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Biomedical subjects

M Keller

Publications and source records attributed to M Keller.

At least 145 records · Page 8Linked to original sources
PubMed1994

A prospective follow-along study of the course of social phobia.

The goals of this study were to delineate the courses of social phobia and to determine whether the course of generalized and specific social phobia differed. In the Harvard/Brown Longitudinal Study of Anxiety Research Project, 66 specific and 74 generalized social phobic subjects were identified for whom adequate course data were available. These subjects had been followed prospectively with a standardized follow-along measure of psychopathology. The probability of remission was calculated for each individual group and both groups combined. Demographics were the same for both groups except that the specific social phobia group had a marginally higher mean score on the Global Assessment Scale. Complete remission for the combined group was not different from that for either subgroup and was 0.11 at 65 weeks. Social phobia appears to be a disorder with considerable long-term morbidity. Surprisingly, both subtypes took a comparably long time to remit and were similar in their high level of psychosocial dysfunction.

Adult↗
PubMed1994

[Von Willebrand syndrome--risk of hemorrhage in ENT interventions in childhood].

Von Willebrand's disease (vWD) is the most common inherited bleeding disorder. Typical clinical features such as bleeding after surgery or trauma might suggest the disease. We present a series of 24 patients with vWD treated between 1989 and 1992. Diagnosis was confirmed by a reduction in plasma factor VIII antigen concentration, reduction of ristocetin cofactor activity and reduced factor VIII activity. Seventeen of the patients underwent surgery (7 adenoidectomies, 8 tonsillectomies, 2 paranasal sinus operations) and received preoperative stimulation of von Willebrand factor (vWF) using DDAVP. This resulted in a rapid increase in plasma vWF concentration from an average of 56% before stimulation to 190% of the normal value after stimulation. A reduction of partial thromboplastin time from an average of 44.4 seconds to 34.4 seconds was observed following DDAVP. No bleeding complications or other side-effects occurred. Preoperative stimulation of vWF using DDAVP proved to be a safe method to reduce the risk of bleeding in patients with vWD undergoing surgery.

Adolescent↗
PubMed1994

Rapid increases in load of human immunodeficiency virus correlate with early disease progression and loss of CD4 cells in vertically infected infants.

The relationship between viral burden, timing of transmission, and clinical progression was investigated in 110 children at risk for vertical human immunodeficiency virus (HIV) infection using quantitative polymerase chain reaction, coculture, and immune complex-dissociated p24 antigen assay. In a cross-sectional study, the mean HIV DNA copy number in 19 symptomatic children was significantly higher than in 31 infected, asymptomatic children (420 +/- 125 vs. 87 +/- 78; P < .0001). In a second group of 8 vertically infected infants followed prospectively from birth, 4 defined as infected in utero showed a more rapid increase in virus load, an accelerated loss of CD4 cells, and early progression to symptomatic disease (3-12 weeks) compared with 4 children with late in utero or intrapartum transmission (10-31 months). These data suggest that a direct relationship exists between HIV replication, the timing of transmission and onset and progression of HIV disease in vertically infected children.

Acquired Immunodeficiency Syndrome↗
PubMed1994

A prospective, follow-along study of the course of social phobia: II. Testing for basic predictors of course.

This study examined the 65-week outcome of a group of subjects with social phobia to determine predictors of course. Social phobic patients in the Harvard/Brown Anxiety Disorders Research Project study were followed for 65 weeks using the Longitudinal Interval Follow-Up Evaluation-UpJohn scale. The following variables did not predict outcome over the course of the study: sex, age of onset, duration of illness, lifetime history of various anxiety disorders, current comorbidity of anxiety or depressive disorders, Global Assessment Scale score, or measures of role functioning. We find that in a social phobic population with a mean duration of illness of 18 years, none of the tested variables examined predicted 65-week outcome.

Age of Onset↗
PubMed1994

Physiological assessment of coronary artery disease and myocardial viability in ischemic syndromes using adenosine echocardiography.

