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M Sachs

Publications and source records attributed to M Sachs.

At least 73 records · Page 4Linked to original sources

[From the history of surgical instruments: 3. The dressing forceps (16th century)].

The dressing forceps ("Kornzange") is one of the very few surgical instruments that have extensively preserved its form, its function and even its name throughout the centuries. In the Germany of the 16th century, the dressing forceps was mentioned as a widely used instrument among the barber-surgeons (Stromayr 1559, Ryff 1559). At that time, it mostly found use as a foreign body removing forceps. The dressing forceps can be traced back until today in German or English surgery instrument-books in nearly unchanged shape.

Barber Surgeons↗

[Not Available].

Explore the source record for details and available documents.

General Surgery↗

[The history of surgical instruments: 1. The Mikulicz peritoneal clamp].

The peritoneal clamp, which has been developed by the Breslau surgeon Johann von Mikulicz-Radecki (1850-1905), is presented on the basis of original publications from 1900. At this time, Mikulicz had been a full professor of surgery at the Medical Faculty of the University of Breslau. After laparotomy, Mikulicz recommended to seize the peritoneum with 4 to 8 clamps, developed by him to protect the wound of the abdominal wall from manipulations and to prevent a retraction of the peritoneum: "The fastened clamps are changed in their position in a way, that the grips lie out of the area of the wound on the abdominal wall." Moreover, a brief description of the Breslau surgeon's life and work is given. Further, we refer on his importance on the development of modern surgery in Germany.

History, 19th Century↗

Biochemical and functional characterization of the murine ros protooncogene.

The ros gene was originally found because it can, when mutated, induce malignant transformation. The protooncogene encodes an orphan receptor tyrosine kinase. We report here the isolation and characterization of the mouse c-ros cDNA and, in addition, the biochemical characterization of the receptor. Both, the endogenous c-ros protein from embryonal tissues and the recombinant protein are glycosylated molecules with an apparent molecular weight of 260,000. Pulse-chase analysis in Sf9 cells demonstrates that the c-ros protein is synthesized as a single chain, uncleaved molecule. Since the specific ligand of c-ros is not known, a hybrid receptor (trk/c-ros) which transmits c-ros-specific signals in response to nerve growth factor (NGF) was used to study the biological activities. In NIH3T3 cells, this trk/c-ros hybrid induces growth, a fusiform cell shape, and loss of contact inhibition of growth. However, the active hybrid receptor cannot replace IL-3 as survival factor in 32D myeloid cells. Compared to other receptors, the active c-ros tyrosine kinase domain displays thus overlapping, but not identical signalling specificities.

3T3 Cells↗

[Entero-enteral invagination of the small intestine in adults. A rare cause of "uncertain abdomen"].

The present paper reports on a 43-year-old female patient who complained over a number of weeks of paroxysms of crampy pain in the mesogastrium. The diagnosis of ileoileal invagination was only made after she had been admitted to hospital for the third time. The following false diagnoses had been made during the 4-week course of the condition: "pyelonephritis", "acute appendicitis", "chronic appendicitis" and, most recently "psychosomatic abdominal distress". The patient was initially treated with antibiotics and finally with psychotropic drugs. Eventually ultrasound suggested the diagnosis of invagination of the small intestine, which was then verified by conventional barium follow-through radiography. The patient subsequently underwent resection of a segment of the small intestine. Entero-enteric invagination is a very rare event in adults, in which a single (often malignant) cause is identified as triggering the invagination. Peristalsis and ingested food push the tumor distad, thus acting as a motor for invagination. The preferred localizations are the junctions between freely moving segments to retroperitoneally fixed segments (e.g., ileocecal region). Ultrasound of the abdomen is the examination of choice for diagnosis of enteroenteric invagination. Surgical resection of the invagination and its cause (generally tumors) is indicated in adults.

Abdomen, Acute↗

[Repeated perioperative administration of fructose and sorbitol in a female patient with hereditary fructose intolerance [HFI)].

The present paper reports on an adult female patient whose hereditary fructose intolerance (HFI) was at first not diagnosed and who, within the space of 2 years after repeated elective surgery and the perioperative administration of fructose and sorbitol, developed "hepatic and renal failure of unclear origin." At a later stage we were able to establish the diagnosis of HFI by means of a fructose tolerance test in both she and her brother, for whom intolerance to fruit and desserts had been known since early childhood. In addition, literature references to fatalities following the parenteral application of fructose and sorbitol were analyzed. During the course of fructose infusion in both the patient and her brother with HFI, the following metabolic changes were noted: hypoglycemia, elevated rise in the blood fructose concentration, hyperlactacidemia, elevated rise in the blood fructose concentration, hyperlactacidemia, and hyperammonemia. These metabolic changes proved to be reversible after discontinuing the fructose infusion. Analysis of the literature on the fatalities following parenteral fructose administration established that fruit and dessert intolerance was known for all collated patients with HFI, and that, clearly, no regular metabolic tests had been conducted.

