PubMed Health⌕ Search

Biomedical subjects

J Reich

Publications and source records attributed to J Reich.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prediction of nonsynonymous single nucleotide polymorphisms in human disease-associated genes.

Analysis of human genetic variation can shed light on the problem of the genetic basis of complex disorders. Nonsynonymous single nucleotide polymorphisms (SNPs), which affect the amino acid sequence of proteins, are believed to be the most frequent type of variation associated with the respective disease phenotype. Complete enumeration of nonsynonymous SNPs in the candidate genes will enable further association studies on panels of affected and unaffected individuals. Experimental detection of SNPs requires implementation of expensive technologies and is still far from being routine. Alternatively, SNPs can be identified by computational analysis of a publicly available expressed sequence tag (EST) database following experimental verification. We performed in silico analysis of amino acid variation for 471 of proteins with a documented history of experimental variation studies and with confirmed association with human diseases. This allowed us to evaluate the level of completeness of the current knowledge of nonsynonymous SNPs in well studied, medically relevant genes and to estimate the proportion of new variants which can be added with the help of computer-aided mining in EST databases. Our results suggest that approx. 50% of frequent nonsynonymous variants are already stored in public databases. Computational methods based on the scan of an EST database can add significantly to the current knowledge, but they are greatly limited by the size of EST databases and the nonuniform coverage of genes by ESTs. Nevertheless, a considerable number of new candidate nonsynonymous SNPs in genes of medical interest were found by EST screening procedure.

Databases, Factual↗
PubMed1998

Characterization of naturally occurring myosin heavy chain antisense mRNA in rat heart.

Analysis of mRNA by Northern blot and reverse transcription-polymerase chain reaction demonstrated the expression of sense and considerable amounts of naturally occurring antisense mRNA for beta-myosin heavy chain (MHC) and alpha-MHC in the neonatal rat heart: antisense MHC mRNA expression of alpha-MHC and beta-MHC was approximately half of the corresponding sense MHC mRNA expression. Using a computational approach, we could identify a reverse Pol II promoter in the beta-MHC gene. Both sense and antisense MHC mRNA demonstrated similar sizes of approximately 6,000 bp in the Northern blot. Alpha-MHC antisense mRNA consisted of approximately 3,700 bp of complementary exon sequences and beta-MHC consisted of approximately 2,700 bp, suggesting a higher probability of alpha-MHC mRNA dimerization. Hence, sense mRNA transcripts and protein of alpha-MHC should exist at different relative levels in the neonatal state. In fact, the relative proportion of alpha-MHC was 52.0 +/- 2.6% on the sense mRNA but only 36.3 +/- 1.8% on the protein level. Because of its high abundance in the heart, we suggest that in the neonatal heart naturally occurring antisense mRNA may play a role in the regulation of MHC expression and, therefore, in the control of the energetical and contractile behaviour of the heart.

Aging↗
PubMed1998

Formation of large nucleoprotein complexes upon binding of the high-mobility-group (HMG) box B-domain of HMG1 protein to supercoiled DNA.

High-mobility group (HMG) 1 is a relatively highly abundant chromosomal protein with structural- rather than sequence-specific preference for binding to DNA. HMG1 has two highly related, folded domains A and B (HMG boxes), attached by a short basic region to an acidic C-terminal domain. We have studied binding of the B-domain of HMG1 protein and its mutants to supercoiled DNA by a gel-retardation assay and electron microscopy. Using a gel-retardation assay, we have demonstrated that HMG1 or HMG1 lacking the acidic C-terminal domain [i.e. HMG1(A+B) bi-domain], but not the isolated B-domain, could preferentially bind supercoiled over-relaxed closed circular or linear DNA. Mutational analysis of the HMG1 B-domain revealed that replacement of Lys96 of the extended N-terminal segment (and much less the neighboring Arg97) and Lys128 of helix II to glutamic acid severely impaired binding of the HMG box domain to supercoiled DNA. The latter mutation within helix II significantly decreased the alpha-helical content of the B-domain as revealed by circular dichroism. We have also shown that mutation of several residues within helix I of the B-domain, in particular Arg110, resulted in a diminished binding to supercoiled DNA as revealed by intensive smearing and reduced retardation of the protein/DNA complexes. These findings indicated that the extended N-terminus, helix I and helix II of the HMG1 B-domain are likely in contact with DNA. Electron microscopy revealed that the B-domain could bind to supercoiled DNA at higher HMG/DNA molar ratios as oligomeric protein beads with subsequent association of the beads into large nucleoprotein complexes from which many looped DNA molecules emerged. Most of the introduced mutations within all three helices of the B-domain (involving mainly basic and aromatic residues) abolished formation of the large nucleoprotein complexes even though the binding of the HMG box to supercoiled DNA was retained as revealed by a gel-retardation assay. A model for the interaction of the B-domain of HMG 1 with supercoiled DNA is presented and discussed.

