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Biomedical subjects

M Grimm

Publications and source records attributed to M Grimm.

At least 91 records · Page 5Linked to original sources
PubMed1999

From the other side of the door: patient views of seclusion.

1. Patient participants viewed seclusion as a form of punishment that maintains physical, and at times, psychological control over the secluded person. 2. A seclusion episode should serve a greater function than simply containment or preserving safety. During this period of crisis for the patient, they felt an even greater need for a therapeutic intervention. 3. Environmental, procedural, and attitudinal changes were emphasized by the patients in this study as a means to enhance the therapeutic potential of seclusion.

Adolescent↗
PubMed1998

Combined heart and kidney transplantation using a single donor: a single center's experience with nine cases.

BACKGROUND: Simultaneous double-organ transplants comprising various organ combinations have become frequent. The purpose of this article is to report on a single center's experience of simultaneous heart and kidney transplantation (HNTX) with particular emphasis on selection criteria and patient outcome. METHODS: From September 1990 to January 1997, nine patients underwent HNTX, receiving both grafts from a single donor selected on ABO blood group compatibility and a negative lymphocytotoxic crossmatch, but without regard to HLA-antigen matching. RESULTS: One patient died of acute humoral rejection of the cardiac graft shortly after surgery. Eight patients are alive and well and have normal cardiac and renal function at a mean follow-up of 44+/-28 months. CONCLUSION: HNTX offers a compelling therapeutic solution in the treatment of advanced cardiac and renal failure in carefully selected patients. Because the heart and kidney rejection episodes were independent of each other, rejection surveillance should be carried out separately for each transplanted organ.

Adult↗
PubMed1998

The hypotrichous ciliate Euplotes octocarinatus has only one type of tRNACys with GCA anticodon encoded on a single macronuclear DNA molecule.

Deviations from the universal genetic code have evolved independently several times in ciliated protozoa. Thus, in some species UAA and UAG are no longer used as termination codons, but are read as glutamine, whereas in the genus Euplotes , UGA is translated as cysteine. We have investigated the nature of the tRNACys isoacceptor responsible for decoding UGA in Euplotes cells. Southern hybridization analyses indicated that a single DNA molecule of 630 bp encoding tRNACys exists in the macronucleus of Euplotes octocarinatus . Cloning and sequencing of this fragment revealed that it contains only one copy of a tRNACys gene, which codes for a normal tRNACys with GCA anticodon. This is the first report of the characterization of a tRNA gene in any hypotrichous ciliate. It contains putative signals for initiation and termination of transcription by RNA polymerase III and can be transcribed efficiently in vitro in HeLa cell nuclear extract. Intensive studies on the DNA and tRNA level involving PCR analyses have not disclosed the existence of any tRNA Cys isoacceptor with UCA or ICA anticodons. Translation of the UGA codon by tRNA sub GCA sup Cys necessitates a G:A mispairing in the first anticodon position. We discuss a number of aspects which might contribute to the finding that a near-cognate tRNA isoacceptor efficiently translates the UGA stop codon.

Animals↗
PubMed1998

Noninvasive monitoring using serum amyloid A and serum neopterin in cardiac transplantation.

The monitoring of allograft function for cardiac transplant patients still relies on endomyocardial routine biopsies. We investigated the diagnostic value of noninvasive monitoring using the parameters serum amyloid A protein and serum neopterin. The circulating levels of the acute phase reactant, amyloid A protein, and the macrophage product, neopterin, were measured serially in 13 patients after cardiac transplantation. The mean period of observation was 240 days. Nine acute cardiac allograft rejections, five cases of viral infection and eight cases of bacterial infection occurred. The levels of serum amyloid A protein and serum neopterin remained low (x = 6.0 mg/dL and 12.6 nmol/L, respectively) during the periods of stable graft function. In contrast, both parameters were significantly elevated (p < 0.01) during the rejection episodes (x = 12.7 mg/dL and 38.0 nmol/L for serum amyloid A protein and serum neopterin, respectively). For a reliable differentiation between rejection and stable graft function, serum amyloid A protein had a diagnostic accuracy of 84% (with a cut-off level of 10 mg/dL) and serum neopterin had one of 75% (with a cut-off level of 23 nmol/L). However, significant increases in the circulating levels of serum amyloid A protein and serum neopterin were also observed during bacterial (x = 14.9 and 88 nmol/L, respectively) and viral (x = 6.2 mg/dL and 44 nmol/L, respectively) infections. The detection of immunological complications after cardiac transplantation using serial measurements of serum amyloid A protein and serum neopterin is possible. These parameters can be used to help in judging both the need and the optimal timing for the otherwise frequent endomyocardial biopsies.

