Ultrastructural changes in A-cells exposed to diabetic hyperglycaemia. Observations made on pancreas of chinese hamsters

Summary Pancreatic A-cells of chinese hamsters with diabetes of varying severity and duration were examined by electron microscopy. Two predominant changes were observed: 1. Lysosomal digestion of secretory granules (granulolysis, crinophagy) occurred in practically all A-cells of diabetic animals but was rarely observed in those of normoglycemic controls. This is considered a response of A-cells to the cessation of glucagon release secondary to hyperglycemia. 2. In relatively degranulated A-cells of ketotic diabetic animals, dilatation of the cisternae of the RER was seen together with accumulation of pale, flocculent material, possibly reflecting persisting or enhanced glucagon synthesis. In addition, numerous maturing secretory granules were seen in the cisternae of the Golgi complex. Since these apparently contradictory phenomena may be seen in the same cell, it is suggested that granulolysis may not only result from decreased hormone release secondary to hyperglycemia but that different and independent stimulatory signals may exist for glucagon synthesis, for glucagon release, and for the initiation of granulolysis.Supported in part by the Fonds national suisse de la Recherche scientifique (Grants. No. 4848.3 and 3.154.69).     

Extraction,gel filtration pattern,and receptor binding of porcine gastrointestinal glucagon-like immunoreactivity

Summary Different techniques for the extraction and initial purification of porcine gastrointestinal glucagon-like immunoreactivity (GLI) were compared with reference to yield, and preservation of number and pattern of GLI components. The conventional acid-ethanol technique combined with ethanol-ether purification gave high yields and a reproducible pattern of components. Large amounts of tissue were more easily extracted using another technique, based on extraction by boiling, extraction and precipitation with acetone, and — if necessary — salting out. — By means of the latter two techniques mucosal tissue from all of the porcine gastrointestinal tract was extracted and subjected to gel filtration. Glucagon-like peptides were searched for using: — 1. a radioimmunoassay which quantifies gut type glucagon (GTG), as well as pancreatic type glucagon (PTG), 2. a radioimmunoassay highly specific for pancreatic type glucagon (PTG), and 3. a radioreceptor assay based on binding of glucagon to porcine liver cell membranes. — The oesophageal, the fundic, and the antro-pyloric parts of the gastric mucosa contained very small amounts of GLI. The cardiac gland region contained small amounts of a peptide indistinguishable from true glucagon. The duodenal mucosa contained small amounts of true glucagon and may be a smaller, glucagon-like peptide. The mucosa of the small intestine contained large amounts of both high and low molecular weight GTG and, in addition, PTG of high molecular weight and true glucagon. The colon also contained these components with true glucagon in high concentrations. Only small GTG and true glucagon were receptor-active, the former with less than its immunometric potency.     

Untersuchungen zur Wechselwirkung zwischen aromatischen Kohlenwasserstoffen und Aminen mit Desoxyribonucleinsäure

Zusammenfassung Zur Untersuchung der Wechselwirkung mit DNA wurden Lösungen von hochmolekularer Kalbsthymus-DNA mit Dimethylformamid-Lösungen von zwölf krebserzeugend unwirksamen und wirksamen aromatischen Kohlenwasserstoffen und Aminen versetzt. Anschließend wurden die Lösungen dialysiert, mit organischen Lösungsmitteln extrahiert und zentrifugiert. Aus den UV-Spektren der Lösungen wurden bestimmt: a) aus den Banden der Aromaten oberhalb 300 m die Menge an gebundener Verbindung, b) die Extinktion bei 260 m als Maß für die in Lösung vorhandene DNA und durch Verfolgung der Extinktion bei Temperaturerhöhung der hyperchrome Effekt und der Schmelzpunkt der DNA. Beziehungen zwischen den erhaltenen Daten und der krebserzeugenden Wirksamkeit der Verbindungen wurden nicht gefunden. Ohne Effekt waren ferner Pyridino-[2,3:3,4]-phenoxazon-(2) und das Follikelhormon Östradiol(3,17 ). Bestätigt wurde die Wechselwirkung mit DNA für die Mutagene Proflavin und Acridinorange. Auffallend ist eine deutliche Erhöhung des Schmelzpunktes der DNA durch N-Phthalyl-glutaminsäure-imid.