Amino Acid Sequence↗
PubMed1998

The relationship of suicide attempts, borderline personality traits, and major depressive disorder in a veteran outpatient population.

BACKGROUND: Suicide attempts have been associated to both Major Depression and Borderline Personality Disorder. This report hypothesized that there would be significant clinical differences between psychiatric outpatients with Major Depression, Major Depression with a history of a suicide attempt (but low Borderline traits) and Major Depression high levels of Borderline personality traits. METHODS: Male psychiatric outpatients who had Major Depression were divided into three groups: No suicide attempts and low Borderline traits (Depression), suicide and low Borderline traits (Suicide) and high Borderline traits (Borderline traits.) A screened control group was also used (Controls). Standardized measures of Axis I and Axis II variables were gathered by trained interviewers. RESULTS: "Suicide" had significantly higher levels of anxiety and depression than all other groups. "Borderline traits" had higher levels of pathological personality traits and familial Generalized Anxiety Disorder (GAD) than all other groups. CONCLUSIONS AND CLINICAL RELEVANCE: The Suicide group appears to identify a group that is more symptomatically severe in Axis I symptoms than other Major Depression groups. Different Major Depression groups may require different treatments. The association between Borderline and GAD warrants further research. LIMITATIONS: This study used male veterans in middle age. The usual cautions about generalizing findings to other demographic groups apply.

Adult↗
PubMed1998

Gradual loss of vision.

BACKGROUND: With the increasing age of our population many of the causes of vision loss are becoming more frequent. Not all gradual loss of vision can be considered non urgent and those patients requiring early attention are highlighted. OBJECTIVE: This article discusses the tools available to the general practitioner for the assessment of visual loss as well as the common causes. DISCUSSION: Advances in cataract surgery with improved visual outcome, minimally invasive surgery and a reduction in surgical risk have made this operation the commonest performed in Australia. Blindness from chronic open angle glaucoma and diabetes can be mostly prevented by early diagnosis and compliance with treatment. Age related macular degeneration apart from a small subgroup, is still largely untreatable.

Amblyopia↗
PubMed1997

Antisocial traits in psychiatrically ill veterans without antisocial personality disorder: relationship to Axis I disorders and effects on functioning.

The prevalence of antisocial traits was investigated in a group of veterans who were in treatment at an out-patient psychiatric clinic and who did not meet diagnostic criteria for an antisocial personality disorder. Standardized DSM-III-R interviews were used to diagnose Axis I disorders and antisocial personality disorders and traits. Frequencies of antisocial traits were compared between patients and controls as well as between diagnostic subgroups in the clinical population. Odds ratios were used to assess the effect of antisocial traits on several standardized measures of functioning. There was no overall difference in the dimensional measure of antisocial traits between the clinical and normal groups. There were trends for the frequency of individual traits to vary by Axis I diagnosis. The amount of antisocial traits (measured dimensionally) negatively affected measures of functioning for the overall clinical population. Different specific antisocial traits were associated with trends towards poorer functioning in the alcohol, major depression and post-traumatic stress syndrome subgroups. It is recommended that future research in the area of antisocial traits pay careful attention to the possible negative effects on functioning of subthreshold antisocial traits and also to Axis I comorbidity.

Alcoholism↗
PubMed1997

Panic disorder versus panic disorder with major depression; defining and understanding differences in psychiatric morbidity.

