significant effect of high-resolution HLA-DRB1 matching in high-risk corneal transplantation.

The effect of HLA matching in corneal transplantation is still--after numerous of studies--disputable. We investigated the effect of DRB1 matching in high-risk cases with vascularization and/or retransplantation. Only class II antigens were matched because we were unable to obtain donor lymphocytes for HLA typing. Typing was performed on DNA isolated from the ocular tissues up to 24 hr after death. When this study was initiated, DNA-based methods had been developed only for class II typing. The first part of the study concerns 74 cases with at least 3 years of observation fully matched for 17 DRB1 specificities detected using restriction fragment-length polymorphism. This showed an improved long-term graft survival of 72% compared with 45% in a historical control group of 23 comparable cases. In the second part of the study, stored DNA samples from the restriction fragment-length polymorphism-matched donor-recipient pairs were subjected to retyping with a new method based on sequence-specific polymerase chain reaction. It was possible to split DRB1*01, *04, and *11 in 3, 14, and 5 alleles, respectively. The matching was then re-assigned taking all splits into account. This showed that 36 cases had at least one incompatibility, whereas 38 cases were fully compatible. The long-term graft survival rate was 79% in the matched group compared with only 59% in the mismatched group, which is significantly different at P=0.032. This retrospective, but blinded, randomized study is strong evidence for the effect of matching and may give scope for international collaboration to obtain completely matched corneas for this group of patients.

Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein.

Mannan-binding protein (MBP) is a serum lectin participating in the innate immune defense by opsonizing various microorganisms for phagocytosis. Opsonization defect due to MBP deficiency and low levels of the protein can partially be explained by the dominant effect of three different mutations in the structural part of the MBP gene. Large interracial differences in the frequencies of these variants have previously been described, but they cannot explain the large interindividual variation in MBP serum concentration. We describe the existence of additional polymorphisms at positions -550 (H/L variants) and -221 (X/Y variants) in the promoter region of the gene. The promoter haplotypes, HY, LY, and LX, show associations with high, medium, and low levels of MBP serum concentrations, respectively. Moreover, this represents a genetic system with additive effect of haplotypes in which a low producing LX haplotype in the homozygous state down-regulates the basal expression of MBP as effectively as a single structural variant. Populations of pure Eskimos, Caucasoids, and black Africans show marked interethnic differences in the frequencies of promoter haplotypes regulating the expression of the normal peptide, with the HY haplotype frequency varying from 0.83 in Eskimos via 0.33 in Caucasoids to 0.08 in Africans. The LY haplotype frequency varies from 0.04 in Eskimos via 0.39 in Caucasoids to 0.23 in Africans. The LX haplotype frequency varies from 0.03 in Eskimos via 0.24 in Caucasoids to 0.23 in Africans. The effect of the promoter variants can explain almost all of the ethnic differences not explainable by the structural variants alone.

Antigenic characteristics and cDNA sequences of HLA-B73.

The cDNA sequence and serological data for HLA-B73 are reported. Anti-B73 sera are found relatively frequently, considering the rarity of the antigen. It was noted early that in some cases the antibodies in sera of multiparous women did not react with the eliciting cells (fathers) and thus all behaved as a naturally occurring antibody. We report on 18 B73 antisera found during the screening of 55,000 Danish sera. Only one of the 17 stimulators typed also had the B73 tissue type. Ten of the stimulators had antigens from the B7 CREG (B7, B22, B27, B42, B67, B73), whereas none of the responders had such tissue types. In seven cases the serum was not able to react with the stimulator's lymphocytes in a cytotoxicity assay and in four cases the stimulator lymphocytes could not deplete the anti-B73 activity from the serum in absorption experiments. The cDNA of B73 was expressed correctly in COS cells and was recognized on the cell surface by a monospecific serum. The alpha 1 alpha 2 domains of B73 are most similar to those of the HLA-B22 family. Interestingly, the alpha 3 and transmembrane domains of HLA-B73 are not standard human domains, but are most similar to the corresponding domains of some gorilla and chimpanzee HLA-B genes.

Cancer risk after renal transplantation in the Nordic countries, 1964-1986.

The theory that cancer may arise under conditions of reduced immune capacity is supported by observations of humans with immune deficiencies such as occur following organ transplants. However, no study on humans has been done in which the reference population was the same as that in which the cancer cases arose and in which there was a sufficiently long period of follow-up. Information on 5,692 Nordic recipients of renal transplants in 1964-1982 was linked with the national cancer registries (1964-1986) and population registries. Person-years at risk were calculated from the date of first transplantation until death or the end of the study period and were multiplied by the appropriate age- and calender-specific incidence rates to obtain the expected numbers of cancers. Standardized incidence ratios (SIR) were calculated after stratification by a number of recorded variables. Altogether, 32,392 person-years were accrued, and 471 cancers occurred, yielding overall SIR of 4.6 (95% CI, 4.0 to 5.2) for males and 4.5 (95% CI, 4.0 to 5.2) for females. Significant overall 2- to 5-fold excess risks in both sexes were seen for cancers of the colon, larynx, lung and bladder, and in men also for cancers of the prostate and testis. Notably high risks, 10-fold to 30-fold above expectation, were associated with cancers of the lip, skin (non-melanoma), kidney and endocrine glands, also with non-Hodgkin's lymphoma, and in women also with cancers of the cervix and vulva-vagina. Among a number of donor and recipient variables studied, including tissue types and compatibility (ABO, HLA, DR), age below 45 years at the time of transplantation was the most important determinant for increased risk at most sites. Kidney transplantation increases the risk of cancer in the short and in the long term, consistent with the theory that an impaired immune system allows carcinogenic factors to act. The tumor risk is small in comparison with the benefits of transplants, but patients should be followed up for signs of cancer.

