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Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 487 records · Page 27Linked to original sources

Stereoselective synthesis of 1,1-dialkyl-1-methoxymethyl glucosides (acetal-glucosides).

The synthesis is described of highly acid-sensitive, 1,1-dialkyl-1-methoxymethyl glucosides (acetal-glucosides) as potential anti-cancer prodrugs. Reaction of 2,3,4,6-tetra-O-acetyl-1-O-trimethylsilyl-beta-D-glucopyranose (4) severally with various aliphatic and alicyclic ketones and methyl trimethylsilyl ether, in the presence of catalytic amounts of trimethylsilyl trifluoromethanesulfonate, afforded the corresponding acetylated acetal-beta-glucosides, e.g., acetone gave 1-methoxy-1-methylethyl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside (7a). Likewise the alpha-anomer (8a) of 7a was obtained from the alpha-anomer of 4. Deacetylation of the tetra-acetates then gave the acetal-alpha- and -beta-glucosides.

Acetals↗

Cloning, sequencing and overexpression of the mannitol-specific enzyme-III-encoding gene of Staphylococcus carnosus.

The gene which encodes the mannitol-specific enzyme III (EIIImtl) of the phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus carnosus, has been cloned. Genomic libraries of S. carnosus DNA were constructed using the expression vector pUC19 and EIIImtl-producing clones were identified using rabbit polyclonal antiserum. A 700-bp Dde I fragment, containing the complete gene encoding EIIImtl, was sequenced by the dideoxy chain-termination technique. Upstream from the ORF for EIIImtl one can find a sequence analogous to that of the Escherichia coli promoter. This region acts as a strong promoter when subcloned into the promoter test vector M13HDL17. EIIImtl was overproduced using the inducible T7 polymerase system and purified to homogeneity. Amino acid sequence comparison confirmed a 38% similarity to the hydrophilic enzyme-III-like portion of enzyme IImtl of E. coli. There is also a 36% similarity to the N terminus of the fructose-specific phospho-carrier protein from E. coli.

Amino Acid Sequence↗

[Histomorphologic findings of the bone marrow in chronic myeloproliferative diseases].

Our survey on the histology of the bone marrow in chronic myeloproliferative disorders (CMPD) basically gives a description of the relevant lesions of the different subtypes (i.e. chronic myeloid leukemia, primary osteomyelofibrosis, polycythemia vera rubra, and primary thrombocythemia) in correlation with important clinical findings, such as the myelofibrosis/sclerosis syndrome, blast crisis, and prognosis. In a schematic presentation, we assigned the main features of hematopoiesis, interstitial space, and bone tissue to the various subtypes of CMPD, taking into consideration, as well, the evolution of histomorphological lesions in the course of the disease process, which could be determined by means of sequential biopsies. Particularly in the early hyperplastic stages of primary osteomyelofibrosis and in primary (essential) thrombocythemia, we observed a considerable elevation of the platelet count, possibly leading to thrombosis and hemorrhage.

Bone Marrow↗

Proton-mediated liberation of aldophosphamide from a nontoxic prodrug: a strategy for tumor-selective activation of cytocidal drugs.

Based on the findings that the pH in malignant tumors can be preferentially decreased by stimulation of their aerobic glycolysis, acid-sensible prodrugs, which are nearly nontoxic at physiological pH, were synthesized. At lower pH, however, these compounds are cleaved with liberation of a cytotoxic species. The prototypic drug compound 2-hexenopyranoside of aldophosphamide was prepared, which releases aldophosphamide by acid-catalyzed hydrolysis. Exposure of cultured M1R rat mammary carcinoma cells to this agent at pH 7.4 only resulted in slight toxicity. However, when drug treatment was performed at pH 6.2, the mean pH in malignant tumors of hyperglycemic hosts, the colony-forming fraction of M1R cells decreased to 0.05 and 0.0001 of controls treated at pH 7.4 after exposure for 24 h and 48 h, respectively. The synthesis of the 2-hexenopyranoside of aldophosphamide is described in detail.

Animals↗

La différence.