---

Summary Solutions of high molecular calf-thymus-DNA were mixed with dimethyl formamide solutions of 12 cancerogenic inactive and active aromatic hydrocarbons and amines in order to study the reciprocal effect with DNA. The solutions were then dialyzed, extracted with organic solvents, and centrifuged. From the UV spectra of the solutions the following were determined: (a) the amount of bound compounds from the bands of aromatics above 300 m; (b) the extinction at 260 m as a measure of the DNA present in the solution. By following the extinction with increases in temperature the hyperchrome effect and the melting point of DNA were determined. Relationships between the data obtained and the cancerogenic activity of the compounds were not found. In addition, pyridino-[2,33,4]-phenoxazon-(2) and the follicle hormone estradiol-(3,17 ) were without effect. The reciprocal effect of DNA with the mutagens, proflavin and acridine orange, was confirmed. A distinct increase of the melting point of DNA by means of N-phthalyl-glutaminic acid-imide was striking.

---

---

Mit 1 Textabbildung

---

Herrn Prof. Dr. K. H. Bauer zum 75. Geburtstag gewidmet.     

The treatment of hypertension: New lamps for old?

Summary Meta-analysis of clinical trials does not help the clinician to treat individual patients. A general conclusion that the reduction of high blood pressure is beneficial has to be matched by specific information about the level of blood pressure that is acceptable and about the effect of particular doses of specific drugs. Results obtained from trials of old-fashioned antihypertensive drugs cannot confidently be extrapolated to modern agents. Sufficient data do not exist to encourage universal drug treatment for patients with mild hypertension.     

NMR monitoring of rheumatoid arthritis patients receiving anti-TNF-α monoclonal antibody therapy

The aim of this study was to investigate if dynamic gadolinium-DTPA-supported magnetic resonance (MR) imaging can monitor the therapeutic effect of a fast-acting immuno-modulating drug like anti-tumour necrosis factor alpha (anti-TNF-) monoclonal antibody (moab) in patients with rheumatoid arthritis (RA). Dynamic MR imaging was performed on 64 joints in a total of 18 patients before and after infusion with either a placebo or 1 or 10 mg/kg of anti-TNF- moab. Additionally, treating the placebo group and reinfusing the verum group with either 3 or 10 mg/kg was monitored by quantitative nuclear magnetic resonance (NMR). Time-dependent signal intensity changes were then correlated with a total of five Paulus criteria and with ESR and C-reactive protein (CRP). No changes in either the gadolinium uptake or clinical parameters were seen after the infusion of a placebo. Therapy with 1 mg/kg anti-TNF- moab resulted in a significant decrease in clinical disease activity, as well as in gadolinium-DTPA uptake in dynamic NMR studies. However, correlations between signal intensity changes and Paulus criteria were only demonstrated for the variable doctor's evaluation of disease activity. Patients given 10 mg/kg moab demonstrated a very significant improvement in all clinical manifestations of their disease, as well as a high significant reduction in gadolinium uptake (P=0.004). In addition, the latter group showed significant correlations between time-dependent signal intensity changes and five Paulus criteria: number of swollen joints, number of painful joints, duration of morning stiffness, doctor's evaluation of disease activity and patient's evaluation of disease activity. No differences and correlations were seen for ESR and CRP. We concluded that dynamic NMR studies are suitable to monitor inflammatory activity in RA patients under therapy with biological response modifiers such as anti-TNF- moab.     

Experimentelle Untersuchungen zur Frage der Seltenheit von Geschwulstmetastasen in der Skeletmuskulatur

Summary Authors injected a suspension of Brown-Pearce cancer cells into the left ventricle of 10 rabbits. The venous blood of the lower extremities of these first rabbits was injected into the ear vein of 20 intact second rabbits. In the surviving 7 first rabbits metastases in the skeletal muscles frequently developed. The majority of second rabbits developed tumors indicating a transmuscular passage of tumour cells emboli in the first rabbits. Transmuscular passage of tumour cell was found not only immediately after the injection of the tumour cells, but also three minutes later.These facts contradict the rather speculative theory according to which the skeletal muscle is an unsuitable soil for the development of secondary tumours.     

