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Biomedical subjects

I Miller

Publications and source records attributed to I Miller.

At least 19 recordsLinked to original sources
PubMed2001

Proteins of rat serum, urine, and cerebrospinal fluid: VI. Further protein identifications and interstrain comparison.

We have investigated the biological fluids--serum, cerebrospinal fluid, and urine--of three strains of rats; the present data extend our database (also available on-line) and may be of interest for pharmacological and toxicological investigation. Specifically, we have defined reference maps of the major protein components in cerebrospinal fluid and urine. Compartment-specific isoforms were recognized for transferrin and transthyretin. Mass spectrometric data established the cleavage site of the signal peptide and identified the N-terminal blocking group of prostaglandin D synthase from rat cerebrospinal fluid. A previously undescribed member of the family of low molecular mass rat urinary proteins was characterized as containing a sequence similar, but not identical, to the N-terminal region of rat urinary protein-2 (RUP-2), and divergent from RUP-1.

Amino Acid Sequence↗
PubMed2001

Untreated short-term course of major depression: a meta-analysis of outcomes from studies using wait-list control groups.

INTRODUCTION: While the short-term response rates to antidepressant medication and placebo are well established, very little is known about the short-term course of untreated depression. Knowledge of the course of untreated depression can serve as a benchmark for assessing the true benefits of active treatment. METHOD: A meta-analysis was performed analyzing the outcomes of all psychotherapy studies that randomized adult outpatients with major depressive disorder to a wait-list control group. RESULTS: Nineteen studies involving 221 subjects were reviewed. The mean decrease in Hamilton Rating Scale for Depression scores over 2-20 weeks was 11.9%, while the mean decrease in Beck Depression Inventory scores was 15.7%. Using a subsample of studies that reported individual outcomes, we estimated that 15 of 76 subjects (19.7%) improved to a degree comparable to what would be considered a positive response in antidepressant trials. CONCLUSIONS: In the short-term, depressive symptomatology can be expected to decrease by about 10-15% on average without treatment. As many as 20% of subjects who participate in a short-term antidepressant trial may experience a spontaneous remission.

Adult↗
PubMed2001

IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy.

Abnormalities of chromosome 1q21 are common in B cell malignancies, but their target genes are largely unknown. By cloning the breakpoints of a (1;14) (q21;q32) chromosomal translocation in a myeloma cell line, we have identified two novel genes, IRTA1 and IRTA2, encoding cell surface receptors homologous to the Fc and inhibitory receptor families. Both genes are selectively expressed in mature B cells: IRTA1 in marginal zone B cells and IRTA2 in centrocytes, marginal zone B cells, and immunoblasts. As a result of the t(1;14), IRTA1 is fused to the immunoglobulin Calpha domain to produce a chimeric IRTA1/Calpha fusion protein. In tumor cell lines with 1q21 abnormalities, IRTA2 expression is deregulated. Thus, IRTA1 and IRTA2 are novel immunoreceptors implicated in B cell development and lymphomagenesis.

Amino Acid Sequence↗
PubMed2001

Caseload in rural general surgical practice and implications for training.

BACKGROUND: Despite increasing specialization within general surgery, many general surgeons, particularly in rural practice, continue to treat a wide range of conditions. The aim of the present paper was to provide accurate information on three rural surgeons' case-loads to illustrate the spectrum of surgery encountered and to assist in the planning of rural general surgical training. METHODS: A review was conducted of a prospectively maintained database of operations performed by three rural general surgeons in different parts of Victoria, Australia over a 5-year period. RESULTS: A large volume and wide range of procedures was performed by each surgeon, who averaged more than 500 operations per year (excluding endoscopies). Although most were within the range of procedures covered in the Royal Australasian College of Surgeons (RACS) Fellowship in general surgery, some encroached upon other specialties such as orthopaedics, urology, paediatric surgery and obstetrics/gynaecology. Operations outside of 'general' surgery reflected individual training and local community needs. CONCLUSIONS: The current RACS Fellowship in general surgery, augmented by training in other specialties as required, will help prepare general surgeons for rural practice.

Curriculum↗
PubMed2001

Epidemiological studies on animal and human trichinellosis in Estonia.

From 1992 to 1999, muscle samples from 814 sylvatic animals and 1,173 domestic and synanthropic animals were collected in 15 districts of Estonia; the prevalence of trichinellosis ranged from 1.0% to 79.4% for sylvatic animals and from 0.6% to 24.5% for domestic or synanthropic animals and for animals from fur-bearing farms. The most important reservoirs of Trichinella in nature were the raccoon dog, the red fox, the lynx and the wolf. Three species of Trichinella (T. spiralis, T. nativa, and T. britovi) were identified by several types of PCR-based analyses. Meat from sylvatic animals was the main source of Trichinella infection for humans.