Antilymphocyte Serum↗
PubMed1998

Small molecule inhibitor of HIV-1 cell fusion blocks chemokine receptor-mediated function.

The intersection of the HIV and the chemokine fields began with the observation that HIV entry into cells could be blocked by certain chemokines. Subsequent work showed that HIV entry is dependent on the presence of specific chemokine receptors. These observations led us to evaluate a series of compounds, ureido analogs of distamycin previously reported to block HIV entry into cells in vitro, for chemokine antagonist activity. One of the distamycin analogs, 2,2'[4,4'-[[aminocarbonyl]amino]bis[N,4'-di[pyrrole-2-carboxamide- 1,1'-dimethyl]]-6,8 napthalenedisulfonic acid] hexasodium salt (NSC 651016), is shown here to inhibit syncytia formation and cell fusion. Mechanistic studies showed that this inhibition was not due to conformational changes in gp120-gp41 induced by target cell CD4 and chemokine co-receptor and was therefore not due to interference with binding of HIV-1. Additional mechanistic studies demonstrated that NSC 651016 inhibited chemokine binding to specific chemokine receptors, induced CXCR4 and CCR5 receptor internalization, and inhibited chemokine-induced chemotaxis by macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, and stromal-derived factor-1alpha but not monocyte chemotactic protein-1. Thus, we describe a novel compound that inhibits in vivo replication of HIV-1 by down-regulation of co-receptors. These data lead us to propose that NSC 651016 may have in vivo anti-inflammatory activity.

Anti-HIV Agents↗
PubMed1998

Inactivation of (Gialpha) proteins increases arrhythmogenic effects of beta-adrenergic stimulation in the heart.

Chronic treatment of rats with carbachol downregulates M-cholinoceptors and inhibitory, pertussis toxin (PTX)-sensitive G proteinalpha-subunits (Gialpha) and sensitizes the heart to arrhythmogenic effects of isoprenaline (ISO), suggesting a causal relationship. To test this hypothesis by a more direct and quantitative approach, nine groups of rats were treated for 24 h with increasing doses of PTX (1.25-200 microg/kg i.v.). Inactivation of cardiac Gialpha was determined biochemically by 32P-ADP-ribosylationin vitro and functionally by measuring contractile effects of carbachol. Effects of ISO were studied in spontaneously beating right atria (RA) and isolated papillary muscles (PM; paced at 1 Hz). PTX increased heart rate in conscious animals (ECG) with a bell-shaped dose-dependency (maximal increase 120 beats/min at 7.5 microg/kg). PTX dose-dependently inactivated 25-85% of total cardiac Gialpha, which linearly correlated with a loss of the direct negative chronotropic effect of carbachol in atria, but not with a loss of its indirect negative inotropic effect in PM. The latter was resistant up to PTX 20 microg/kg (=70% inactivation). The decrease in Gialpha closely correlated with an increased efficacy of ISO to induce spontaneous contractile activity (automaticity) in PM. At 3 micromol/l ISO, all PM from PTX 200 microg/kg beat spontaneously compared to 10% in control. In contrast, pretreatment with PTX only modestly and not clearly dose-dependently increased the inotropic potency of ISO (PTX 100 microg/kg: EC50 28v 81 nmol/l in control) and did not affect the chronotropic effect of ISO. The disparity of the functional consequences of PTX treatment suggest that under physiological conditions, Gialpha serve mainly to suppress arrhythmogenic, but not or to a minor extent, positive chronotropic or inotropic effects of beta-adrenoceptor activation.

Adenosine Diphosphate Ribose↗
PubMed1998

Endovascular stent graft repair for aneurysms on the descending thoracic aorta.