Estimation of the malignant potential of gastrointestinal stromal tumors: the value of contrast-enhanced coded phase-inversion harmonics US

Background Recently, contrast agents for ultrasonography (US) such as Levovist have been introduced for routine clinical use. The contrast-enhanced US with Levovist permits evaluation of the intratumoral vascularity of hepatic and pancreatic tumors and is useful for their differential diagnosis. The purpose of the present study was to assess tumor vessels and the parenchymal flow of gastrointestinal stromal tumors (GISTs) by contrast-enhanced coded phase-inversion harmonic US and to evaluate whether vascularity is related to the malignant grade of the GISTs.Methods Thirteen patients with GISTs were included in the present study. Tumors were observed in a real-time fashion of contrast-enhanced coded phase-inversion harmonic US after the injection of Levovist (400mg/ml). The vascular patterns were compared with tumor size, histological diagnosis, KIT mutations, and clinical findings such as metastasis.Results The contrast-enhanced US images of the GISTs were classified into two types according to the blood flow area of the tumors as seen by real-time continuous imaging of the tumor vessels. The image pattern Poor represented vessels flowing only in the peripheral part of the tumor, and Rich represented abundant vessels flowing from the periphery to the central part of the tumor. According to the contrast-enhanced US images, five GISTs were classified as Poor and the others as Rich. Based on the final diagnosis, all tumors with Poor images were determined to be benign GISTs, and the rest tumors except one with Rich images were determined to be malignant GISTs.Conclusions Contrast-enhanced US image is more closely correlated with the final diagnosis than the histological findings.     

The ability of heat stress and metabolic preconditioning to protect primary rat cardiac myocytes

Primary rat cardiocytes were subjected to either thermal preconditioning for 30 min at 43°C or 20 min metabolic preconditioning (10 mM deoxyglucose, 20 mM lactate, pH 6.5). Eighteen hours later cells were analysed either for hsp 70i expression or subjected to a subsequent lethal heat stress or simulated ischaemia (10 mM deoxyglucose, 20 mM lactate, 0.75 mM sodium dithionite, 12 mM potassium chloride, pH 6.5) for 2 hours and assessed for survival by trypan blue exclusion.Hsp 70i was induced over 100 fold by thermal preconditioning and 30 fold by metabolic preconditioning (p<0.001, p<0.05), hsp 90 was induced 2.71 fold and 2.24 fold (p<0.001, p<0.001) by thermal and metabolic preconditioning respectively, while hsp 60 was not induced by either treatment. Preconditioned cultures had improved survival against subsequent lethal heat stress or simulated ischaemia: Thermal preconditioning reduced death from 69.22% to 52.46% upon subsequent lethal heat stress and from 49.13% to 36.66% upon subsequent lethal simulated ischaemia. Metabolic preconditioning reduced cell death from 51.29% to 33.8% against subsequent lethal heat stress, and from 69.09% to 55.61% upon subsequent lethal simulated ischaemia. A second marker of cell death, the release of lactate dehydrogenase activity into the culture media, was reduced to 65% and 60% of control values for thermally preconditioned cells subjected to lethal heat or lethal simulated ischaemia respectively. Metabolically preconditioned cells demonstrated lactate dehydrogenase activity of 59% and 51% that of control values, when subjected to lethal heat or lethal simulated ischaemia respectively.Abbreviations hsp heat stress protein - hsp 70i inducible 70 kDa heat stress protein - LDH lactate dehydrogenase - PBS phosphate buffered saline     

Analytical Performance of the New Coagulation Monitoring System INRatio™ for the Determination of INR Compared with the Coagulation Monitor Coaguchek® S and an Established Laboratory Method

