Association and Linkage Disequilibrium Analyses Suggest Genetic Effects of Estrogen Receptor α and Collagen IA1 Genes on Bone Mineral Density in Caucasian Women

Estrogen receptor alpha (ER) and collagen IA1 (COLIA1) genes have been suggested as possibly implicated in reduced bone mineral density (BMD). The present study investigated the occurrence of association and linkage disequilibrium between radiographic hand BMD and polymorphic alleles of ER and COLIA1 genes, in human pedigrees of a Chuvasha population in Russia. The study sample included 463 members of 113 pedigrees, mostly nuclear families. We performed association and transmission disequilibrium test (TDT) analyses of the combined PvuII and XbaI RFLPs alleles on the same chromosome (haplotype) of the ER gene with BMD Z scores of cancellous or cortical bone in the hand phalanges. The association analyses were performed separately for both genders in the parental generation, i.e., fathers (n = 114; average age 64.2 y) and mothers (n = 122; average age 62.7 y). The Px haplotype was associated significantly with lower BMD Z scores in mothers only. The difference between subjects who carried one or two copies of the Px haplotype and those lacking it was 0.68 Z scores, P = 0.003 and 0.51 Z scores, P = 0.025 for cancellous and cortical bone, respectively. Multiple linear regression model with age, height, weight, and Px haplotype status as predictors explained 26.7% and 28.3% of the total observed variance in BMD with Px haplotype as independent predictor explaining 5.9%; P = 0.002 and 3%; P = 0.028 (cancellous and cortical bone, respectively). Results of t-TDT for triads of two parents and just one of their female offspring (but not male offspring) suggested the existence of linkage disequilibrium between the two loci of Px haplotype and BMD trait (P = 0.047). No association was found between polymorphic alleles of COLIA1 gene and BMD, but mothers with combined genotypes of Px haplotype of ER gene and s allele of COLIA1 gene had the lowest mean Z scores (–0.944 and –0.788 for cancellous and cortical bone, respectively). We conclude that the Px haplotype of the ER gene is associated with low BMD values in females, as the phenotype is gender dependent (the association was not observed in males), and the s allele of COLIA1 gene in combination with this haplotype contributes to reduced BMD.     

Effect of hyperfiltration on long-term follow-up of glomerular filtration rate in male Wistar rats

It has been suggested that a prolonged course of hyperfiltration could lead to progressive deterioration of renal function. In order to test this hypothesis, the following protocol was applied to 60 male Wistar rats. At 12 weeks of life, the rats were submitted to a surgical procedure: sham operation (25 rats), unilateral nephrectomy (25 rats) or 3/4 nephrectomy (10 rats). The three groups were again divided into two subgroups: one with high-protein intake (36%) and one with a low-protein intake (12%). In order to avoid any additional traumatic procedure which could shorten the animal's life, the glomerular filtration rate (GFR) was measured without blood sampling, using a previously validated technique based on an image recorded by a gamma camera between the 9th and the 10th min after intravenous injection of^99m technetium diethylenetriaminepentaacetate (DTPA). The sum of both kidneys and bladder activity was expressed as a percentage of the injected dose. The test was performed before surgery and every month thereafter. Six weeks after surgery, the highest filtration rate was found in the rats with two kidneys/high-protein diet, followed by the two kidneys/low-protein diet, the one kidney/high-protein diet, the one kidney/low-protein diet and the 1/2 kidney. The overall GFR in the one kidney/high-protein diet rat and in the 1/2 kidney rat was respectively 80% and 55% of the pre-operative values. Until 109 weeks of age, the survival rate was comparable in the five groups of rats. At 109 weeks of age, non-significant changes in renal function were observed, the follow-up slopes of the different subgroups being more or less parallel. At that age, the lesions of glomerular sclerosis were focal and discrete, without significant differences in the five groups.     

