ABO, Rh, MNS, Duffy, Kidd,Yt, Scianna, and Colton blood group systems in indigenous Chinese

The frequencies of selected alleles in the ABO, Rh, MNS, Duffy, Kidd, Yt, Scianna, and Colton blood group systems were determined among four indigenous Chinese ethnic populations: Han, Tajik, She, and Yugu. Genotypes were determined by PCR or PCR with sequence specific primers (PCR-SSP). In the Han population, the frequencies of A1, A2, B, and O1 alleles were 0.189, 0.003, 0.170, and 0.638, respectively, and the O2 allele was not identified. Among D+ Hans, the frequencies of C and c alleles were 0.67 and 0.33 and the frequencies of E and e were 0.22 and 0.78, respectively. Among D- Hans, the frequencies of C and c alleles were 0.23 and 0.77 and the frequencies of E and e were 0.04 and 0.96, respectively. The frequencies of M and N alleles were 0.478 and 0.522 among Hans and 0.655 and 0.345 among Tajiks, respectively. The frequencies of Fya and Fyb alleles were 0.94 and 0.06 among Hans and 0.98 and 0.02 among Shes, respectively. The frequencies of Jka and Jkb alleles were 0.49 and 0.51 among Hans and 0.56 and 0.44 among Shes, respectively. The frequency of the Yta allele was 1.00 among Hans. The frequencies of Yta and Ytb alleles were 0.94 and 0.06 among Tajiks, respectively. The frequency of the Sc1 allele was 1.00 in both Han and Tajik ethnic populations. The frequency of the Coa allele was 1.00 in Han, She, and Tajik ethnic populations.     

Frataxin, iron-sulfur clusters, heme, ROS, and aging

A deficiency in mitochondrial frataxin causes an increased generation of mitochondrial reactive oxygen species (ROS), which may contribute to the cell degenerative features of Friedreich's ataxia. In this work the authors demonstrate mitochondrial iron-sulfur cluster (ISC) defects and mitochondrial heme defects, and suggest how both may contribute to increased mitochondrial ROS in lymphoblasts from human patients. Mutant cells are deficient in the ISC-requiring mitochondrial enzymes aconitase and succinate dehydrogenase, but not in the non-ISC mitochondrial enzyme citrate synthase; also, the mitochondrial iron-sulfur scaffold protein IscU2 co-immunoprecipitates with frataxin in vivo. Presumably as a consequence of the iron-sulfur cluster defect, cytochrome c heme is deficient in mutants, as well as heme-dependent Complex IV. Mitochondrial superoxide is elevated in mutants, which may be a consequence of cytochrome c deficiency. Hydrogen peroxide, glutathione peroxidase activity, and oxidized glutathione (GSSG) are each elevated in mutants, consistent with activation of the glutathione peroxidase pathway. Mutant status blunted the effects of Complex III and IV inhibitors, but not a Complex I inhibitor, on superoxide production. This suggests that heme defects late in the electron transport chain of mutants are responsible for increased mutant superoxide. The impact of ISC and heme defects on ROS production with age are discussed.     

Postnatal growth failure,microcephaly, mental retardation,cataracts, large joint contractures,osteoporosis, cortical dysplasia,and cerebellar atrophy

We describe two sibs with postnatal-onset growth deficiency, microcephaly, cataract, prominent supraorbital ridge, large joint contractures, severe osteoporosis, cortical dysplasia, cerebellar atrophy, and mental retardation. The combination appears to constitute a previously undescribed syndrome inherited in an autosomal recessive pattern.     

Osteochondrodysplasia with rhizomelia, platyspondyly, callosal agenesis, thrombocytopenia, hydrocephalus, and hypertension

A female infant born at term to phenotypically normal nonconsanguinous parents had hypertension, thrombocytopenia, hydrocephalus, callosal agenesis, and nonlethal rhizomelic osteochondrodysplasia. Her osteochondrodysplasia was characterized roentgenographically by shortening and metaphyseal broadening of long bones, without bowing, and by platyspondyly, with deficient ossification of dorsal and central portions of vertebral bodies. By light microscopy, the iliac crest growth plate showed expansion of the zone of chondrocyte hypertrophy and degeneration, with faulty columnar alignment, sparse vascular ingrowth, and irregular mineralization at the zone of chondroosseous transformation. These findings appear to define a novel osteochondrodysplasia, which in association with hypertension, thrombocytopenia, hydrocephalus, and callosal agenesis may constitute a new syndrome.     

