Regioselective functionalization of starch: synthesis and 1H NMR characterization of 6-O-silyl ethers.

A high regioselective 6-O silylation of starch by using thexyldimethylchlorosilane (TDSCl, chlorodimethyl-(2,3-dimethylbut-2-yl)silane) as bulky silylating agent in the reaction system N-methylpyrrolidone (NMP)/ammonia was carried out and investigated. The control of the degree of substitution (DSSi), the control of the regioselectivity, and the control of the reaction pathway are described in detail. After peracetylation of the silyl ethers of starch, the distribution of the silyl and acetyl substituents was characterized not only in the anhydroglucose repeating units (AGU) but also in the nonreducing end groups (NEG) by means of multidimensional 1H NMR techniques. In both cases, the silyl substituents were detected exclusively in the 6-O position, and the acetyl groups in the 2-O and 3-O positions of the AGU and in the 2-O, 3-O, and 4-O positions of the NEG, respectively. The described 6-O-thexyldimethylsilyl (TDS) units are potentially protecting groups of the primary OH position of starches.

[The Dresden Cord Blood Bank. Experiences of the Cord Blood Bank in Dresden, promoted by the German bone Marrow Donor Registry]. / Dresdner Nabelschnurblutbank. Erfahrungen der Nabelschnurblutbank in Dresden, unterstützt durch die Deutsche Knochenmarkspenderdatei.

BACKGROUND: Allogeneic bone marrow and peripheral blood stem cell transplantation is the treatment of choice for a number of malignant hematological diseases, marrow failure syndromes and severe congenital immunodeficiency states. As a new, valuable source of hematopoietic stem cells, cord blood has become increasingly attractive to the medical community. More than 1500 related and unrelated cord blood transplantations have already been performed worldwide. Cord blood can be a particularly good alternative source of stem cells for pediatric patients, if no HLA-identical donor can be found. MATERIAL AND METHODS: In August 1997 the Cord Blood Bank at the University Hospital of Dresden initiated the collection, processing and cryopreservation of placental blood. This Cord Blood bank is promoted by the German bone marrow donor registry DKMS in Tübingen/Germany collaborating with 8 gynecological clinics in Dresden, Bautzen and Erlabrunn. Before cryopreservation, volume reduction of cord blood units is routinely performed by centrifugation and by separation of the buffy coat. RESULTS: As of March 2000, more than 2200 cord blood units have been collected. 60% of the samples had to be discarded because of insufficient quality (low volume and/or cell count, bacterial contamination, positive infectious disease markers). However, more than 800 cord blood units met all quality control criteria and were cryopreserved. CONCLUSION: These data from the Cord Blood Bank at the University Hospital of Dresden are comparable with results from other cord blood banks. Efforts directed toward the cryopreservation and banking of increased numbers of cord blood units are being continued worldwide and should be supported by the general public.

Experiences of the Dresdner Cord Blood Bank, supported by the Deutsche Knochenmarkspenderdatei.

Allogeneic bone marrow and peripheral blood stem cell transplantation is the treatment of choice for some malignant hematologic diseases, marrow failure syndromes, and severe congenital immunodeficiency states. Since Gluckman et al reported in 1988 the first successful human leukocyte antigen (HLA)-matched sibling umbilical cord blood stem cell transplantation, it has been known that cord blood is a valuable source of hematopoietic stem cells. The Cord Blood Bank at the University Hospital of Dresden was founded in 1997 and started collecting, processing, and cryoconserving umbilical cord blood in August 1997. The cord blood bank is supported by the largest German donor registry: Deutsche Knochenmarkspenderdatei (DKMS) in Tubingen, Germany. With the informed consent of the mothers, the collection is performed in collaboration with six hospitals in Dresden, Berlin, and Bautzen. We routinely perform a volume reduction by centrifuging the blood bag and expressing the leukocyte-rich supernatant. Routinely, sterility, total nucleated cells (TNC), CD34+ cell count, HLA class I and II, ABO/Rh blood group, and colony-forming units are evaluated. The maternal blood is screened for anti-immunodeficiency virus (anti-HIV), anti-hepatitis C virus (anti-HCV), anti-hepatitis B surface antigen (HBsAg), anti-hepatitis B surface (anti-HBs), anti-hepatitis B core (anti-HBc), anticytomegalovirus (anti-CMV), and toxoplasmosis and with Treponema pallidum hemagglutination assay (TPHA). More than 1,000 cord blood units could be collected. Because of the required volume and cell count and because of sterility, 50% of the collected units had to be discharged. Our results are comparable with data of other cord blood banks: mean volume 79 mL; cell count after volume reduction-TNC, 7.16 x 10(8); mononucleated cells (MNC), 3.75 x 10(8); CD34+ cells, 1.95 x 10(6); colony-forming units (CFU), 67.1 x 10(4). To increase the pool of potential umbilical cord blood units and in order to evaluate the possibility for unrelated transplants, cryopreservation and banking of large numbers of cord bloods are necessary.

