PubMed Health⌕ Search

Biomedical subjects

L Kirstein

Publications and source records attributed to L Kirstein.

At least 19 recordsLinked to original sources
PubMed2000

Regulation of human myocilin/TIGR gene transcription in trabecular meshwork cells and astrocytes: role of upstream stimulatory factor.

BACKGROUND: Mutations in the myocilin (MYOC)/TIGR gene are responsible for autosomal-dominant juvenile primary open-angle glaucoma (POAG). In patients with non-autosomal-dominant POAG, such mutations are rare, but the expression of MYOC/TIGR in the trabecular meshwork (TM) of the eye is considerably higher than in normals. We performed transfection, DNAse I footprinting, mutagenesis and electrophoretic mobility shift assays (EMSA) to identify elements responsible for the basal transcription of MYOC/TIGR in TM cells and astrocytes. RESULTS: DNAse I footprinting experiments of the human MYOC/TIGR promoter showed a major protected area between nt -106 to -77, which was not conserved in the homologous region of the mouse myoc/tigr promoter. In addition, the TATA-box was protected, as well as at least three downstream sites, including an AP-1-like sequence. Deletion of the -106 to -77 region caused a substantial loss of functional promotor activity in all cell types. Site-directed mutagenesis and EMSA experiments revealed the presence of two regulatory elements in the -106 to -77 region. Each of these cis-elements is essential for minimal promoter activity. The 5'-half of the region contains a sequence with similarities to NF-kappaB-related sites, however, binding of NF-kappaB could not be confirmed by EMSA. The 3'-half contains a canonical E-box sequence. EMSA experiments showed that the upstream regulatory factor (USF) was binding to the E-box sequence and that the binding can be supershifted by specific antibodies. CONCLUSIONS: Several DNA-protein binding elements contribute to a transcription of MYOC/TIGR, and USF is critically required for its basal transcription in trabecular meshwork cells and astrocytes.

Animals↗
PubMed1999

TbetaR-I(6A) is a candidate tumor susceptibility allele.

We have previously described a type I transforming growth factor (TGF)-beta receptor (TbetaR-I) polymorphic allele, TbetaR-I(6A), that has a deletion of three alanines from a nine-alanine stretch. We observed a higher than expected number of TbetaR-I(6A) homozygotes among tumor and nontumor DNA from patients with a diagnosis of cancer. To test the hypothesis that TbetaR-I(6A) homozygosity is associated with cancer, we performed a case-control study in patients with a diagnosis of cancer and matched healthy individuals with no history of cancer and who were identical in their gender and their geographical and ethnic background to determine the relative germ-line frequencies of this allele. We found nine TbetaR-I(6A) homozygotes among 851 patients with cancer. In comparison, there were no TbetaR-I(6A) homozygotes among 735 healthy volunteers (P < 0.01). We also observed an excess of TbetaR-I(6A) heterozygotes in cancer cases compared to controls (14.6% versus 10.6%; P = 0.02, Fisher's exact test). A subset analysis revealed that 4 of 112 patients with colorectal cancer were TbetaR-I(6A) homozygotes (P < 0.01). Using mink lung epithelial cell lines devoid of TbetaR-I, we established stably transfected TbetaR-I and TbetaR-I(6A) cell lines. We found that, compared to TbetaR-I, TbetaR-I(6A) was impaired as a mediator of TGF-beta antiproliferative signals. We conclude that TbetaR-I(6A) acts as a tumor susceptibility allele that may contribute to the development of cancer, especially colon cancer, by means of reduced TGF-beta-mediated growth inhibition.

Activin Receptors, Type I↗
PubMed1987

Enzyme electrodes and their application.

Starting from the state of the art, principles for improving the analytical characteristics of enzyme electrodes are discussed. Coupling of appropriate amperometric electrode processes with enzyme systems, e.g. urease or aminopeptidases, results in a simplification of operation. Optimal sample frequencies are realized on the basis of enzyme membranes, with both a small characteristic diffusion time and a high enzyme activity, applied in a well-designed sample-processing system. Coupled enzyme reactions of the sequence or competition type are successfully used for extension to new analytes, e.g. inhibitors, cofactors or alternative substrates. Cyclization of the analyte enhances the sensitivity of enzyme electrodes to the nanomolar concentration range. Enzymic anti-interference layers are a tool for improving the sensor specificity. The operational characteristics of enzyme electrodes are thus adaptable to any given analytical problem.

Biotechnology↗
PubMed1985

Enzyme electrode for urea with amperometric indication: Part I--Basic principle.

A novel method for amperometric determination of substrates of hydrolytic enzymes has been developed. As an example the pH dependence of electrochemical oxidation of hydrazine in the Tafel region was combined with the urease catalysed splitting of urea to construct an amperometric membrane electrode for urea. The characteristic features of this sensor are: a linear dependence of the current of hydrazine oxidation on hydrogen ion concentration (as opposed to the logarithmic response of potentiometric sensors), linear urea concentration-signal relationship between 0.8 and 35 mmol/litre sample concentration, a response time of about 20 s, a relative standard deviation of 1% and measuring frequency up to 40 samples/h with an electrode operational stability of 2 weeks. Calibration curves for aqueous urea solutions are given as functions of starting pH, urease and hydrazine concentration and the potential dependence of the signal was determined.

Buffers↗
PubMed1984

Neuroendocrine dysfunction and response to tricyclic antidepressants.