An immunohistochemical study of glucagonoma conducted on the metastatic lymph nodes from a patient with recurrent metastatic glucagonoma: Report of a case

In this report, we briefly present the case of a 67-year-old woman who developed recurrent glucagonoma with lymph node metastasis. An immunohistochemical study of the metastatic tumor revealed immunoreactivity of glucagon and protein kinase C (PKC)-, -, and - in the tumor cells, two types of which were seen by electron microscopy. One type had abundant secretory granules and mitochondria, while the other had few granules and mitochondria. Some granules were similar to typical A cell granules and others were atypical. An immunoelectron microscopic demonstration revealed PKC-, -, and - immunostaining in the cytoplasm of all the tumor cells, while some secretory granules had PKC immunostaining, and others had no immunostaining. Thus, it appears that metastatic glucagonoma and its associated granules are composed of two types of mature and immature cells or granules. As immunoreactivity of PKC- and - was found in the tumor cells, but not in the normal A cells of the islets of Langerhans, the PKC subspecies and , which are not present in normal pancreatic A cells, may exist in human glucagonoma cells.     

TGF-β and functional differentiation

A review of the pertinent literature suggests that TGF-1 may play a multifaceted role in functional differentiation of mammary epithelium. Evidence for the expression of TGF-1 RNA and the presence of functional TGF-1 protein in differentiating mammary epithelial cells from a pregnant mouse has been recently reported. The specific role of mammary-epithelial-cell-produced TGF-1 in the differentiating mammary gland is presently unclear. However, several possible functions are suggested from the following observations. Milk protein production is negatively regulated by exogenous TGF-1 during gestational development of the gland but not during lactation. Consistent with reports linking TGF-1 gene expression with mammary gland involution following lactation, overexpression of TGF-1 in the differentiating secretory epithelium leads to premature programmed cell death in the absence of a negative effect on secretory epithelial cell proliferation. A role for TGF-1 in cell cycle control and suppression of malignant progression independent from its inhibitory effect on epithelial cell growth has been demonstrated in keratinocytes. A similar function could provide protection against malignancy in proliferating mammary epithelium and account for TGF-1 suppression of mammary tumorigenesis in transgenic mice overexpressing transforming growth factor alpha (TGF-).³     

34. Akute und chronische Pankreatitis. Morphologische Grundlagen

Zusammenfassung Die akute Pankreatitis zeigt mit der jauchigen Nekrose und der Vielfalt der Fettgewebsnekrosen ein eindrucksvolles Bild. Dennoch sind einige Teilaspekte wenig bekannt und für das Verständnis der Krankheit wichtig, z. B. die häufige Aussparung des Kerns der Drüse. Die anatomischen Äquivalente von Schock, Schmerz, Ileus werden erläutert, auf das Krankheitsbild Pankreatitis ohne Pankreatitis wird kurz eingegangen. Als Komplikationen werden die Chronifizierung und die Pseudocysten dargestellt. Die chronische Pankreatitis bis zur ausgebrannten Drüse mit Stein, Diabetes und möglicherweise Carcinom wird in ihrer Entstehung anatomisch gezeigt.

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Fundamental morphological aspects of acute and chronic pancreatitis

Summary Acute pancreatitis presents an impressive picture, with autodigestic necrosis and various types of necrosis of fat tissue. Nevertheless, some side aspects are little known, although they are important to the understanding of the disease, e.g. the frequent sparing of the kernel of the gland. The anatomical equivalents of shock, pain, ileus are exvlained, and the syndrome of pancreatitis without pancreatitis will be briefly discussed. The complications of progression to a chronic state and of pseudocysts will be shown. The development of chronic pancreatitis leading to the burnt out gland with stones, diabetes and possibly carcinoma will be shown anatomically.

     

Role of TGFβ in the anti-estrogen response/resistance of human breast cancer

Transforming growth factor (TGF) has potent inhibitory effects upon epithelial proliferation and malignant progression may be associated with breakdown of the autocrine and paracrine inhibitory loops in which TGF participates. The therapeutic effects of anti-estrogens may be partially attributable to boosting of local endogenous levels of TGF. This article reviews the evidence in support of TGF being a proximate effector in mediation of the anti-neoplastic effects of anti-estrogens. Both the conventional estrogen receptor (ER)³ dependent and ER independent mechanisms of action are likely to be involved. Evidence for preferential stromal induction of TGF by anti-estrogens is emphasized, together with the therapeutic potential of this strategy for improving outcome in early breast cancer irrespective of ER status.     