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Body Composition↗

Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/-sclerosis (agnogenic myeloid metaplasia)--correlations between clinical and morphological features.

Histomorphometry was performed on representative trephine biopsies of the bone marrow on admission of 50 patients (21 male, 29 female - age 67 years) with so-called primary osteomyelofibrosis/-sclerosis (OMF) not preceded by any other subtype of chronic myeloproliferative disorders. This study was firstly aimed at testing correlations between histological features (amount of haematopoiesis, cytological aspects of megakaryocytes, density of reticulin and collagen fibres and degree of osteosclerosis) and laboratory data, as well as spleen size and duration of relevant prediagnostic symptoms. Secondly, we concentrated on a discrimination of OMF patients into two subgroups according to bone marrow morphology and clinical variables. Statistical evaluation of histomorphometric variables and haematological findings disclosed that there was a progressive fibro-osteosclerotic process in the evolution of disease features. Increase in medullary fibrosis was significantly paralleled by an abnormal or pleomorphic megakaryopoiesis in the bone marrow: there was an increase in irregularity of perimeters for megakaryocytes and naked nuclei combined with smaller sizes of these elements including the nuclei. Additionally, there was a greater number of pycnotic bare nuclei. A number of morphometric features (density of fibres, degree of osteosclerosis, amount of haematopoiesis) were associated with corresponding clinical data (spleen size, length of preclinical history). By consideration of a set of basic histomorphometric variables our cohort of 50 patients could be divided into an early hyperplastic subtype with no or minimal medullary reticulin and another group with conspicuous fibrotic and osteosclerotic alterations of the bone marrow. It was noticeable that we found no significant correlation between amount of haematopoiesis or marrow cellularity with splenomegaly. This result suggests that splenic haematopoiesis (myeloid metaplasia) may represent an autonomous or neoplastic process and not only compensation for a failing fibro-osteosclerotic bone marrow.

Aged↗

[Recommendation for primary resection with primary anastomosis in complicated sigmoid diverticulitis. Report of experiences of the Herford Surgical Clinic 1973 to 1986].

Of the 107 patients with complicated diverticulitis operated from 1973-1986 47 were females and 60 males. In 14 of the 107 patients a perforated diverticulitis with diffuse purulent/faecal peritonitis was found, a perforated diverticulitis with localized purulent peritonitis/paracolic abscess in 68 patients and an acute phlegmonous diverticulitis without perforation in 25 patients. Additional pathologic findings were internal fistulae (13 patients), necrotizing fasciitis (3 patients), obstruction (3 patients) and synchronous carcinoma (7 patients). The overall mortality of the 107 patients was 9.3% (= 10 patients) and the morbidity of the 97 survivors 34% (= 33 patients). The mortality of the 14 patients with perforated diverticulitis and diffuse purulent peritonitis was 50% of the 68 patients with perforated diverticulitis and localized purulent peritonitis 4.4% and of the 25 patients with acute phlegmonous diverticulitis 0%. Seven of the 10 patients died after operation of the perforated diverticulitis with diffuse purulent peritonitis - 1 (5) after primary resection with primary anastomosis. 3 (5) after Hartmann procedure, 3 (4) after loop colostomy alone. Three patients died after operation of the perforated diverticulitis with localized purulent peritonitis - 2 (6) after Hartmann procedure, 1 (5) after loop colostomy alone. In spite of forcing the primary resection with primary anastomosis in the years from 1980 - 1986 the mortality decreased for these operations from 35.7% in 1973 - 1979 to 0% in 1980 - 1986. The indication of primary resection with primary anastomosis is justified also for perforated diverticulitis with localized and diffuse peritonitis.

Adult↗

Osteoclasts and bone remodeling in chronic myeloproliferative disorders. A histochemical and morphometric study on trephine biopsies in 165 patients.

