Dermatoglyphics in Congenital Adrenal Hyperplasia (CAH)

Dermatoglyphic findings were compared in 42 patients (32 females, 10 males) with Congenital Adrenal Hyperplasia (CAH) and 110 normal controls (70 females, 40 males). In CAH males, an excess of whorls (p less than 0.001), an increased total finger ridge count (p less than 0.05), and an increased frequency of patterns in the fourth interdigital area (p less than 0.025) was found. A main line A terminating high in the hypothenar area (p less than 0.05), and a missing c-triradius or an abortive main line C (p less than 0.05) was observed in CAH females. Both sexes displayed an increase in the frequency of small radially directed hypothenar patterns (p less than 0.05) and sydney lines (p less than 0.01).     

Detection of perforin and granzyme A mRNA in infiltrating cells during infection of mice with lymphocytic choriomeningitis virus

The analysis of gene expression in cytotoxic T cells by in situ hybridization of serial liver and brain sections from mice infected with lymphocytic choriomeningitis virus (LCMV) and immunostaining with T cell marker- and virus-specific antibodies revealed a close histological association of infiltrating lymphocytes expressing the perforin and granzyme A genes with virally infected cells. Maximal frequency of perforin and granzyme A mRNA-containing cells on liver sections preceded by about 2 days maximal LCMV-specific cytotoxicity of the lymphoid liver infiltrating cells. These results are most consistent with an involvement of perforin and granzyme A in cell-mediated cytotoxicity in vivo.     

Long-term maintenance of hematopoietic stem cells does not require contact with embryo-derived stromal cells in cocultures

We recently established that two midgestation-derived stromal clones--UG26-1B6, urogenital ridge-derived, and EL08-1D2, embryonic liver-derived--support the maintenance of murine adult bone marrow and human cord blood hematopoietic repopulating stem cells (HSCs). In this study, we investigate whether direct HSC-stroma contact is required for this stem cell maintenance. Adult bone marrow ckit+ Ly-6C- side population (K6-SP) cells and stromal cells were cocultured under contact or noncontact conditions. These experiments showed that HSCs were maintained for at least 4 weeks in culture and that direct contact between HSCs and stromal cells was not required. To find out which factors might be involved in HSC maintenance, we compared the gene expression profile of EL08-1D2 and UG26-1B6 with four HSC-nonsupportive clones. We found that EL08-1D2 and UG26-1B6 both expressed 21 genes at a higher level, including the putative secreted factors fibroblast growth factor-7, insulin-like growth factor-binding proteins 3 and 4, pleiotrophin, pentaxin-related, and thrombospondin 2, whereas 11 genes, including GPX-3 and HSP27, were expressed at a lower level. In summary, we show for the first time long-term maintenance of adult bone marrow HSCs in stroma noncontact cultures and identify some secreted molecules that may be involved in this support.     

Änderungen der Herzdynamik durch arterielle Gegenpulsation

Zusammenfassung Bei nicht exakt erfolgender diastolischer arterieller Gegenpulsation kommt es nicht allein zu dem erwünschten Absinken des herzeigenen systolischen Druckes sowie des Spannungszeitindexes. Zusätzlich werden Anteile der Systole durch den Druckvolumenstoß miterfaßt. Die resultierenden Druckänderungen vor allem des LV konnten in drei Abschnitte gegliedert werden.I. Trifft der absteigende Anteil des Gegenimpulses auf das Ende der isometrischen Phase bzw. den Beginn der Austreibungsperiode des linken Ventrikels, so wird der enddiastolische Aortendruck erhöht, die Aortenklappen öffnen sich verspätet, der LV-Druck liegt bei unverändertem LVEDD höher als beim Kontrollschlag, ohne daß immer eine Minderung des Schlagvolumens eintritt. Dieser anscheinende Widerspruch zu den Frank-Starlingschen Gesetzen konnte in der vorliegenden Untersuchungsanordnung nicht eindeutig geklärt werden, weil das normale systolische Durchflußvolumen mit der aufgezwungenen Volumenänderung interferiert und dadurch ein zu hohes Schlagvolumen vorgetäuscht werden kann.II. Fällt der Druckvolumenstoß zeitlich mit dem Maximum der ventrikulären Druckentwicklung zusammen, so nimmt nach den Frank-Starlingschen Gesetzen das Schlagvolumen bei vermehrter ventrikulärer Druckentwicklung ab.III. Erfaßt der Beginn des Gegenimpulses das Ende der ventrikulären Austreibungsphase, so resultiert eine zusätzliche isometrische Kontraktion, die sich der Form des Gegenimpulses angleicht. Die Aortenklappen schließen vorzeitig, und die Austreibungsphase wird verkürzt.Mit 5 TextabbildungenMit Unterstützung der Deutschen Forschungsgemeinschaft.     