Chiropractic scope of practice: what the law allows--update 1993.

OBJECTIVE: To determine on a state by state, province by province basis what diagnostic and treatment procedures are allowed by statute in the various practice acts. DESIGN: A survey administered by mail. SUBJECTS: All state and provincial licensing boards. RESULTS: The response rate to the survey was 90%. More than 50% of the responding licensing boards allow chiropractors to order or perform clinical lab procedures, conduct components of a routine physical exam, examine the female pelvis, perform rectal exams, and conduct electromyographic, electrocardiographic and nerve conduction studies. More than 80% can perform a variety of X-ray procedures, use thermography, administer a vascularizer (Doppler) and order CT or MRI studies. More than 90% of the respondents permit chiropractors to employ some form of physiotherapy, adjust soft tissue or extremities, supplement with vitamins and conduct impairment ratings. CONCLUSIONS: These findings demonstrate that the chiropractic profession offers a broad range of diagnostic and treatment procedures.

Cadaveric organ donation in Scandinavia, 1992.

In countries with active organ transplant programs and wide acceptance criteria for transplant recipients, such as the four Scandinavian countries, the need for organ grafts has outgrown the supply of cadaveric organs. We cannot expect to attain the maximum number of cadaveric donors every year and in every procurement area because the number of donors depends not only on the efficacy of the procurement program but also on the age of the population, incidence of road traffic accidents, treatment facilities, and other factors. The maximum numbers are set as a goal to strive for, however, Countries that participate in an exchange of cadaver organs to obtain well-matched kidneys for uremic patients and life-saving grafts at a suitable time for heart, lung, and liver recipients, must all have the same approximate number of cadaver donors. Major imbalances in the number of donors and also in the number of patients waiting for a transplantation may result in the supply of organ allografts for one country or region being met by the population of another region. With confidence we are looking forward to the impact of intensified public information and education of hospital personnel on the gap between demand and supply of organ allografts.

[Scandiatransplant]. / Scandiatransplant.

Scandiatransplant is an organ exchange organisation serving a population of about 23 million inhabitants in the five Nordic countries, Iceland, Finland, Sweden, Norway and Denmark. Scandiatransplant maintains a central waiting list for Scandinavian patients scheduled for cadaver organ transplantation. Since its establishment in 1969, more than 13,000 cadaver renal transplants have been performed, and the numbers of liver, heart and lung transplantations are steadily increasing.

A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding protein.

Human mannan-binding protein (MBP) is a serum lectin participating in the innate immune defence. Low MBP concentrations are explained by the dominant action of a point mutation at codon 54 of the MBP gene in Eskimos, partially in Caucasians, but not in Africans. A previously described point mutation at codon 57 was very frequent (0.23) in East Africans, low in Caucasians (0.02), and absent in Eskimos. The African population only conformed to Hardy-Weinberg expectation when assuming the existence of an unknown allele, which was subsequently found as a point mutation at codon 52. This allele appeared with a relatively high frequency (0.05) in both Africans and Caucasians, but was absent in Eskimos. Hardy-Weinberg equilibrium is now seen in the investigated ethnic groups. All cases of MBP deficiency may be explained by these three variants.

Diallelic polymorphism may explain variations of the blood concentration of mannan-binding protein in Eskimos, but not in black Africans.

Mannan-binding protein (MBP) is a lectin which, upon binding to certain carbohydrates, activates the classical pathway of complement without the involvement of antibody or C1q. Deficiency of the MBP is associated with an opsonic defect and recurrent infections during early life. An amino acid substitution in the exon 1 at codon 54 in the MBP gene (GGC [glycine] to GAC [aspartic acid]) has been shown to be closely associated with low MBP concentration in Caucasoids. The gene frequency of the mutant allele in this population has been estimated at 0.13. In the study described here, we investigated the association between the mutant allele and MBP protein concentration in Eskimos from East-Greenland and black Africans from the Baringo District in Kenya. The frequency of the GAC allele was identical in Eskimos and Caucasoids (0.13). No overlap with regard to MBP concentration between the genotypes was found in the Eskimos. In contrast, the Africans revealed a low frequency of the GAC allele (0.009). However, the median MBP protein concentration was approximately 5 times lower among the Africans than the Eskimos. In 12.6% of the Africans and in 2.5% of the Eskimos, MBP was undetectable. Thus, MBP deficiency is the most frequent immunodeficiency so far described. The high prevalence of MBP deficiency among healthy individuals indicates that MBP deficiency also confers some selective advantages. We advance the hypothesis that MBP deficiency is maintained in populations because MBP deficiency decreases the infectivity of some intracellular micro-organisms which are dependent on opsonization.