Neuronal targets of serum and cerebrospinal fluid autoantibodies in amyotrophic lateral sclerosis.

Sera and cerebrospinal fluid (CSF) from 25 patients with amyotrophic lateral sclerosis (ALS) were tested by immunofluorescence on fetal, juvenile and adult central and peripheral neuronal (CNS/PNS) tissues and on nerve biopsy material from affected patients for the presence of autoantibodies. Results were compared with control sera from normal blood donors (n = 45) and patients with other neurological diseases (OND) (n = 11). Three different types of tissue reactivity (glial, axonal, and small blood vessels) were found. Antibodies binding to glial and axonal structures were found in 32% of ALS patients as compared to 12% in normal and 27% in OND controls. In contrast, staining of endothelial cells was found with 24% of ALS sera and CSF but not with normal and OND control sera and was demonstrated only with fetal and juvenile nervous tissue and with suralis nerve biopsies of two of five ALS patients. However, normal or inflamed adult CNS/PNS tissue was not stained with these sera. We conclude that ALS is most likely a heterogeneous group of diseases and only a subgroup of ALS may have an autoimmune pathogenesis. These findings may, therefore, have implications for the evaluation of any immunosuppressive treatment in ALS.

Hyperinsulinemia and macrosomia in the fetus of the diabetic mother.

OBJECTIVE: To determine 1) whether macrosomia in the fetus of the diabetic mother is related to fetal hyperinsulinemia and 2) whether hyperinsulinemia and macrosomia are related to maternal metabolic control. RESEARCH DESIGN AND METHODS: Normal pregnant women (n = 95) were compared with insulin-treated pregnant women (n = 155), who were subdivided according to White's class, hypertension, and mode of delivery. All women were treated to achieve optimal metabolic control. HbA1c was determined at each visit. At delivery, umbilical plasma was analyzed for glucose, insulin antibodies, total insulin, free insulin, C-peptide, proinsulin components, and total and individual amino acids. RESULTS: Macrosomia, defined as > 2 standard deviation units (97.75%), was found in 10-27% of the diabetic groups. It was not related to maternal mass or size, but was significantly correlated with umbilical total insulin, free insulin, and C-peptide. Proinsulin components were not different among groups. Amino acids also were not different. Glycosylated hemoglobin was a weak predictor of birth weight and fetal hyperinsulinism. CONCLUSIONS: Macrosomia in the fetus of the diabetic mother remains inadequately explained. In a large population of pregnant women with strict metabolic control, macrosomia was mainly independent of glycosylated hemoglobin. Nevertheless, fetal hyperinsulinism remains the driving force for excessive fetal growth. The stimulus for fetal insulin excess in humans remains to be defined.

Rapid fluctuations in glycohemoglobin (hemoglobin Alc) related to acute changes in glucose.

Since glycohemoglobin (Hb Alc) has been observed to change acutely, Hb Alc was studied in both human and monkey subjects to determine whether acute changes occurred with rapid changes in plasma glucose concentration. A marked increase in Hb Alc was observed over 2 days in a 3 1/2-year-old boy who developed steroid-induced diabetes mellitus. In addition, a significant fall in Hb Alc was observed over 7 days in a pregnant woman recovering from hyperglycemia and ketoacidosis. During marked acute hyperglycemia and its recovery, three normal rhesus monkeys were studied for changes in plasma glucose and Hb Alc over 1 day. Hb Alc more than doubled in each study by the time plasma glucose reached approximately 90 mmol/L and then declined by 12 hr. While maintained at their usual stable glucose concentrations, human and monkey subjects showed little differences in Hb Alc levels for dialyzed and nondialyzed hemolysates. With acute changes in blood glucose, however, the dialysis for 48 hr yielded lower Hb Alc values. Hb Alc increased when hemolysates were dialyzed against high glucose concentrations. Thus the effect of dialysis in sample preparation may be an important factor in correlating glycohemoglobin with acute and chronic changes in glucose status.