Animals↗
PubMed2001

Acute-phase proteins before cerebral ischemia in stroke-prone rats: identification by proteomics.

BACKGROUND AND PURPOSE: A high degree of proteinuria has been reported in stroke-prone spontaneously hypertensive rats (SHRSP). We studied the effect of salt loading on the detailed protein pattern of serum and urine in 3 rat strains: Wistar-Kyoto, spontaneously hypertensive rats, and SHRSP, an inbred animal model for a complex form of cerebrovascular disorder resembling the human disease. METHODS: Rats were given a permissive diet and received 1% NaCl in drinking water. The protein pattern in body fluids was assessed over time by 2-dimensional electrophoretic analysis. Brain alterations were monitored by MRI and histology. RESULTS: Several proteins were excreted in urine after weeks of treatment and in advance of stroke: transferrin, hemopexin, albumin, alpha(2)-HS-glycoprotein, kallikrein-binding protein, alpha(1)-antitrypsin, Gc-globulin, and transthyretin. Markers of an inflammatory response, including very high levels of thiostatin, were detected in the serum of SHRSP at least 4 weeks before a stroke occurred. CONCLUSIONS: In SHRSP subjected to salt loading, an atypical inflammatory condition and widespread alterations of vascular permeability developed before the appearance of anomalous features in the brain detected by MRI. Urinary concentrations of each of the excreted serum proteins correlated positively with time before stroke occurred.

Acute-Phase Proteins↗
PubMed2000

Proteins of rat serum V: adjuvant arthritis and its modulation by nonsteroidal anti-inflammatory drugs.

The effect of adjuvant arthritis (AA) on the pattern of rat serum proteins includes the upregulation of haptoglobin, orosomucoid, alpha2-macroglobulin, serine protease inhibitor-3, thiostatin, alpha1-antitrypsin, C-reactive protein, and the downregulation of kallikrein-binding protein, alpha1-inhibitor III, apolipoprotein A-I, alpha2-HS-glycoprotein, albumin, apolipoprotein A-IV, transthyretin and transferrin. Minor changes (+/- 20%) are observed for Gc-globulin, ceruloplasmin, and alpha1-macroglobulin. AA thus grossly resembles the acute inflammatory response elicited by the injection of turpentine, although the changes in the levels of negative acute-phase proteins (APP) are smaller in acute inflammation. Indomethacine and ibuprofen inhibit the effects of arthritis on the synthesis of rat serum proteins in different ways: The former is, on average, three times as effective as the latter. Each drug interferes differently with different proteins. In animals without AA, both nonsteroidal anti-inflammatory drugs (NSAID) mimic the inflammatory pattern to a certain extent, with more effect on the negative than on the positive APPs. Overall, the shifts in serum protein levels parallel changes in inflammatory parameters such as joint swelling and serum interleukin-6 (IL-6) activity. Protein quantitation after two-dimensional electrophoresis (2-DE) reveals some effects of the drugs per se which escape detection by other routine tests.

Animals↗
PubMed2000

Increases in manic symptoms after life events involving goal attainment.

Bipolar disorder has been conceptualized as an outcome of dysregulation in the behavioral activation system (BAS), a brain system that regulates goal-directed activity. On the basis of the BAS model, the authors hypothesized that life events involving goal attainment would promote manic symptoms in bipolar individuals. The authors followed 43 bipolar I individuals monthly with standardized symptom severity assessments (the Modified Hamilton Rating Scale for Depression and the Bech-Rafaelsen Mania Rating Scale). Life events were assessed using the Goal Attainment and Positivity scales of the Life Events and Difficulties Schedule. As hypothesized, manic symptoms increased in the 2 months following goal-attainment events, but depressed symptoms were not changed following goal-attainment events. These results are congruent with a series of recent polarity-specific findings.

Achievement↗
PubMed1999

RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules.

