Diagnostic and prognostic utility of the serum free light chain assay in patients with AL amyloidosis.

BACKGROUND: Organ dysfunction in AL amyloidosis is related to the production and deposition of amyloidogenic monoclonal light chains. These pathological light chains can now be quantified using the recently developed serum free light chain assay. METHODS: We retrospectively reviewed 31 patients with AL amyloidosis to determine the frequency of abnormal free light chain assay results at diagnosis and whether changes in the serum free light chain assay predict outcome after therapy. RESULTS: An abnormal free light chain assay was found in 30 of 31 patients (97%) at the time of diagnosis. In the subset of our patients who received treatment for AL amyloidosis, a >50% reduction of the pathological free light chain following treatment was shown to predict improved overall survival. In our series of analyses, achievement of greater magnitudes of reduction of the free light chain result did not appear to provide additional prognostic information, nor did the baseline free light chain result predict outcome. CONCLUSION: Our findings support the use of the free light chain assay in the diagnostic work-up of patients with suspected AL amyloidosis, and also as a sensitive biomarker of response to therapy.

Effect of gemtuzumab ozogamicin on acute myeloid leukemia blast cells in vitro, as a single agent and combined with other cytotoxic cells.

The effect of gemtuzumab ozogamicin (GO) alone, or combined with low-dose cytarabine or etoposide, on the proliferation of acute myeloid leukaemia blast cells in vitro was investigated. GO alone induced a dose-dependent inhibition of proliferation although an increase in apoptosis was only seen in a minority of patients. A correlation was found between PgP function and GO sensitivity but not between CD33 or PgP expression and GO. Combinations of GO with varying concentrations of cytarabine or etoposide were additive in inhibiting proliferation, reducing cell viability and increasing apoptosis.

The mathematical basis of sexual attraction.

Computer programs have been written to study the dynamic interaction in humans between environmental mutagenesis, the genomic load of deleterious mutations and the probability of zygote survival. The human genome is complex and highly redundant and as a consequence deleterious mutations accumulate. The computer programs are based on a model of the human genome in which deleterious mutations interact synergistically causing impaired performance in individual systems and this leads to a positive correlation between the total number of deleterious mutations in the genome and impaired performance across the whole spectrum of biological capability. This includes performance in intellectual tasks, sporting ability, the ability to fight disease and preserve health and the development of a symmetrical physical form. Sexual reproduction distributes deleterious mutations unequally amongst zygotes and the model predicts that zygote survival will correlate negatively with zygote mutational load. The computer simulation shows that rising environmental mutagenesis will lead to a rise in the human genomic mutational load and to decreased zygote survival, although the full effect would take several generations. If this occurred the health of future generations would suffer and methods to monitor environmental mutagenesis are required. The model also shows that a marked rise in environmental mutagenesis would lead to species extinction if mate choice were random, i.e., unrelated to the genomic mutational load. The biological imperfections caused by mutations, however, in health, intelligence and physical symmetry are all, to varying degrees, related to sexual attraction. The model shows that if mates are chosen in response to sexual attraction the species can be maintained in the presence of high environmental mutagenesis. A polygamous pattern in which females mate with a minority of males has the most marked effect in reducing the number of deleterious mutations in the next generation. The model also shows that as environmental mutagenesis falls the number of eligible males would increase and a species would change from a polygamous to a monogamous pattern of mating. These results imply that we are not attracted by good genes, but by a lack of bad genes. Sexual attraction is a force which counteracts genomic degradation.

Glycemic index, cardiovascular disease, and obesity.

Although Americans have decreased the percent of energy they consume from fat, obesity and obesity-related comorbidities have progressively increased. Less attention has been paid to the role of carbohydrates, especially carbohydrate source, in these metabolic diseases. However, recent epidemiologic studies demonstrate consistently higher rates of cardiovascular disease and type II diabetes in individuals deriving a greater percentage of energy from refined grains and simple carbohydrates than from whole grains. Differences in the metabolic response to carbohydrates can be classified by glycemic index (GI), the blood glucose response to a given food compared with a standard (typically white bread or glucose). Classification of carbohydrates as "simple" or "complex" is of little use in predicting GI, because GI is influenced by starch structure (amylose versus amylopectin), fiber content, food processing, physical structure of the food, and other macronutrients in the meal. Low-GI diets have been reported to lower postprandial glucose and insulin responses, improve lipid profiles, and increase insulin sensitivity. Moreover, high-GI diets stimulate de novo lipogenesis and result in increased adipocyte size, whereas low-GI diets have been reported to inhibit these responses. Thus, the GI of dietary carbohydrates appears to play an important role in the metabolic fate of carbohydrates and, consequently, may significantly affect the risk of cardiovascular disease, diabetes, and obesity.