We hypothesized that it would be feasible and safe to use adenosine echocardiography to assess the physiological significance of coronary stenoses, detect ischemic myocardium, and assess myocardial viability in a high risk group of patients with coronary artery disease (CAD). Therefore, in 40 patients with either unstable angina, non-Q myocardial infarction, or myocardial infarction treated with thrombolytic therapy, we performed adenosine echocardiography (140 mug/kg per min for 5 mins with a 16 segment model for analysis) and compared the findings with quantitative planar thallium-201 scintigraphy, and (in 26 patients) coronary angiography. The technique was safe, and there were no serious complications. Adenosine resulted in a significant increase in heart rate and decrease in blood pressure. The sensitivity of adenosine echocardiography and thallium scintigraphy were 96% and 88%, respectively, for detecting greater than 75% stenosis. The change in echo score from baseline during adenosine infusion was significantly higher with more severe coronary disease (single vessel right coronary artery {RCA} or left circumflex {LCX} disease = 0.125 +/- 0.15, proximal left anterior descending coronary artery {LAD} disease = 0.23 +/- 0.15, RCA and LCX disease = 0.30 +/- 0.14, LAD and RCA and/or LCX disease = 0.62 +/- 0.13). Likewise, the echo score during adenosine infusion was significantly higher in patients with high risk thallium scans (low risk = 1.29 +/- 0.26, medium risk = 1.74 +/- 0.22, and high risk = 2.21 +/- 0.37). In 13 patients receiving thrombolytic therapy, adenosine echocardiography identified 12 with viable myocardium as defined by quantitative thallium criteria. Furthermore, the wall-motion response of the viable segment was indicative of the degree of stenosis of the artery subtending the segment. Regional function deteriorated in patients with high grade (95 +/- 2%) stenoses and improved in those with nonflow limiting stenoses (66 +/- 25%, P = 0.03). Therefore, we conclude that adenosine echocardiography can detect significant coronary stenoses, has a high degree of concordance with thallium in detecting cardiac perfusion abnormalities, and can assess myocardial viability following thrombolytic therapy.

Adenosine↗
PubMed1994

Interaction of virulent and non-virulent Rhodococcus equi human isolates with phagocytes, fibroblast- and epithelial-derived cells.

Rhodococcus equi is a facultative, intracellular, Gram-positive coccobacillus, increasingly reported in pneumonia of AIDS-infected patients. We investigated killing resistance properties of human R. equi virulent and avirulent human strains. Avirulent beta-lactam-susceptible strains had lower intracellular colony forming units after 45 min incubation in murine macrophages J774 and human monocyte-macrophage TPH-1 than those of virulent strains. Only virulent beta-lactam-resistant strains persisted within macrophages for at least 18 min only. A beta-lactam-resistant mutant was obtained from a beta-lactam-susceptible strain after selection in a penicillin G-containing culture medium. This mutant strain, like the natural virulent strains, persisted within macrophages, harboured cell-associated appendages, produced phage-like particles and induced, after its intravenous inoculation, a chronic infection in BALB/c nude mice. Supernatant culture of virulent strains transferred partial macrophage-killing resistance properties to avirulent strains. The same supernatant was toxic for L-929, HeLa and Vero cell cultures. These supernatant effects were heat-inactivated, trypsin-inactivated and did not seem to be linked to phage-like particle presence. These data argue that virulence, beta-lactam-resistance, and macrophage-killing resistance are associated in human R. equi isolates. Moreover, only virulent strains produced uncharacterized toxic factors.

Animals↗
PubMed1994

Manic-depressive (bipolar) disorder: the course in light of a prospective ten-year follow-up of 131 patients.

For a five-year period, 131 bipolar patients were followed every 6 months; for the next 5 years, they were followed yearly. Each patient was interviewed in a systematic way that gave information about episodes, hospitalizations, cycle lengths and the presence of alcoholism. Women and men were not significantly different in the number of follow-up manic or depressive episodes or hospitalizations. Chronicity from index episode to the end of the 10-year follow-up was uncommon (4%). Alcoholism, which was common in these patients, showed a great diminution at the end of 10 years. Contrary to expectation, cycle lengths showed no systematic decrease in length over the follow-up. In this naturalistic study, treatment intensity was not related to decreasing episodes or to changes in cycle length. The number of episodes in the first 5 years of follow-up was not correlated with the number of episodes in the last 5 years. Cycle lengths in the first 5 years of follow-up were similar in length to the last 5 years of follow-up. A family history of mania in these bipolar patients was associated with more episodes in follow-up than if such a family history were absent. The patients whose alcoholism predated the onset of their affective illness were less likely to have episodes in the follow-up than the patients in whom affective illness predated the onset of the alcoholism.