Correction of the acid-base balance and postoperative diuresis

The significance of the correction of postoperative acidosis for the kidney's excretory activity has been studied on clinical material. The volume of the urine discharged during the first 24 postoperative hours was significantly increased in patients (corrected group) whose acid-base balance had been restored according to careful calculation. Intensified diuresis in the first 12 hours accounted for 70% of this increase. There was no appreciable difference between the corrected and the noncorrected group concerning specific gravity and pH-value of the urine and serum ionogram. Values of urinary electrolytes, as observed in the corrected group, were not essentially different from the usual postoperative values. It is suggested that the correction has no effect on the hormonal factors influencing postoperative renal functions. Readjustment of the acid-base balance facilitates a quicker normalization of tubular function.     

Transforming growth factor-beta localization during mouse prostate morphogenesis and in prostatic growth abnormalities

Summary Growth and morphogenesis of the prostate involves mesenchymal-epithelial interactions. Transforming growth factor-beta 1 (TGF-1) is one growth factor that may play a role in these paracrine interactions. We have localized TGF-1 by molecular and immunohistochemical analysis in the developing mouse prostate. Accumulations of TGF-1 protein were localized in the mesenchyme surrounding ductules in fetal and neonatal prostate. Previous studies in the mouse prostate reconstitution (MPR) model system have localized accumulations of TGF-1 to regions of oncogene-induced abnormalities. In surgically excised adult human prostate tissues, localized accumulations of TGF-1 are associated with prostate cancer and benign prostatic hyperplasia (BPH). Intracellular TGF-1 was more often associated with stromal cells in BPH and with neoplastic epithelial cells in prostate cancer. The production and accumulation of TGF-1 appears to involve interactions between mesenchymal and epithelial cells. Further experimental studies may clarify the relationships between TGF-1 and abnormal prostatic growth.     

Validity and interobserver agreement of a new radiographic grading system for intervertebral disc degeneration: Part II. Cervical spine

A new radiographic grading system for a more objective assessment of lumbar intervertebral disc degeneration has been described and tested in Part I of this study. The aim of the present Part II of the study was to adapt this system to the cervical spine, and to test it for validity and interobserver agreement. Some modifications of the grading system described in Part I were necessary to make it applicable to the cervical spine. Its basic structure, however, stayed untouched. The three variables Height Loss, Osteophyte Formation and Diffuse Sclerosis first have to be graded individually. Then, the Overall Degree of Degeneration is assigned on a four-point scale from 0 (no degeneration) to 3 (severe degeneration). For validation, the radiographic degrees of degeneration of 28 cervical discs were compared to the respective macroscopic ones, which were defined as real degrees of degeneration. The interobserver agreement was determined between one experienced and one unexperienced observer using the radiographs of 57 cervical discs. Quadratic weighted Kappa coefficients () with 95% confidence limits (95% CL) were used for statistical evaluation. The validation of the new version of the radiographic grading system showed a moderate agreement with the real, macroscopic overall degree of degeneration (=0.599, 95% CL 0.421–0.786). In 64% of all discs the real overall degree of degeneration was underestimated but never overestimated. This underestimation, however, was much less pronounced and the Kappa coefficients were significantly higher for the three variables: Height Loss, Osteophyte Formation, and Diffuse Sclerosis separately. The agreement between the radiographic ratings of the experienced and the unexperienced observer was substantial for the overall degree of degeneration (=0.688, 95% CL 0.580–0.796), almost perfect for the variable, Height Loss, moderate for Osteophyte Formation and fair for Diffuse Sclerosis. In conclusion, we believe that the new version of the radiographic grading system is a sufficiently valid and reliable tool to quantify the degree of degeneration of individual cervical intervertebral discs. In comparison to the version for the lumbar spine described in Part I, however, a slightly higher tendency to underestimate the real overall degree of degeneration and somewhat higher interobserver differences have to be expected.Part I of this article can be found at http://dx.doi.org/10.1007/s00586-005-1029-9     

Antibodies directed at mouse IL-2-R α and β chains act in synergy to abolish T-cell proliferation in vitro and delayed type hypersensitivity reaction in vivo