Acute Kidney Injury↗

The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells.

Depending on the target cells and culture conditions, scatter factor/hepatocyte growth factor (SF/HGF) mediates several distinct activities, i.e., cell motility, proliferation, invasiveness, tubular morphogenesis, angiogenesis, or cytotoxicity. A small isoform of SF/HGF encoded by a natural splice variant, which consists of the NH2-terminal hairpin structure and the first two kringle domains but not the protease homology region, induces cell motility but not mitogenesis. Two types of SF/HGF receptors have recently been discovered in epithelial cells, the high affinity c-Met receptor tyrosine kinase, and low affinity/high capacity binding sites, which are probably located on heparan sulfate proteoglycans. In the present study, we have addressed the question whether the various biological activities of SF/HGF are transduced into cells by a single type of receptor. We have here examined MDCK epithelial cells transfected with a hybrid cDNA encoding the ligand binding domain of the nerve growth factor (NGF) receptor and the membrane-spanning and tyrosine kinase domains of the Met receptor. We demonstrate that all biological effects of SF/HGF upon epithelial cells such as the induction of cell motility, proliferation, invasiveness, and tubular morphogenesis can now be triggered by the addition of NGF. Thus, it is likely that all known biological signals of SF/HGF are transduced through the receptor tyrosine kinase encoded by the c-Met protooncogene.

Amino Acid Sequence↗

Properties and functions of scatter factor/hepatocyte growth factor and its receptor c-Met.

Scatter factor (SF), a cell motility factor with a multimodular structure, is identical to hepatocyte growth factor (HGF), a potent mitogen of various cell types. The receptor for SF/HGF has recently been identified as the c-Met proto-oncogene product, a transmembrane receptor tyrosine kinase. Depending on the target cells and culture conditions, SF/HGF has several distinct activities in vitro, i.e., it induces cell motility, proliferation, invasiveness, tubular morphogenesis, angiogenesis, or cytotoxicity. In vivo, SF/HGF might be involved in tissue regeneration, tumor progression, and embryological processes.

Amino Acid Sequence↗

[Effect of extrahepatic cholestasis on amino acid metabolism in the animal experiment].

UNLABELLED: The knowledge of pathobiochemical processes in extrahepatic cholestasis is one of the prerequisites for the application of infusion solutions adjusted to meet the requirements. Early changes of amino acid metabolism in rats after bile-duct ligation, which indicate disorders in the urea cycle are reported. For this purpose 60 male Wistar rats were laparotomized and the common bile duct was twice ligated under narcosis with pentobarbital. Exsanguination of the animals from the aorta abdominalis occurred after 3, 6, 12, 24, 48 and 72 hours. Analysis of the free amino acids in serum was performed by means of middle pressure liquid column chromatography at fully automatic analytical apparatus (Liquimat III, Kontron). RESULTS: Of 23 free amino acids investigated in serum only Ornithin and Arginin showed significant changes in their serum concentrations after ligature of the common bile duct. The increase of the serum concentration of Ornithin and the simultaneous decrease of Arginin suggests the inhibition of the urea cycle induced by resorptive jaundice. This might be due to the inhibition of the ATP-dependent, mitochondrial carbamyl phosphate synthetase or to the activation of the cytoplasmatic arginase.

Amino Acids↗

[Repair procedures in surgery of inguinal hernia in their historical evolution].

The last decades have witnessed a great number of "novelties" published for inguinal hernia surgery. However, these are generally modifications of well-known operative procedures. The sole genuinely new method is laparoscopy for which, however, no long-term results are available. An analysis of original articles shows that all surgical techniques for repair of the hernial orifice can be traced back to two simple repair principles: 1) reinforcement of the anterior wall of the inguinal canal and tightening of the external inguinal ring [Stromayr 1559, Purmann 1692, Czerny 1877]. 2) reinforcement of the posterior wall of the inguinal canal and tightening the internal inguinal ring a) externally [Lucas-Championnière 1881, Bassini 1889, Brenner 1898, Lotheissen 1898, McVay 1942, Shouldice 1945, Lichtenstein 1987, Stoppa 1989] or b) via an intra-abdominal approach (by laparotomy [Tait 1891] or laparoscopically [Ger 1990, Velez und Klein 1990]).

Europe↗

[Classification of acute pancreatitis from a surgical viewpoint].

