Biomedical subjects

J Blum

Publications and source records attributed to J Blum.

At least 19 recordsLinked to original sources

PubMed1999

Involvement of calyculin A-sensitive phosphatase(s) in the differentiation of Trypanosoma cruzi trypomastigotes to amastigotes.

Differentiation of the non-dividing trypomastigote form of Trypanosoma cruzi, the causative agent of Chagas disease, to the dividing amastigote form normally occurs in cytoplasm of infected cells. Here we show that calyculin A. a potent inhibitor of protein phosphatases 1 and 2A, induces at pH 7.5 extracellular transformation of long slender trypomastigotes to round amastigote-like forms which acquire characteristic features observed after the normal differentiation process: repositioning and structural changes of the kinetoplast, release of surface neuraminidase, and expression of amastigote-specific epitopes. Calyculin A inhibits parasite phosphatases and changes in the phosphorylation of specific proteins occur during the transformation process. As an exposure of trypomastigotes to calyculin A concentrations as low as 1 nM and for only 1-2 h is sufficient to induce transformation, the inhibition of calyculin A-sensitive phosphatase(s) appears to play a major role in initiating the trypomastigote differentiation.

Animals↗

PubMed1998

[Retrograde nailing of humerus shaft fractures with the unreamed humerus nail. An international multicenter study].

Combined with the new unreamed humeral nail (UHN) (Synthes), the retrograde approach to the endomedullary canal of the humeral shaft promises careful reduction and fixation of humeral shaft fractures. This prospective multicenter study reports and analyses 102 retrograde nailings with the UHN and their operative procedures. Seven patients with pathological fractures have died meanwhile, but 75 patients could be followed up until bone healing. Seventy-three fresh humeral shaft fractures, 12 pseudarthrosis, 3 refractures and 14 pathological fractures have been treated with the UHN. In 98 cases (96.1%) the surgeon estimated fracture stability well enough to initiate immediate postoperative elbow and shoulder mobilization. The difficulties involved with free-hand interlocking proximally at the nail tip in 5.9%, fissure or avulsion at the insertion point in 3.9% and radial nerve palsy also in 3.9% of the cases were the most important intraoperative complications. In all 75 patients followed up, bone healing occurred, but five fractures (6.7%) needed more than 8 months connected with a second operative procedure. In one case spongious bone transplantation and new locking bolts had been performed. In three cases a special compression device has been used, whereas in one case also a new nail and in the second spongious bone transplantation had been added. In the fifth case plate osteosynthesis had been performed. At the end of treatment 89.4% of the patients had excellent shoulder function and 88.0% excellent elbow function. Once the indication for surgery is established, the UHN can be considered a reliable and safe implant for stabilizing humeral shaft fractures.

Adolescent↗

PubMed1998

Inhalation anaesthesia for the castration of piglets: CO2 compared to halothane.

General anaesthesia with 80% CO2/20% O2 and 5% halothane in O2 (mask induction) was compared for castration of 3-4 week-old piglets. One group was castrated without anaesthesia. Of the noncastrated control groups one had CO2- and one halothane anaesthesia, one breathed room air through the induction system, and one was held in castration position. The behaviour to induction and castration was assessed, and the cortisol-, ACTH- and beta-endorphin plasma concentrations were determined to quantify the stress elicited by anaesthesia, castration and handling. Violent struggling and vocalization were elicited by CO2 and positioning into the mask induction system while breathing room air; halothane induction was quiet. CO2 induced profound surgical anaesthesia; whereas under halothane anaesthesia some animals exhibited still a slight reaction to castration. Recovery was fast, smooth and quite. Permanent violent struggling and vocalization were elicited by castration without anaesthesia. Plasma cortisol was not a sensitive tool to judge castration stress. The high ACTH and beta-endorphin plasma concentrations elicited by CO2 anaesthesia confirm our clinical experience. General anaesthesia is fast and safely induced with CO2 in piglets and castration can be performed without any reaction, but with CO2 anaesthesia the stress is not reduced.

