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Biomedical subjects

S Johns

Publications and source records attributed to S Johns.

At least 19 recordsLinked to original sources

StuAp is a sequence-specific transcription factor that regulates developmental complexity in Aspergillus nidulans.

The Aspergillus nidulans Stunted protein (StuAp) regulates multicellular complexity during asexual reproduction by moderating the core developmental program that directs differentiation of uninucleate, terminally differentiated spores from multinucleate, vegetative hyphae. StuAp is also required for ascosporogenesis and multicellular development during sexual reproduction. StuAp is a member of a family of fungal transcription factors that regulate development or cell cycle progression. Further, StuAp characterizes a sub-family possessing the conserved APSES domain. We demonstrate for the first time that the APSES domain is a sequence-specific DNA-binding domain that can be modeled as a basic helix-loop-helix (bHLH)-like structure. We have found that StuAp response elements (A/TCGCGT/ANA/C) are located upstream of both critical developmental regulatory genes and cell cycle genes in A.nidulans. StuAp is shown to act as a transcriptional repressor in A.nidulans, but as a weak activator in budding yeast. Our data suggest that the differentiation of pseudohyphal-like sterigmatal cells during multicellular conidiophore development requires correct StuAp-regulated expression of both developmental and cell cycle genes in A.nidulans. The budding pattern of sterigmata may involve processes related to those controlling pseudohyphal growth in budding yeast.

Amino Acid Sequence

The effect of PHA stimulation on lymphocyte sub-populations in whole-blood cultures.

Although lymphocytes in phytohaemagglutinin (PHA)-stimulated whole blood cultures are routinely used to assess genotoxin-induced chromosome damage, very little information is available on the effect of PHA on the various cell populations present, and there appear to be no data for the protocols used in routine genotoxicity assays. In this study, we used flow cytometric analysis to examine the size/complexity of the white blood cell (WBC) population and the expression of key antigenic markers by the lymphocytes over a 96-h period following PHA stimulation. The changes in the WBC population are complex, and would seem to represent different populations dying out, remaining static or starting to divide. The initial decrease seen in overall cell numbers probably reflects death of the neutrophil and monocyte populations. The subsequent increase in cell numbers appears to be due to division of the lymphocytes and, by 96 h post-stimulation, they comprise about half the total cell number and, as expected, > 90% are activated T-cells; it seems reasonable to assume that these represent the target cells in genotoxicity assays. Although we do not suggest that these findings should alter the routine conduct of clastogenicity assays using PHA-stimulated whole-blood cultures, they indicate that such tests are empirical and that closer investigation will only confirm their relatively imprecise nature.

Cell Division

Changing trends in explanted intraocular lenses: a single center study.

Over a nine-year period, our practice removed 1,091 intraocular lenses. The most common type of lens requiring explantation was the closed-loop anterior chamber lens (58.6%). The Stableflex lens represented the largest percentage of all removed lens types (28.8%). The number of closed-loop anterior chamber lenses requiring removal peaked in 1988 and then gradually declined. All other lens styles have shown gradually increasing removal rates. Older style iris-fixated lenses and rigid anterior chamber lenses, which have not been implanted for several years, have increasing removal rates. Late breakage of fixational polypropylene sutures with pupil-supported iris-fixated lenses have occurred in five cases; the average time from implantation to suture breakage was 112 months.

Anterior Chamber

Explantation of posterior chamber lenses.

A consecutive series of 119 explanted posterior chamber lenses is reviewed. Seventy (58.8%) were removed because of dislocation or improper fixation, 15 (12.6%) because of anisometropia, and 18 (15.1%) because of chronic inflammation. Sixty-two (52.1%) of these explantations probably occurred for reasons that can be avoided by changes in preoperative, operative, or postoperative techniques. The rate of posterior chamber lens explantations is quite low considering the large number of lenses implanted; with changing surgical techniques, we anticipate that the number of lenses requiring removal will decrease.