An evaluation of the INRatio Prothrombin Time Monitoring system for determination of INR was done in two centers with a total of 5 healthy subjects and 77 subjects on oral anticoagulation. The INRatio and the Coaguchek® S were compared with an established laboratory method. The correlation coefficient of the comparison with the laboratory was r = 0.954 for INRatio and r = 0.937 for Coaguchek® S. The mean relative deviation from the lab method calculated according to Hill was 6.87% for INRatio, which is rated very goo, and 9.72% for Coaguchek® S (goo). The imprecision in the normal range (INR = 1.1) showed a coefficient of variation (CV) of 7.8% and a standard deviation (SD) of 0.09. In the therapeutic range (INR 3.9) the CV was 5.4%, the SD 0.21 and above therapeutic range (INR 5.3), the CV was 8.4% (SD 0.44), rated satisfactory. The concordances of the compared methods with the routine were 81% for INRatio and 79% for Coaguchek® S, which is considered state-of-the-art. Most of the patients perceptions of the INRatio were very positive.In the hands of professionals the INRatio demonstrated very good accuracy and precision and an excellent technical reliability. Further studies using INRatio for self testing by patients are warranted.     

“Mini-perforation” of the colon—Not all postpolypectomy perforations require laparotomy

In a 10-year experience with 4,784 consecutive colonoscopic polypectomies, the need for operative intervention in just two of seven perforations indicates that patients with specially defined, limited perforations can usually be treated nonoperatively. This specific complication, which has been termed mini-perforation, is generally detected within 6–24 hours of polypectomy, and is characterized by local pain and tenderness, without signs of diffuse or spreading peritoneal irritation. Free intra-abdominal or retroperitoneal air on x-ray documents the actual perforation. Complete resolution of symptoms within 24–48 hours confirms the diagnosis of mini-perforation. Success depends on good bowel preparation for colonoscopy, and early recognition of perforation, with institution of bowel rest and intravenous antibiotics. The mini-perforation spontaneously closes, probably by omental adherence. Frequent serial clinical examinations are mandatory so that frank perforation with advancing peritonitis will be promptly recognized and treated surgically. An understanding of the three levels of cautery injury to the colon wall—serosal burn, mini-perforation, and frank perforation are essential in managing the complications of colonoscopic polypectomy.Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, April 29–May 4, 1990.     

Binding of lectins to “young” and “old” human erythrocytes

Summary Old human erythrocytes showed a 21.2% decrease in cell surface area and a 2% decrease in the number of WGA receptor sites, but a 27% increase in the distribution density of the WGA (lectin) receptor site, when compared with young human erythrocytes. For a list of lectin abbreviations, see Materials and methods). Both young and old erythrocytes exhibited very weak binding activity for ¹²⁵I-labeled PNA, but there was no difference in binding activity for PNA between young erythrocytes and old ones. Compared with young erythrocytes, decreases in the number and distribution density of receptor sites for five lectins including LPA, Con A, RCA-II, SBA and BPA on the cell surface were observed in aged erythrocytes. Old erythrocytes also showed a decrease in the number of PHA-E receptor sites, while the distribution density of the same receptor site remained unchanged. In view of these and other observations, it is thought that human erythrocyte aging is accompanied by elimination of some glycoconjugates which have affinity for six lectins, LPA, Con A, RCA-II, PHA-E, SBA and BPA, whereas no WGA receptor-containing glycoconjugates are released from erythrocyte membranes. Elimination of the glycoconjugates results in shrinkage of erythrocytes to reduce their cell surface areas.     

Prognostic relevance of histological findings on bone marrow biopsy in myelodysplastic syndromes

Summary Bone marrow biopsy (BMB) has aroused growing interest as a possible aid in the diagnostic and prognostic evaluation of myelodysplastic syndromes (MDS). Previous reports have pointed out that MDS patients with blastic aggregates or severe bone marrow (BM) fibrosis are characterized by a worse clinical outcome. BMBs of 106 MDS patients were retrospectively reviewed, and relationships among the different histological parameters as well as clinicopathological correlations were looked for. Three patterns of BM blastic infiltration (diffuse, cluster, and large) were recognized. Overt leukemic transformation and overall survival were selected as prognostic end points. BM infiltration was diffuse in 18, cluster in 48, and large in 40 cases. RAEB-t patients accounted for about half of the large cases, and none had a diffuse pattern (p<0.01). Nineteen patients showed extensive BM fibrosis; most of them were characterized by cluster blastic infiltration and megakaryocyte hyperplasia. Leukemic transformation occurred in 67% of large cases (p<0.001) and in none of the cluster cases with severe BM fibrosis (p<0.01); however, survival was equally poor in these two groups because of early leukemic transformation (large cases) and BM failure (cluster cases). The FAB classification did not significantly correlate with prognosis. Patients with cluster BM infiltration and severe fibrosis can be regarded as a true separate MDS subset characterized by unique clinicopathological and prognostic features. Because of the subacute clinical behavior of most cases, and the poor performance status of many elderly patients, there is still controversy as to the best therapeutic approach in MDS. Histological analysis allowed two groups of MDS patients to be identified, both characterized by poor life expectancy, who could benefit from early aggressive chemotherapy.     