Anesthesia, Inhalation↗

PubMed1998

Design of an epidemiologic study of drinking water arsenic exposure and skin and bladder cancer risk in a U.S. population.

Ingestion of arsenic-contaminated drinking water is associated with an increased risk of several cancers, including skin and bladder malignancies; but it is not yet clear whether such adverse effects are present at levels to which the U.S. population is exposed. In New Hampshire, detectable levels of arsenic have been reported in drinking water supplies throughout the state. Therefore, we have begun a population-based epidemiologic case-control study in which residents of New Hampshire diagnosed with primary squamous cell (n = 900) and basal cell (n = 1200) skin cancers are being selected from a special statewide skin cancer incidence survey; patients diagnosed with primary bladder cancers (n = 450) are being identified through the New Hampshire State Cancer Registry. Exposure histories of these patients will be compared to a control group of individuals randomly selected from population lists (n = 1200). Along with a detailed personal interview, arsenic and other trace elements are being measured in toenail clipping samples using instrumental neutron activation analysis. Household water samples are being tested on selected participants using a hydride generation technique with high-resolution inductively coupled plasma mass spectrometry. In the first 793 households tested arsenic concentrations ranged from undetectable (0.01 microgram/l) to 180 microgram/l. Over 10% of the private wells contained levels above 10 microgram/l and 2.5% were above 50 microgram/l. Based on our projected sample size, we expect at least 80% power to detect a 2-fold risk of basal cell or squamous cell skin cancer or bladder cancer among individuals with the highest 5% toenail concentrations of arsenic.

Adult↗

PubMed1998

Retrograde nailing of humeral shaft fractures.

The use of intramedullary nailing in the upper extremity is still controversial. Those who have experience with antegrade nailing have either great enthusiasm or strong criticism for the procedure. Criticism of the procedure is because of the trauma that can occur to the rotator cuff and possible impingement syndrome, which can occur after antegrade nail insertion. The technique of retrograde nail insertion with the unreamed humeral nail is described in detail. In a series of 190 retrograde nailings performed in a prospective multicenter study, the most frequent intraoperative problems were fissure or avulsion at the entry portal (n = 8; 4.2%) and secondary radial nerve palsy (n = 8; 4.2%). All radial nerve palsies recovered spontaneously. Sixty-eight patients were followed up until the fractures healed. There were five (7.4%) bone healing problems. Four of five could be solved with use of the unreamed humeral nail in a second operative procedure, whereas the fifth bone healing problem required plate osteosynthesis. Function of the shoulder and elbow joint was excellent in 89.7% and 88.3% of the patients, respectively. Retrograde humeral nailing is a safe and reliable procedure if done properly. It is a valuable stabilization technique for acute and pathologic fractures and for pseudarthrosis. Bone healing problems after unreamed humeral nailing must be analyzed individually, but they can be treated with the same implant in combination with cancellous bone grafts, reaming, additional hardware, or intrafragmentary compression.

Adolescent↗

PubMed1997

Modulation of the swelling-activated amino acid channel of Leishmania major promastigotes by protein kinases.