In 165 patients with chronic myeloproliferative disorders (CMPD) a morphometric and histochemical study was performed on trephine biopsies of the bone marrow to elucidate osseous remodeling by assessment of trabecular bone area (planimetry) and number of osteoclasts. Osteoclastic elements were identified by the tartrate-resistant acid phosphatase method. In addition to control specimens (n = 20) subtypes of CMPD included chronic myeloid leukemia (CML, n = 65), primary (essential) thrombocythemia (PTH, n = 25), polycythemia vera rubra (P. vera, n = 25) and agnogenic myeloid metaplasia (AMM, n = 50). AMM was discriminated into a so-called early hyperplastic stage without gross myelofibrosis (n = 19) and an overt or advanced stage showing fibro-osteosclerotic changes (n = 31). Total area of trabecular bone and counts for osteoclasts (uni- and multi-nucleated cells as well as a-nuclear cytoplasmic fragments) were not significantly increased in CML, PTH, P. vera and in the initial hypercellular stages of AMM. In contrast to these results, in advanced stages of AMM there was a significant increase in total bone area associated with a high count for all osteoclastic elements and apparently also an increased number of osteoblasts. It is speculated that the marked increase in osteoclastic-osteoblastic elements in late stages of AMM possibly reflects an imbalance of calcitriol (1.25-dihydroxyvitamin D 3) on skeletal homeostasis. This abnormal osseous remodeling may be mediated by the atypical megakaryocytic proliferation in this disorder, which is always a conspicuous feature of bone marrow biopsies.

Biopsy↗

[Pathogenicity of the open processus vaginalis peritonei].

In 100 postmortem examination on adults whose age at the time of death had been between 21 and 85 years, an only partially obliterated processus vaginalis or Nuck's diverticulum was seen in 29 cases. Whereas in women the peritoneal bulges often represented only pointers to a patent diverticulum, never being longer than 1 cm, in every fourth man there was a unilateral or bilateral processus longer than 2 cm and wider than 0.5 cm. However, none of the p.m. examined adults had been suffering from inguinal hernia during lifetime. The results point to the possible conclusion that persistence of a processus vaginalis without development of hernia is by no means unusual--in fact, it is even normal. Since the alleged pathogenicity of the patent processus supplies the basis for applying herniography and contralateral exploration, we must doubt whether this procedure is justified. In addition, it must be borne in mind that both x-ray diagnosis and surgery of processus vaginalis can be associated with risks, such as excessive radioexposure of the gonads and atrophy of the testes as a result of lesions of the spermatic cord system. Even if these risks are kept at a minimum, the following reasons can be advanced against the x-ray method and hence also routine bilateral herniotomy: 1. the processus vaginalis is already obliterated; herniography and surgery would be unnecessary; 2. a patent processus vaginalis can be obliterated on its own even after x-ray demonstration; 3. a patent processus is not a hernial sac and will not necessarily result in subsequent inguinal hernia.

Adult↗

Usefulness of trehalose fermentation and L-glutamic acid decarboxylation for identification of biochemically aberrant Providencia stuartii strains.

A total of 849 Providencia isolates were collected during a 4-year period when an increased incidence of nosocomial Providencia stuartii infection was noted in urologic wards. Of these isolates, 630 were identified as P. stuartii, 206 were identified as Providencia rettgeri, and 1 was identified as Providencia alcalifaciens. Twelve inositol-positive isolates from 10 patients (10 strains) resembled P. stuartii in fermenting trehalose but resembled P. rettgeri in fermenting D-arabitol or meso-erythritol or both. The latter traits, however, were not stable in all cases. These aberrant strains were identified as P. stuartii on the basis of their O antigens and DNA hybridization experiments. All isolates were tested for L-glutamic acid decarboxylase activity by a qualitative thin-layer chromatography method. All P. stuartii isolates, including the aberrant ones, were trehalose positive and L-glutamic acid decarboxylase negative. None of the P. rettgeri isolates fermented trehalose, while 99.0% of them and the single P. alcalifaciens strain were L-glutamic acid decarboxylase positive. Thus, trehalose fermentation and L-glutamic acid decarboxylation are more useful for separating P. stuartii from P. rettgeri than are D-arabitol and meso-erythritol fermentation.

