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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 325 records · Page 18Linked to original sources
PubMed1994

Tuberculosis in liver transplant patients.

Tuberculosis has been increasing especially in urban areas and in immunosuppressed patients; however, the incidence and factors associated with tuberculosis in OLT patients are unknown. Five of 550 patients who underwent OLT at the Mount Sinai Medical Center during a 5-year period were noted to have tuberculosis. The mean age of the patients was 49.2 years; there were 3 males and 2 females and 3 were foreign born. One of 5 had a prior history of tuberculosis. Tuberculin skin tests performed before transplant revealed 1 positive and 2 anergic reactions. The preoperative chest x-ray revealed apical fibrosis in 2 patients and bilateral apical disease with a nodule in 1 patient. Tuberculosis developed from 2 to 57 months after surgery in 4/5 patients. One had miliary lesions of the peritoneum discovered at the time of OLT. One patient had recent contact with a patient with pulmonary tuberculosis. At presentation, fever was present in 4 of 5 patients, pulmonary lesions in 3 patients, meningitis in 2; during hospitalization, 1 had a liver abscess and disseminated intravascular coagulation and peripheral gangrene. Lymphocytosis was noted in the pleural (1), peritoneal (1), and cerebrospinal fluid (1). Acid-fast smears were positive in bronchoalveolar lavage fluid (1), peritoneal isolates (1), and liver biopsy (1). All patients had positive cultures for Mycobacterium tuberculosis. These isolates were all sensitive to isoniazid, streptomycin, rifampin, ethambutol, and pyrazinamide. Four of 5 patients were treated with isoniazid and rifampin, 2 received pyrazinamide, 2, amikacin, 2, ofloxacin, and 2, ethambutol. Three of 5 patients are doing well on antituberculous therapy and 2 expired with tuberculosis as the cause of death. In OLT patients with unexplained fever, tuberculosis including extrapulmonary and disseminated disease should be considered since the mortality rate is very high. Liver transplantation can be performed in the presence of active peritoneal tuberculosis with the use of judicious antituberculous therapy. The role of preventive therapy is controversial, though use in certain high risk patients is suggested.

Adult↗
PubMed1994

Transformation of adult ventricular myocytes with the temperature sensitive A58 (tsA58) mutant of the SV40 large T antigen.

Freshly isolated ventricular myocytes have been used extensively as an adult cardiac model system. Due to their inability to undergo cytokinesis in vitro and their dedifferentiated properties in long-term culture, they can not be used for extended studies. Recent reports tell of the establishment of fetal and neonatal cardiac cell lines and the development of adult cardiomyocytes from transgenic animals. A recent report by Kirshenbaum [1], is the first to demonstrate insertion of genes in to adult ventricular myocytes using viral infection. This paper discusses the infection of primary adult differentiated cardiomyocytes with the SV40 large T antigen and subsequent proliferation under temperature sensitive control. Upon further characterization, the cells could be used as a model to study muscle differentiation and repair as well as adult cardiac cell physiology.

Age Factors↗
PubMed1994

Dibutyryl cAMP, interleukin-1 beta, and macrophage conditioned medium enhance the ability of astrocytes to promote neurite growth.

Astrocytes purified from the neonatal rat brain were cultured for up to 3 weeks prior to being treated with agents that can induce reactive changes in astrocytes. These agents included dibutyryl cAMP, interleukin-1 beta, and macrophage conditioned media. After treating astrocytes for 3 days, the agents were removed and the ability of the astrocytes to support neurite growth was assessed by plating neonatal rat cerebellar cortical neurons. All the agents increased the ability of astrocytes to support the growth of long neurites. This was particularly evident with astrocytes treated with dibutyryl cAMP and LPS macrophage-conditioned medium. These results provide direct evidence that the reactive changes induced in astrocytes in this in vitro model might aid the growth of neurites. Similar changes may underlie the injury-induced axonal sprouting that occurs in vivo.

Animals↗
PubMed1994

Dynamic properties of actin. Structural changes induced by beryllium fluoride.

