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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 19 recordsLinked to original sources
PubMed1992

Escherichia coli genes involved in cell survival during dormancy: role of oxidative stress.

When Escherichia coli cells reach stationary phase of growth, specific gene products are synthesized that protect cells while dormant. "Aged" cells may remain viable in cultures for years. For example, agar cultures stored for 38 years still had more than 10(5) viable cells/ml. However, when specific mutants were cultured, the population of these mutants dropped sharply after 4-10 days. This defect is termed "Stationary-Phase-Death". Each mutant strain was hypersensitive to near-ultraviolet radiation and other oxidative agents. Bovine catalase rescued many of the mutants from death in dormancy, suggesting that specific gene products protect "aged" cells against oxidative damage.

Escherichia coli↗
PubMed1992

The human brain resonance of choline-containing compounds is similar in patients receiving lithium treatment and controls: an in vivo proton magnetic resonance spectroscopy study.

Lithium specifically and potentially inhibits membrane transport of choline. However, the effect of lithium on human neuronal choline content is unknown. This study was performed to determine if lithium alters the human brain choline concentration in vivo. In vivo proton magnetic resonance spectroscopy was used to compare the relative brain concentration of choline-containing compounds in seven lithium-treated patients and six lithium-free controls. No significant difference was observed in the mean relative choline resonance between the patient and control groups. Lithium treatment did not appear to alter the overall brain content of choline-containing compounds. It remains possible that a component of these compounds, particularly free choline, is elevated during lithium treatment.

Adult↗
PubMed1992

Mapping function to structure in a channel-blocking peptide: electrostatic mutants of charybdotoxin.

Electrostatic interactions between charybdotoxin (CTX), a specific peptide pore blocker of K+ channels, and a Ca(2+)-activated K+ channel were investigated with a genetically manipulable recombinant CTX. Point mutations at certain charged residues showed only small effects on the binding affinity of the toxin molecule: Lys11, Glu12, Arg19, His21, Lys31, and Lys32. Replacement by Gln at Arg25, Lys27, or Lys34 strongly decreased the affinity of the toxin. These affinity changes were mainly due to large increases of toxin dissociation rates without much effect on association rates, as if close-range interactions between the toxin and its receptor site of the channel were disrupted. We also found that the neutralization of Lys27 to Gln removed the toxin's characteristic voltage dependence in dissociation rate. Mutation and functional mapping of charged residues revealed a molecular surface of CTX which makes direct contact with the extracellular mouth of the K+ channel.

Animals↗
PubMed1992

Anti-tumor necrosis factor antibody therapy fails to prevent lethality after cecal ligation and puncture or endotoxemia.

Cytokines have been studied intensively to delineate their role in the altered pathophysiology observed in septic shock. We studied the role of TNF in the lethality of two well characterized models of septic shock by inhibiting TNF's activity with a specific antibody. In the first model, sepsis was induced by cecal ligation and puncture (CLP), and in the second model sepsis was induced by either an i.p. or i.v. injection of LPS. After CLP, plasma endotoxin was detectable within 4 h and reached a peak at 8 h (136 +/- 109 ng/ml). TNF bioactivity peaked at 12 h (528 +/- 267 pg/ml) at a significantly higher level than sham-operated control mice (64 +/- 31 pg/ml). After i.p. LPS, TNF peaked much more quickly (90 min) compared with CLP and at a significantly higher level (107,900 +/- 25,000 pg/ml). Another cytokine studied in septic shock, IL-6, peaked at 12 h after CLP at 1011 +/- 431 pg/ml, and at 90 min after lethal LPS at 16,300 +/- 3,700 pg/ml. Mice were treated with an anti-TNF antibody that has been shown previously to inhibit in vivo TNF activity. Antibody treatment of mice subjected to CLP significantly reduced TNF bioactivity but did not reduce mortality or pulmonary neutrophilic infiltration. In the i.v. LPS model, anti-TNF antibody treatment concomitant with LPS injection reduced plasma TNF activity from 80,000 +/- 20,000 pg/ml to undetectable levels. However, anti-TNF treatment immediately before either i.v. or i.p. LPS did not reduce mortality. Additionally, when the antibody was administered 4 h before the lethal i.v. LPS, there was no reduction in lethality. These data show that in two separate models of septic shock blockade of TNF biologic activity will not prevent lethality.

Animals↗
PubMed1992

Stability of psychiatric diagnoses. An application to the affective disorders.