The anti-mouse IL-2-R chain mAb TM-1 which, by itself, does not affect IL-2-dependent proliferation throught the high affinity mouse IL-2 receptor, was shown to cooperate in a synergistic way with a set of anti-IL-2-R chain mAbs both in vitro and in vivo. In vitro, when associated at equimolar concentrations, the TM-1/anti- mAb association was four to ten times more efficient at inhibiting the proliferation of the CTL-L2 cell line than was a similar concentration of anti- mAb alone. In addition, a bispecific antibody in which a Fab' fragment of TM-1 was covalently linked to a Fab' fragment of one of the anti- mAb (5A2) was shown to be as efficient as the TM-1/5A2 association. The association of TM-1 with 5A2 was also tested in vivo in a sheep red blood cell-induced delayed type hypersensitivity (DTH) model. TM-1 which, by itself, had no effect on DTH, induced a two- to threefold decrease in the doses of 5A2 required to suppress this cell-mediated immune reaction.     

Der Einfluß des niederfrequenten Wechselstrom-Systems Kraus-Lechner auf das Knochenwachstum

Zusammenfassung Osteone behandelter und kontrollierter Beagle-Ulnae werden in ihrem Flächenzuwachs berechnet. Die Stimulation erfolgte über Elektronägel System Kraus-Lechner. Die Mittelwerte der therapierten Osteone übertreffen die Kontrollen. Die Grundsatzfrage, ob eine meßbare Induktion des Kno chens durch niederfrequenten Elektromagnetismus er folgt, kann mit Wahrscheinlichkeit bejaht werden.

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The influence of low-frequency DC (System Kraus-Lechner) on bone growth

Summary Osteons of Beagle-ulnae were calculated in growth. Controlled osteons were compared with osteons after therapy. Stimulation was made with electro-nails system Kraus-Lechner. The mean-values of osteons after therapy surpass control. The fundamental question, whether induction of bone growth occurs with low frequency electromagnetism will in all probability be have to answered in the affirmative.

     

Enflurane impairs canine diaphragmatic contractilityin vivo

We examined the effect of enflurane on diaphragmatic contractility in six anesthetized mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Pdi-stimulus frequency relationship was compared at three levels of anesthesia, namely 1, 1.5, and 2 MAC (minimum alveolar concentration) of enflurane. The sequence of changing anesthetic concentration was randomized between animals. Pdi at 50 and 100Hz stimulation was significantly decreased with increasing MAC while Pdi at 10Hz stimulation was not affected by the depth of anesthesia. Pdi of 20Hz stimulation was significantly decreased at 2 MAC as compared to those at 1 and 1.5 MAC. We conclude that enflurane decreases contractility of the diaphragm mainly through impairment of the neuromuscular transmission and/or membrane excitability. Part of its effects is, however, probably related to the impairment of excitation-contraction coupling, as suggested by the depression of Pdi at 2 MAC in response to 20Hz stimulation.(Kochi T, Ide T, Isono S et al.: Enflurane impairs canine diaphragmatic contractility in vivo. J Anesth 4: 226–231, 1990)     

33. Der „kalte” Schilddrüsenknoten

Zusammenfassung Der kalte Schilddrüsenknoten gilt als typischer Verdachtsbefund für ein Schilddrüsencarcinom. Seine tatsächliche Dignität ist mit klinischen Mitteln sowie Szintigraphie und Sonographie letztlich nicht zu klären. Das beste abgrenzende Selektionskriterium ist die Feinnadel-Punktionscytologie, wodurch mit Gültigkeit für das Kropfendemiegebiet etwa die Hälfte als suspekte Befunde von dem anderen Teil hochwahrscheinlich gutartiger Veränderungen getrennt und für die Operationsindikation reserviert werden kann.     

