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Biomedical subjects

C Hess

Publications and source records attributed to C Hess.

At least 37 records · Page 2Linked to original sources

Molecular analysis of hemolysin-mediated secretion of a human interleukin-6 fusion protein in Salmonella typhimurium.

Previously, we reported a plasmid-bearing Salmonella typhimurium strain capable of secreting human interleukin-6 (hIL-6) when genetically fused to the Escherichia coli hemolysin transport signal (HlyA(S)). Stationary phase culture supernatants of this strain revealed three major forms of hIL-6-HlyA(S) fusion protein (apparent molecular masses 32.4, 30.3, 27.0 kDa), at which the largest protein presumably represented full-length hIL-6-HlyA(S). The biological activity of the hIL-6-HlyA(S) protein mixture was similar to that of mature hIL-6. Accumulation of hIL-6-HlyA(S) in the culture supernatant occurred only during the initial growth phase, whereas in stationary phase and under in vitro conditions successive cleavage into the two truncated forms was observed. On the other hand, in whole cell lysates only full-length hIL-6-HlyA(S) could be detected, accounting for more than 50% of the totally synthesized protein. Upon cell fractionation, cellular hIL-6-HlyA(S) was exclusively found in the membrane fraction. These results suggest, that in S. typhimurium production and secretion of hIL-6-HlyA(S) is restricted to growing cells. A specific processing by a Salmonella-derived protease did not affect the biological activity of the fusion protein.

Animals↗

Textured-surface saline-filled silicone breast implants for augmentation mammaplasty.

The earliest silicone breast implants were smooth-surface, silicone rubber devices filled with either silicone gel or saline. Because of persistent problems with capsular contracture, polyurethane-covered silicone implants were developed as an alternative. Particularly in the short run, these alternatives proved highly successful at reducing the incidence of capsular contracture. By 1990, polyurethane-covered implants were rapidly becoming the preferred implant choice of many plastic surgeons, but for legal, regulatory, financial, and safety reasons they were withdrawn from the market by Bristol-Myers in 1991. Meanwhile, during the late 1980s, surface texturing and improved materials became available on other silicone breast implants and expanders. Most studies suggest that textured-surface silicone gel-filled implants, saline-filled implants, and tissue expanders have less frequent capsular contracture than their smooth-surface counterparts.

Breast Implants↗

Monomeric complement-activating IgG paraproteins.

Three patients presented a unique syndrome of recurrent panniculitis with an IgGkappa paraprotein and depletion of the early components of the classical pathway of complement. The IgGkappa paraproteins were monomers with a normal structure, and with no evidence for aggregation, as assessed by electron microscopy and ultracentrifugation. Both heavy and light chains were of normal molecular size (SDS-PAGE), and the paraproteins were not heavily glycosylated. However, the paraproteins from all three patients had unusual features that included abnormal behavior on gel filtration chromatography and a heavy chain of high pI. When analyzed by fast protein liquid chromatography (Superdex 200), elution of the paraproteins was retarded, particularly when the ionic strength was increased. This retardation was partially reversed in 20% alcohol, and fully reversed in 6 M guanidine-HCl. Neither anti-C1 inhibitor nor anti-C1q autoantibodies were found in any of the patients' sera. However, the paraproteins bound to the globular heads of C1q at normal ionic strength. They activated C4 in normal human serum, but not in C1q-deficient serum. Activation led to the formation of C1s-C1 inhibitor complexes. Taken together, the data suggest that the unusual paraproteins have the capacity to bind C1q, which then leads to activation of C1. The ability of these paraproteins to activate C1, in spite of their being soluble monomers, is likely to be related to their unique physicochemical features.

Chromatography, Gel↗

Ectosomes released by human neutrophils are specialized functional units.