In response to environmental stress, the related RNA-binding proteins TIA-1 and TIAR colocalize with poly(A)(+) RNA at cytoplasmic foci that resemble the stress granules (SGs) that harbor untranslated mRNAs in heat shocked plant cells (Nover et al. 1989; Nover et al. 1983; Scharf et al. 1998). The accumulation of untranslated mRNA at SGs is reversible in cells that recover from a sublethal stress, but irreversible in cells subjected to a lethal stress. We have found that the assembly of TIA-1/R(+) SGs is initiated by the phosphorylation of eIF-2alpha. A phosphomimetic eIF-2alpha mutant (S51D) induces the assembly of SGs, whereas a nonphosphorylatable eIF-2alpha mutant (S51A) prevents the assembly of SGs. The ability of a TIA-1 mutant lacking its RNA-binding domains to function as a transdominant inhibitor of SG formation suggests that this RNA-binding protein acts downstream of the phosphorylation of eIF-2alpha to promote the sequestration of untranslated mRNAs at SGs. The assembly and disassembly of SGs could regulate the duration of stress- induced translational arrest in cells recovering from environmental stress.

Animals↗
PubMed1999

Low-tech electrophoresis, small but beautiful, and effective: electrophoretic titration curves of proteins.

Migration across a stationary pH gradient results in the electrophoretic titration of a protein's dissociable groups. From the resulting curves, some properties of the protein may be derived, including overall amino acid composition and type of mutation between polymorphic variants, as well as range of stability or, for enzymes, of catalytic activity. Analysis with this technique is a stringent purity criterion; other applications allow the study of interacting systems and the planning of chromatographic fractionations based on differences in surface charge.

Amino Acids↗
PubMed1999

A web site for the rat serum protein study group.

We describe a site http://users.unimi.it/-ratserum/homeframed.ht ml with clickable maps of serum proteins of control and inflamed rats as well as quantitative data on the expression of such serum proteins under varying physiological and experimental conditions. This information enhances the value of minimally invasive techniques, thus reducing the number of animals to be treated, and eventually sacrificed, in pharmacological/toxicological research projects.

Animals↗
PubMed1999

Comparison of an orally disintegrating ondansetron tablet with the conventional ondansetron tablet for cyclophosphamide-induced emesis in cancer patients: a multicenter, double-masked study. Ondansetron Orally Disintegrating Tablet Emesis Study Group.

A total of 427 cancer patients receiving cyclophosphamide chemotherapy participated in this multicenter, double-masked, double-dummy, parallel-group, randomized study comparing the antiemetic efficacy and safety of an 8-mg conventional ondansetron tablet (OT, n = 212) taken twice daily with an 8-mg orally disintegrating ondansetron tablet (ODT, n = 215) taken twice daily for 3 days. In the primary efficacy analysis, complete or major control of emesis (0 to 2 emetic episodes) between days 1 and 3 was seen in 80% of OT and 78% of ODT patients. The 90% confidence interval for the differences between treatments was -8.6% to 4.4% (defined interval of equivalence, +/-15%), showing that the formulations were equivalent. In the secondary efficacy analysis, no significant differences were observed in the rates of complete control of emesis (no episodes of emesis) over 3 days (63% and 64% of the respective groups) and on day 1 (84% and 81%, respectively) and in the complete control of nausea over 3 days (37% and 43%, respectively) and on day 1 (59% and 61% of patients, respectively). The taste of ODT was acceptable to the majority of patients (89%) who received it. OT and ODT were both well tolerated. Thus 8 mg ODT twice daily represents a palatable, well-tolerated, and effective antiemetic treatment for the control of cyclophosphamide-induced emesis and nausea and provides equivalent treatment to OT 8 mg twice daily.

Administration, Oral↗
PubMed1999

Social support and the course of bipolar disorder.

The current study prospectively examined the impact of social support on symptom severity and recovery from episodes in bipolar disorder, both as a direct influence and as a buffer of life events. Fifty-nine individuals with Bipolar I disorder were followed longitudinally with monthly symptom severity interviews. Social support was measured by the Interpersonal Support Evaluation List and the Interview Schedule for Social Interaction, and life events were assessed using the Life Events and Difficulties Schedule. Individuals with low social support took longer to recover from episodes and were more symptomatic across a 6-month follow-up. Results suggest a polarity-specific effect, in that social support influences depression but not mania. Discussion focuses on theoretical implications of a series of polarity-specific findings within the field.

Adult↗
PubMed1999

Zanamivir: a review of clinical safety.