Leishmania promastigotes respond to hypotonic challenges by a mechanism of regulatory volume decrease (RVD), whereby anionic amino acid channels (HAAC) are hypotonically-activated and intracellular amino acids are released from the cells. Irrespective of the experimental conditions, restoration of isotonicity triggered an immediate blockage of the amino acid release. Both the speed and amplitude of the response depended on the hypotonic stimulus and on the operation of intracellular signaling mechanisms. The initial (5 s) hypotonic-induced release of amino acids (ri) and the steady state levels of amino acids attained (5 min) or amplitude (A), were markedly affected by modulators of protein kinase C: phorbol 12-myristate 13-acetate, 1-oleoyl-2-acetylglycerol and phorbol 12,13-diacetate whereas staurosporine and the related analog, bis-indolylmaleimide I (GF-109203.X) inhibited the RVD response. Agonists of cAMP-dependent protein kinase A such as forskolin or (8-(4-chlorophenylthio))-adenosine-3',5'cyclic-monophosphate enhanced the speed of the response but had little effect on its amplitude. Neither 4alpha-phorbol 12,13-didecanoate,1,9-dideoxyforskolin nor genistein, tamoxifen or thapsigargin had any apparent effect on either parameter tested. The most striking stimulation of hypotonic-induced amino acid release was exerted by arachidonic acid or by its non-metabolizable analog, 5,8,11,14-eicosatetraynoic acid (ETYA). These agents caused a major increase in the initial rate of amino acid release as well as a higher amplitude of the response, both of which were markedly inhibited by an anion channel blocker. The present studies indicate not only that hypotonicity is an obligatory and dominant component in HAAC activation, but implicate specific second messengers in the modulation of the RVD response. The modes of activation or attenuation of HAAC activity apparently differ for PKC and PKA modulators as well as for arachidonic acid. The involvement of Ca2+ in HAAC was studied in hypotonic challenged cells which were treated with intracellular Ca2+-chelators or Ca2+-free medium. These cells showed a lag in AA release and a modest inhibition of the amplitude. The inhibition of HAAC was markedly increased when cells were treated with the ionophore A23187 in Ca2+-free media. The HAAC activity was accompanied by a significant increase in internal Ca2+ when performed in Ca2+-containing medium (from 88+/-9 to 179+/-22 nM) but by no significant change when measured in Ca2+-free medium. These studies indicate that although Ca2+ might be involved in the early activation phase of HAAC, it is either not absolutely required or its action might be associated with localized events.

Amino Acids↗

PubMed1997

Analysis of the FHIT gene and FRA3B region in sporadic breast cancer, preneoplastic lesions, and familial breast cancer probands.

The FHIT gene, which spans the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene in breast and other cancers. We investigated FHIT and FRA3B for loss of heterozygosity (LOH); homozygous deletions; abnormal transcripts; and acquired/germ-line point mutations in breast cancer cell lines (n = 32), breast epithelial and stromal cell cultures (n = 18), microdissected invasive (n = 16) and ductal in situ carcinomas (n = 6), and their accompanying normal and abnormal epithelial foci (n = 14). LOH at 3p14.2, especially at FHIT intragenic marker D3S1300, was found in 6 of 16 microdissected invasive tumors and 3 of 6 ductal in situ carcinomas. In accompanying preneoplastic foci, LOH occurred in two of eight intraductal hyperplasias but not in histologically normal ductal epithelium (n = 6). Three of 32 (9%) breast cancer cell lines demonstrated homozygous deletions of FHIT exon 4 (two cases) and exon 5 (one case), which correlated with exon 4-deleted transcripts and loss of the cDNA transcript containing the coding exons 5-9, respectively. Normal mammary cultures and 31 of 32 tumor cell lines (97%) expressed wild-type coding transcripts as well as a minor exon 8-deleted message. Single-strand conformation polymorphism analysis of the coding exons in the 32 tumor and 18 normal breast cell lines and their sequencing revealed four silent polymorphisms and a germ-line histidine triad point mutation (651 G-->T) in a tumor arising in a 70-year-old woman. This mutation was also present in one of her two thus far unaffected daughters. Analysis of additional DNAs from 280 probands of high-risk breast cancer families for other FHIT exon 8 mutations detected an intronic point mutation 13 bases upstream of exon 8. Thus, we have demonstrated relatively early abnormalities of the FHIT/FRA3B region in breast cancer and discovered two rare FHIT germ-line mutations. The expression of a transcript containing the coding exons in nearly all cell lines, including those with germ-line mutations, suggests the possibility that another gene in the FRA3B region may be involved in the pathogenesis of breast cancer.