Adult↗
PubMed1994

Correlation between antibiotic resistance, phage-like particle presence, and virulence in Rhodococcus equi human isolates.

Rhodococcus equi is a gram-positive coccobacillus that appears to be emerging as a pulmonary pathogen in AIDS patients. In four human clinical isolates, two antibiotic resistance phenotypes were found to coexist: one beta-lactam resistant and the other beta-lactam susceptible. In vitro, beta-lactam-resistant mutants were obtained at a frequency of 1 x 10(-5) to 5 x 10(-5) from beta-lactam-susceptible strains on cephalothin-containing plates. Neither beta-lactamase nor plasmid DNA was detected in beta-lactam-resistant or -susceptible strains. The penicillin-binding protein patterns for the two types of strains were identical. Electron microscopy revealed that the beta-lactam-resistant strains possessed cell-surface-associated appendages and produced phage-like particles. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total cell protein showed at least three additional bands of 42, 39, and 30 kDa found only in the beta-lactam-resistant strains. Testing for virulence in Swiss mice revealed that (i) phage-like-particle-producing strains had lower 50% lethal doses when injected intravenously in euthymic and nude mice than the non-phage-like-particle-producing strains did and (ii) intravenous inoculation of a sublethal dose (5 x 10(6) CFU) in nude mice led to chronic infection by the phage-like-particle-producing bacteria only. Finally, in vitro growth curves indicated that the phage-like-particle-producing strains possessed an ecological selection advantage. These results suggest that, among R. equi human isolates, the antibiotic resistance phenotype is associated with virulence and may be phage mediated.

AIDS-Related Opportunistic Infections↗
PubMed1994

Comparison of personality disorders in different anxiety disorder diagnoses: panic, agoraphobia, generalized anxiety, and social phobia.

Recently there has been increasing interest in the relationship of the personality and the anxiety disorders. This paper presents comorbidity findings between DSM-III-R personality pathology and several DSM-III-R anxiety disorders and makes direct comparisons between anxiety groups. This is the most extensive comparison of this kind reported thus far. This report is on the first 475 anxiety patients who were recruited from multiple sites to take part in a naturalistic study of anxiety. All had a DSM-III-R diagnosis of panic, agoraphobia, social phobia, or generalized anxiety disorder (GAD). Previous studies which found a high comorbidity between the anxiety and the personality pathology were confirmed, with a significantly higher prevalence of personality pathology occurring with social phobia and GAD. Among our patients, all of whom had anxiety disorders, the presence of comorbid major depression is associated with an increase in the levels of comorbid personality pathology--as previously described in the literature. The relationship between low social functioning and the presence of personality pathology was confirmed, however, the relationship appears to be specific to certain areas of functioning, a new finding. There is a clinically important relationship between Personality Diagnostic Questionnaire--Revised personality pathology and the anxiety disorders characterized by different prevalences of personality disorders in different anxiety disorders and specific areas of social dysfunction.

Adult↗
PubMed1993

A prospective follow-up of patients with bipolar and primary unipolar affective disorder.

OBJECTIVE: As part of the National Institute of Mental Health Collaborative Study of the Psychobiology of Depression, the comparative course of manic depressive (bipolar) and primary unipolar patients was assessed. DESIGN: Systematic evaluation using structured instruments every 6 months for a period of 5 years with the recording of remissions, new episodes, and subsequent hospitalizations. PATIENTS: The number of subjects varied somewhat depending on the analyses conducted. For a comparison of course in bipolar patients and unipolar patients, 148 bipolars were compared with 172 unipolar patients. RESULTS: Both unipolar and bipolar patients were more likely to have episodes if they had episodes prior to index admission. Likewise, prior hospitalizations predicted multiple hospitalizations in follow-up. Chronicity was significantly more prevalent among unipolar depressives but in both unipolar and bipolar patients, chronicity diminished over time. Bipolar patients were more likely than unipolar patients to have multiple episodes at the 2-year and 5-year follow-ups. In bipolar patients, there was no difference in the number of episodes in follow-up between males and females but in unipolar patients, females were significantly more likely to have subsequent hospitalizations and episodes than males. Treatment variables did not relate to these differences. A family history of mania or schizoaffective mania predicted multiple episodes in bipolar patients but not in primary unipolar depressives. A family history of all affective illness (mania, schizoaffective mania, bipolar II illness, and depression) did not predict a multiple-episode course in either bipolar or unipolar illness. In unipolar patients, the independent variables leading to multiple-episode course in follow-up are being female, an early age of onset, and prior episodes. CONCLUSIONS: As a result of this systematic follow-up study, new data add to the distinction between bipolar and primary unipolar patients both as regards number of episodes in follow-up and also as regards risk factors that are associated with the multiple-episode course.