Aged

Day hospital therapeutic community treatment for patients with personality disorders. An empirical evaluation of the containment function.

Does a day hospital format represent an adequate level of treatment for decompensated patients with personality disorders? The study concerns 97 consecutive patients, 50 of whom belonged to cluster A and B personality disorders. The patients were referred partly from an acute admission ward and partly from outpatient departments. The mean treatment time was approximately 6 months. The dropout rate for schizotypal and borderline patients was 38%. No patient committed suicide. Two patients made suicidal attempts during treatment. The level of medication was moderate, and 58% of the patients were drug-free at discharge. Treatment results at discharge, measured by SCL-90 and Health Sickness Rating Scale, were very good for patients with axis I disorders only, good for cluster C personality disorders, modest for borderline patients, and very modest for schizotypal patients. In general, the results indicate that the containing capacity of a day hospital therapeutic community is substantial and that it may reduce the need for long-term inpatient treatment.

Adult

Personality disorders 2-5 years after treatment: a prospective follow-up study.

Ninety-seven patients consecutively admitted to a day unit specializing in the treatment of personality disorders were included in a prospective follow-up study. At follow-up an average of 3 years after index admission, patients with borderline personality disorder (BPD) displayed a moderate symptom reduction and a fair global outcome. Patients with schizotypal personality disorder (STP) showed a similar reduction in symptoms but retained relatively poor global functioning. Individuals with cluster C personality disorders, in contrast, showed both a good global outcome and a marked symptom reduction. STP individuals were the least socially adjusted, employed and self-supporting of all diagnostic subgroups. STP and BPD individuals had far more inpatient treatment in the follow-up period than other groups. The overall suicide rate was low compared with most similar studies.

Adult

The hormonal environment of post-natal depression.

The incidence of post-natal depression is high, and dramatic changes in steroid hormones and prolactin occur in the post-partum period. In an attempt to correlate these events, 147 mothers, six to eight weeks after delivery of a healthy infant, completed standard psychological tests, including the Edinburgh, Montgomery-Asberg, and Raskin scales. They also provided matched samples of plasma for assay of cortisol, oestradiol, progesterone and prolactin, and saliva for assay of cortisol and progesterone. All steroid concentrations were within the appropriate normal ranges. Of the mothers, 14.9% were depressed on all three scales. Significant correlations were seen between depression ratings and salivary progesterone and prolactin. In bottle-feeders, salivary progesterone was positively associated with depression, whereas in breast-feeders it was negatively associated. Plasma prolactin levels were inappropriately low in depressed breast-feeders. These data indicate that differing therapies may be appropriate for depression in breast- and bottle-feeders.

Adolescent

The use of rating scales to identify post-natal depression.

One hundred and forty-seven mothers were screened for major depression at six to eight weeks post-partum. Using predetermined cut-off points, the Edinburgh Postnatal Depression Scale and the Beck scale were compared in their abilities to identify the 15% of subjects who had major depression according to DSM-III criteria. The sensitivity of Edinburgh scale was 95% and its specificity 93%. The performance of the Beck scale was markedly inferior, with a sensitivity of 68% and specificity of 88%.

Adult

Clinical utility of the dexamethasone suppression test assessed by plasma and salivary cortisol determinations.

Concentrations of cortisol in saliva and plasma were compared in matched samples during a standard 1 mg dexamethasone suppression test. The study involved 185 routine psychiatric admissions, all of whom were classified according to DSM-III criteria. In a group of 122 matched samples of saliva and plasma, there was a Pearson correlation coefficient of 0.867 and a Spearman rank correlation coefficient of 0.869. Medication with anticholinergic side effects had little effect on the correlation and was not associated with major difficulties in salivary sampling due to "dry mouth." In a group of 178 diagnoses where both saliva and plasma were obtained, results were almost identical. Although nonsuppression was found in all psychiatric conditions, there was a very significant association with major depressive episode with melancholia.