The present study examined the impact of comorbid major depressive disorder (MDD) on psychiatric morbidity, panic symptomatology and frequency of other comorbid psychiatric conditions in subjects with panic disorder (PD). Four hundred thirty-seven patients with PD were evaluated at intake as part of a multicenter longitudinal study of anxiety disorders; 113 of these patients were also in an episode of MDD. Patients were diagnosed by DSM-III-R criteria utilizing structured clinical interviews. The 113 PD/MDD patients were compared with the 324 remaining PD subjects regarding panic symptoms at intake, sociodemographic, quality of life and psychiatric morbidity variables. Differences in frequency of other comorbid Axis I psychiatric disorders were assessed at intake; personality disorders were evaluated twelve months after intake. The results revealed the PD/MDD patients exhibit increased morbidity and decreased psychosocial functioning as compared to PD patients. Personality disorders were more prevalent in the PD/MDD group at six month follow-up assessment; the PD/MDD group also had an increased frequency of posttraumatic stress disorder (PTSD) and more comorbid Axis I anxiety disorders as compared to the PD group. The total number and frequency of panic symptoms was highly consistent between the two patient groups.

Adolescent↗
PubMed1996

Resistance to bismuth among gram-negative bacteria is dependent upon iron and its uptake.

Bismuth antimicrobial action is poorly understood. Many trivalent metals possess antibacterial activity, especially under low iron conditions. Protection of bacteria from the deleterious effects of bismuth and other trivalent metals was demonstrated in iron-fortified media. Near-equimolar quantities of Fe3+ neutralized the growth-inhibitory effects of 250 microM Bi3+. Resistance to bismuth action also depended on the production of virulence-related siderophores. Escherichia coli, Aeromonas hydrophila or Pseudomonas aeruginosa producing aerobactin, amonabactin or pyoverdin respectively, were most resistant to Bi3+. Enterochelin or pyochelin producers were less resistant to Bi3+, but more resistant than strains lacking siderophores. Purified pyoverdin restored Bi3+ resistance in a mutant lacking this siderophore, but not in one lacking the pyoverdin receptor. Bismuth-treated bacteria exhibited unique outer membrane proteins, similar in size to iron-repressible proteins. Thus, resistance to the inhibitory action of Bi3+ among Gram-negative bacteria is inversely related to iron concentration and strongly dependent on iron transport mechanisms. The data suggest that bismuth action is largely a nonspecific, competitive interference with iron-transport, related primarily to atomic valence Furthermore, resistance to Bi3+ among bacteria is predictive of virulence.

Bacterial Outer Membrane Proteins↗
PubMed1996

The morbidity of DSM-III-R dependent personality disorder.

Dependent personality has long been discussed by clinicians, and by empirical researchers more recently. Little empirical evidence so far has been presented as the type and degree of disability with which it is associated. This report provides some empirical data in that regard. To examine this question, those with and without DSM-III-R dependent personality were compared in male veterans drawn from an outpatient psychiatry clinic (dependent and nondependent groups). Standardized interview assessments were used to determine axes I and II disorders and family history. The dependent personality disorder group had significantly lower socioeconomic status and poorer functioning in the family/home sphere. They had significantly more social phobia, borderline traits, and histrionic traits. In relatives, there was significantly more generalized anxiety disorder, simple phobia, drug abuse, and dramatic personality disorder cluster. There are clearly documentable vulnerabilities and morbidities associated with dependent personality disorder.

Ambulatory Care↗
PubMed1996

Familial vulnerability factors to post-traumatic stress disorder in male military veterans.

The question has been frequently raised about whether there are emotional disorders that predispose to post-traumatic stress disorder (PTSD). We do know that those with PTSD do have many comorbid disorders, but due to the difficulty in performing prospective studies it is hard to tell what is cause and what is effect. This study bypassed the problem caused by comorbidity by examining family history of four proband groups: PTSD, mixed anxiety disorders, coexisting anxiety and depressive disorders, and screened normal controls. Two questions were examined. First, whether family history predicted who experienced combat situations and second, whether the proband groups could be distinguished by family history. Logistic regression identified two variables that predicted the experience of combat: major depression (odds ratio 2.17) and the DSM-III dramatic personality disorder cluster (odds ratio 1.36). Although there was considerable overlap, family history variables distinguished PTSD from other proband groups. Overall, the pattern of psychopathology in the families of the PTSD probands most closely resembled that in the families of the coexisting anxiety and depressive disorders probands. We conclude that family history methods may be an addition to possible variables that predict who will be exposed to combat and also that family history variables may be able to distinguish a PTSD population from some other types of emotional disorders.

Adult↗
PubMed1996

The infrequency of "pure culture" diagnoses among the anxiety disorders.