BACKGROUND: The traditional treatment of aneurysms of the descending thoracic aorta includes posterolateral thoracotomy and aortic replacement with a prosthetic graft. In this study, we report our experiences and results in endovascular stent graft placement as an alternative to surgical repair. METHODS: Between January 1989 and July 1997, a total of 68 patients (24 women) underwent replacement of the thoracic aorta. Mean age at operation was 51 years. Fifty-eight patients underwent conventional surgical treatment. All of these patients were suitable candidates for endovascular stenting; however, no stent graft material was available at the time of operation. Ten patients (1 chronic dissection, 9 atherosclerotic aneurysm) received in the past 8 months the first commercially manufactured endovascular stent graft. The mean diameter of the aneurysms in this group was 7 cm (range, 6 to 8 cm). Two stent patients were operated on using only spinal cord analgesia. All stent grafts were custom designed for each of the 10 patients. RESULTS: The 30-day mortality in the conventional group was 31% versus 10% in the stent group. Mean length of intervention was 320 minutes in the conventional group versus 150 minutes in the endovascular group. Spinal cord injury occurred in 5 patients (12%) in the surgical group, whereas none of the stented patients developed any neurologic sequelae. Mean intensive care unit stay was 13 days, followed by a mean of 10 days on a ward in the first group compared to 4 days in the intensive care unit and 6 days on the ward in the stent group. One stent was required in 2 patients, two stents were required in 3 patients, and four stents were deployed in 5 patients of our series. Five patients required transposition of the left subclavian artery to achieve a sufficient neck for the proximal placement of the stent. There was complete thrombosis of the thoracic aortic aneurysm surrounding the stent graft in 8 patients (80%). Two patients required restenting as a result of leakage (20%). Stent graft placing was performed through the femoral artery in 8 patients, whereas access was only achieved through the abdominal aorta in 2 patients. CONCLUSIONS: These preliminary results demonstrate that endovascular stent graft replacement might be a promising, cheaper, and safe alternative method in selected patients with descending thoracic aneurysms.

Adult↗
PubMed1998

Nucleotide sequences and functional characterization of two tobacco UAG suppressor tRNA(Gln) isoacceptors and their genes.

We isolated and sequenced the two major tRNA(Gln) isoacceptors with CUG and UmUG anticodons from the cytoplasm of Nicotiana rustica. These are the first tRNAs(Gln) of nuclear origin characterized in plants. The tRNA(Gln) sequences were used to design probes for the isolation of the corresponding genes from a nuclear DNA library of N. rustica. The two cloned Nicotiana tRNA(Gln) genes, coding for either of the two isoacceptors, are efficiently transcribed in HeLa cell nuclear extract. In vitro translation in the presence of purified Nicotiana tRNAs(Gln) was carried out in a wheat germ extract partially depleted of endogenous tRNAs. Cytoplasmic (cyt) tRNA(Gln)CUG and to a lesser extent cyt tRNA(Gln)UmUG stimulated readthrough over the UAG stop codon present in the tobacco mosaic virus-specific context. The two tRNA(Gln) isoacceptors are the second class of natural UAG suppressors identified in plants, in addition to cyt tRNA(Tyr)GpsiA which has previously been characterized as the first natural UAG suppressor.

Anticodon↗
PubMed1998

Benign prognosis of early sinus node dysfunction after orthotopic cardiac transplantation.

Previous reports raised concern about the prognosis of patients with sinus node (SN) dysfunction after cardiac transplantation and led to a low threshold for permanent pacemaker (PM) placement at most institutions. The present study addresses the survival in patients with normal and impaired post operative SN function and the effect of permanent pacing with respect to overall and cardiac mortality. There were 120 patients with normal (corrected SN recovery time < 520 ms, group I) and 47 patients with imparied SN function (corrected SN recovery time > 520 ms and/or sinus arrest +/- escape rhythms). Pacing support was deemed unnecessary in 23 of 47 patients with SN dysfunction (group II; asymptomatic SN bradycardia and corrected SN recovery time 3,812 +/- 5,800 ms) while a total of 24 patients had PM placement a mean of 29 +/- 44 days after transplantation (symptomatic bradycardia or absence of sinus rhythm at discharge, group III). Patients were followed for a mean of 46.7 months. Thirty-five deaths occurred during the study period. Sixteen deaths were cardiac but none were causally related to the SN dysfunction (graft failure due to rejection or atheropathy n = 14; myocardial infarction n = 2). Four of these cardiac deaths were sudden and all occurred in the presence of widespread structural abnormalities (rejection/vasculopathy/myocardial infarction). SN dysfunction was not related to overall (P = 0.25) or cardiac mortality (P = 0.33). Regarding either endpoint, patients who had permanent PM placement did no better than their unpaced counterparts in group II (P = 0.53 and P = 0.33, overall and cardiac mortality, respectively). Likewise, survival did not differ between groups I and III for either endpoint (P = 0.77, P = 0.65, respectively). These data suggest that patients with mild SN abnormality, who are in sinus rhythm at the time of discharge, can be followed by observation without specific therapy.