Beryllium fluoride (BeFx) has been widely used as a phosphate analogue in nucleotide-binding proteins. It was found to bind tightly to F- but not G-actin (Combeau C., and Carlier M. F. (1988) J. Biol. Chem. 263, 17429-17436) and to affect the three-dimensional structure of filaments by stabilizing the subdomain 2 region of the actin promoter (Orlova, A., and Egelman, E. H. (1992) J. Mol. Biol. 227, 1043-1053). In this work we examined the BeFx-induced structural and functional changes in G- and F-actin by using proteolysis, chemical modifications, ATPase, and in vitro motility assays. The results of proteolysis studies show that BeFx binds also to MgADP-G-actin and renders its subdomain 2 region more similar to that in MgATP-G-actin. This is manifested in enhanced subtilisin and decreased tryptic digestions in subdomain 2 of G-actin. BeFx had a strong effect on the proteolysis of MgADP-F-actin: both the tryptic and subtilisin digestions in subdomain 2 were completely inhibited. Significant protection against proteolysis in this region was observed even at 1:14 molar ratios of BeFx to actin indicating cooperative effects on the structure of the actin filament. A similar although milder effect of phosphate on the proteolysis of F-actin suggests that BeFx acts as a phosphate analogue in this system. BeFx also induces changes in the subdomain 1 region of F-actin. This is revealed via reduced rates of Cys-374 alkylation with 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin and an increased subtilisin cleavage near the C terminus of actin in the presence of BeFx. The BeFx-induced structural changes in actin have little effect on its interactions with myosin. BeFx inhibits only slightly the actin-activated ATPase activity of S1 by decreasing Vmax without affecting KM. Additionally, the binding of BeFx to actin does not change the sliding velocity of actin filaments in the in vitro motility assays. The BeFx-induced specific and distinct changes in G- and F-actin point to the dynamic nature of actin structure and the local differences between monomeric and polymeric forms of actin.

Actins↗
PubMed1994

Caldesmon, N-terminal yeast actin mutants, and the regulation of actomyosin interactions.

N-Terminal yeast actin mutants were used to assess the role of N-terminal acidic residues in the interactions of caldesmon with actin. The yeast actins differed only in their N-terminal charge: wild type, two negative charges; 4Ac, four negative charges; DNEQ, neutral charge; delta DSE, one positive charge. Caldesmon inhibition of actomyosin subfragment 1 ATPase was affected by alterations in the N-terminus of actin. This inhibition was similar for skeletal muscle alpha-actin and the yeast 4Ac and wild-type actins (80%), but much smaller for the neutral and deletion mutants (15%). However, cosedimentation experiments revealed similar binding of caldesmon to polymerized rabbit skeletal muscle alpha-actin and each yeast actin. This result shows that the N-terminal acidic residues of actin are not required for the binding of caldesmon to F-actin. Caldesmon-actin interactions were also examined by monitoring the polymerization of G-actin induced by caldesmon. Although the final extent of polymerization was similar for all actins tested, the rates of polymerization differed. Skeletal muscle and 4Ac actins had similar rates of polymerization, and the wild-type actin polymerized at a slower rate. The neutral and deletion mutants had even slower rates of polymerization by caldesmon. The slow polymerization of DNEQ G-actin was traced to a greatly reduced binding of caldesmon to this mutant G-actin when compared to wild-type and alpha-actin. MgCl2-induced actin polymerization proceeded at identical rates for all actins.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1994

Intimations of K+ channel structure from a complete functional map of the molecular surface of charybdotoxin.

The external vestibules of many K+ channels carry a high-affinity receptor for charybdotoxin, a peptide of known structure. Point mutations of a recombinant toxin identified the residues directly involved in the interaction with a Ca(2+)-activated K+ channel. The interaction surface is formed from 8 of the 37 residues and covers about 25% of the peptide's molecular surface. The shape of the toxin permits a deduced picture of the complementary receptor site in the external vestibule of the K+ channel.