Experimental study of drainage and granulation in response to the intra-articular injection of particles in rat knee joints

Reactive granulation and drainage of intraarticularly injected plastic particles in rat knee joints was examined by light and electron microscopy. The knee joints and associated iliac lymph nodes were excised at various intervals after the injection of latex beads (1 m) or fluoresbrite particles (0.2 m or 10 m) from 5 min until 3 months after the injection. Particles in the lymphatic or blood vessels were successfully demonstrated by an enzyme-histochemical method (5-nucleotidase staining). Five min after the injection, most of the particles were scattered on the surface of the synovial membrane, and some particles were phagocytosed by synovial lining cells. After 5 h, neutrophils had phagocytosed particles which adhered to fibrin in the joint cavity. Twelve h after the injection, after the neutrophils had died, those same particles were phagocytosed by macrophages in the joint cavity. One day after the injection, Fluoresbrite particles (0.2 m) phagocytosed by macrophages were found in the iliac lymph nodes, while latex particles (1 m) were detected in the iliac lymph nodes 3 days after the injection. Some Fluoresbrite particles (10 m) were seen in the 5-nucleotidase-positive lymphatic vessels in the synovial membrane. Three months after the injection, many macrophages filled with particles had formed granulation tissue in the synovial membrane, and macrophages containing phagocytosed particles were also seen increasingly in the iliac lymph nodes. Our findings suggested that neutrophils and macrophages phagocytosed injected particles in the joint cavity, and that the macrophages brought the particles into the deep layer of the synovial membrane. Phagocytic macrophages also carried the particles to the iliac lymph nodes through lymphatic vessels in the synovial membrane. There were no morphological differences in the processes of granulation and drainage between the two different sized plastic particles (1 m and 0.2 m), except for the behavior of the macrophages phagocytosing the particles.     

The Normal and Malignant Mammary Gland: A Fresh Look with ERβ Onboard

Estrogens are important for the development and function of the normal mammary gland as well as for development of mammary cancer. The frontline therapy for treatment of estrogen receptor (ER)⁴ positive breast cancer is antiestrogens. A second estrogen receptor (ER) is also expressed in the breast but it has not been measured because it is not detected by the immunoassays used to detect ER. In many cell systems ER has actions which are opposite to those of ER and this finding has raised questions about the role of ER in the development and treatment of breast cancer.     

Primary bladder neck obstruction

Summary Primary bladder neck obstruction is not uncommon in young and middle age men. The symptoms are confounding and routine urologic investigation including cystometry, uroflow, voiding cystourethrography and cystourethroscopy often leads to an erroneous diagnosis of psychogenic voiding dysfunction, neurogenic bladder or prostatitis. An accurate diagnosis can be obtained by the simultaneous measurement of detrusor pressure and uroflow, preferably accompanied by radiographic visualization of the lower urinary tract during micturition. Treatment with bladder neck incision is usually curative, but often results in retrograde ejaculation.     

Flow cytometric study on cell kinetics of brain tumours and their cultured cells

Summary With the aid of flow cytometry (FCM), distribution of DNA content in 40 cases of brain tumour, primary culture cell, and secondary culture cell can be determined and chronological change after subculture is studied from the analysis of their cell cycle. In most primary cultures, proliferating index (PI) is likely to decrease, which suggests that environmental change might affect the growth activity. In comparison with that of the original sample, DNA-histogram of the secondary culture can be divided into the following 3 types: the type recovering to the original pattern (adapting type), in which astrocytoma, ependymoma, glioblastoma and medulloblastoma are included, 2) the type increasing more at G2 + M phase than the original (proliferating type), in which meningioma and some of glioblastoma are included, and 3) the type decreasing so far as to induce degeneration or death (degenerating type), in which pituitary adenoma and neurinoma are included. FCM is of great usefulness for the study of cell kinetics of a tumour cell undergoing culture and the present method will be available for the respective study of biological characteristics of the cultured cell, established cell line or sensitivity test for antineoplastic agents.     

Small intestinal lymphoma

This paper reviews small intestinal lymphoma. Although a major emphasis is placed on primary small intestinal lymphoma of the Western type, the important topic of lymphoma in celiac disease is discussed. Our own recent experience of 7 patients with lymphoma in celiac disease is presented. The lymphoma of immunoproliferative small intestinal disease (Mediterranean lymphoma) and the associated -chain disease are also reviewed, with emphasis on the differences from the Western type of primary small intestinal lymphoma.

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Resumen Este artículo revisa el tema del linfoma intestinal. Aunque se hace énfasis principal en el linfoma intestinal primario del tipo Occidental, también se discute el tópico relativo al linfoma en la enfermedad celiaca. Se presenta un estudio sobre nuestra experiencia reciente con 7 pacientes con linfoma en enfermedad celiaca. También se revisan la enfermedad inmunoproliferativa del intestino delgado (linfoma Mediterráneo) y la enfermedad de cadena asociada, con énfasis en sus diferencias con el tipo Occidental de linfoma primario del intestino delgado.