Adolescent

Tremor.

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Humans

Evidence that trypsin digestion exposes a channel in the sarcoplasmic reticulum membrane.

We present evidence that proteolytic digestion of sarcoplasmic reticulum membranes with trypsin exposes an ionophore that is capable of translocating calcium across the membrane of preloaded vesicles. Net transport of calcium appears to stop when the chemical potential of the ion on both sides of the membrane is equal. The temperature coefficient of steady-state leakage suggests that the ionophore is of the channel or pore type. We suggest that tryptic digestion exposes a channel in sarcoplasmic reticulum membranes through which calcium, and perhaps other ions as well, can diffuse down concentration gradients.

Adenosine Triphosphate

Activation of classical complement pathway by naturally occurring heteroantibodies in normal rabbit serum. Effect on subpopulations of human lymphoid cells.

Heteroantibodies present in normal rabbit serum (NRS) are toxic to human B lymphocytes, T lymphocytes, and monocytes. Even NRS, which exhibits little back ground cytotoxicity for human lymphoid cells in conventional HLA or B-cell lymphocytotoxic assays, can be shown to contain considerable activity by making two modifications in usual procedures: by washing cells in saline or balanced salt solutions devoid of protein or sugar substances, and by increasing incubation time for 1 h to 3--4 h. Using such modifications, the cytotoxic activity of NRS towards human lymphoid cells was investigated and was found to involve activation of the classical complement pathway rather than activation of the alternate complement pathway. Residual unwanted background cytotoxicity of NRS toward human lymphoid cells can be decreased without loss of desired complement activity either by heating NRS for 15 min at 50 degrees C or by mixing NRS with small amounts of normal human serum.

Animals

Transient post-partum thyroid dysfunction and postnatal depression.

In the course of a population study of thyroid dysfunction in pregnancy and the post-partum period, 65 women, considered to be antibody-positive (microsomal and thyroglobulin), and 82 antibody-negative women were assessed for postnatal depression at 6-8 weeks post partum. The women were also assessed for the development of post-partum thyroid dysfunction. Of the 147 women, 22 met DSM-III criteria for major depression. The presence of autoantibodies showed little association with depressed mood but there was a minor association of postnatal depression with actual thyroid dysfunction in that incidence of the latter condition was higher in depressed women (Raskin scale P less than 0.01; Edinburgh scale P less than 0.05; Montgomery-Asberg scale P less than 0.1). Three of eight mothers with thyroid dysfunction had major depression and were depressed on all three scales.

Adult

Corneal tissue levels of topically applied ofloxacin.

PURPOSE: To evaluate the levels of ofloxacin (Ocuflox) in human corneal tissue in patients exposed to various dosing regimens and application methods. SETTING: Corneal Consultants of Indiana, Indianapolis, Indiana, USA. METHODS: Forty patients meeting inclusion criteria were recruited from persons scheduled to have penetrating keratoplasty (PKP). Patients were placed into one of two study groups of 20 each based on dosing regimen and application method. The SAS GLM (General Linear Models) procedure was used to test for differences in mean Ocuflox tissue concentration among study groups and for interaction effects of preoperative diagnosis, trephine size, dosing regimen, and corneal integrity. RESULTS: Corneal tissue concentrations of Ocuflox were elevated significantly by varying drug application methods and dosing schedules before PKP. Eyes receiving medication every 15 minutes for 4 hours had significantly higher levels of Ocuflox than those receiving the drug in six doses over 24 hours before surgery. Ocuflox concentrations exceeded the MIC90 (minimum inhibitory concentration) for key ocular pathogens in essentially all cornea specimens studied. CONCLUSION: Ocuflox penetration was improved by administering it in a controlled setting at 15 minute intervals over 4 hours. The drug provided high tissue levels in both the cornea and aqueous humor, which together with its broad range of antibacterial coverage, should make it a good choice for prophylactic treatment.

Administration, Topical