Amino Acid Sequence↗
PubMed1994

Fibromyalgia--the effect of relaxation and hydrogalvanic bath therapy on the subjective pain experience.

In the present study, two established non-medicinal treatment methods are compared with regard to their effect on various psychological pain parameters in patients with fibromyalgia. Twelve patients underwent hydrogalvanic baths, 13 patients the Jacobson relaxation training. Statistical evaluation showed only one significant difference in the different dimensions of pain measured at the beginning and end of the therapy. In comparison with patients receiving Jacobson-therapy, there is a significantly higher decrease in pain intensity in the period from breakfast till lunch in patients receiving bath-therapy. Apart from this, no differences between the two treatment groups could be found, either in the quality of pain, the psychological symptoms accompanying it, in sleep quality or in pain behaviour.

Adult↗
PubMed1994

Molecular characterization of immunoreactivities of peptides derived from chromogranin A (GE-25) and from secretogranin II (secretoneurin) in human and bovine cerebrospinal fluid.

Chromogranin A and secretogranin II are members of the so-called chromogranins, the acidic proteins stored in neuroendocrine large dense-core vesicles. We characterized chromogranin A and secretogranin II immunoreactivities in cerebrospinal fluid by radioimmunoassays using synthetic peptides derived from these components (GE-25 for chromogranin A and secretoneurin for secretogranin II). In lumbar cerebrospinal fluid, high levels (more than 1000 fmol/ml) of these two components were found, whereas in ventricular cerebrospinal fluid the secretoneurin levels were relatively low. The cerebrospinal fluid/serum ratio for secretoneurin was close to 170. High-performance liquid chromatography revealed that in both cerebrospinal fluid and extracts from human brain secretoneurin was the predominant immunoreactive component. In cerebrospinal fluid chromogranin A immunoreactivity was present as intermediate-sized peptides with little intact chromogranin A and free GE-25 peptide. In human brain samples smaller peptides including GE-25 were more predominant. Analogous findings for secretoneurin and chromogranin A were obtained for bovine brain samples. We can conclude that chromogranins are present in cerebrospinal fluid in concentrations much higher than those of classical neuropeptides also stored in large dense-core vesicles. Therefore, their degree of proteolytic processing can be analysed with small samples of cerebrospinal fluid. A possible disturbance of proteolytic processing in large dense-core vesicles in various pathological conditions can now be discovered.

Adult↗
PubMed1994

The charybdotoxin receptor of a Shaker K+ channel: peptide and channel residues mediating molecular recognition.

Charybdotoxin (CTX) is a peptide of known structure that inhibits Shaker K+ channels by a pore-blocking mechanism. Point mutagenesis of all 30 solvent-exposed residues identified the part of the CTX molecular surface making contact with the receptor in the K+ channel. All close-contact residues are clustered in a well-defined interaction surface; the shape of this surface implies that the outer opening of the Shaker channel conduction pore abruptly widens to a 25 x 35 A plateau. A mutagenic scan of the S5-S6 linker sequence of the Shaker K+ channel identified those channel residues influencing CTX binding affinity. The Shaker residues making the strongest contribution to toxin binding are located close to the pore-lining sequence, and more distant residues on both sides of this region influence CTX binding weakly, probably by an electrostatic mechanism. Complementary mutagenesis of both CTX and Shaker suggests that Shaker-F425 contacts a specific area near T8 and T9 on the CTX molecular surface. This contact point constrains Shaker-F425 to be located at a 20 A radial distance from the pore axis and 10-15 A above the "floor" of the CTX receptor.

Amino Acid Sequence↗
PubMed1994

Structural connectivity in actin: effect of C-terminal modifications on the properties of actin.