Knochenregeneration,Kalk, Rachitis,Tetanie

Zusammenfassung Kalkablagerung und Wachstum des Knochens bei der Frakturheilung lassen sich durch künstlich herbeigeführten periodischen Wechsel der Blutreaktion fördern, durch Übersäuerung (außer durch solche mit Phosphorsäure) hemmen. Daher dürften die vonH. Straub für den gesunden Organismus nachgewiesenen rhythmischen Schwankungen der Blutreaktion für den normalen Kalkstoffwechsel, für das Knochenwachstum und für den Kalkspiegel im Blut ebenfalls von Bedeutung sein. Unter Berücksichtigung dieser Zusammenhänge ergeben sich neue Gesichtspunkte für die Beurteilung der Rachitis und Tetanie.     

HLA-A, -B, -C, -DQA1, -DQB1, -DRB1, -E, -F and -G genotyping of 130 individuals from Terceira Island,Azores, Portugal

One hundred and thirty unrelated Azorean individuals were randomly selected to study the frequencies of high-resolution HLA alleles and haplotypes in the Azorean (Terceira) population. HLA-A, -B, -Cw, -DRB1, -DQA1 and -DQB1 high-resolution genotyping was performed by polymerase chain reaction using commercial kits. HLA-E, -F and -G alleles, were genotyped by sequence-based typing. All loci were in HWE, showing no locus-level deviations. The genotype data is available in the Allele Frequencies Net Database under the population name “Azores Terceira Island” and the identifier (AFND112579).     

GENETIC MUCOPOLYSACCHARIDOSES, MANNOSIDOSIS, SIALIDOSIS, GALACTOSIALIDOSIS, and I-CELL DISEASE

The cultured skin fibroblasts biopsied from 6 cases of galactosialidosis, 4 of I-cell disease, 3 of Scheie syndrome and one of Sanfllippo B syndrome, Morquio A syndrome, sialidosis, and mannosidosis, respectively, were investigated electron microscopically to detect any cytoplasmic storage inclusions. In the cases of genetic mucopolysaccharidosis, vacuolar inclusions containing fine reticulogranular materials of low electron density predominated, showing no significant difference in fine structure among the Sanfllippo B syndrome, Scheie syndrome, and Morquio A syndrome. Similar storage Inclusions were observed in sialidosis and mannosidosis and also revealed no obvious difference among the diseases and the above-mentioned syndromes of genetic mucopolysaccharidosis. In galactosialidosis, two types of inclusions, vacuolar and lamellar, were distinguished, resembling those usually seen in generalized gangliosidosis. In I-cell disease, the cytoplasmic storage Inclusions were variegated; vacuolar, concentric lamellar or osmiophilic amorphous. The availability of electron microscopy in tissue culture is discussed for making the diagnosis of these diseases, and the pathogenesis of lysosomal storage inclusions in the cultured cells of the diseases is briefly viewed.     

Eighty-fourth annual session. He Hahnemann Medical College,Philiadelphia, April 19, 20, 21, 22, 1971. Officers,abstracts, demonstrations

The mature ultimobranchial follicle of the rat consists of two or more layers of cells (U cells) surrounding a lumen containing cell debris. The ultrastructure of the outer, or basal, U cell is characterized by the presence of half desmosomes on the basal plasma membrane and pinocytotic vesicles near it, by little granular reticulum but an abundance of free ribosomes, by clusters of fibrils connected to desmosomes and possibly free in the cytoplasm. The cell ages by accumulation of clusters of fibrils and it undergoes differentiation to form more apical U cells which contain fewer ribosomes and have fibrils dispersed in the cytoplasm. The apical U cell is desquamated into the lumen and ultimately becomes a carcass containing a dense matting of fibers and vacuoles containing a reticulated material resembling that in the lumen. U cells are observed associated with typical thyroid epithelium in the thyroid of the newborn rat in relatively large follicles containing colloid and desquamated cells. They also form rods of cells in the very young rat. Mixed follicles containing both U cells and typical thyroid epithelium occur at all ages.     

