Affinity chromatographic identification and quantitation of blood group A-active oligosaccharides in human milk and feces of breast-fed infants

The finding of large quantities of blood group A-active oligosaccharides in the feces of a blood group A breast-fed infant motivated a search for the origin of these compounds. Using an affinity chromatographic technique, the nature of A-active oligosaccharides in human milk is demonstrated. The amounts of A-active tetrasaccharide (A-tetra) and the Lewis b-active lacto-N-difucohexaose I (LND-I) varied between 19-375 mg/L for A-tetra and 14-710 mg/L for LND-I. Using the same technique, the amounts of A-tetra and LND-I in milk samples from five women of different blood groups were compared with those in the feces of their breast-fed infants. The A-tetra was present only in feces from infants of blood group A or AB mothers and the amount per 24 h corresponded roughly to that in a I-L portion of milk. One of the milk samples was also analyzed for the presence of larger A-active oligosaccharides (A-pentasaccharide, A-hexasaccharide, and A-heptasaccharide). Their amounts were much less as compared to the amounts present in feces. These results indicate that milk is a possible source for the smallest A-tetrasaccharide found in the feces of breast-fed infants, while the larger A-active oligosaccharides might be the result of an intestinal metabolic modification.     

Sialylated oligosaccharides in human milk and feces of preterm, full-term, and weaning infants

The amount of free and glycosidically bound sialic acid was quantitated in the oligosaccharide fraction of breast milk from nine women in the 2nd-3rd week of lactation. These amounts showed a certain individual variation but the amount of bound sialic acid was higher than the free sialic acid in each sample. A similar study on the feces from preterm and full-term breast-fed infants revealed that the amount of free sialic acid increased while the bound sialic acid decreased during maturation, which could possibly be a result of increasing activity of an intestinal sialidase in the newborn child. The fecal oligosaccharide patterns in one blood group A secretor breast-fed infant were studied every 2 months during weaning until the age of 1 year. It was seen that the fecal oligosaccharide pattern disappears, along with the blood group A-active compounds, with a corresponding decrease in the amount of breast milk in the diet.     

Priapism in sickle cell anaemia: a case report.

Priapism is an unusual and distressing complication of sickle cell anaemia and its management has been varied and generally unsatisfactory. We report priapism in a Libyan boy with sickle cell anaemia, managed successfully by blood transfusion.     

Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study

We conducted a multicenter, double-blind, placebo-controlled randomized trial of aspirin treatment (324 mg in buffered solution daily) for 12 weeks in 1266 men with unstable angina (625 taking aspirin and 641 placebo). The principal end points were death and acute myocardial infarction diagnosed by the presence of creatine kinase MB or pathologic Q-wave changes on electrocardiograms. The incidence of death or acute myocardial infarction was 51 per cent lower in the aspirin group than in the placebo group: 31 patients (5.0 per cent) as compared with 65 (10.1 per cent); P = 0.0005. Nonfatal acute myocardial infarction was 51 per cent lower in the aspirin group: 21 patients (3.4 per cent) as compared with 44 (6.9 per cent); P = 0.005. The reduction in mortality in the aspirin group was also 51 per cent--10 patients (1.6 per cent) as compared with 21 (3.3 per cent)--although it was not statistically significant; P = 0.054. There was no difference in gastrointestinal symptoms or evidence of blood loss between the treatment and control groups. Our data show that aspirin has a protective effect against acute myocardial infarction in men with unstable angina, and they suggest a similar effect on mortality.     

Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX.

Factor IX is a multidomain protein and is the proenzyme of a serine protease, factor IXa, essential for hemostasis. In this report, we describe the molecular basis of hemophilia B (deficiency of factor IX activity) in five patients who have neither deletions nor rearrangements of the factor IX gene. By enzymatic amplification and sequencing of all exons and promoter regions, the following causative mutation in the protease domain of factor IX was identified in each patient: IXSchmallenberg: nucleotide 31,215G----T, Ser365Ile; IXVarel: nucleotide 31,214A----G, Ser365Gly; IXMechtal: nucleotide 31,211G----C, Asp364His; IXDreihacken: nucleotide 30,864G----A, Arg248Gln; and IXMonschau: nucleotide 30,855A----T, Glu245Val. In IXVarel, nucleotide 31,213T was also replaced by C, which results in a silent mutation (GAT----GAC) at Asp-364. Thus, this patient has a double base-pair substitution of TA to CG at nucleotides 31,213 and 31,214 but only a single amino acid change of Ser-365 to Gly. This patient also developed an antibody to factor IX during replacement therapy, which suggests that deletion of the factor IX gene is not necessary for development of the antibody in hemophilia B patients. The levels of plasma factor IX antigen in the patients ranged from 40% to 100% except for IXDreihacken (Arg248Gln), in which case it was approximately 4% of normal. The Ser365Gly and Ser365Ile mutants are nonfunctional because of lack of the active site serine residue. Mutant Asp364His is inactive because it cannot form the hydrogen bond between the carboxylate group of Asp-364 and the alpha-amino group of Val-181 generated after activation. As observed in other homologous serine proteases, this hydrogen bond is essential for maintaining the correct active site conformation in normal factor IXa (IXaN). Purified Arg248Gln had approximately 41% and Glu245Val had approximately 17% of the activity of normal factor IX (IXN) in a partial thromboplastin time (aPTT) assay. In immunodot blot experiments, the isolated Glu245Val mutant did and the Arg248Gln mutant did not bind to an anti-IXN monoclonal antibody that has been shown previously to inhibit the interaction of factor VIIIa with factor IXaN. We have recently shown that a high-affinity calcium binding site exists in the protease domain of IXN; among the proposed Ca(2+)-binding ligands is the carboxyl group of Glu-245. Further, a part of the epitope for the above antibody was shown to be contained in the 231 to 265 residue segment of factor IX.(ABSTRACT TRUNCATED AT 400 WORDS)     

Acute Flaccid Quadriparesis in a Recovering COVID-19 Patient: A Clinical Dilemma

How to cite this article: Sabharwal P, Chakraborty S, Tyagi N, Kumar A. Acute Flaccid Quadriparesis in a Recovering COVID-19 Patient: A Clinical Dilemma. Indian J Crit Care Med 2021;25(2):238–239.     

The Reverse-Direction Method Links Mass Experimental Data to Human Diseases

Genome-wide analyses such as DNA microarray, RNA sequencing and RNA interference-based high-throughput screening are prevalent to decipher a biological process of interest, and provide a large quantity of data to be processed. An ultimate goal for researchers must be extrapolation of their data to human diseases. We have conducted functional genome-wide screenings to elucidate molecular mechanisms of the inflammation amplifier, a NFκB/STAT3-dependent machinery that potently drives recruitment of immune cells to promote inflammation. Using a public database of genome-wide association studies (GWAS), we recently reported the reverse-direction method by which our mass screening data were successfully linked to many human diseases. As an example, the epiregulin–epidermal growth factor receptor pathway was identified as a regulator of the inflammation amplifier, and associated with human diseases by GWAS. In fact, serum epiregulin levels were higher in patients with chronic inflammatory disorders. The reverse-direction method can be a useful tool to narrow mass data down to focus on human disease-related genes.