Der Glucoseverbrauch des menschlichen Gehirns unter dem Einfluß intravenöser Infusionen von Glucose,Glucagon und Glucose-Insulin

Zusammenfassung 1. Bei Kranken mit cerebraler Arteriosklerose findet sich eine Verminderung der Hirndurchblutung sowie der cerebralen Sauerstoff-und Glucoseutilisation. Die Glucoseaufnahme ist besonders stark reduziert, der Quotient aus Glucoseverbrauch: O₂-Verbrauch sowie der cerebrale RQ sind statistisch signifikant vermindert. Daraus läßt sich ableiten, daß als Folge einer gestörten Glucosepermeation oder -utilisation im Gehirn vermehrt Nicht-Kohlenhydrate verbrannt werden.2. Es wurde geprüft, ob durch Erhöhung des arteriellen Blutzuckers eine Verbesserung der Glucoseaufnahme im Gehirn zu erreichen sei. Die Hirndurchblutung wurde mit der Stickoxydulmethode vonKety undSchmidt bestimmt. Gleichzeitig erfolgten Analysen des cerebralen O₂- und Glucoseverbrauchs sowie der Abgabe von CO₂, Lactat und Pyruvat. Enzymatische substratspezifische Meßmethoden kamen zur Anwendung.3. Intravenöse Glucoseinfusionen von 60 ml 50%-iger Glucose hatten trotz eines Blutzuckeranstiegs von 96 auf 265 mg-% keinen statistisch signifikanten Einfluß auf Hirndurchblutung und cerebralen Stoffwechsel.4. Auch nach intravenösen Glucagoninjektionen von 20/kg war trotz Hyperglykämie eine Änderung der Hirnzirkulation, sowie der O₂- und Glucoseutilisation nicht erkennbar.5. In 23 Untersuchungen wurden intravenöse Infusionen von 60 ml 50%iger Glucose mit 24 E Insulin verabfolgt. In neun Messungen mit normalen Ausgangswerten stieg die cerebrale Glucoseaufnahme um 47%, von 5,62 auf 8,29 mg/100 g·min an. Die Hirndurchblutung, der cerebrale O₂-Verbrauch und RQ sowie die Abgabe von Lactat und Pyruvat blieben unverändert normal.Bei 14 Kranken mit cerebraler Arteriosklerose und stark verminderten Hirnstoffwechselwerten nahm bei unveränderter Durchblutung und O₂-Verbrauch die Glucoseaufnahme im Hirn um 84% zu: Die arteriohirnvenöse Glucosedifferenz stieg von 6,8 auf 12,2mg-%, die Glucoseaufnahme von 2,80 auf 5,11 mg/100 g·min. Mit dieser Normalisierung der Glucoseutilisationswerte ging eine statistisch gesicherte Normalisierung auch des Quotienten aus Glucoseverbrauch: Sauerstoffverbrauch sowie des zuvor erniedrigten cerebralen RQ einher.6. Aus den Ergebnissen wird gefolgert, daß das Insulin einen fördernden Einfluß auf die Glucosepermeation in die Ganglienzellen hat. Die vermehrt aufgenommene Glucose kann einer gesteigerten Synthese von Hirnglykogen und Aminosäuren dienen, und bei pathologischen Ausgangswerten zu einer Normalisierung des cerebralen Glucosestoffwechsels führen, erkennbar am Anstieg des cerebralen RQ von 0,88 auf 0,99.7. Die Bedeutung dieser Befunde für die Therapie wird diskutiert.

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Summary 1. In patients suffering from cerebral arteriosclerosis cerebral blood flow and cerebral utilization of oxygen and glucose are decreased. There is a marked reduction in cerebral uptake of glucose, and the quotient Q of glucose-uptake: oxygen consumption and the cerebral RQ are diminished significantly. From these observations it may be concluded that the cerebral metabolism of Non-Carbohydrates is increased as a consequence of disturbed permeation or utilization of glucose.2. We investigated whether an improved cerebral uptake of glucose could be achieved by elevating the level of arterial glucose. The cerebral blood flow was measured by the nitrous oxide method ofKety andSchmidt. Simultaneously the consumption of oxygen and glucose and the delivery of CO₂, lactate and pyruvate were analysed. The determinations were performed by enzymatic substrate-specific methods.3. Intravenous infusions of 60 ml 50% glucose influenced neither cerebral blood flow nor cerebral metabolism significantly, in spite of an elevated blood sugar level from 96 to 265 mg-%.4. A hyperglycemia induced by the intravenous injection of glucagon (20/kg) did not change cerebral blood flow or cerebral metabolism essentially.5. In 23 investigations an infusion of 60 ml 50% glucose and 24 U insulin was given intravenously.In 9 patients showing normal control values the cerebral uptake of glucose increased significantly from 5,62 to 8,29 mg/100 g · min (= 47%). Cerebral blood flow, cerebral oxygen consumption, cerebral RQ and the delivery of lactate and pyruvate remained within normal limits.In 14 patients with cerebral arteriosclerosis and markedlyreduced reduced values of cerebral metabolism the glucose consumption increased significantly by 84%: The arteriovenous difference of glucose rose from 6,8 to 12,2 mg-%, the cerebral uptake of glucose from 2,80 to 5,11 mg/100 g · min. Together with the normalization of the values of glucose utilization the quotient Q of glucose-uptake/oxygen-consumption rose from the previously decreased value of 1,06 to 1,82, and the cerebral RQ became normalized by a significant increase from 0,88 to 0,99.6. It is concluded from theses results that insulin has an improving effect upon the permeation of glucose into the brain cells. The augmented uptake of glucose may serve to an increased synthesis of cerebral glycogen and amino acids and may under pathological conditions restore normal cerebral glucose metabolism.7. The therapeutic implications of these findings are discussed.Die Untersuchungen wurden mit Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt.