In the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression study, data were collected on 2226 first-degree relatives of 612 probands. A second, "blind" reassessment of all relatives was attempted 6 years after the initial evaluation. We report on a final sample of 1629 relatives assessed twice using the Schedule for Affective Disorders and Schizophrenia-Lifetime version. We summarize methods for using stability of diagnosis to model the relationship between clinical covariates and the probability of being a true case. Moreover, we define an index of caseness that can be used to narrow the criteria for who is a case. Of those positive for major depressive disorder at initial evaluation, 74% were positive (on a lifetime basis) at follow-up (ie, were stable). There is a gradient: 48% of those who had three symptoms and no treatment were stable, compared with 96% of those with eight symptoms and treatment. For major depressive disorder, we found the caseness index for those with lifetime mania more severe than that of nonbipolar patients, with those who had hypomania being intermediate. A hierarchical analysis indicated that bipolar I tends to be diagnosed as schizoaffective-manic across occasions, and vice versa. This is consistent with the prior familial analyses that suggest these two diagnoses be combined into a single bipolar phenotype. The analysis for major depressive disorder indicates that caseness appears to represent quantitative, rather than qualitative, differences, with no natural cutoff to identify distinct subgroups. Finally, we discuss implications including utility in genetic analyses, estimation of incidence or prevalence allowing for diagnostic error, and examination of cohort effects.

Adolescent↗
PubMed1992

Macroregenerative nodules and hepatocellular carcinoma in forty-four sequential adult liver explants with cirrhosis.

Macroregenerative nodules, also called nodules of adenomatous hyperplasia, have been well documented in Japan. Extensive studies support the hypothesis that in the Japanese population these lesions represent a possible pathway for hepatocarcinogenesis. However, reporting of these lesions in non-Japanese populations has so far been rare. We examined 44 sequential cirrhotic hepatectomy specimens from adult patients who underwent orthotopic liver transplantation at our institution. All livers were serially sectioned every 0.5 cm. Macroregenerative nodules were defined as regenerative nodules at least 1 cm in diameter. Forty-eight macroregenerative nodules were found in 11 livers (25% of livers). The antecedent diseases in these livers included hepatitis C (3), alcoholism (2), primary biliary cirrhosis (2) (one with iron overload), cryptogenic cirrhosis (2), hepatitis B (1) and alpha 1-antitrypsin deficiency (1). The macroregenerative nodules often differed from the surrounding nodular parenchyma in color, texture or the degree to which they bulged beyond the cut liver surface. Three livers contained grossly apparent hepatocellular carcinomas. Microscopically, macroregenerative nodules could be classified as those with (type 2) and without (type 1) dysplasia. Four livers had type 1 lesions, two had type 2 lesions and five had lesions of both types. We found 36 type 1 lesions in all and 12 type 2 lesions, 3 containing foci of microscopic carcinoma. All hepatocellular carcinomas arose in livers containing macroregenerative nodules (either type). Liver cell dysplasia, large-cell or small-cell, was observed in cirrhotic nodules of 27 livers. Microscopic or macroscopic hepatocellular carcinoma occurred in three livers with large-cell but not small-cell dysplasia and in one liver without dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1992

Interaction of charybdotoxin with permeant ions inside the pore of a K+ channel.

Charybdotoxin (CTX) blocks high conductance Ca(2+)-activated K+ channels by binding to a receptor site in the externally facing "mouth." Toxin bound to the channel can be destabilized from its site by K+ entering the channel from the opposite, internal, solution. By analyzing point mutants of CTX expressed in E. coli, assayed with single Ca(2+)-activated K+ channels reconstituted into planar lipid bilayers, we show that a single positively charged residue of the peptide, Lys-27, wholly mediates this interaction of K+ with CTX. If position 27 carries a positively charged residue, internal K+ accelerates the dissociation rate of CTX in a voltage-dependent manner; however, if a neutral Asn or Gln is substituted at this position, the dissociation rate is completely insensitive to either internal K+ or applied voltage. Position 27 is unique in this respect; charge-neutral substitutions made at other positions fail to eliminate the K+ destabilization phenomenon. The results argue that CTX bound to the channel positions Lys-27 physically close to a K(+)-specific binding site on the external end of the conduction pathway and that a K+ ion occupying this site destabilizes CTX via direct electrostatic repulsion with the epsilon-amino group of Lys-27.

Animals↗
PubMed1992

Investigation of an outbreak of methicillin-resistant Staphylococcus aureus in patients with skin disease using DNA restriction patterns.