Preclinical and clinical studies have clearly demonstrated that zanamivir, a potent and highly selective inhibitor of the influenza A and B virus neuraminidase, has an impressive safety profile. This report describes the safety and tolerability findings from the clinical studies completed up to the 17 July 1998 involving over 6000 adult and adolescent patients from North America, Europe and the Southern Hemisphere. Serious adverse events from an ongoing Japanese clinical programme are also reported. Zanamivir was administered in various dose forms and frequencies and was found to have a comparable safety profile with placebo when given for both the treatment and prophylaxis of influenza-like illness. These findings were independent of age and underlying medical condition. 4152 patients received zanamivir and the most commonly reported adverse events were consistent with the signs and symptoms of influenza-like illness. Most of the adverse events were mild and did not result in patient withdrawal from the studies. Less than 1% of zanamivir and placebo recipients reported a serious adverse event. In addition, 490 healthy volunteers received zanamivir in clinical pharmacology studies. It was well tolerated and the incidence of adverse events was similar in zanamivir and placebo recipients. In addition, no clinically significant laboratory abnormalities were detected. Results from in vitro and in vivo animal studies suggest that zanamivir has low acute toxicity and no significant systemic toxicity or respiratory tract irritancy at plasma exposures more than 100-fold higher than those anticipated following clinical use. Neither genotoxic nor reproductive types of toxicity have been observed in toxicology studies at doses equal to 17 to 197 times the current therapeutic dose (20 mg/day). The characteristics of the molecule and the low systemic exposure indicate a very low potential for drug interactions with the inhaled route. Furthermore, repeated 600mg intravenous doses were well tolerated in healthy volunteers. The observed safety profile of zanamivir compares favourably with currently available agents with anti-influenza virus activity, such as rimantadine and amantadine, as well as GS4104, a neuraminidase inhibitor currently in phase III development. This may be attributed to the low systemic bioavailability of zanamivir, which is given by oral inhalation, direct to the primary site of viral replication. The potential advantages of this include a reduced risk of drug-drug interactions, other nontarget organ toxicities (e.g. brain) and drug clearance issues from both kidney and liver. Therefore, the safety profile of zanamivir supports its use in the management of influenza.

Animals↗
PubMed1999

Coadministration of orally inhaled zanamivir with inactivated trivalent influenza vaccine does not adversely affect the production of antihaemagglutinin antibodies in the serum of healthy volunteers.

OBJECTIVE: Zanamivir, a clinically proven potent and specific inhibitor of influenza A and B neuraminidase, has been approved in some countries for the treatment of influenza and is in late-stage development for the prophylaxis of influenza. This study investigated whether the coadministration of zanamivir and influenza vaccine affected the development of antibody responses to injected influenza haemagglutinin. DESIGN: This double-blind randomised placebo-controlled study compared the antihaemagglutinin antibody production [haemagglutination inhibition (HAI) titre] after administration of inactivated trivalent influenza vaccine in healthy volunteers receiving zanamivir or placebo once daily for 28 days. STUDY PARTICIPANTS: 138 healthy volunteers (52 men and 86 nonpregnant women, mean age 32.7 years) were randomised to the zanamivir (70 participants) or placebo (68 participants) groups. INTERVENTIONS: Participants received a single intramuscular dose (deltoid muscle) of the 1997/1998 trivalent inactivated influenza vaccine (surface antigen) PhEur (Fluvirin) on day 1, and were then randomised to receive zanamivir 10 mg/day by oral inhalation or placebo for 28 days. Serum samples for determination of HAI titres were obtained before vaccination and on days 15 and 29. Compliance, adverse events and laboratory parameters were monitored. RESULTS: The primary measure of response was the geometric mean increase in HAI titre against the 3 viral antigens contained in the vaccine, calculated as the ratio of the value 4 weeks after vaccination to the baseline value. The means (and 2-sided 95% confidence intervals) for the ratio between the geometric mean increase with placebo and the increase with zanamivir were as follows: 1.1 (0.7, 1.5) for influenza B, 0.7 (0.4, 1.2) for influenza A H1N1, and 0.6 (0.4, 1.1) for influenza AH3N2. (This corresponds to a test level of alpha = 0.025 for the hypothesis that the increase with placebo was > or = 2-fold greater than the increase with zanamivir.) A lack of effect was concluded as values of 2.0 or greater (i.e. a 2-fold difference) were excluded. Comparisons were also made of the increase in titre at 2 weeks, the proportions of participants with at least a 4-fold increase in titre and the proportions of participants with a titre of at least 1:40. These comparisons revealed no differences between zanamivir- and placebo-treated groups. The nature and incidence of adverse events observed with zanamivir were similar to those observed with placebo. CONCLUSIONS: Overall, zanamivir was not associated with a reduced response in HAI titre against the 3 vaccine antigens when compared with placebo. In addition, zanamivir was well tolerated. Inhaled zanamivir 10 mg once daily has been demonstrated to prevent symptomatic laboratory-confirmed influenza in a community outbreak. Zanamivir should have the potential to provide protection during the 2- to 4-week period before full immunity is induced, following vaccination at a time when influenza is circulating in the community.

Administration, Oral↗