BACKGROUND: Anxiety disorders are known to commonly coexist in individuals, both with other anxiety disorders and with mental disorders from other groupings, such as affective disorders. We questioned how frequently anxiety disorders actually occur in isolation, as "pure cultures." METHOD: We examined diagnostic patterns among the 711 subjects entered into a large, multicenter study of anxiety disorders, the Harvard/ Brown Anxiety Disorders Research Program (HARP), which focused on panic, agoraphobia, generalized anxiety disorder, and social phobias as "index disorders" required for intake. RESULTS: We used various definitions for "pure culture." By all definitions, subjects with "pure culture" represented a minority, especially in cases of generalized anxiety disorder and social phobia, where comorbidity was virtually ubiquitous. "Pure culture" status was associated with later onset of illness and less chronicity. CONCLUSION: Future studies of anxiety disorder should aim to document the extensive comorbidity, rather than eliminate it by restrictive diagnostic exclusion criteria, lest they yield atypical or even misrepresented groups of patients. Clinicians should not stop at identifying only the "main" diagnosis but look for other, comorbid diagnoses that are often present.

Adult↗
PubMed1996

Early visual recovery after excimer laser surgery for myopia: the Melbourne OmniMed results.

BACKGROUND AND OBJECTIVE: Although the refractive outcome can change for months after photorefractive keratectomy (PRK), early visual results are of particular importance during pre-operative counseling of prospective PRK candidates. The expected vision in the first week post-operatively, following 6.0 mm or larger zone photoablation for myopia with the Summit OmniMed (Apex) laser, has not been analyzed in the literature to date. This study is intended to provide an indication of the early visual acuity that may be experienced by a patient undergoing PRK for myopia. PATIENTS AND METHODS: The visual acuity recorded for 123 consecutive patients, (79 low myopes [-1.00 to -5.90 diopters (D)], 44 high extreme myopes [-6.00 to -19.00 D]), one week after they had undergone PRK, was analyzed. All patients included in the study had undergone PRK with the Summit OmniMed (Apex) excimer laser, leaving small degrees of astigmatism uncorrected. RESULTS: One week after PRK, uncorrected visual acuity was better for low myopes than high myopes. Of the low myopes, 83.0% were 20/40 or better compared with high myopes of whom 61.4% were 20/40 or better. CONCLUSION: Patients can be counseled that functional vision will be present in the period immediately after re-epithelialization.

Adult↗
PubMed1995

Family history of DSM-III-R dramatic personality disorder cluster and functioning in patients with major depressive disorder.

Clinicians and researchers have noted that personality dysfunction related to borderline personality significantly predicts a poorer course in major depressive disorder. There is also some evidence that some aspects of personality are heritable. The goal of this report was to determine whether family history of dramatic personality disorder cluster indicated differences in functioning in patients with major depressive disorder. Patients with major depression were divided into two groups: those with a family history of dramatic personality disorder cluster (N = 49) and those without (N = 22). These were the clinical groups. A screened normal group was also added to determine how far the clinical groups differed from ordinary functioning (N = 31). Compared with the other clinical group, the group with the family history of dramatic personality disorder tended, in general, to have fewer personality traits as measured by the Personality Disorder Examination, similar Hamilton Anxiety and Depression scores and several significantly better functioning measures. It appears that a family history of dramatic personality disorder cluster identifies a group with different, but not necessarily lower, levels of functioning. Implications of these findings are discussed.

Depressive Disorder↗
PubMed1995

Family psychiatric histories in male patients with generalized anxiety disorder and major depressive disorder.

It has been hypothesized, from twin study results in females, that the genetic predisposition in females for major depressive disorder (MDD) and generalized anxiety disorder (GAD) is identical. This report attempted to replicate these findings on a male population using family history methods. There were 119 subjects who completed standardized assessment of Axis I, Axis II, and family history. The family history of four groups was compared--GAD without MDD, MDD without GAD, GAD/MDD, and normals. As expected, GAD and MDD subjects showed trends toward more MDD family history than normals. The GAD and MDD groups showed only trend differences in family history of relatives. Unexpectedly, however, the MDD/GAD group had no higher level of either anxiety or depressive family history than normals (although they did have higher levels of personality family history). Both the GAD and the MDD groups had a significantly higher level of family history of depression than the GAD/MDD group. Within the limits of the family history method, the finding of similarity of the family predisposition of MDD and GAD was confirmed in a male population. However, it does appear that the combined disorder of MDD/GAD in clinical settings might have very different family history predispositions and possibly could be a separate disorder from both MDD and GAD when they are not comorbid.

Adult↗