The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

Studien zur humoralen Regulation des erythropoetischen Proliferationsspeichers beim Menschen

Zusammenfassung Die Beeinflussung der Erythroblasten-Proliferation durch das Mikromilieu wurde in vitro mittels Auswertung durch Differential- und Mitosezählungen und Signifikanzberechnung vieler Versuchsreihen auch unter verschiedenen pathologischen Bedingungen getestet.Sowohl die Mitosehäufigkeit wie die Ausreifung waren positiv mit dem Erythropoetingehalt des Medium korreliert. Der Effekt wurde durch Folsäure, Ätiocholanolon und cAMP verstärkt. Cobalt stimulierte ebenso wie Testosteron und Methenolon in vitro unabhängig von der Erythropoetinkonzentration im Medium die Erythroblastenproliferation. Ein vermindertes Eisenangebot störte die endgültige Ausreifung der Erythroblasten zu Retikulozyten und bewirkte dadurch eine Ineffektivität der Erythorpoese. Anhaltspunkte für ein Erythrozyten-Chalon oder einen Erythropoetinhemmkörper ließen sich aus unserem Versuchsansatz nicht gewinnen, weil er die Transformation der pluripotenten in die erythropoetin-sensible Stammzelle nicht einschließt. Als Nebenbefund ergab sich eine Stimulation des granulozytopoetischen Proliferationsspeichers durch Serumzusatz zum Medium von Patienten nach akutem Blutverlust und bei Polycythämia vera.Unterstützt durch die Deutsche Forschungsgemeinschaft     

HLA study in Amerindian Bolivia La Paz Aymaras

Aymara people has been a relatively homogeneous group since Spanish Conquest by 1,532 CE, even if previously represented a group of various cultural defined populations who gave rise to them. They were and are established in Andean Altiplano around Titikaka Lake (Bolivia, Peru), Argentina and Chile neighborhood, speak Aymara language and have been maintained after Europeans arrival at a lower social status than Quechua (Inca) speaking people. However, both Aymara and Quechua populations acknowledge Titikaka Lake as center of their origins; both languages are also related. Specific high frequencies of HLA-A*02, -A*24 and -A*68, HLA-B*35, -B*39 and -B*48, HLA-DRB1*08:02, -DRB1*09:01, and -DRB1*14:02, and HLA-DQB1*04:02, -DQB1*03:02 and -DQB1*03:01 alleles are found in Aymaras and HLA class II haplotypes common to Andean Amerindians (DRB1*08:02-DQB1*04:02 and DRB1*04:03-DQB1*03:02), like Quechua, Aymara, Uros, Lamas and Mapuche are also found in Easter and other Pacific Islands. Giant human head stone statues at Tiwanaku (Titikaka Lake, Bolivia) are also found at Easter Island. Thus, it is possible a gene and cultural flow between Andean Amerindians and Easter and other Pacific Islands, as it was demonstrated by Thor Heyerdahl in his Kon-Tiki expedition which reached Pacific Islands sailing from El Callao Harbour (Lima, Peru).     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Lipid composition of metacestodes of Taenia taeniaeformis and lipid changes during growth

A lipid analysis was performed on developing metacestodes of Taenia taeniaeformis removed from the livers of rats at times varying from 3 to 35 weeks post infection. Lipid accounted for 7–21% of the dry weight of the parasites. The highest proportions were found at the earlier stages. The distribution was as follows; neutral lipid 27–45%; glycolipid 5–11%; and phospholipid 50–61%. The major neutral lipid was cholesterol, and minor neutral lipids were sterol esters, triglycerides, diglycerides and monoglycerides. Hydrocarbons were present throughout development, but in the highest amounts at the earlier stages. Five different glycolipids were found, all of which were identified as glycosphingolipids. An increase in the proportion of more complex glycolipids was noted as parasites grew older. Ten different phospholipids were identified, with the major components being phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Other phospholipids were: lysophosphatides, phosphatidylinositol, phosphatidic acid, diphosphatidylglycerol, sphingomyelin, and an unknown phospholipid component. Changes in the relative amounts of the two major phospholipids were found when the early and late stages were compared. Two lipids found throughout development were identified as glycosylated dolichol phosphates, and they comprised between 1 and 3% of the total phospholipid fraction. Nineteen fatty acids were detected, and the fatty acid distribution for each lipid class at each stage was determined. Seven major fatty acids were common to each. These were: hexadecanoic, octadecanoic, oleic, linoleic, arachidonic, docosanoic, and docosahexaenoic.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