Children,Technology, Problems,and Preferences

Increasingly, young people are using various forms of technology in the service of communicating with others, and many have noted the possibility of various dire consequences of this phenomenon, including sexting, cyberbullying, online harassment, and Internet addiction. In our own survey of over 300 adolescents, we found that texting and face‐to‐face communication were considered the most “convenient” forms of communication, while face‐to‐face communication and phone conversations were perceived as most likely to lead to “feeling understood” and “feeling intimate.” Face‐to‐face communication and texting were perceived as most likely to result in feeling regret for sharing too much information. By choosing to communicate through technology, many young people, including our patients, can continue to be social and, at the same time, keep a somewhat safer emotional distance.     

Campomelia, cervical lymphocele, polycystic dysplasia, short gut, polysplenia

An aborted fetus, the offspring of consanguineous parents, had the unusual combination of campomelia, cervical lymphocele, polycystic kidneys, pancreas, and liver, short gut, and polysplenia. Births of earlier similarly affected fetuses suggest an autosomal recessive inheritance. Skeletal, lymphatic, and renal lesions were seen at 26 weeks' gestation by ultrasonography, but not at 16 weeks.     

Sequence-based HLA-A,B, C,DP, DQ,and DR typing of 496 adults from San Diego,California, USA

DNA sequence-based typing at the HLA-A, -B, -C, -DPB1, -DQA1, -DQB1, and -DRB1 loci was performed on 496 healthy adult donors from San Diego, California, to characterize allele frequencies in support of studies of T cell responses to common allergens. Deviations from Hardy Weinberg proportions were detected at each locus except A and C. Several alleles were found in more than 15% of individuals, including the class II alleles DPB1102:01, DPB1104:01, DQA1101:02, DQA1105:01, DQB1103:01, and the class I allele A102:01. Genotype data will be available in the Allele Frequencies Net Database (AFND 3562).     

Orlando C. Kirton, MD, FACS, FCCM, FCCP

The chair is named for Ludwig J. Pyrtek, MD, an esteemed surgeon at Hartford Hospital, who was devoted to the care of his patients and was an outstanding educator within his chosen field. A unique aspect of the chair is that its income is not used to support the salary of the director but is used to enhance the education activities of the department, such as the purchasing of state-of-the-art teaching devices, support of surgical resident research activities, educational travel for residents and honoraria for nationally/internationally known clinicians/scientists to speak at grand rounds.     

Synergism among oxidants,proteinases, phospholipases,microbial hemolysins,cationic proteins,and cytokines