DNA, Bacterial↗

Primary (essential) thrombocythemia versus initial (hyperplastic) stages of agnogenic myeloid metaplasia with thrombocytosis--a critical evaluation of clinical and histomorphological data.

In 40 patients (17 male, 23 female, median age 57 years) with the presumptive diagnosis of primary (essential) thrombocythemia (PTH) according to the diagnostic requirements of the Polycythemia-Vera-Study-Group (PVSG) a follow-up study and a histological evaluation of initial trephine biopsies of the bone marrow were performed. Thorough review of the hematological data during the lengthy course of disease (observation time ranging from 1.5-10.5 years) and the histomorphology of the bone marrow implied a discrimination into two groups of patients. Group I patients (n = 26; 10 male, 16 female) were compatible with PTH according to our follow-up studies. Group II patients consisted of 14 cases (7 male, 7 female) which suggested retrospectively early hyperplastic stages of agnogenic myeloid metaplasia (AMM) with concomitant thrombocytosis. In PTH (group I patients) there was a sustained elevation of the platelet count lasting for several years accompanied by stable other blood values. Early AMM (group II patients) was characterized by an insidious decline of the initially elevated thrombocyte count, starting in a few patients already 4-6 months after admission. In AMM there was further an increase in hepatosplenomegaly observable together with the level of LDH and the score of the leukocyte alkaline phosphatase, and finally an evolution of a leukoerythroblastic blood picture could be noticed. Initial histopathology of the bone marrow revealed a profound proliferation of a not severely dysplastic megakaryopoiesis in group I patients (PTH) and a normal content of reticulin fibers. In early thrombocythemic AMM (group II patients) conspicuous abnormalities of megakaryocytes were accompanied by a slight to moderate increase in argyrophilic fibers and a left-shifted neutrophilic granulocyto- as well as erythropoiesis. These differences of certain histomorphological features could be substantiated by morphometric analysis. Our findings suggest that even the rigid requirements for the diagnosis of PTH as proposed by the PVSG may not be sufficiently restrictive to exclude patients with early hyperplastic stages of thrombocythemic AMM.

Biopsy, Needle↗

Blunt chest trauma. Extrapericardial cardiac tamponade by a mediastinal hematoma.

Mediastinal hematoma resulting from blunt chest trauma can cause compression of the right ventricle and extrapericardial cardiac tamponade. The diagnosis in this instance was aided by conventional two-dimensional echocardiography in addition to hemodynamic measurements. The atypical aspects of this form of cardiac tamponade are discussed.

Cardiac Tamponade↗

[Topography and mechanisms of adhesion of uropathogenic Escherichia coli bacteria in the human kidney and renal pelvis].

The occurrence and significance of bacterial carbohydrate recognition proteins (bacterial lectins) and endogenous carbohydrate binding proteins (endogenous lectins) of human urothelium as well as kidney tubulus epithelium was analyzed with respect to the adhesion of urotoxogenic Escherichia coli bacteria. Using biotinylated neoglycoproteins, we demonstrated a wide spectrum of endogenous lectins with Galactose-, Mannose-, Fucose-, N-Acetylgalactosamine-, and N-Acetylglucosamine binding activities in the urothelium. In the kidney the distal nephron and especially the medullar collecting ducts exhibited a similar spectrum of endogenous carbohydrate binding activities as detected for the urothelium. Adhesion- as well as inhibition-experiments with selective blocking of either bacterial lectins or endogenous lectins of the target cells by different carbohydrates both reduced the bacterial adhesion. However, maximal inhibition of bacterial adhesion was achieved by simultanous blocking of microbial and target cell lectins with mannose or mannan. From these results it is reasonable to conclude that specific adhesion which may result in an organotropism (urotropism) of E. coli infection is due to a dual recognition mechanism which is accomplished by the combined interaction of the bachterial and host cell lectins with the corresponding carbohydrates of E. coli and that of the target cells respectively. Further studies showed that normal human serum possesses natural antiadhesins which are represented by the glycan parts of the serum-glycoproteins.

Bacterial Adhesion↗