Patients with DSM-III unipolar major depression (N = 26) were treated with tricyclic antidepressants after 2 weeks of inpatient drug-free observation and neuroendocrine testing. Medication was prescribed with individualized dosages and was monitored with blood levels. Treatment response (greater than or equal to 50% decrease in Hamilton depression score after 4 weeks) was seen in 6 of 13 patients given desipramine and 7 of 13 given nortriptyline. Of the 13 nonresponders, 9 accepted treatment with another drug and/or ECT; 5 responded. Thus, 18 of the 26 patients responded to treatment. Abnormal pretreatment DST was correlated with increased responsiveness to treatment, although all patients had a high probability of response.

Antidepressive Agents, Tricyclic↗
PubMed1983

The TRH test and urinary MHPG in unipolar depression.

Twenty-five men and 26 women with major unipolar depression were evaluated by the TRH test and urinary MHPG excretion. A significant positive correlation between TSH response to TRH and urinary MHPG was found in the men, though not in the women. These findings suggest that at least for depressed men, central norepinephrine deficiency may be the neurobiological substrate of blunted TSH responses to TRH.

Adolescent↗
PubMed1982

Clinical correlates of the TRH infusion test in primary depression.

Relationships between clinical measures, diagnosis and neuroendocrine findings were examined in a group of 25 primary depressives maintained drug free on a Neuropsychiatric Evaluation Unit. The TSH response to TRH infusion curves for unipolar and bipolar depressives were significantly different. Agitated patients but not psychomotor retarded patients demonstrated a blunted TSH response curve. No relationships were noted for cortisol hypersecretion and/or loss of diurnality and either diagnosis or psychomotor activity levels in depression. Biochemical and diagnostic implications of these findings are discussed.

Adult↗
PubMed1981

Diagnostic issues in primary anorexia nervosa.

A literature review and clinical case presentation approach are employed to highlight unresolved diagnostic issues in Primary Anorexia Nervosa. The material is examined and discussed along a multidimensional list of variables considered important for the diagnosis, including definitions of weight loss, associated biological symptoms, eating patterns and body image disturbances.

Adult↗
PubMed1981

Thyrotropin-releasing hormone test and male unipolar depression.

Change in maximal TSH response to a TRH infusion were measured in 18 unipolar depressed males and 2 control groups matched for age, sex, and base-line thyroid status. The mean maximal change in TSH response was significantly lower for the unipolar than the control groups. Clinical and research implications of these findings are discussed. By using a deltaTSH cutoff of 7.0 rather than 5 microIU/ml, 14 rather than 7 depressed patients were correctly identified as having a blunted deltaTSH; 29 rather than 32 to 36 control patients were correctly identified as having a normal deltaTSH score.

Adult↗
PubMed1980

Racing thoughts in primary depression.

The incidence of and relationship between racing thoughts and clinical variables in primary depression were examined. More than 50% of a group of 32 hospitalized patients reported moderate to severe levels of racing thoughts. Only 13% of patients did not experience racing thoughts. Racing thoughts were significantly related to symptom measures of anxiety, excitation and retardation but not to overall severity of illness or total Hamilton Depression Scale scores. Age but neither sex nor unipolar bipolar classification distinguished patients who did and did not experience racing thoughts.

Adult↗
PubMed1979

A health care program for hospital staff.

This paper illustrates the significance of one aspect of psychiatric consultation to questions of general hospital health care delivery. The contractual arrangements, implementation, and evaluation of a health care delivery program for nonprofessional hospital employees are presented. Changes in patients' perception of treatment were evaluated by random surveys of representative clinic and ward populations before and after this program was implemented. The program was evaluated by precourse-postcourse questionnaires completed anonymously by the hospital personnel group. The program was found to be successful in generating lists of major health care delivery problems and some possible solutions. The majority of personnel enjoyed and benefited from this program. A conceptual framework and implications of psychiatric consultation for problems of general health care delivery are discussed.

Adaptation, Psychological↗
PubMed1979

Temporal disorganization and primary affective disorder.

The authors used a self-rating scale of thinking process disorganization to measure degree of temporal disorganization in a group of 38 rigorously categorized psychiatric inpatients. Patients diagnosed as having primary affective disorder, depressed type, were significantly different from those with either a character disorder or schizophrenic diagnosis; both schizophrenic and character disorder groups showed variable temporal disorganization scores, and the primary affective disorder group showed consistently high levels of temporal disorganization. Diagnosis was more important than symptom measures in relationship to temporal disorganization scores.

Adult↗
PubMed1978

Sociodemographic factors and military psychiatric hospitalization.

This study of race, rank, and psychiatric hospitalization was conducted to provie more information about the impact of social class factors on military inpatient treatment. A retrospective review of the charts of all commissioned officers admitted over a 16-month period along with control groups of airmen and sergeants matche for time of admission was undertaken at a large military training center. Groups were compared on sociodemographic variables (age, race, rank, sex, marital status, length of service, and education background) as well aa clinical variables (referral source, chief complaint, diagnosis, length of stay, and outcome). The implications of briefer hospitalizations for the youngest group of patients (the airmen) are discussed. The over-representation of black enlisted soldiers as psychiatric patients and organizational means of rectifying this situation are discussed.

Adult↗
PubMed1978

Sexual involvement with patients.

Three cases of sexual activity between patients and staff members were presented and determinants and consequences of this type of acting out behavior were discussed. Patients sexual behavior was in part motivated by a need to avoid feelings of loneliness and anxiety and a consequence of the sexual behavior was the recurrence of symptoms and behaviors noted upon admission. The staff members were noted to become more self preoccupied and less involved with both staff and patients following the sexual behavior. The role of the ward psychiatrist in preventing such patient staff interactions includes his taking responsibility for educational and supervisory needs of the staff, his being involved in the creation and maintenance of the ward's moral code and his awareness of group and organizational factors that may impede open staff communications.

Acting Out↗