Adult↗
PubMed1993

A micropipette which allows in situ perfusion of arterioles and capillaries.

In order to investigate capillary physiology, a glass micropipette system was developed that allowed in situ perfusion of microvessels as well as rapid changes of perfusion solutions. Theta tube (WPI, Inc.; 1.5-mm o.d. glass stock capillary tubing which is divided into two hemicylindrical sides by a central glass septum) was pulled to a smaller diameter of approx 300-600 microns and inserted into the shank of a sharpened cannulating micropipette tip constructed from large-bore glass stock (1.6 mm i.d.). The resulting dead volume between the end of the Theta supply tube and the tip of the outer cannulating tip was approximately 90 nl. The perfusate was driven in a circuit from a pressurized feed reservoir down one side of the Theta supply tube pipette and back through the second side into a reservoir maintained at a lower pressure. The pressure gradient between the two reservoirs established a high-volume flow rate and subsequently a short perfusate transit time from the feed to the collection reservoir. The average pressure in the two reservoirs determined the pressure which drove the perfusate from the cannulating tip. At normal pressures and flows, the time required to change perfusion fluid composition at the pipette tip was less than 1 min, and discharge hematocrit of a red blood cell suspension was indistinguishable from the hematocrit measured in the feed reservoir.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Identification and analysis of the Rhizobium meliloti exoAMONP genes involved in exopolysaccharide biosynthesis and mapping of promoters located on the exoHKLAMONP fragment.

Sequence analysis of a 7.494 kb DNA fragment from megaplasmid 2 of Rhizobium meliloti 2011 involved in exopolysaccharide I (EPS I) biosynthesis revealed the presence of five exo genes designated exoA, exoM, exoN, exoO, and exoP. ExoN was found to show strong homology to a UDP-glucose pyrophosphorylase from Acetobacter xylinum, whereas ExoO displayed weak homologies to the NodC proteins from R. meliloti and R. loti. Surprisingly, different mutations in exoP resulted in divergent phenotypes. One exoP mutant was able to establish an effective symbiosis with alfalfa, although no EPS I polymer could be detected. In contrast, other exoP mutations prevented the formation of an effective symbiosis. The transcriptional organization of the exoA-exoP gene region has been analysed in conjunction with the exoH, exoK and exoL genes. Using exo-lacZ transcription fusions in association with plasmid integration mutagenesis a strong promoter was identified upstream of exoH, which is able to direct transcription of the whole exoHKLAMONP gene cluster. A much weaker promoter upstream of exoL was found to be involved in the transcription of the exoLAMONP genes. In addition, weak promoters were identified upstream of exoK, exoA, exoN and exoP.

Amino Acid Sequence↗
PubMed1993

Comorbidity of panic and major depressive disorder.

The objective of this report is to determine whether those patients with panic disorder who have current major depression disorder (MDD) differ from those who do not in terms of demographics, comorbid disorders, severity of illness, nature of symptoms of panic attacks and psychosocial functioning. The sample consisted of 182 patients with current or history of panic disorder measured by standardized interview techniques. For analysis these patients were then divided by presence or absence of current MDD. The two groups were not different in age, sex, or marital status, age of onset, or symptom characteristics of panic attacks. However, patients with MDD were more likely to have Social Phobia and Generalized Anxiety Disorder, been hospitalized, made suicide attempts or gestures, have poorer psychosocial functioning, and currently be experiencing panic with more severe symptoms. These findings are discussed in terms of previous literature in the area.

Adult↗
PubMed1993

Immunochemical analysis of insect carbohydrate antigenic determinants: recognition of a terminal alpha-linked N-acetylgalactosamine-containing epitope of Calliphora vicina neutral glyco(sphingo)lipids and detection in additional orthopteran and dipteran species.