Here we show that human polymorphonuclear leukocytes (PMN) release ectosomes independently of complement attack during their activation both in vitro and at the site of inflammation in vivo. Patterns of biotinylated proteins on the surface of PMN and on PMN-derived ectosomes indicated a specific sorting of cell surface proteins into and out of ectosomes. Ectosomes expressed clusters of complement receptor 1 (CR1), which allowed them to bind efficiently to opsonized bacteria. Myeloperoxidase and human leukocyte elastase, both stored within the azurophilic granules of PMN, were found to colocalize on ectosomes with CR1. Furthermore, myeloperoxidase colocalized with human leukocyte elastase. In contrast, not present on CR1-expressing ectosomes were CD63, a selective marker for the azurophilic granules, and CD14, which is located within the same granules and the secretory vesicles as CR1. Of the other complement regulatory proteins expressed by PMN, only CD59 colocalized with CR1, while CD55 and CD46 were almost absent. Ectosomes released by activated PMN at the site of inflammation may function as a well organized element (ecto-organelle), designed to focus antimicrobial activity onto opsonized surfaces.

Animals↗

Phonon- versus electron-mediated desorption and oxidation of CO on Ru(0001)

Heating of a ruthenium surface on which carbon monoxide and atomic oxygen are coadsorbed leads exclusively to desorption of carbon monoxide. In contrast, excitation with femtosecond infrared laser pulses enables also the formation of carbon dioxide. The desorption is caused by coupling of the adsorbate to the phonon bath of the ruthenium substrate, whereas the oxidation reaction is initiated by hot substrate electrons, as evidenced by the observed subpicosecond reaction dynamics and density functional calculations. The presence of this laser-induced reaction pathway allows elucidation of the microscopic mechanism and the dynamics of the carbon monoxide oxidation reaction.

Journal Article↗

Elastase and metalloproteinase activities regulate soluble complement receptor 1 release.

Complement receptor 1 (CR1) is cleaved from the surface of polymorphonuclear cells (PMN) in the membrane-proximal region to yield a soluble fragment (sCR1) that contains the functional domains. The enzymes involved in this cleavage are produced by the PMN itself, since in vitro stimulation of purified PMN is followed by sCR1 release. Purified human neutrophil elastase (HNE) cleaved CR1 from erythrocytes and urinary vesicles originating from podocytes and enhanced tenfold the cleavage of CR1 from activated PMN. The largest fragment released from PMN by HNE was identical in size to CR1 shed spontaneously. The CR1 fragments cleaved from erythrocytes were functional. The shedding of sCR1 by activated PMN was inhibited by phenylmethylsulfonyl fluoride (80 +/- 10%), alpha1-antiprotease (50 +/- 5%) and elafin (60 +/- 5%). Furthermore the cleavage was blocked by the metalloprotease inhibitor 1,10-phenanthroline (70 +/- 6 %) as well as by a monoclonal antibody against human neutrophil collagenase MMP8 (40 +/- 10%). Maximal inhibition of sCR1 shedding was obtained by a combination of 1,10-phenanthroline with elafin (86 +/- 6%). These inhibitors had no effect on L-selectin shedding, indicating that the cleavage of CR1 was specific. In conclusion, elastase or elastase-like activity may be responsible for the shedding of functional sCR1 in vivo, and this activity is controlled by the local release of PMN metalloproteases and alpha1antiprotease.

Complement C3b↗

[Complement and its role in immune response].

The complement system as a part of innate immunity is considered to provide rapid tough incomplete antimicrobial activity. However, besides providing a first-line defence, innate immunity plays additional important roles: it initiates and improves the slower, but more specific, acquired immune response. The recognition and destruction of noxious substances, as well as initiation of the acquired immune response, are accompanied by potentially hazardous inflammation. The inflammatory process has thus to be tightly regulated. In this overview, innate immunity and its interactions with acquired immunity are discussed with the main focus on the complement system. Our scientific interests are integrated into the discussion on complement.

Animals↗

Testing of chelating agents and vitamins against lead toxicity using mammalian cell cultures.