Simple Serological Assays for Detecting Rice Tungro Viruses

An attempt was made to produce sensitive and specific polyclonal antisera against the viruses causing rice tungro disease, and to assess their potential for use in simple diagnostic tests. Using a multiple, sequential injection procedure, seven batches of polyclonal antisera against rice tungro bacilliform virus (RTBV) and rice tungro spherical virus (RTSV) were produced. These were characterized for their sensitivity and specificity using ring-interface precipitin test and double antibody sandwich (DAS) ELISA. Thirty-one weeks after the first immunization, antiserum batch B6b for RTBV showed the highest ring interface titer (DEP = 1:1920). For RTSV, batches S3, S4b and S5b all had similar titres (DEP = 1:640). In DAS-ELISA, however, significant differences among purified antisera (IgG) batches were observed only at IgG dilution of 10^-3. At that dilution, IgGB4b showed the greatest sensitivity, while IgGS3 showed greatest sensitivity for RTSV. When all IgG batches were tested against 11 tungro field isolates (dual RTBV-RTSV infections) at sample dilution of 1:10, IgGB4b and IgGB6b for RTBV and IgGS3 and IgGS6b for RTSV performed equally well. However, after cross adsorption with healthy plant extracts in a specially prepared healthy plant-Sepharose affinity column, only IgGB6b could be used specifically to detect RTBV in a simple tissue-print assay.     

Is it worthy to take full-course immunotherapy for allergic rhinitis? About efficacy biomarker of allergen immunotherapy

Nowadays, people pay more attention to biomarkers that can predict clinical efficacy of immunotherapy for allergic rhinitis. As the only recognized aetiological treatment, the efficacy of allergen immunotherapy (AIT) has been proved by many studies. However, treatment success depends on compliance and persistence greatly, which can be impaired by the lengthy duration of AIT and socioeconomic status of patients. Besides, ineffectiveness is another factor that accounts for non-adherence. If the clinical efficacy can be predicted in the early stage of immunotherapy, it can help patients choose appropriate treatment plans, increase patient compliance and optimize the allocation of medical resources. This paper mainly focuses on five candidate biomarkers, the sIgE/tIgE ratio before treatment, serum inhibitory activity for IgE, decreased basophil activation, upregulation of Tregs and tolerogenic DCs, reviews the time when potential biomarkers can predict or monitor the efficacy of AIT, discusses the reason why these indicators could serve as efficacy biomarkers and interactions among potential biomarkers.     

Neurotransmitter signaling pathways required for normal development in Xenopus laevis embryos: a pharmacological survey screen

Neurotransmitters are not only involved in brain function but are also important signaling molecules for many diverse cell types. Neurotransmitters are widely conserved, from evolutionarily ancient organisms lacking nervous systems through man. Here, results are reported from a loss‐ and gain‐of‐function survey, using pharmacological modulators of several neurotransmitter pathways to examine possible roles for these pathways in normal embryogenesis. Applying reagents targeting the glutamatergic, adrenergic and dopaminergic pathways to embryos of Xenopus laevis from gastrulation to organogenesis stages, we observed and quantified numerous malformations, including craniofacial defects, hyperpigmentation, muscle mispatterning and miscoiling of the gut. These data implicate several key neurotransmitters in new embryonic patterning roles, reveal novel earlier stages for processes involved in eye development, suggest new targets for subsequent molecular‐genetic investigation, and highlight the necessity for in‐depth toxicology studies of psychoactive compounds to which human embryos might be exposed during pregnancy.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

Uncombable Hair (cheveux incoiffables, pili trianguli et canaliculi) Syndrome: Brief Review and Role of Scanning Electron Microscopy in Diagnosis

Uncombable hair syndrome was first described some 3 decades ago as "cheveux incoiffables" and is also known as spun-glass hair and pili trianguli et canaliculi. Both inherited (autosomal dominant and recessive with variable levels of penetrance) and sporadic forms of uncombable hair syndrome have been described, both being characterized by scalp hair that is impossible to comb due to the haphazard arrangement of the hair bundles. A characteristic morphologic feature of hair in this syndrome is a triangular to reniform to heart shape on cross-sections, and a groove, canal or flattening along the entire length of the hair in at least 50%of hairs examined by scanning electron microscopy. Most individuals are affected early in childhood and the hair takeson a spun-glassappearance with the hair becoming dry, curly, glossy, lighter in color, and progressively uncombable. Only the scalp hair is affected. Several conditions are associated with uncombable hair, such as ectodermal dysplasia, retinal dysplasia/ pigmentary dystrophy, juvenile cataract, digit abnormalities, tooth enamel anomalies, oligodontia, and phalangoepiphyseal dysplasia. Other syndromes with hair abnormalities may also mimic uncombable hair syndrome clinically and these include, Rapp-Hodgkin ectodermal dysplasia; loose anagen hair syndrome; ectodermal dysplasia, ectrodatyly, cleft lip/ palate (EEC) syndrome; and familial tricho-odonto-onchyial ectodermal dysplasia with syndactyly. Unlike other conditions with an uncombable hair component, uncombable hair syndrome alone (cheveux incoiffables, pili trianguli etcanaliculi) is not associated with physical, neurologic, or mental abnormalities. In most cases of uncombable hair syndrome, the hair is grossly abnormal in infancy and early childhood, but may have improved manageability later in life. Scanning electron microscopy of hair samples provides definitive evidence for diagnosis of clinically suspected uncombable hair syndrome and eliminates other hair abnormalities from the differential diagnosis.     

