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Biomedical subjects

G Stein

Publications and source records attributed to G Stein.

At least 19 recordsLinked to original sources

The rapid nongenomic actions of 1 alpha,25-dihydroxyvitamin D3 modulate the hormone-induced increments in osteocalcin gene transcription in osteoblast-like cells.

We have previously shown that one of the rapid nongenomic actions of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3), the increase in intracellular calcium (Ca2+), accompanies the increased osteocalcin (OC) mRNA steady-state levels in rat osteosarcoma cells. To determine the functional significance of the nongenomic actions, we have measured changes in intracellular Ca2+ as an indicator of the rapid effects and have assessed the effect of inhibition of the rapid increase in cellular Ca2+ by the inactive epimer, 1 beta, 25-dihydroxyvitamin D3 (1 beta,25-(OH)2D3), on OC mRNA steady-state levels and transcription. 1 beta,25-dihydroxyvitamin D3 inhibited 1 alpha,25-(OH)2D3 induced increases in intracellular Ca2+ and OC mRNA transcription at 1 hr and OC mRNA steady state levels at 3 hr. 1 beta,25-Dihydroxyvitamin D3 did not alter the binding of the vitamin D receptor complex to the vitamin D responsive element of the OC gene. The results demonstrate the functional importance of the rapid, nongenomic actions of 1 alpha,25-(OH)2D3 in the genomic activation of the OC gene by the hormone in rat osteoblast-like cells, perhaps by modifying subtle structural and/or functional properties of the vitamin D-receptor DNA complex or by affecting other protein DNA interactions that support OC gene transcription.

Animals

The retrospective diagnosis of postnatal depression by questionnaire.

The Bromley postnatal depression scale is a new screening instrument specifically developed for detecting the presence of both current and previous episodes of postnatal depression. The scale gives a brief description of postnatal depression and respondents are asked to decide whether or not they had experienced such an illness following childbirth. The scale has satisfactory test-retest reliability and a Cohen's Kappa of 0.80 for previous postnatal depressive episodes. Using another scale which measures DSM.III major depression, the Bromley scale has a sensitivity of 62% and a specificity of 94%. The principle advantages of this method are that it provides information about previous postnatal periods and so provides longitudinal information and the method can be also used in postal surveys.

Depressive Disorder

Molecular approaches to the characterization of cell and blood/biomaterial interactions.

In order to address questions related to cell/biomaterial interactions with respect to cell function and production of extracellular matrix proteins that support or maintain cell/tissue specific properties, we have developed molecular approaches for analysis of in vivo implanted materials and in vitro studies. In an explant of a human left ventricular assist device (LVAD), intact total cellular RNA could be isolated in sufficient quantities for hybridization analyses with gene-specific probes to evaluate cell growth, cytoskeletal organization, and production of extracellular matrix proteins. Cells harvested from a 132-day implanted LVAD exhibited proliferative activity and expressed genes for fibronectin and collagen types I, III, and IV. In vitro studies revealed that endothelial cells cultured on two different segmented polyurethane biomaterials (Biomer and Tecoflex 60D) exhibited different patterns of gene expression that reflected differences in cell growth rates, morphology, and composition of the extracellular matrix. These methodologies provide a valuable approach for a detailed evaluation of: (1) the biocompatibility of cells colonizing implanted cardiac assist devices; and (2) the functionality of cells seeded onto biomaterials.

Adult

Beta-2-microglobulin-derived amyloidosis: onset, distribution and clinical features in 13 hemodialysed patients.

Postmortem examinations were carried out in 13 patients (6 males, 7 females, age 58 +/- 9 years) who had been on regular hemodialysis treatment for 10-90 months using disposable regenerated cellulose membrane dialyzers. The prevalence of beta 2-microglobulin (beta 2m)-derived AB-amyloid deposits in different sites was determined. At autopsy, specimens were obtained from different joints, paravertebral tissue, intervertebral discs and from visceral organs. During life, routine laboratory parameters and radiographic studies had been carried out at 6-month intervals. Serum levels of beta 2m were elevated in all patients (57.5 +/- 13.4 mg/l). Synovial AB-amyloid deposits were shown in different joints of 4 patients, aged between 59 and 73 years, and dialysed for 10-90 months, respectively. All had been unremarkable by X-ray and asymptomatic. No amyloid could be detected in the intervertebral discs of 2 further patients suffering from destructive spondylarthropathy. In 11 of the 13 patients, extracellular beta 2m deposits were observed by immunohistochemistry in different tissues. The results document that (a) AB-amyloidosis may occur in elderly patients even when dialysed for less than 5 years; (b) most cases are completely asymptomatic; the appearance of symptoms must be dependent on additional factors, e.g., site of AB-amyloid deposition and intensity of inflammatory reaction, and (c) AB-amyloid is not the exclusive cause of destructive spondylarthropathy, as 2 typical cases were observed who were devoid of amyloid.

Amyloidosis

Drug treatment of the personality disorders.

Many people with well defined borderline and schizotypal personality disorders may benefit considerably from small doses of neuroleptics. Depression that occurs with personality disorders, which is frequent, responds poorly to tricyclics but may respond better to neuroleptics, while the response to ECT is usually short lived. Selected borderline subjects may respond to MAOIs, particularly where there is a history of childhood hyperactivity. Carbamazepine and lithium may help some individuals with episodic behavioural dyscontrol and aggression, even in the absence of epileptic, affective or organic features. Drug treatments can be combined with psychotherapy, but further placebo-controlled trials are needed to clarify which drugs are most useful, and whether there are any useful clinical predictors of drug responsiveness.