Since it has been not yet proved possible to establish an internationally accepted, uniform classification for inflammatory disorders of the pancreas, the present review contrasts and compares the various classifications for acute pancreatitis, and points out the advantages and disadvantages for surgeons in clinical practice. All the categories published so far have been based principally on five different classification criteria: the clinical course (e.g. acute, chronic) histological findings (e.g. oedematous, necrotising), aetiological factors (e.g. biliary ethyltoxic), biochemical parameters (not specifically) with prognostic value (e.g. CRP), or the morphology of the inflammatory process as shown on a CT scan. At present, a reliable, reproducible and clinically applicable classification of acute pancreatitis can only be achieved on the basis of the CT scan with concurrent intravenous contrast medium injections (contrast-enhanced computed tomography). A combination of clinical and CT findings has proven a valuable support for the surgeon, especially in defining the indications for surgery.

Acute Disease↗

[Study of the pancreas and its inflammatory diseases from the 16th-19th century].

The author describes the development of medical research since the 16th century based on a literary review of the study of the anatomy, physiology and pathology of the pancreas. The anatomical basis was first created in the 17th century when the pancreatic duct was discovered (J.C. Wirsung 1642) and the duodenal papilla was described (J.K. Brunner 1683, C.B. Holdefreund 1713 and A. Vater 1750). The physiological function of the pancreas as a secretary gland was first experimentally investigated by R. Graaf (1671). A few decades later the enzymatic breakdown of nutrients by pancreatic juice was demonstrated in animal experiments (G. Valentin 1844, Cl. Bernard 1849). The earliest case reports of patients dying of suppurative inflammation or tumours of the pancreas were presented by S. Alberti (1578), J. Schenck (1600), and N. Tulp (1641). The presence of fatty necrosis in acute pancreatitis was first indicated by W. Balser (1882), and the autodigestive genesis was suspected by H. Chiari (1896). The discovery in the 19th century that diabetes mellitus occurs in dogs following total pancreatectomy (J. von Mering and O. Minkowski 1890) and the first operation on a pancreatic cyst by "marsupialisation" (C. Gussenbauer 1883) as well as the emergence of the connection between cholelithiasis and acute pancreatitis (E.L. Opie and W. St. Halsted 1901) laid the foundation for 20th century research.

Animals↗

Molecular characteristics of HGF-SF and its role in cell motility and invasion.

Scatter factor (SF), a secretory protein of fibroblasts, dissociates and increases the motility of epithelial cells and may be involved in cell migration processes during embryogenesis and tumor progression. Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and other cells, and is thought to play a role in liver regeneration. We have presented structural and functional evidence that human SF and human HGF are identical proteins encoded by a single gene, since (i) no differences could be found by protein sequencing, by cDNA analysis, or by immunological comparison, and (ii) SF acts as a hepatocyte growth factor--i.e., stimulates DNA synthesis of primary hepatocytes and is a morphogen of kidney epithelial cells--whereas HGF exhibits SF activity--i.e., dissociates and induces invasiveness of various epithelial cells. Furthermore, there exists only one gene for human HGF-SF which is located on chromosome 7, bands q11.2-21 (Weidner et al., Proc. Natl. Acad. Sci. USA 88, 7001-7005, 1991). HGF-SF has been found to be the ligand of the c-met receptor tyrosine kinase (Naldini et al., EMBO J. 10, 2867-2878, 1991b). We have recently used transient expression of naturally occurring and in vitro mutagenized cDNAs of HGF-SF in order to delineate the protein domains necessary for biological activity and c-met receptor activation. (i) A single-chain HGF-SF resulting from the destruction of the protease cleavage site between heavy and light chain (Arg494 to Gln) was largely inactive, indicating that proteolytic cleavage is essential for acquisition of the biologically active conformation. (ii) A HGF-SF splice variant encoding a protein with a 5 amino acid deletion in the first kringle domain was as highly active as the wild type molecule. (iii) The separately expressed light chain (with serine protease homology) was inactive in all assays tested. (iv) The separate heavy chain as well as a naturally occurring splice variant consisting of the N-terminus and the first two kringle domains bound the met receptor, stimulated its tyrosine phosphorylation, and induced dissociation of epithelial cells but not mitogenesis. These data indicate that a functional domain in the N-terminal region and/or the first two kringle domains of HGF-SF is sufficient for binding to and activation of the met receptor (Hartmann et al., Proc. Natl. Acad. Sci. USA, in press).

Animals↗

[Ménétrier disease--a rare disease of the stomach].

The present reports on a 51-year-old patient who presented with weight loss, anaemia, hypoalbuminaemia and ankle oedema, and was referred for laparotomy by a radiologist on the grounds of suspected carcinoma of the stomach suggested by an upper gastrointestinal x-ray series. Surgery revealed excessively thickened rugae with gyrus-like, tortuous surface epithelium folds (histologically Ménétrier's disease). A gastrectomy was performed, and the patient has been symptom-free and active ever since. In addition, the author presents a review of the literature published to date describing case reports of patients with Ménétrier's disease. Ménétrier's disease is a benign condition of the gastric mucosa in which gastric loss of albumin has been shown to be responsible for hypoalbuminaemia. The diagnostic procedure of choice is gastroscopy because upper gastrointestinal x-ray series cannot distinguish between carcinoma of the stomach with certainty. Since this is a chronic disease that does not respond to medication, treatment of choice today is (partial) gastrectomy dictated by the extent and severity of the findings.