A comparative study of cholinergic systems of the neocortex and hippocampus in rats with low and high resistance to hypoxia

Synaptic structures in the neocortex and hippocampus of the intact brain were compared between rats with low and high resistance to hypobaric hypoxia. Activities of choline acetyltransferase, acetylcholinesterase, Na,K-ATPase, and the portion of protein in the light and heavy synaptosome fractions and subfractions were measured. A discrepancy in cholinergic metabolism molecular mechanisms between high and low resistance animals have been found in the heavy somatosoma fraction from the neocortex. Activities of choline acetyltransferase, acetylcholinesterase, and Na,K-ATPase in the synaptolemmal subfraction of low resistant rats were much lower than in high resistant rats. This implies a less effective synaptic transmission in proper cholinergic neurons in the low resistance animals and, therefore, specifically changed neuron functioning in the circulation control. No differences in the cholinergic components of either neocortical light synaptosome fraction or hippocampal light and heavy synaptosome fractions were found between low and high resistance rats. Translated fromByulleten' Eksperimental'noi Biologii I Meditsiny, Vol. 125, No. 5, pp. 521–525, May, 1998     

Untersuchungen zum Einfluß von Körperlage und Schwerkraft auf die Eigenschaften von Blut und Blutplasma

Zusammenfassung Die Lagerung des Körpers hat wesentlichen Einfluß auf die Balance der transkapillären Bewegung eiweißarmer Flüssigkeit, das heißt auf das Gesamt-Starling-Gleichgewicht im Kreislauf. Aufrichten aus der horizontalen Lage hat Hämokonzentration, Hinlegen Hämodilution zur Folge. Folglich beeinflußt Lageänderung das Blut- und Plasmavolumen und darüber hinaus Werte wie Eiweißkonzentration, Hämatokrit oder Hämoglobinkonzentration im Blut.In der vorliegenden Arbeit wird die Möglichkeit vorgestellt, mittels der Biegeschwingermethode durch Dichtemessungen an Kapillarblut und -plasma diese orthostatischen Einflüsse auf hämatologische Zustandsvariable zu quantifizieren und ihren zeitlichen Verlauf mit hoher Auflösung zu erfassen.Im Durchschnitt ergab sich infolge Aufrichten des Körpers (70°) aus der Horizontalen eine Verringerung des Plasmavolumens um 6,6% nach 10 und um 11,1% nach 30 min; Hinlegen bewirkte nach 10 min eine Erhöhung des Plasmavolumens um 6,5% und nach 30 min um 10,5%. Entsprechende Blutvolumenveränderungen zwischen 5 und 10% gingen auch aus den Blutdichteänderungen bei orthostatischen Reizen hervor.Eine wichtige praktische Konsequenz ist die Forderung nach Beachtung der Körperlage vor und während Blutabnahmen, vor allem bei Verlaufsmessungen hämatologischer Größen bei ein und demselben Patienten oder bei statistischen Vergleichen verschiedener Kollektive.Diese Arbeit wurde vom Fonds zur Förderung der Wissenschaftlichen Forschung unterstützt     

BSACI guideline for the diagnosis and management of cow's milk allergy

This guideline advises on the management of patients with cow's milk allergy. Cow's milk allergy presents in the first year of life with estimated population prevalence between 2% and 3%. The clinical manifestations of cow's milk allergy are very variable in type and severity making it the most difficult food allergy to diagnose. A careful age‐ and disease‐specific history with relevant allergy tests including detection of milk‐specific IgE (by skin prick test or serum assay), diagnostic elimination diet, and oral challenge will aid in diagnosis in most cases. Treatment is advice on cow's milk avoidance and suitable substitute milks. Cow's milk allergy often resolves. Reintroduction can be achieved by the graded exposure, either at home or supervised in hospital depending on severity, using a milk ladder. Where cow's milk allergy persists, novel treatment options may include oral tolerance induction, although most authors do not currently recommend it for routine clinical practice. Cow's milk allergy must be distinguished from primary lactose intolerance. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for clinicians in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking the panel of experts in the committee reached consensus. Grades of recommendation are shown throughout. The document encompasses epidemiology, natural history, clinical presentations, diagnosis, and treatment.     