Distribution pattern of α and β myosin in normal and diseased human ventricular myocardium

Summary All fibers in three normal, four dilated, and two ischemic human ventricles were classified according to their myosin content using three sets of monoclonal antibodies each specific for one myosin heavy chain isoform (, and ). Numerous fibers contained only myosin heavy chain (denoted as fibers), others contained either and , or and myosin heavy chain (denoted as and fibers, respectively). The percentages of fibers were systematically determined along the walls of seven homologous regions of the ventricular myocardium.In all ventricles, there was an -fiber transmural gradient, with less fiber in the subendocardium than in the subepicardium. More fibers were found in the right than in the left ventricular wall but there was no difference between the mid-portion and the apex of the free wall of each ventricle. The diseased ventricles contained a lower fiber percentage than the normal hearts. fibers were very rare in the normal ventricles (less than 5%) and almost inexistent in pathological hearts. The correlation between the mean fiber percentages of the diseased hearts and their cardiac indices (r=0.88, P<0.05) suggests that the small amount of myosin distributed in a large number of ventricular fibers could play a role in the contractile performance of the heart. In conclusion, this study provides evidence for 1) an fiber transmural gradient, and 2) a lower myosin ratio in discased than in normal human ventricle.This work was supported in part by L'Institut National de la Santé et de la Recherche Médicale 101 rue de Tolbiac, 75013 Paris     

Acute insulin response to intravenous glucose,glucagon and arginine in some subjects at risk for Type 1 (insulin-dependent) diabetes mellitus

Summary The relationships between first-phase insulin secretion to i.v. glucagon and i.v. arginine were studied in 19 healthy adult volunteers (Group I) and in 21 subjects at risk for Type 1 (insulin-dependent) diabetes mellitus with either a normal (n=11; Group II a) or a low insulin response to i.v. glucose (n=10; Group II b). Groups I and II a displayed similar insulin responses to the three secretagogues. In contrast, Group II b demonstrated lower insulin responses to both glucagon and arginine than control subjects (p}<0.007 and (p}<0.04 respectively) orthan normo-responders to glucose (#x007D;<0.007 and p<0.04 respectively). In Group II b however, arginine-stimulated insulin release was increased compared to the response to glucose (p}<0.006), while glucagon and glucose led to non-statistically different responses. Five low-responders developed Type 1 diabetes. As a group, they displayed lower responses to glucagon and to arginine than subjects who up to now have not developed the disease (p<0.05 and p<0.0003 respectively). In the subjects who progressed to diabetes, the responses to glucose and glucagon were similarly blunted. In the low-responders who have not developed the disease, no statistical difference could be detected between mean responses to glucagon and glucose, but four out of these five subjects had a glucagon-stimulated response within the control range and higher than their corresponding response to glucose. Arginine led to a higher stimulation than glucose, in subgroups that either progressed to diabetes (p<0.006) or did not (p<0.002). Finally, low-responders who did not develop diabetes displayed similar responses to both glucagon and arginine than normo-responders to glucose. A progressive decrease of arginine-stimulated insulin response may be a later event during pre-Type 1 diabetes than a blunted response to glucose, while a loss of glucagon-stimulated insulin release may be intermediate. Diminished response to all secretagogues may offer better prediction than a low response to glucose alone.     