In this study, we use fluorescent probes and proteolytic digestions to demonstrate structural coupling between distant regions of actin. We show that modifications of Cys-374 in the C-terminus of actin slow the rate of nucleotide exchange in the nucleotide cleft. Conformational coupling between the C-terminus and the DNasal loop in subdomain II is observed in proteolytic digestion experiments in which a new C-terminal cleavage site is exposed upon DNasel binding. The functional consequences of C-terminal modification are evident from S-1 ATPase activity and the in vitro motility experiments with modified actins. Pyrene actin, labeled at Cys-374, activates S-1 ATPase activity only half as well as control actin. This reduction is attributed to a lower Vmax value because the affinity of pyrene actin to S-1 is not significantly altered. The in vitro sliding velocity of pyrene actin is also decreased. However, IAEDANS labeling of actin (also at Cys-374) enhances the Vmax of acto-S-1 ATPase activity and the in vitro sliding velocity by approximately 25%. These results are discussed in terms of conformational coupling between distant regions in actin and the functional implications of the interactions of actin-binding proteins with the C-terminus of actin.

Actins↗
PubMed1994

Engineering a uniquely reactive thiol into a cysteine-rich peptide.

Cysteine mutagenesis for the purpose of chemical labelling was applied to the K+ channel neurotoxin charybdotoxin, a 37-residue peptide with six functionally essential cysteines. An additional 'spinster cysteine' was introduced at a position far away in space from the toxin's known interaction surface where it contacts its K+ channel receptor. Despite the presence of the extra unpaired cysteine residue, the toxin still folds efficiently and may be labelled by fluorescent and radioactive reagents to give a functionally competent toxin.

Animals↗
PubMed1994

Cisplatin-induced peptic ulcers, vagotomy, adrenal and calcium modulation.

Cytochemical and autoradiographic studies in Wistar rats [Crl:(WI)BR] show that cisplatin treatment (9 mg/kg) inhibits the release of acetylcholine from the axonal endings of the stomach smooth muscle resulting in bloating of the stomach and ulceration. Cisplatin also induces corticosteroid release from the adrenal gland stimulating peptic ulceration. Vagotomy helps ameliorate the effect but not eliminate it. Calcium supplementation restores normal neuromuscular function to gastric smooth muscle, thereby eliminating the gastro-intestinal toxicity due to cisplatin.

Acetylcholinesterase↗
PubMed1994

Increases in human epidermal DR+CD1+, DR+CD1-CD36+, and DR-CD3+ cells in allergic versus irritant patch test responses.

In an attempt to differentiate an allergic patch test response from an irritant response, we evaluated by flow cytometry the percentages of various epidermal cell populations isolated from allergen and irritant-treated patch test sites. Nine allergic individuals were patch tested with various allergens (Rhus, dinitrochlorobenzene [DNCB], or nickel chloride) and a vehicle control for 48 h. Eight additional individuals were patch tested with irritating chemicals (sodium lauryl sulfate or nonanoic acid) and with a vehicle control for 48 h. Epidermal cells, isolated from suction blisters, were double labeled for CD1/HLA-DR, CD3/HLA-DR, or CD36/HLA-DR cell surface markers and analyzed by flow cytometry to determine the percentage of various cell populations. A mean increase of 0.91 +/- 0.3 in the percentage of DR+CD1+ Langerhans cells over the vehicle control patch test site was detected in allergen-positive patch test sites in allergic individuals, whereas a decrease of 0.19 +/- 0.2 in the percentage of DR+CD1+ Langerhans cells from the vehicle control patch test site was detected in irritant-treated patch test sites. Epidermal cells from allergen-positive patch test sites also exhibited an increase of 5.2 +/- 1.8 in percentage of DR+CD1- cells over the vehicle control patch test site compared to an increase change of 0.8 +/- 0.4 in epidermal cells isolated from irritant-treated patch test sites. We also found that DR+ cells that lacked the CD1 determinant expressed the macrophage/monocyte antigen CD36 (OKM5). Finally, a 2.3 +/- 0.8 increase in the percentage of DR-CD3+ cells over the vehicle control patch test site was observed in allergen-positive patch test sites compared to an increase of 0.2 +/- 0.2 observed in irritant-treated patch test sites. These results demonstrate a significant increase in DR+CD1+, DR+CD1-CD36+, and DR-CD3+ epidermal cells in allergen-positive patch test sites compared to irritant patch test sites.