Diversité génétique d’un génotype rare du virus de l’hépatite A

Purpose of the study

Very few is known on genotype II hepatitis A virus (HAV) since it is rarely isolated. From 2002 to 2007, the French observatory of HAV identified six sub-genotype IIA strains of which one from a patient having travelled to West Africa. To investigate the possible African origin of sub-genotype IIA, we determined its prevalence among French travellers in 2008 and characterised its genetic variability.

Patients and methods

The 2008 mandatory notification records were screened for travel to Africa. Viral genotype was determined on the nucleotide sequencing of the VP1/2A junction region. The P1 region coding for capsid proteins was used to compare the genetic diversity of IIA isolates to those of other genotypes.

Results

In 2008, five out of 54 patients returning from West Africa were infected by IIA strains and an additional “autochthonous” case was identified. Two more African cases were identified in 2009. A total of 14 IIA isolates (eight African and six “autochthonous”) were analysed. Nucleotide and amino-acid variability of IIA sequences was lower than that of the other genotypes. Phylogenetic analysis revealed the clustering of two “autochthonous” cases with African isolates whereas the other ones belonged to a different lineage.

Conclusion

Most IIA strains isolated in France are imported by travellers returning from West Africa. However, the unexplained contamination mode of some “autochthonous” cases suggests another geographical origin to discover or a French reservoir to explore.     

Tracheomalacia in a neonate with kniest dysplasia: histopathologic and ultrastructural features

Kniest dysplasia is an autosomal-dominant chondrodysplastic condition characterized by disproportionate dwarfism, short trunk, small pelvis, kyphoscoliosis, short limbs, prominent joints, premature osteoarthritis, and craniofacial manifestations. The craniofacial abnormalities include tracheomalacia, midface hypoplasia, cleft palate, early onset myopia, retinal detachment, prominent eyes, and sensorineural hearing loss. Radiologic features include dumbbell-shaped femora, platyspondylia with anterior wedging of vertebral bodies, coronal clefts of thoracolumbar vertebral bodies, low broad ilia, and short tubular bones with broad metaphyses and deformed large epiphyses. This form of chondrodysplasia is associated with mutations in type II collagen splicing sequences. Mutations have been identified in the COL2A1 (type II collagen) gene between exons 12 and 24. Type II collagen is the predominant structural protein in cartilage, and mutations in this collagen account for the Kniest dysplasia phenotype. Histopathologic and ultrastructural features of epiphyseal plate cartilage have been described, but tracheal cartilage in an affected neonate has not been examined. The authors report the histopathologic and ultrastructural findings of anterior tracheal cartilage from a 35-day-old female with suspected chondrodysplasia who had tracheomalacia with airway obstruction. The tracheal cartilage was moderately cellular, but lacked cystic and myxoid changes in its matrix. The chondrocytes had abundant cytoplasmic PAS-positive inclusions. Some of these inclusions were diastase-resistant and were also highlighted on Alcian blue staining. Ultrastructural examination revealed chondrocytes with greatly dilated rough endoplasmic reticulum containing granular proteinaceous material. There were also frequent aggregates of typical glycogen. The defect in the COL2A1 gene is secondary to mutations, especially at splice junctions, and this markedly disrupts triple helix formation. The mutated type II procollagen results in intracellular retention within the chondrocytes, as abundant granular proteinaceous material within the dilated RER. A relationship is known to exist between the proportion of mutated to normal type II collagen in the matrix and the severity of the phenotype. With low levels of normal type II collagen, the phenotypic manifestations become more severe, such as in achondrogenesis type II. Both the quantity and quality of type II collagen modulates the phenotypic expression of type II collagenopathies.     

Antriebe und effektorische Maßnahmen der Thermoregulation bei Ruhe und während körperlicher Arbeit

Zusammenfassung Durch die während der Versuche in warmer Umgebung verursachten Wasserverluste nehmen Schweißrate und innere Wärmeübergangszahl bei konstanten thermischen Antrieben ab. Für die Berechnung der beiden effektorischen Größen aus thermischen Daten muß daher ein Korrekturfaktor eingeführt werden, der dem Wasserverlust Rechnung trägt. Bei Versuchen mit fortlaufendem Ersatz der verlorenen Flüssigkeit ist diese Korrektur überflüssig. Die Kerntemperatur steigt in solchen Versuchen in warmem Klima weniger stark an als ohne Ersatz der Flüssigkeit und erreicht bereits in der ersten 1/2 Std einen konstanten Endwert.