Morphologie und klinische Bedeutung des meningealen Hämangiopericytoms

Zusammenfassung Hämangiopericytome der Meningen sind selten. Es wird über drei derartige Tumoren mit einem jeweils über 10 Jahre währenden Beobachtungszeitraum berichtet. Primär erfolgte die Klassifizierung in allen Fällen als Meningeom (1mal gefäßreich, 2mal angioblastisch). Erst nach z.T. mehrfachen Rezidiven sowie extracranieller Metastasierung in zwei Fällen wurden die Diagnosen revidiert und die Tumoren als Hämangiopericytom aufgefaßt.Morphologisch zeigen angioblastisches Meningeom und Hämangiopericytom der Meningen auffällige Gemeinsamkeiten. Das fundamentale Baumuster beruht auf der blastomatösen Vermehrung capillärer Blutgefäße mit normaler Endothelauskleidung, extracapillär proliferierter mesenchymaler Zellen vom Typ der Pericyten und einem intercellulären Netzwerk reticulärer Fasern. Die erhobenen licht- und elektronenmikroskopischen Befunde zeigen nicht die typischen Merkmale eines Meningeoms. Da zudem Klinik und Wachstumsverhalten von angioblastischem Meningeom und Hämangiopericytom der Meningen vergleichbar sind, erscheint es gerechtfertigt, diese Tumoren als einheitliche Geschwulstform mit gemeinsamer Histogenese anzusehen. Wegen der bekanntermaßen hohen Rezidiv- und Metastasierungsrate des Hämangiopericytoms einerseits — im Gegensatz zu der Gutartigkeit der üblichen Meningeome andererseits — halten wir es für sinnvoll, diese meningealen Tumoren einheitlich als Hämangiopericytom der Meningen zu bezeichnen, um hinsichtlich des therapeutischen Vorgehens und prognostischer Aussagen die Besonderheit dieser meningealen Tumorform hervorzuheben.

---

Morphology and clinical significance of the meningeal hemangiopericytoma

Summary Hemangiopericytomas of the meninges are rare tumors. Three tumors of this type with a course over more than 10 years each are reported. All three tumors were primary diagnosed as meningiomas (one: vascular, two angioblastic). The diagnosis was changed to hemangiopericytoma only then when recurrences and extracranial metastases had occurred. Morphologically, angioblastic meningioma and hemangiopericytoma of the meninges show striking common features. The principal pattern bases on the blastomatous increase of capillary blood vessels lined by a normal endothelium, extracapillary proliferation of pericyte-like mesenchymal cells and an intercellular network of reticulin fibres. Light- and electron microsopic findings do not demonstrate the characteristics of a meningioma. Furthermore, clinical data and growth pattern of angioblastic meningioma and hemangiopericytoma of the meninges are well comparable. Therefore, it seems to be justified to interpret these tumors as a tumor entity with identical histogenesis. It is well known that hemangiopericytomas frequently recur and metastasise. On the other hand, meningiomas are usually benign. For those reasons we suggest that these tumors should be uniformly classified as hemangiopericytoma of the meninges in order to stress the significance of these particular tumors of the meninges regarding their treatment and behaviour.

---

---

Herrn Prof. Dr. med. Dr. phil. Rudolf Janzen gewidmet.     

Insulin and growth hormone responses to glucose loading in treated acromegalics

Summary The insulin and growth hormone responses to oral glucose load (100 g) in 23 acronaegalic patients, previously treated by external irradiation, are described. Based on current clinical findings, sixteen acromegalics were considered inactive and seven patients active. Two of the latter were treated diabetics. Thirteen healthy, non-obese subjects formed the control group. Five inactive acromegalics had blood glucose values exceeding the upper limits of normal after the glucose load. Both the inactive and active acromegalics had hyperinsulinemia in the fasting state and after glucose load. The observation of an exaggerated serum insulin response to glucose load in clinically inactive acromegalics suggested that chronically elevated levels of circulating growth hormone may have led to permanent changes in the responsiveness of the pancreatic islets to glucose stimulation. The mean fasting value of serum growth hormone was about the same in the controls and the inactive acromegalics; the latter did not show suppression in serum growth hormone levels after glucose load.Research Fellow, Medical Research Council of Canada     

Homeless Youth: Drug Use Patterns and HIV Risk Profiles According to Peer Group Affiliation

Research was conducted to identify subcultural peer groups within a homeless youth population and determine whether these groups differ with respect to drug use patterns and HIV risk. Using systematic sampling methods, 309 homeless youth (ages 13–23 years) were recruited from street and service sites. Drug use patterns and HIV risk profiles were found to vary according to group affiliation. Respondents in the punks and gay/bisexual groups were more likely to have a substance abuse disorder. Respondents in the punker group also were at increased risk for having unprotected sex and sharing needles. Respondents in the gay/bisexual and hustler groups were at increased risk for having survival sex. Yet, unlike the gay/bisexual group, the hustler group was more likely to report being tested for HIV. These findings suggest that outreach and intervention strategies may need to be tailored to the specific norms, values, and behavioral risk profiles of each peer group.     