Adult↗
PubMed1994

A trial of pre-emptive analgesia. Influence of timing of peroperative alfentanil on postoperative pain and analgesic requirements.

The influence of timing of administration of peroperative alfentanil on pain and analgesic requirements after surgery was studied in 60 patients undergoing total abdominal hysterectomy with or without bilateral salpingo-oophorectomy. Thirty patients received alfentanil 7.5 micrograms.kg-1 on induction of anaesthesia, followed by alfentanil 7.5 micrograms.kg-1 90 s before surgical incision (group A). Thirty control patients received alfentanil 15 micrograms.kg-1, 10 min after abdominal incision (group B). In addition, 10 min after surgical incision both groups received morphine 0.2 mg.kg-1, given over a 10 min period. The visual analogue scores (median, interquartile range) for pain 24 h after operation were 28.5 mm (11.25-47.0) in group A and 21.0 mm (10.5-47.5) in group B, p = 0.76. There were no differences in visual analogue scores at intermediate times. Morphine consumption in the first 24 h after surgery (median, interquartile range) was 53.5 mg (37.25-60.0) in group A and 52.0 mg (39.75-71.0) in group B, p = 0.52. We conclude that postoperative morphine consumption and pain scores are no different when alfentanil 15 micrograms.kg-1 is given before or after skin incision for abdominal hysterectomy.

Adult↗
PubMed1994

Role of rpoS (katF) in oxyR-independent regulation of hydroperoxidase I in Escherichia coli.

We present evidence showing that rpoS (katF) is a regulator of katG gene transcription in an oxyR-independent manner. Mutation of the rpoS gene in several different Escherichia coli strains caused a significant reduction in catalase HPI activity. In rpoS-delta oxyR double mutants, the level of HPI was considerably lower compared to the delta oxyR parent strain, and was restored when transformed with an rpoS+ plasmid. Overproduction of HPI in oxyR- suppressor strains was greatly diminished after inactivation of the rpoS gene and was accompanied by a substantial increase in sensitivity to menadione. Beta-galactosidase expression from a katG::lacZ promoter was lower in rpoS strains compared to rpoS+ isogenic parents. Several delta oxyR strains had detectable levels of katG transcription that was significantly diminished after rpoS gene inactivation.

Catalase↗
PubMed1994

Comparison of short and long-term renal function in liver transplant patients receiving cyclosporin or FK 506.

Long-term renal function was compared in 49 liver recipients [25 patients received cyclosporin (CyA) and 24 patients received FK 506] followed for a period of 1 year. Creatinine (CR) and glomerular filtration rate (GFR) pretransplantation (pre-Tx) and at 1, 3, 5, and 12 months post-Tx were recorded, as well as incidences of hyperkalemia, post-Tx hypertension, and insulin-dependent diabetes mellitus (IDDM) in the two groups. At 1 year post-Tx, the mean Cr had risen from baseline by 56% and 60% in the FK and CyA groups, respectively; the mean GFR had dropped by 32% in FK patients and by 27% in CyA patients. Acute nephrotoxicity occurred in 7/25 CyA patients (2/7 required dialysis) and 9/26 FK patients (7/9 required dialysis; 2/7 were switched to CyA). None remained on dialysis at 3 months. Renal insufficiency persisted at 1 year in 7/16 patients with early toxicity (CyA, 4; FK, 3) and in 3 of the remaining 36 pts (P < 0.001). Hyperkalemia occurred in 4/25 CyA, and in 12/24 FK patients (P < 0.025), post-Tx hypertension occurred in 15 CyA, and 7 FK patients (P < 0.05), and IDDM occurred in 4 CyA and 7 FK patients (P = ns). FK 506 and CyA, thus, exerted similar chronic renal effects. Although acute renal insufficiency improved upon dose reduction, renal impairment was permanent in some cases.

Creatinine↗