A striking similarity exists between the pathogenetic properties of group A streptococci and those of activated mammalian professional phagocytes (neutrophils, macrophages). Both types of cells are endowed by the ability to adhere to target cells; to elaborate oxidants, hydrolases, and membrane-active agents (hemolysins, phospholipases); and to freely invade tissues and destroy cells. From the evolutionary point of view, streptococci might justifiably be considered the forefathers of modern leukocytes. Our earlier findings that synergy between a streptococcal hemolysin (streptolysin S, SLS) and a streptococcal thiol-dependent proteinase and between cytotoxic antibodies + complement and streptokinase-activated plasmin readily killed tumor cells, led us to hypothesize that by analogy to the pathogenetic mechanisms of streptococci, the mechanisms of tissue destruction initiated by activated leukocytes in inflammatory sites, as well as in tissues undergoing episodes of ischemia and reperfusion, might also be the result of the synergistic effects among leukocyte-derived oxidants, phospholipases, proteinases, cytokines, and cationic proteins. The current report extends our previous synergy studies with endothelial cells to two additional cell types-monkey kidney epithelial cells and rat beating heart cells. Monolayers of⁵¹Cr-labeled cells that had been treated by combinations of sublytic amounts of hydrogen peroxide (generated either by glucose oxidase, xanthine-xanthine oxidase, or by paraquat) and with sublytic amounts of a variety of membrane-active agents (streptolysin S, phospholipases A₂ and C, lysophosphatides, histone, chlorhexidine) were killed in a synergistic manner (double synergy). Crystalline trypsin markedly enhanced cell killing by combinations of oxidant and the membrane-active agents (triple synergy). Injury to the cells was characterized by the appearance of large membrane blebs that detached from the cells and floated freely in the media, looking like lipid droplets. Cytotoxicity induced by the various combinations of agonists was depressed, to a large extent, by scavengers of hydrogen peroxide (catalase, dimethyl thiourea, and by Mn²⁺) but not by SOD or by deferoxamine. When cationic agents were employed together with hydrogen peroxide, polyanions (heparin, polyanethole sulfonate) were also found to inhibit cell killing. It is proposed that in order to effectively combat the deleterious toxic effects of leukocyte-derived agonists on cells and tissues, antagonistic cocktails comprised of cationized catalase, cationized SOD, dimethylthiourea, Mn²⁺ + glycine, proteinase inhibitors, putative inhibitors of phospholipases, and polyanions might be concocted. The current literature on synergistic phenomena pertaining to mechanisms of cell and tissue injury in inflammation is selectively reviewed.     

Recessive, sex-Iinked, progressive, oculocerebral degeneration

Norrie's disease is a rare condition with a recessive sex-linked mode of inheritance, blindness with progressive ocular degeneration, and mental retardation of varying severity. Deafness and epilepsy may occasionally occur.
The findings in a 42-year-old, male. mentally retarded patient suffering from Norrie's disease are reported. His family tree is noted and the differential diagnosis of this condition is discussed.     

IgA, IgG, IgM, and IgE levels in normal, healthy, non-atopic Israeli children

IgA, IgG, IgM, and IgE levels in healthy, non-atopic, Israeli-born children aged 20 days to 16 years were analyzed and showed similar age-related values and dynamics as those of white populations found in other countries. No significant effect of sex of the individual or ethnic origin of the parents was found on the IgE values at different ages. This may indicate that total IgE levels are strongly influenced by environmental factors. Establishing tolerance limits at 97.5, 95, 75, 25 and 5th percentiles and the geometric mean provides the practitioner with more complete reference values. The use of multivariate control charts with tolerance limits from normal IgA, IgG, IgM, and IgE levels is described and is offered as an additional tool for the diagnosis of an allergic individual.     

Lipids,inflammasomes, metabolism,and disease

Inflammasomes are multi-protein complexes that regulate the cleavage of cysteine protease caspase-1, secretion of inflammatory cytokines, and induction of inflammatory cell death, pyroptosis. Several members of the nod-like receptor family assemble inflammasome in response to specific ligands. An exception to this is the NLRP3 inflammasome which is activated by structurally diverse entities. Recent studies have suggested that NLRP3 might be a sensor of cellular homeostasis, and any perturbation in distinct metabolic pathways results in the activation of this inflammasome. Lipid metabolism is exceedingly important in maintaining cellular homeostasis, and it is recognized that cells and tissues undergo extensive lipid remodeling during activation and disease. Some lipids are involved in instigating chronic inflammatory diseases, and new studies have highlighted critical upstream roles for lipids, particularly cholesterol, in regulating inflammasome activation implying key functions for inflammasomes in diseases with defective lipid metabolism. The focus of this review is to highlight how lipids regulate inflammasome activation and how this leads to the progression of inflammatory diseases. The key roles of cholesterol metabolism in the activation of inflammasomes have been comprehensively discussed. Besides, the roles of oxysterols, fatty acids, phospholipids, and lipid second messengers are also summarized in the context of inflammasomes. The overriding theme is that lipid metabolism has numerous but complex functions in inflammasome activation. A detailed understanding of this area will help us develop therapeutic interventions for diseases where dysregulated lipid metabolism is the underlying cause.