Cellular basis of diabetic nephropathy: III. In vitro GLUT1 mRNA expression and risk of diabetic nephropathy in Type 1 diabetic patients

Aims/hypothesis Altered glucose transporter expression has been implicated in the pathogenesis of diabetic nephropathy. There is increasing evidence that genetic factors convey risk of, or protection from, diabetic nephropathy and that the behaviour of cultured skin fibroblasts from Type 1 diabetic patients may reflect these genetic influences. This study aimed to compare GLUT1 mRNA expression levels in skin fibroblasts from Type 1 diabetic patients with either rapid (fast-track, n=25) or slow (slow-track, n=25) development of diabetic nephropathy and from non-diabetic normal control subjects (controls, n=25).Methods Skin fibroblasts were cultured in Dulbeccos Modified Eagles Medium with 25 mmol/l glucose for 36 h. Total RNA was isolated, and GLUT1 mRNA levels were estimated by microarray analysis and RT-PCR.Results Levels of GLUT1 mRNA expression in skin fibroblasts from slow-track patients were greater than those from fast-track patients (p=0.02), as initially detected by microarray. GLUT1 mRNA expression levels were confirmed by RT-PCR to be higher in skin fibroblasts from slow-track patients (4.59±2.04) than in those from fast-track patients (3.34±1.2, p=0.02), and were also higher than in skin fibroblasts from control subjects (3.52±1.66, p=0.03). There was no statistically significant difference between levels of expression in the fast-track patients and the control subjects.Conclusions/interpretation This finding is consistent with the presence of cellular protection factors against diabetic nephropathy in the slow-track patients. These factors could be associated with the regulation of the GLUT1 pathway and may be genetically determined.     

Histomorphologische und cytologische Befunde bei einem Fall von Gewebsmastzell-Retikulose mit akutem leukämieartigem Verlauf

Zusammenfassung Es wird über einen Krankheitsfall berichtet, welcher nach der bisherigen Nomenklatur als Gewebsmastzellen-Leukämie oder als maligne Mastocytose mit leukämieartigen Manifestationen (Efrati et al., 1957) bezeichnet worden ist; er muß als akute subleukämische Gewebsmastzellen-Reticulose klassifiziert werden.

---

Summary The author reports a case which, according to the past nomenclature, was designated as tissue-mast-cell leukemia or as malignant mastocytosis with leukemia-like manifestations (Efrati et al., 1957). This case must be classified as an acute subleucemic tissue-mast-cell reticulosis.

---

---

Vortrag auf dem 12. Kongreß der Deutschen Gesellschaft für Hämatologie, Berlin 1966.     

Metastatic patterns of renal carcinoma: An analysis of 687 necropsies

Summary The metastatic behaviour of renal cell carcinoma has been studied in a series of 687 necropsies. The observations were consistent with the concept of metastatic inefficiency, in that in 295 cases, including 25 with renal vein invasion, there were no detectable metastases. In the present series, renal vein involvement was not an important prognostic factor in stage 1 or 2 disease. In 73% of cases without lung metastases there were none in other sites, and in 84% of those with lung metastases there were others elsewhere, consistent with a metastatic cascade in which metastases first developed in the lungs and were later detected in other organs. However, the observations did not permit discrimination between anatomic cascades, in which other organs were seeded from metastasizing pulmonary metastases, and temporal cascades, in which the other were seeded at the same time as the lungs, but with fewer cancer cells. The patterns of arterial metastasis were consistent with the seed-and-soil hypothesis, and a novel index was developed to quantify differential organ soils. The contralateral kidney was not the best soil for metastases from renal carcinoma. Given the presence of lymph node metastasis, the probability of heamatogenous metastasis is 90%. However, in the absence of nodal metastasis, approximately half the cases had haematogenous metastasis.