Acute Epstein-Barr virus infection complicated by severe thrombocytopenia.

We describe one patient with acute Epstein-Barr virus (EBV) infection associated with severe thrombocytopenia and review 36 additional cases reported in the literature. Complications of EBV infection due to severe thrombocytopenia occurred in 10 (27.0%) of 37 patients, and 2 (5.4%) of 37 patients died. Although acute EBV infections are generally benign and self-limiting, thrombocytopenia, a potentially serious complication, should not be overlooked.

Introgression of Elymus trachycaulus chromatin into common wheat.

A number of wheat-Elymus trachycaulus (2n = 4x = 28, genomically StStHtHt) chromosome addition, substitution, and translocation lines were isolated from the derivatives of an E. trachycaulus x wheat hybrid. Eighteen out of a total of 28 chromosome arms of E. trachycaulus were recovered in the addition lines. The genomic affinity of individual E. trachycaulus chromosomes was analysed by comparative chromosome banding and in situ hybridization using genome-specific repetitive DNA sequences as probes. The homoeology of the E. trachycaulus chromosomes added to wheat was determined by storage protein, isozyme, and restriction fragment length polymorphism analysis. Alloplasmic wheat-E. trachycaulus chromosome additions were isolated which only involved chromosome 1Ht and 1St that carry fertility restoration gene Rf-Ht1 and Rf-St1, respectively. Based on the results of production and characterization of a wheat-E. trachycaulus 5Ht(5B) substitution line, it is likely that some wheat chromosomes can be well compensated genetically by E. trachycaulus chromosomes. Several spontaneous wheat-E. trachycaulus chromosome translocation lines were detected. All the translocation lines involved either 1Ht or 1St. To estimate the potential of recombination between wheat and E. trachycaulus chromosomes, a backcross population derived from a plant which was double monosomic for chromosomes 7A and 7AL.7AS-1StS and a ph1b gene was developed. The plants from this population were analysed for 1St-specific genetic markers and no recombinant was recovered.

Medial column instability in the Lisfranc's fracture dislocation injury.

The authors present a descriptive report on medial column instability with Lisfranc's fracture dislocation injuries. Subtleties of recognizing and diagnosing this injury are emphasized within a literature review. Eleven cases of tarsometatarsal injuries were reviewed over an 18-month period. Eight cases involved acute injuries, while three cases presented as delayed or misdiagnosed injuries. Due to the instability of the medial column, failure in reduction methods for this injury consistently occurred. With proper sequential placement of Kirschner wires, reduction failure is minimized. A fixation method for medial column Lisfranc's injuries with Kirschner wire placement is described.

Classifications of radiopaque lesions of the tendo Achillis.

The authors present an anatomically-based classification to identify radiopaque lesions of the tendo Achillis. Numerous etiologic and pathologic processes are responsible for the formation of radiopaque lesions found in this tendon. The anatomical location and morphologic appearance of the lesions are represented in this classification system to better acquaint the physician with reported etiologic causes. Treatment based upon classification sites are discussed to complete this historical presentation.

Identification of Intracellular Carbonic Anhydrase in Chlamydomonas reinhardtii which Is Distinct from the Periplasmic Form of the Enzyme.

A physiologically significant level of intracellular carbonic anhydrase has been identified in Chlamydomonas reinhardtii after lysis of the cell wall-less mutant, cw15, and two intracellular polypeptides have been identified which bind to anti-carbonic anhydrase antisera. The susceptibility of the intracellular activity to sulfonamide carbonic anhydrase inhibitors is more than three orders-of-magnitude less than that of the periplasmic enzyme, indicating that the intracellular activity was distinct from the periplasmic from of the enzyme. When electrophoretically separated cell extracts or chloroplast stromal fractions were probed with either anti-C. reinhardtii periplasmic carbonic anhydrase antiserum or anti-spinach carbonic anhydrase antiserum, immunoreactive polypeptides of 45 kilodaltons and 110 kilodaltons were observed with both antisera. The strongly immunoreactive 37 kilodalton polypeptide due to the periplasmic carbonic anhydrase was also observed in lysed cells, but neither the 37 kilodalton nor the 110 kilodalton polypeptides were present in the chloroplast stromal fraction. These studies have identified intracellular carbonic anhydrase activity, and putative intracellular carbonic anhydrase polypeptides in Chlamydomonas reinhardtii represented by a 45 kilodalton polypeptide in the chloroplast and a 110 kilodalton form probably in the cytoplasm, which may be associated with an intracellular inorganic carbon concentrating system.