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Herrn Prof. Dr. Drs. h. c.K. H. Bauer zum 75. Geburtstag.     

C-reactive protein concentration is not related to islet autoimmunity status in offspring of parents with type 1 diabetes

Autoimmunity may be associated with acute or chronic inflammation. In order to determine whether the inflammatory marker C-reactive protein (CRP) was an indicator of inflammatory events that precede, predict, or associate with islet autoimmunity or type 1 diabetes, CRP was measured in sequential antibody-negative, seroconversion, and follow-up-positive samples from 65 prospectively studied islet autoantibody-positive children. Although changes in CRP concentrations were observed in some children, overall CRP concentrations were similar in antibody-negative samples (median, 0.21 mg/L), antibody-positive samples (median, 0.26 mg/L), and samples at seroconversion (median, 0.26 mg/L). CRP concentrations at diabetes onset (median, 0.59 mg/L) were not significantly increased over antibody-negative samples (P = 0.07). CRP concentrations did not predict diabetes development. CRP concentrations were related to age (r = 0.26; P < 0.001) and were increased in samples obtained from October to January (P < 0.001). These findings suggest that CRP concentrations are not a valuable marker of progression to type 1 diabetes and highlight the importance of correcting analyses for seasonal variations.     

Cross-reactive trinitrophenylated peptides as antigens for class II major histocompatibility complex-restricted T cells and inducers of contact sensitivity in mice. Limited T cell receptor repertoire

The induction of contact sensitivity in mice by hapten reagents such as trinitrochlorobenzene (TNCB) involves the activation of class II major histocompatibility complex (MHC)-restricted, hapten-specific, CD4⁺ T cells. Reports from different laboratories have indicated that the relevant antigenic epitopes in such reactions might include hapten-conjugated, MHC class II-associated peptides. This study for the first time directly demonstrates that hapten-peptides account for the majority of determinants recognized by trinitrophenyl (TNP)-specific CD4⁺ T lymphocytes. The sequences of those TNP carrier peptides do not have to be related to mouse proteins. Thus, we show that TNP-modified peptides derived from mouse IgG, pigeon cytochrome c or staphylococcal nuclease known to bind to I-A^b or from λ represser with specificity to I-A^d as well as TNP-proteins such as bovine serum albumin, ovalbumin or keyhole limpet hemocyanin all create class II-restricted hapten determinants for a number of TNP-specific T cell clones and hybridomas. All of these cells were induced with cells modified by trinitrobenzene sulfonic acid (TNBS). In addition, we present arguments indicating that individual TNP-specific helper T cells may cross-react with different TNP-peptides bound to identical class II molecules. Chemical treatment of antigen-presenting cells with TNCB or TNBS may thus result in a limited number of particularly repetitive immunodominant hapten epitopes. Immunodominant epitopes were also indicated by an overrepresentation of the TCR elements Vβ2 and Vα10 in I-A^b/TNP-specific T cells. Most importantly, however, we demonstrate that TNP attached to lysine 97 in the staphylococcal nuclease peptide 93–105 (i.e. a clearly “non-self” sequence) is able to prime mice for subsequent elicitation of contact sensitivity by TNCB in the absence of foreign protein. We take this to indicate that those TNP-peptide determinants defined by us as immuno-dominant are responsible for the induction of contact sensitivity to haptens.     

Provider-patient relations and treatment choice in the era of fiscal incentives: the case of the end-stage renal disease program

Debates about the extent to which patients can and should participate in medical decision making take on new urgency as cost-containment efforts give patients more financial incentives. The Health Care Financing Administration's recent proposal to enable dialysis patients to "price shop" aroused consternation among nephrologists. A working seminar elucidated their fears about professional incomes and about increased patient autonomy.     

Epidemiologische Ansätze zur Klärung wichtiger Forschungsfragen zu COVID-19 – eine Übersicht

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die Epidemiologie als wissenschaftliche Disziplin ist prädestiniert dafür, Kernfragen der COVID-19-Pandemie zu...