Acid Anhydride Hydrolases↗

PubMed1997

[Whole body spiral CT in primary diagnosis of patients with multiple trauma in emergency situations].

PURPOSE: The aim of this study was to evaluate the role of a fast whole body helical CT scanner for primary diagnosis in trauma patients. METHODS: 27 severely injured patients (9 women, 18 men; mean age 43 years) were first examined with a helical CT scanner allowing for digital radiograms up to a length of 1024 mm and continuous helical scans of up to 70 seconds (slice thickness 3 to 10 mm, pitch factor up to 2). The primary CT diagnosis was verified either by x-ray after the CT examination or during the subsequent days, by abdominal ultrasound, by additional CT scans in the following days, and by clinical follow-up. RESULTS: CT showed all clinically relevant injuries of the head, spine, chest, abdomen and pelvis. The diagnosis and classification of vertebral fractures was performed immediately. 4% of the fractures of the extremities and the ribs were not seen primarily. 6% of the injuries were outside the CT scan field. CONCLUSION: Helical CT is a reliable and fast method to obtain vital information and to improve management planning in severely injured patients. It reduces the number of conventional x-ray examinations. In certain cases, additional x-rays of extremity fractures may be required.

Abdominal Injuries↗

PubMed1997

The unreamed humeral nail--a biological osteosynthesis of the upper arm.

One hundred humeral shaft fractures have been treated by closed retrograde locked intramedullary nailing. The Russell-Taylor nail was used in 58, a Synthes prototype of an unreamed humeral nail in 42 cases. Excellent shoulder function after consolidation has been found in 90%, excellent elbow joint function in 86%. Among four cases of postoperative radial nerve palsy, three fully recovered within three months and one patient needed a secondary exploration. In three cases additional comminution at the fracture site occurred. Interlocking bolt breakage has been seen in three, slight nail migration with no adverse consequences in two cases, an additional supracondylar fracture in one case. Nine patients needed a secondary internal fixation because of disturbed fracture healing. Compared to complication rates and end results in shoulder and elbow function of plate fixation or anterograde nailing in the treatment of humeral shaft fractures, the retrograde locked humeral nail seems to present itself as the better implant for these fracture types. The number of radial nerve palsies is significantly lower than in plate osteosynthesis. A huge advantage compared to plate osteosynthesis is also the biological type of stabilization with minimal invasion of the soft tissues. There is also minimal damage to periosteal and endosteal blood supply.

Adolescent↗

PubMed1997

Surgical approaches to the humeral shaft.

Open fractures, transverse, short oblique and spiroid fractures of the humeral shaft, as well as comminuted fractures with radial palsy or vascular injury, mostly lead to bad end-results if treated conservatively. The same is valid in the case of bilateral humeral shaft fractures, multiple injuries, polytrauma, pathologic fractures and pseudarthrosis. Good end-results and a low rate of complications in the operative procedure require an adequate approach to the fractured limb as well as a meticulous care of the soft tissues. In plate osteosynthesis, the anterolateral approach for the proximal third of the shaft, the anterolateral approach with radial exposure for the middle third of the shaft and the posterior approach for the distal third of the shaft seem to offer the best pathway for reposition and fixation, respecting the biologic requirements for a successful osteosynthesis. The approaches for external fixation demand a thorough knowledge of the course of the axillary and radial nerves. Unreamed intramedullary nailing can be done in an anterograde and in a retrograde way. In anterograde nailing, damage of the rotator cuff must be avoided, in retrograde nailing, the elbow capsule should be left closed and untouched.

Bone Nails↗

PubMed1997

[Complications of endoscopic retinaculum dissection].