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Résumé Cet article est consacré au lymphome de l'intestin grÊle. Bien que centré sur le lymphome primitif (dit lymphome de type occidental) il concerne également le lymphome qui traduit une manifestation d'une maladie immunoproliférative de l'intestin (qualifié de lymphome de type méditerranéen) et ce à partir d'une expérience de 7 malades présentant une maladie coeliaque. Ce second type et la maladie associée de la chainealpha sont également étudiés en s'attachant à souligner les éléments distinctifs qui les séparent du lymphome primitif.

     

Early aseptic loosening of cemented total hip arthroplasty: the influence of non-steroidal anti-inflammatory drugs and smoking

The purpose of this study was to investigate whether the clinical variables of non-steroidal anti-inflammatory drugs (NSAID) usage and cigarette smoking are possibly linked to aseptic loosening around total hip arthroplasty (THA). We performed a retrospective review of the records and radiographs of 224 patients attending for follow-up at Wrightington Hospital between August 2002 and 2003 who had undergone THA. The following information was recorded: age, gender, primary and revision surgery details, radiographic parameters, smoking history and NSAID usage history. Logistic regression analysis was used to determine if there is any statistically significant association between NSAID usage or smoking habit and aseptic loosening. No such association was found.

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Résumé Le but de cette étude était de chercher si les variables cliniques que sont lusage danti-inflammatoires non stéroidiens (AINS) et la consommation de cigarettes pouvaient être liées au descellement aseptique dune arthroplastie de la hanche. Nous avons fait une étude rétrospective des registres et des radiographies de 224 malades revus dans lInstitution entre août 2002 et 2003 et qui avait subi une arthroplastie totale de la hanche. Les informations suivantes ont été enregistrées: âge, genre, détails de la chirurgie primaire et de la chirurgie de révision, paramètres radiographiques, histoire de la consommation tabagique et de lusage dAI NS. Lanalyse régressive a été utilisée pour déterminer sil y avait une association statistiquement notable entre lusage dAINS ou lhabitude de fumer et le descellement aseptique. Aucune association na été trouvée.

     

Die Bedeutung des Antikörpermangelsyndroms für die Chirurgie

Zusammenfassung Bedeutung und Form des Antikörpermangelsyndroms (Synonyma in der Literatur: A- und Hypogammaglobulinämie, Immunkörperparese, Immunkörpermangel) werden beschrieben. Für die Diagnose und erforderliche Therapie sind die anamnestischen und klinischen Daten (Kette von Infektionen; schwerer Verlauf blander Infektionen; klinischer Verlauf durch Antibiotica allein unbeeinflußbar, durch Kombination mit -Globulinlösung gut beeinflußbar; Summation von Infekten mehrerer Organe in der postoperativen Phase) wichtiger als die Laboratoriumsdaten (A- und Hypogammaglobulinämie durch Papier- oder Immunoelektrophorese oder Fehlen des -Globulinanstieges im akuten Stadium der Infektion; Ausbleiben der Antikörperbildung nach Immunisierung).Für die Therapie akuter, insbesonder septischer Infektionen werden empfohlen:Alle 6 Std 0,2 g/kg Körpergewicht=10 ml der 16% igen -Globulinlösung intramuskulär oder 10 ml der 5% igen Lösung intravenös (max. 50–60 ml).Wenn aus anderen Gründen (Flüssigkeits- und Elektrolytersatz) eine Infusionstherapie angezeigt ist, kann man 20–40 ml der 5% igen -Globulinlösung der Infusionslösung zufügen.Als Erhaltungsdosis bei besonderer Infektionsgefährdung sind 0,2 g/kg Körpergewichtmonatlich ausreichend, d.h. pro Woche 10 ml der 16% igen Lösung intramuskulär.Fünf eigene Fälle mit AMS und die Erfahrungen mit der -Globulintherapie bei etwa 30 Patienten werden beschrieben.Mit 1 TextabbildungHerrn Professor Dr.A. Fromme zur Vollendung des 80. Lebensjahres.