Adult↗
PubMed1998

WAF1/p21 regulates proliferation, but does not mediate p53-dependent apoptosis in urothelial carcinoma cell lines.

The WAF1/p21 gene product is an inhibitor of cyclin-dependent kinases which can be induced by the tumor suppressor p53 and mediate some of its effects, or function in p53-independent pathways of cell cycle regulation. Although a potential tumor suppressor gene, WAF1/p21 is expressed in bladder cancer. To elucidate the function of p21 in tumor cells we have investigated in urothelial carcinoma cell lines: i) WAF1/p21 mRNA and protein expression, ii) the biological effects of p21 overexpression or down-regulation and (iii) whether p21 can be induced by p53. WAF1/p21 mRNA levels examined in four cell lines were comparable to bladder mucosa. One cell line, HT1376, failed to express p21 protein due to a frame shift mutation. Overexpression of WAF1/p21 cDNA inhibited clone formation in three cell lines, whereas transfection with antisense WAF1 increased clone sizes and numbers. WAF1 sense clones showed diminished cell proliferation compared to the parental cell line. Apoptosis- induced wild-type p53 was not inhibited by overexpression of antisense WAF1/p21. In a cell clone derived from line VMCub1 by stable transfection with wild-type p53 under the control of a metallothionein promotor, p21 was induced along with p53 upon activation of the promoter with zinc chloride. This induction was accompanied by a decrease in cell proliferation but by little apoptosis. These data suggest that p21 inhibits proliferation in a p53-dependent or independent manner but does not mediate p53-induced apoptosis in urothelial carcinoma cells.

Apoptosis↗
PubMed1998

Acidic glycoproteins accumulate in calcified areas of bioprosthetic tissue.

BACKGROUND AND AIMS OF THE STUDY: This study was performed to evaluate the role of collagen fibrils, cellular elements and matrix proteins in calcification of glutaraldehyde (GA)-fixed bioprosthetic material. METHODS: Lyoplant (lyophilized bovine pericardium, type I collagen) was processed according to three protocols. DF-group (double fixation): after conventional fixation in GA (0.5% for 72 h; storage 0.25%) Lyoplant was implanted subcutaneously into rats for 5 days. Specimens were explanted and re-fixed (conventional fixation), followed by autologous or homologous reimplantation in rats for 21 or 63 days. CF-group (conventional fixation): Lyoplant patches were conventionally fixed (as DF-group), kept in 0.9% saline for one week, and then autologously and homologously reimplanted. GF-group (high-concentration GA): Lyoplant patches were processed (as GF-group) but 0.5% GA was used for tissue storage. Explanted specimens were studied by light microscopic histochemistry; calcium contents were measured by atomic absorption spectroscopy. RESULTS: Severe calcification occurred in the DF-group without differences between autologous and homologous reimplantation. In CF- and GF-groups, calcification was negligible, but immunologic response against homologous implants was accompanied by increased calcium content. Histologic characterization of matrix material in calcified areas revealed oxyphilic glycoproteins, identified as sialoglycans. CONCLUSIONS: Modification of extracellular matrix by GA is assumed as essential to cause calcification of bioprosthetic material. Calcium deposition and accumulation of sialoglycans are simultaneous events. A specific role of this glycoprotein for calcification has to be considered.

Analysis of Variance↗
PubMed1997

Simultaneous heart and kidney transplantation as treatment for end-stage heart and kidney failure.