A cloned mouse hybridoma was established that secreted a monoclonal antibody directed against certain neutral glycosphingolipids of the third-instar larvae of Calliphora vicina (Insecta: Diptera). The isotype of the designated monoclonal antibody CNF-I (Calliphora Neutral Fraction) was determined as IgG3. By the use of purified neutral glycosphingolipids of C. vicina, qualitative thin-layer chromatography immunostaining and semi-quantitative enzyme-linked immunosorbent assay determinations, the epitope was specified as a terminal alpha 1-4-linked N-acetylgalactosamine to subterminal N-acetylgalactosamine, which is present on the components GalNAc alpha 4GalNAc beta 4GlcNAc beta 3Man beta 4Glc beta lCer (N5a) and GalNAc alpha 4GalNAc beta 4-(6' PEtn-)GlcNAc beta 3Man beta 4Glc beta lCer (Nz5a). After enzymatic removal of the terminal alpha-N-acetylgalactosamine residue, the epitope reactivity was destroyed. The distribution of the CNF-I recognized epitope among neutral glycolipids of other insects was shown for: Locusta migratoria (Insecta: Orthoptera); and, Chironomus tentans and Drosophila melanogaster (Insecta: Diptera).

Acetylgalactosamine↗
PubMed1993

The enduring psychosocial consequences of mania and depression.

OBJECTIVE: The authors sought to determine the scope, severity, and persistence of psychosocial impairment arising from bipolar and unipolar affective disorder. METHOD: Patients with bipolar (N = 148) or unipolar (N = 240) major affective disorder were assessed as they sought treatment and again after a 5-year follow-up. Concurrently, parents, siblings, and adult children underwent similar assessments and were followed for 6 years. To quantify the impact of affective disorder, probands were individually matched to relatives who had no lifetime history of affective disorder. Sixty-nine relatives who were depressed at intake constituted a separate, nonclinical study group and were also matched to relatives who were well. RESULTS: Both unipolar and bipolar patients began follow-up with deficits in annual income. Relative to comparison subjects, affective disorder groups were significantly more likely to report declines in job status and income at the end of follow-up and significantly less likely to report improvements. Similarly, both bipolar and unipolar patients showed significant deficits in nearly all other areas of psychosocial functioning measured at follow-up. Except for relationships with spouses, deficits did not differ significantly by polarity. Surprisingly, probands with recovery sustained throughout the final 2 years of follow-up also showed severe and widespread impairment. Relatives with major depression exhibited substantial deficits on follow-up, but job status and income were not significantly affected. CONCLUSIONS: The psychosocial impairment associated with mania and major depression extends to essentially all areas of functioning and persists for years, even among individuals who experience sustained resolution of clinical symptoms.

Adaptation, Psychological↗
PubMed1992

Reactions depending on iron sulfide and linking geochemistry with biochemistry.

Iron sulfide gives rise to unusual reducing reactions: some dependent on FeS/H2S synergism [NO-3 --> NH3; HC(three bonds)CH--> H2C=CH2, H3C-CH3; -CH2-CO- --> -CH=CH-, -CH2-CH2-; HS-CH2-COOH --> CH3-COOH; others dependent on FeS alone [HS-CH2-CH2-X --> CH2=CH2 (where X = OH, SH, or NH2)]. The experimental conditions are geochemically plausible: 100 degrees C, aqueous, nearly neutral, and fastidiously anaerobic. These reactions establish additional facts of soil chemistry, organic geochemistry, and the global nitrogen cycle. Further, they point to the common evolutionary denominator of geochemistry and biochemistry.

Journal Article↗
PubMed1992

The Euglena gracilis rbcS gene contains introns with unusual borders.

We have recently shown that, in Euglena gracilis, leader sequences are transferred by trans-splicing to the vast majority of cytoplasmic mRNAs. Trans-splicing is involved in the maturation of the rbcS transcript, which encodes eight small subunits of the ribulose 1,5 bisphosphate carboxylase/oxygenase. In this report, we show that the Euglena rbcS gene introns are different from introns found in plant rbcS genes. In addition these introns do not have the conserved 5' and 3' border sequences found in introns of eucaryotic nuclear-encoded pre-mRNAs, and they do not present any homology with self-splicing introns of groups I and II. Secondary structure analyses show that the 5' and 3' ends of Euglena introns can base-pair, suggesting that an unusual splicing mechanism exists in Euglena.

Amino Acid Sequence↗