Diagnosis, Differential↗

A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis.

We recently found that scatter factor (SF), a cell motility factor with a multimodular structure, is identical to hepatocyte growth factor (HGF), a potent mitogen of various cell types. SF/HGF is the ligand of the c-Met receptor tyrosine kinase. Here we used transient expression of naturally occurring and in vitro mutagenized cDNAs of SF/HGF to delineate the protein domains necessary for biological activity and binding to the c-Met receptor. (i) A single-chain SF/HGF resulting from the destruction of the protease cleavage site between heavy and light chain (Arg-494--> Gln) was largely inactive, indicating that proteolytic cleavage is essential for acquisition of the biologically active conformation. (ii) A SF/HGF splice variant encoding a protein with a 5-amino acid deletion in the first kringle domain was as highly active as the wild-type molecule. (iii) The separately expressed light chain (with serine protease homology) was inactive in all assays tested. (iv) The separate heavy chain as well as a naturally occurring splice variant consisting of the N terminus and the first two kringle domains bound the c-Met receptor, stimulated tyrosine auto-phosphorylation, and induced scattering of epithelial cells but not mitogenesis. These data indicate that a functional domain in the N terminus/first two kringle regions of SF/HGF is sufficient for binding to the Met receptor and that this leads to the activation of the downstream signal cascade involved in the motility response. However, the complete SF/HGF protein seems to be required for mitogenic activity.

Amino Acid Sequence↗

Detection of human immunodeficiency virus type 1 provirus in mononuclear cells by in situ polymerase chain reaction.

BACKGROUND: Studies of human immunodeficiency virus type 1 (HIV-1) infection have attempted to quantitate the viral load correlate it with the degree of immune deficiency. In one study, only about 1 in 10,000 peripheral-blood mononuclear cells (PBMC) expressed HIV-1, but in other studies, at least 1 in 100 CD4-positive cells was infected and harbored the HIV-1 provirus. METHODS: We developed a new, highly sensitive in situ polymerase-chain-reaction (PCR) method that amplifies selected genetic regions within intact single cells. We used this technique to determine the proportion of PBMC carrying HIV-1 provirus in infected patients in different stages of disease. RESULTS: None of the PBMC from 11 HIV-1--seronegative patients were found to be positive for HIV-1 provirus by the in situ PCR method. In 56 patients infected with HIV-1, the percentage of PBMC with HIV-1 ranged from 0.1 percent to 13.5 percent. The mean percentage of infected mononuclear cells was greater in 13 patients with persistent generalized adenopathy (mean, 6.6 percent) and 19 with the acquired immunodeficiency syndrome (Stages IV-A to IV-C) (4.6 percent) than in 19 patients with asymptomatic HIV-1 infection (0.9 percent) (P less than 0.001). However, in five patients with Kaposi's sarcoma (Stage IV-D), an average of only 1.6 percent of mononuclear cells were infected. CONCLUSIONS: In HIV-1 infection, the proportion of PBMC that are infected appears to be at least 10 times higher than previously described. It is likely that most infected cells contain HIV-1 provirus in a latent or defective form that was not detected in some earlier studies.

Acquired Immunodeficiency Syndrome↗

Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor.

The extracellular protease urokinase is known to be crucially involved in morphogenesis, tissue repair and tumor invasion by mediating matrix degradation and cell migration. Hepatocyte growth factor/scatter factor (HGF/SF) is a secretory product of stromal fibroblasts, sharing structural motifs with enzymes of the blood clotting cascade, including a zymogen cleavage site. HGF/SF promotes motility, invasion and growth of epithelial and endothelial cells. Here we show that HGF/SF is secreted as a single-chain biologically inactive precursor (pro-HGF/SF), mostly found in a matrix-associated form. Maturation of the precursor into the active alpha beta heterodimer takes place in the extracellular environment and results from a serum-dependent proteolytic cleavage. In vitro, pro-HGF/SF was cleaved at a single site by nanomolar concentrations of pure urokinase, generating the active mature HGF/SF heterodimer. This cleavage was prevented by specific urokinase inhibitors, such as plasminogen activator inhibitor type-1 and protease nexin-1, and by antibodies directed against the urokinase catalytic domain. Addition of these inhibitors to HGF/SF responsive cells prevented activation of the HGF/SF precursor. These data show that urokinase acts as a pro-HGF/SF convertase, and suggest that some of the growth and invasive cellular responses mediated by this enzyme may involve activation of HGF/SF.

Animals↗