Reviewing the literature on endoscopic carpal tunnel release (biportal Chow-technique and uniportal Agee-technique), we found 31 different intra- and postoperative complications. Of these, 14 affected nerve structures, four vessel structures, two tendon structures, two bony structures, and nine surrounding tissues. The most common complications were analyzed taking anatomical and pathological variations of the carpal tunnel into consideration. In our own prospective series of 88 endoscopic releases of the carpal tunnel using the Agee technique, we had eleven complications: one patient suffered residual symptoms, five patients experienced transient ulnar neurapraxia, and one patient complained of intense pain in the middle- and ringfinger after the operation. In four cases, intraoperative change of technique from endoscopic to open became necessary, due to poor visualization.

Carpal Tunnel Syndrome↗

PubMed1996

Uncoupling of M-phase kinase activation from the completion of S-phase by heat shock.

Chronic exposure of asynchronous HeLa cell cultures to 41.5 degrees C leads to an accumulation of cells in the S-phase, spontaneous premature chromosome condensation, and loss of clonogenicity (M.A. Mackey, S. L. Anolik, and J. L. Roti Roti. Cancer Res., 52: 1101-1106, 1992). In this report, we show that increases in histone H1 kinase activity during 41.5 degrees C exposure occur coincidentally with the appearance of premature chromosome condensation. Furthermore, this kinase activity is shown to be associated with M-phase kinase complexes containing cyclin B1. These increases in the activity of M-phase kinase were found to occur concomitantly with an elevation in cyclin B1 mRNA and an accumulation of cyclin B1 protein. Because cyclin B1 transcription begins in the S-phase, it is probable that the heat-induced delay in the S-phase allows the accumulation of abnormally high cyclin B1 levels. Elevated cyclin B1 levels could then account for the observed abrogation of the cell cycle checkpoint, which usually assures that mitosis does not proceed until DNA replication is complete. This involvement of M-phase kinase in heat-induced cytotoxicity demonstrates the importance of the coordinate regulation of the processes of DNA replication and entry into mitosis.

Cell Cycle↗

PubMed1996

[Bilateral acetabulum fractures of the anterior column and vertebral body fracture after alcohol-induced seizure].

The case of a 54-year-old male with a compression fracture of the T 12 vertebral body and a bilateral anterior column fracture of the acetabulum is presented. The origin of this rare combination of fractures is explained by the action of the patient's own muscle force on bone of very poor quality. The treatment of these lesions is comparable to the treatment of similar fractures in bone of normal quality.

Acetabulum↗

PubMed1996

[Results of primary unreamed tibial nailing of tibial fractures with severe open or closed soft tissue injuries].

Primary stabilization was performed in 72 tibial fractures with sever open (n = 37) or closed (n = 35) soft tissue injury using unreamed interlocking nails. In 60 (83%) cases the fractures healed without additional procedures. There were 2 cases of osteitis, but both these fractures healed after removal of the nail or after reamed nailing. In 9 patients with delayed union reamed nailing (n = 8) or bone grafting (n = 1) led to healing. In 1 patient with hypertrophic pseudarthrosis, union was achieved after substitution of a reamed nail for the anreamed nail. The infection rate was similar to that observed with external fixation. More secondary procedures, such as bone grafting or a change of the osteosynthesis technique, are necessary with external fixation than with unreamed nailing. Further advantages of unreamed nailing are the internal treatment of the fracture and the patient's greater comfort. Therefore, unreamed nailing can be recommended for the primary treatment of tibial fractures with severe open or closed soft tissue trauma.

Adolescent↗

PubMed1996

Tissue engineering scaffolds using superstructures.

Here, scaffolds as cell and tissue carriers are approached from an engineering point of view, emphasizing material superstructuring in the design of supports. Superstructure engineering provides optimal spatial and nutritional conditions for cell maintenance by the arrangement of structural elements (e.g. pores or fibres) so as to vary the order of cell to cell contact. This approach is illustrated in the design of several scaffolds: knitted fabrics as three-dimensional superstructures for optimized osteosynthesis implants, a new injectable open porous implant system, an angiopolar non-degradable ceramic cell carrier, and an injectable or microsurgically implantable entangled carrier system. The implications for tissue engineering are discussed.