BACKGROUND: The aim of the present analysis was to define the role of simultaneous heart and kidney transplantation (HNTX) using organs from the same donor by evaluation of clinical strategy and achieved outcome compared with a reference group of concurrently single heart transplant (HTX) and kidney transplant (NTX) recipients. Compared with other organ combinations (pancreas-kidney, heart-lung), HNTX has been performed infrequently and is reported mainly as case records in the literature. Because of expansion of recipient selection criteria for HTX and NTX, the number of patients requiring simultaneous replacement of both organs is increasing. METHODS: Six HNTX recipients, three of them suffering from long-standing type I diabetes, received transplants between September 1990 and March 1996 and were analyzed in terms of clinical and immunological demographics and outcome. They were compared with 379 HTX and 769 NTX recipients operated upon within this period. RESULTS: Survival for HNTX is 100% with a mean follow-up of 32.7+/-21.1 months. Cold ischemic time of the kidney was significantly shorter for HNTX than for NTX (6.5+/-1.0 hr vs. 22.1+/-6.8 hr, P<0.005). Although HNTX patients received HLA-unmatched grafts, no rejection of the kidney has been observed to date. There was no difference for rejection of the heart in HNTX compared to HTX recipients. CONCLUSIONS: Satisfying results are obtained by HNTX and justify the use of two organs for one recipient. The favorable immunological behavior of the kidney despite use of HLA-unmatched grafts is most probably explained by higher immunosuppression and short cold ischemic time, although a combination effect cannot be excluded.

Adult↗
PubMed1997

The differential ability of IL-8 and neutrophil-activating peptide-2 to induce attenuation of chemotaxis is mediated by their divergent capabilities to phosphorylate CXCR2 (IL-8 receptor B).

IL-8 and neutrophil-activating peptide-2 (NAP-2) are two closely related C-X-C chemokines that differ in their abilities to induce chemotaxis of human polymorphonuclear leukocytes (PMN). Although two IL-8R types are expressed by PMN, only CXCR2 binds NAP-2 and IL-8 with equally high affinity. By using enriched CXCR2-transfected 293 cells, we show that high doses of IL-8 induce attenuation of chemotaxis, while equivalent doses of NAP-2 do not. Phosphorylation analysis shows that IL-8 induces higher levels of phosphorylation of the carboxyl terminus of CXCR2 than does NAP-2, suggesting that the level of phosphorylation contributes to the ability of the chemokines to attenuate the chemotactic response. To directly evaluate this difference, we analyzed the ability of receptors mutated to delete regions that highly express potential phosphorylation sites to be phosphorylated and to mediate chemotactic attenuation. We found that a carboxyl terminus-truncated mutant of CXCR2 was not phosphorylated by high doses of IL-8, as determined by in vivo phosphorylation assays and by analysis of the electrophoretic mobility of the receptors on SDS-PAGE gels. This mutated receptor had a significantly lower ability to attenuate IL-8-induced chemotaxis, indicating that the attenuation of chemotaxis is mediated by chemokine-induced receptor phosphorylation. In conclusion, the data show that the greater ability of IL-8 to induce receptor phosphorylation contributes to its more potent attenuation of chemotaxis as compared with NAP-2. This differential phosphorylation by IL-8 and NAP-2 of CXCR2 provides a basis for the divergent outcome of PMN-induced inflammation in response to these two closely related C-X-C chemokines.

Cells, Cultured↗
PubMed1997

Postimport methylation of the small subunit of ribulose-1,5-bisphosphate carboxylase in chloroplasts.

Electron impact mass spectronomy analysis of the amino-terminal amino acid of the small subunit (SSU) of ribulose-1,5-bisphosphate carboxylase (Rubisco) showed that the amino-terminal methionine residue is post-translationally modified to N-methyl-methionine. Modification of the amino-terminal methionine residue was found in mature SSU proteins from the dicotyledonous plants pea and spinach as well as the monocotyledonous plants barley and corn. SSU methyltransferase is a soluble protein in the chloroplast stroma and accepts heterologously expressed non-methylated SSU as a substrate using S-adenosylmethionine as methyl-group donor. We show that this modification occurs after post-translational uptake of the precursor form of SSU into chloroplasts and processing to its mature size. This reaction represents a new step in the import and assembly pathway of Rubisco holoenzyme.

Chloroplasts↗