OBJECTIVE: To investigate an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) among patients using chromosomal typing of the isolates. DESIGN: Comparison of epidemiological and clinical data to endonuclease restriction fragmentation analysis (RFA) of the MRSA isolates associated with an outbreak. Total DNA from the MRSA isolates was restricted with HINDIII and HAEIII for typing. SETTING: Tertiary care academic medical center. METHODS: An epidemiological investigation of an outbreak of MRSA among patients in private rooms was evaluated by routine infection control methods. The MRSA isolates from blood cultures of 7 patients and the nares of a nurse were collected during the outbreak. MRSA isolates from 23 patients not associated with the outbreak also were collected. The total DNA of the MRSA isolates were restricted with HINDIII and HAEIII and electrophoresed on 0.6% agarose gels. RESULTS: MRSA from 4 of the 7 bacteremic patients and the nurse on the outbreak unit had the same endonuclease restriction pattern. The patients were linked in that they were compromised by severe psoriasis or skin ulcers, were on the unit during the same period, and had oatmeal baths in a common bathtub. Of 50 staff members screened, the nurse was the only person detected as colonized by the strain. The other 3 patients on the unit as well as the 23 patients in other locations not associated with the outbreak had MRSA isolates with different RFA patterns. The use of the bathtub was discontinued and further transmission of MRSA was stopped. CONCLUSIONS: A comparison of the relatedness of MRSA by RFA demonstrated the uniqueness of the epidemiologically linked isolates and the utility of the RFA technique in the performance of routine infection control investigations.

Bacterial Typing Techniques↗
PubMed1992

The epidemiology of subacute sclerosing panencephalitis in England and Wales 1970-1989.

Two hundred and ninety cases of subacute sclerosing panencephalitis (SSPE) registered in England and Wales from 1970 to 1989 were followed at 6-monthly intervals. Male to female ratio was 2.8:1. Age at onset increased significantly over the period. Measles was recorded for 81% of cases; in nearly half this had occurred under 2 years. Measles vaccine was documented in 20 cases; in 10 measles was also documented and it could not be positively excluded in the remainder. The calculated risk of SSPE following measles was 4.0/100,000 cases compared with the risk after vaccine of 0.14/100,000 doses. Measles under 1 year carried a risk 16 times greater than measles over 5 years. There was an excess of cases in third and subsequent children. The incidence was higher in the northwest than in the southeast of the country. Survival time varied from 4 weeks to 16 years and was shorter when measles had occurred over the mean age of 2.5 years. Of the cases 9% had a history of mental retardation before the onset of SSPE. The incidence of SSPE has fallen following the reduction in measles resulting from vaccination. However, because of the median 8-year interval between measles and onset of SSPE, further cases arising from measles during the study period must still be expected, particularly in adolescents.

Adolescent↗
PubMed1992

Zotepine in the treatment of schizophrenic patients with prevailingly negative symptoms. A double-blind trial vs. haloperidol.

Zotepine, a neuroleptic agent with additional 5-HT2 blocking properties, was compared with haloperidol in the treatment of schizophrenic patients with predominantly negative symptoms using a double-blind design. During the investigation period zotepine treated patients showed significant improvements in all rating instruments whereas haloperidol treated patients did not. Patients in the zotepine group developed fewer clinical side effects. The results of the presented study confirm the positive impressions gained in earlier open trials with zotepine.

Adult↗
PubMed1992

Evidence that the systematic analysis of bile cytology permits monitoring of hepatic allograft rejection.

Cytologic analysis was performed on 128 bile specimens collected by schedule from 12 liver transplant recipients over a 4-month period. Clinical diagnoses at the time of specimen collection were determined retrospectively, as follows: clinically stable, 75; acute rejection, 15; CMV hepatitis, 1; systemic infection, 8; ischemic injury, 24 (all within the first 4 days postop); nonclassifiable, 5. Bile analysis was done by a blinded investigator. Specimens contained ductal epithelial cells (EC) and inflammatory cells (IC), which were counted using Cytospin slide preparations. Greater than 10 cells/slide were seen in 93.3% of rejections, 91.7% of ischemic injuries, 100% of systemic infections, and 14.6% of stable patients. In samples collected after POD 4, IC were seen in 86.7% of rejections, yielding a specificity of 94.4% (P less than 0.001). If lymphoblastic cells were also seen, the specificity increased to 96.6%. Five specimens were obtained the day before the clinical diagnosis of rejection; all demonstrated IC. Seven specimens were obtained 3 days after beginning therapy for rejection. In 5 the bile contained no IC, and clinical improvement occurred; in the 2 in whom IC were found, further therapy was subsequently required. IC were seen in 5 of 8 specimens taken when systemic infection was present; the clinical setting allowed differentiation from rejection. Only 1 case of CMV hepatitis was included, thus no conclusions can be drawn for this entity. Cytoplasmic vacuolization of EC was observed in 30% of cases, in these, cyclosporine levels were significantly higher (989.9 +/- 356.9 vs. 672.8 +/- 421.2, P = 0.02). In summary, bile cytology analysis aides in the monitoring of the onset and duration of rejection. It may be an indicator of persistent rejection, and it may help prevent overimmunosuppression in those cases with normal cytological findings.

Antibodies, Monoclonal↗