Anisotropy↗

PubMed1996

Detection of coccidioidal antibodies by 33-kDa spherule antigen, Coccidioides EIA, and standard serologic tests in sera from patients evaluated for coccidioidomycosis.

During a 9-month study of patients being evaluated for coccidioidomycosis, 1 or more serum samples were obtained from 138 patients with an illness suggestive of recent infection. In this group, standard immunodiffusion tests of unconcentrated sera were positive for 25; 49 additional patients had at least 1 reactive test result by newer enzyme-linked serologic tests. At least 11 of these 49 patients had coccidioidomycosis as determined by culture or subsequent standard serologic tests. Patients with coccidioidomycosis identified only by newer tests had fewer or milder clinical abnormalities than did patients in whom the disease was detected by standard tests. For 31 other patients with illness of a chronic or undetermined duration, newer tests detected only 10 more than the 18 identified by standard tests, suggesting that later in the course of illness, standard testing gains in sensitivity for coccidioidal infection.

Antibodies, Fungal↗

PubMed1996

Major histocompatibility complex class II molecules function as a template for the processing of a partially processed insulin peptide into a T-cell epitope.

Our understanding of how an autoantigen is processed and presented during the development of a major histocompatibility complex (MHC) class II-dependent and T-cell-mediated autoimmune disease, such as IDDM, is incompletely understood. We have used insulin as a model autoantigen in IDDM to address the question of whether MHC class II molecules play a role in the generation and/or preservation of an autoantigen peptide that stimulates T-cell activation. Analyses of the requirement of I-Ad class II molecules in the processing of the partially processed porcine insulin peptide A1-A14/B1-B16 demonstrate that the binding of this peptide to I-Ad is essential for it to be further processed and tailored into a T-cell epitope. Based on our observations, we propose a two-step model for insulin processing in which insulin is first processed by an enzyme(s) into an intermediate peptide that binds to class II and then class II functions as a template to guide the processing of this partially processed peptide by cathepsin D into a T-cell epitope. Our data further underscore the important realization that MHC class II-directed processing of an autoantigen (e.g., insulin) may regulate 1) the relative immunodominance of T-cell determinants in an autoantigen, 2) the self-reactivity to cryptic T-cell epitopes in autoantigens, and 3) the susceptibility to autoimmune disease.

Animals↗

PubMed1996

[Reference values of electrodiagnostic and laboratory studies in young Wallis Schwarzhals goats].

Laboratory testing in 10 "Walliser Schwarzhals"-goats included red and white blood cell count, electrolytes, liver enzymes, trace elements and urinalysis, protein determination and cell count of the cerebrospinal fluid (CSF) was also performed. Electrodiagnostic testing included electromyography (EMG) of the head and spinal muscles, motor nerve conduction velocity (MNCV) of the right and left peroneal nerve, brainstem auditory evoked potentials (BAEP) and electroencephalography (EEG). MNCV of the peroneal nerve was 72 +/- 9.24 m/s. Latency and amplitude of the BAEP for P1 was 2.15 +/- 0.08 ms respectively 2.23 +/- 0.7 microV and for P5 5.09 +/- 0.15 ms respectively 0.68 +/- 0.24 microV. P2 (3.2 +/- 0.14 ms/1.37 +/- 0.32 microV) and P3 (3.9 +/- 0.13 ms/0.84 +/- 0.14 microV) were equally distributed between P1 and P5. Whereas the results of EMG and BAEP were similar to those of other species, the electroencephalographic findings consisted of three different patterns depending on duration and depth of isofluran anesthesia. Pattern I had a rhythmic high amplitude (80 microV) and low frequency (1-2 Hz) pattern with aperiodic intervals of relative electric silence. Pattern II was characterized by increased duration of HALF (150 microV), associated with spindles of low amplitude (20-30 microV) and high frequency (10 Hz). Pattern III had generalized delta-activity of high amplitude (70-200 microV). All the results are discussed briefly.

Animals↗