Mammalian cell cultures were used to determine the capacity of antidotes to modify (a) lead uptake, (b) lead toxicity and (c) lead release from cells. The following chelating agents were tested: Na, Ca-ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), nitriloacetic acid, ethylene glycol-bis(aminoethyl)tetraacetic acid (EGTA), D,L-mercaptosuccinic acid (MSA), meso-2,3-dimercaptopropanesuccinic acid (MSA), D,L-2,3-dimercaptopropane-1-sulfonic acid (DMPS), penicillamine (PA), N-acetylpenicillamine (NAPA), and diethylcarbodithioate (DDTC). The following vitamins were tested: thiamine (B1), riboflavine (B2), pyridoxine (B6), cobalamin (B12) and ascorbic acid (C). Inhibition of lead uptake was produced by EDTA, EGTA, DMSA, DMPS, MSA, PA, NAPA and vitamins B1, B6 and C, vitamins B2 and B12 being ineffective. The same compounds reduced lead cytotoxicity. Interestingly DDTC and DTPA increased lead uptake, but did not exacerbate lead toxicity. Significant release of lead from preloaded cells was caused by DTPA, NAPA, DMPS and PA, while the other chelators were ineffective.

Animals↗

A Salmonella typhimurium strain genetically engineered to secrete effectively a bioactive human interleukin (hIL)-6 via the Escherichia coli hemolysin secretion apparatus.

Human interleukin-6 (hIL-6) cDNA was genetically fused with the Escherichia coli hemolysin secretorial signal (hlyA[S]) sequence in a plasmid vector. Recombinant E. coli XL-1 Blue and attenuated Salmonella typhimurium secreted a 30 kDa hIL-6-HlyA(S) fusion protein, with an additional form of higher apparent molecular mass produced by S. typhimurium. In S. typhimurium cultures hIL-6-HlyA(S) concentrations entered a plateau at 500 to 600 ng ml(-1) culture supernatant. In contrast to E. coli XL-1 Blue, in S. typhimurium culture supernatants hIL-6-HlyA(S) was accumulated faster reaching three-fold higher maximal concentrations. The cell proliferating activity of hIL-6-HlyA(S) fusion protein(s) was equivalent to that of mature recombinant hIL-6. Furthermore. hIL-6-secreting S. typhimurium were less invasive than the attenuated control strain. Therefore, the bulky hemolysin secretorial peptide at the C-terminus of the fusion protein does not markably affect hIL-6 activity, suggesting that the hemolysin secretion apparatus provides an excellent system to study immunomodulatory effects of in situ synthesized IL-6 in Salmonella vaccine strains.

Animals↗

[A clinical-pharmacological case (1). Action of cisapride (Prepulsid) on bladder function].

We report the case of a 75 old man with chronic constipation due to traumatic spinal cord injury 25 years ago. Following prostatectomy the patient developed retention of urine and urinary incontinence, which improved significantly during a therapy with cisapride (3 x 10 mg/day). While the administration of cisapride is associated with increased detrusor activity and possibly urinary incontinence in neurologically normal persons, patients with urinary retention due to spinal cord injury may benefit from a therapy with this indirect parasympathomimetic agent.

Aged↗

[Feeding and hydration--an unphysiological answer to the problem of dying].

A short description of the physiological changes caused by dehydration and lack of calories is followed by a framework of guidelines that could provide a basis for care dying patients beyond mere mitigation of suffering. It is derived from the observation of the laws that we perceive to govern the processes of birth and death, living and dying. Polarity and the inherent rules of human developmental changes are defined as perpetually valid aspects of wisdom and are set off against the perpetually changing frontiers of knowledge with their limited validity. In conclusion, we submit an outline of our practical efforts in dealing with dying patients at the Affoltern Bezirksspital.

Death↗

[Fever, headache, diarrhea].

A 26-year-old man suddenly developed fever, headache, pain in the lower extremities, diarrhoea, and lymphadenopathy on the way back from Thailand. Subsequently, leukopenia, thrombocytopenia, coagulation abnormality and a morbilliform exanthema were noted. With symptomatic treatment the patient could be dismissed in good health after nine days. The diagnosis of Dengue and Campylobacter jejuni/coli infection could be verified serologically by a rising antibody titer and by a positive stool culture respectively.

Adult↗

Prevention of hyperbaric-associated middle ear barotrauma.

STUDY OBJECTIVE: To determine the efficacy of topical nasal decongestant in the prevention of middle ear barotrauma in patients undergoing hyperbaric oxygen therapy. DESIGN: Prospective, parallel, double-blind, randomized trial. SETTING: University-affiliated community hospital emergency department with hyperbaric oxygen facilities. PARTICIPANTS: Sixty patients undergoing hyperbaric oxygen therapy; 30 subjects in each treatment arm. INTERVENTIONS: After randomization, consenting patients were given two sprays of oxymetazoline hydrochloride or sterile water, 15 minutes before hyperbaric oxygen therapy. Collected data included patient demographics, ear examinations before and after hyperbaric oxygen treatment, and subjective ear complaints. The otoscopic appearance of the tympanic membrane was graded according to the amount of hemorrhage in the eardrum, with Teed scores ranging from 0 (symptoms only) to 5 (gross hemorrhage and rupture). RESULTS: The treatment groups were similar with regard to age, sex, and medical history. Ear discomfort during hyperbaric oxygen therapy was present in 63% (19 of 30) of those receiving oxymetazoline versus 67% (20 of 30) of the control group (P = .99). Likewise, both groups had similar Teed scores after hyperbaric oxygen therapy (P = .88). No adverse effects were noted. CONCLUSION: The results of this pilot study suggest that topical decongestants may not be effective in preventing middle ear barotrauma during hyperbaric oxygen therapy.

Administration, Topical↗

Management of post-traumatic acute renal failure with peritoneal dialysis.

To evaluate the efficacy of peritoneal dialysis (PD) in the management of post-traumatic renal failure, the authors reviewed the courses of five critically injured patients treated with PD over an 18-month period. Each patient had a double-cuffed PD catheter inserted through a subcutaneous tunnel with PD initiated within 48 hours. The dialysis prescription was individualized for each patient with frequent exchanges performed using either a manual manifold system or a continuous cycling machine. Three of the five patients survived and none of the survivors required dialytic therapy at discharge. Duration of PD ranged from 10 to 57 days. Three patients required intermittent hemodialysis (HD) due to progressive azotemia and hyperkalemia. Two patients developed bacterial peritonitis and three patients developed hyperglycemia with PD continuing without interruption in each patient. When compared to HD, PD offers the advantages of better hemodynamic tolerance, no anticoagulation, no vascular access, and a reduced personnel requirement if continuous cyclic PD is used.

Academic Medical Centers↗

[Intrahippocampal injection of NGF accelerates spontaneous alteration ontogenesis and the maturation of septohippocampal cholinergic innervation in rats].

A single intrahippocampal injection of nerve growth factor (NGF), performed on postnatal (PND) 8 or 13, accelerated the development of spontaneous alternation in rats. This precocity was of approximately 5 days, appearing on the 4th day after the treatment and persisting through to the end of the development (PND 40). Combined microinjections of NGF and an antimuscarinic (atropine) or an antinicotinic (mecamylamine) substance have indicated that NGF probably acts through accelerating the development of the septo-hippocampal cholinergic fibers involved in this behavior.

Animals↗

Hippocampal nicotinic cholinergic mechanisms mediate spontaneous alternation and fear during ontogenesis but not later in the rat.

Spontaneous alternation was examined in young rats following microinjections of antinicotinic agents into one of the 4 hippocampal sites: anterodorsal, or posteroventral dentate gyrus, hippocampal gyrus, or entorhinal cortex. In control and saline-injected animals, the alternation rate was shown to grow suddenly from 40 to 80% between days 15 and 17 (the adult level being 85-90%), to regress partly (to 55%) between days 20 and 30, and return to a near-adult level (75%) by day 40. Meanwhile fear responses to environment (defecation and vocalization) emerged between days 20 and 25, increased to a maximum until day 30, and returned to the typically low adult level by day 40. Injections of mecamylamine (5, 20 micrograms) or hexamethonium (5, 20 micrograms) into any of the 4 sites significantly reduced the rate of alternation from as early as day 10 on, but were no longer effective from day 30 on; on the other hand, they did not alter the level of defecation, but had a tendency to lower the level of vocalization on day 30 only. These results indicate that hippocampal nicotinic cholinergic mechanisms play a role in spontaneous alternation and appear to be involved in the control of one fear reaction (vocalization) until day 30.

Aging↗