Antidepressive Agents, Tricyclic

[The occurrence of aluminum-containing lysosomes in the kidney of experimentally treated rats].

Aluminium was detected by electron spectroscopic imaging and electron energy loss spectra in the lysosomes of all cell types of the nephron in rats treated with aluminium chloride after 5/6 nephrectomy. The lysosomes of kidney cells of untreated rats did not demonstrate any detectable amounts of aluminium. Electron energy loss spectra showed the regular occurrence of iron (and also other elements) in the lysosomes of both groups of rats.

Aluminum

Influence of dietary factors on the renal renin-angiotensin system.

Protein meals and infusion of amino acids cause an increase of glomerular filtration rate in humans and animals with normal renal function despite the circulating renin concentration remaining unchanged. The renal hemodynamic response is not altered by angiotensin converting enzyme inhibitors, but it is obliterated by cyclooxygenase inhibitors. By contrast, chronic exposure to high protein diets raises circulating renin and increases messenger RNA of renin (but not of angiotensinogen) in kidney tissue. Chronically high protein intake raises the glomerular filtration rate and reduces glomerular permselectivity; the reverse is seen with low protein intake. In patients with renal failure, acute amino acid infusion or protein meals cause a paradoxical drop in glomerular filtration rate which is not influenced by converting enzyme inhibitors.

Amino Acids

Studies on the aetiology of hydropericardium syndrome (Angara disease) in broilers.

The study was carried out to determine the aetiological agent(s) associated with hydropericardium syndrome (Angara disease) in broilers in Pakistan. The results indicate that in addition to adenovirus some other agent is involved in causing the disease but that this agent requires co-infection by an adenovirus for the reproduction of the typical signs of the syndrome. The nature of this agent remains unknown because no discrete virus or virus-like particle could be seen by electron microscopy.

Animals

Isolation and characterization of a cDNA from a human histone H2B gene which is reciprocally expressed in relation to replication-dependent H2B histone genes during HL60 cell differentiation.

A variant human histone H2B cDNA (HHC289) has been cloned and characterized and shown to have a complex pattern of regulation with respect to the HeLa S3 cell cycle and HL60 cell differentiation. The H2B protein coding region of HHC289 is flanked at the 3' end by a 1798-nt nontranslated trailer that contains a region of hyphenated dyad symmetry and a poly(A) addition sequence, followed by a poly(A) tail. Nuclear run-on transcription analysis revealed a 2-fold increase in transcription of the HHC289 gene during S phase, in comparison to replication-dependent human histone genes which exhibit a 2-3-fold increase in transcription during S phase. Northern blot analysis indicated that the levels of the 2300-nt HHC289 mRNA species did not vary significantly during the HeLa S3 cell cycle, in comparison to replication-dependent H2B mRNAs which are elevated 15-fold during S phase. Northern blot analysis also revealed a reciprocal relationship during the onset of HL60 differentiation between the expression of the HHC289 H2B gene and the replication-dependent H2B genes. The levels of the 2300-nt HHC289 H2B species increased approximately 10-fold during HL60 cell differentiation whereas the levels of cell cycle dependent H2B mRNAs decreased to less than 1% of those in proliferating cells. These results suggest that complex transcriptional and posttranscriptional regulatory mechanisms control cellular levels of mRNAs from various human H2B histone genes during progression through the cell cycle and at the onset of differentiation.

Amino Acid Sequence

[Destructive spondylarthropathy in dialysis patients].

Back pain and a cervicobrachial syndrome, as well as progressive sensory and motor deficits as far as symptoms of paraplegia, developed in two dialysis patients two and five years after the start of dialysis. One was a 60-year-old woman with pyelonephritis, the other a 55-year-old man with glomerulonephritis. There were typical radiological signs of destructive spondylarthropathy (narrowed intervertebral spaces and slippage of the vertebral bodies). The female patient required several operations (spondylothesis and orthothesis) and both patients received daily 10,000 IU vitamin D and 3-4 g calcium carbonate. In the woman the destructive process no longer progressed one year after onset of symptoms, but she still required many analgesics. She died three months later of circulatory failure. The man died four weeks after the onset of symptoms from purulent meningitis. At autopsy only renal fibrous ostitis was still demonstrable. Amyloidosis resulting from an increase in beta 2-microglobulin level were excluded by both histological and immunohistochemical examinations.

Cervical Vertebrae

1 Alpha,25-dihydroxyvitamin D3 rapidly increases cytosolic calcium in clonal rat osteosarcoma cells lacking the vitamin D receptor.

1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] rapidly increases cytosolic calcium in a variety of cell types. Although these rapid effects do not appear to directly involve genome activation, the requirement for the classic vitamin D receptor is unclear. Clonal rat osteosarcoma cells, ROS 17/2.8, respond to 1 alpha,25-(OH)2D3 with an increase in osteocalcin message but ROS 24/1 cells do not. The lack of the receptor for vitamin D in the ROS 24/1 cells has been confirmed by the absence of any detectable vitamin D-receptor complex binding to the vitamin D-responsive element (VDRE) of the osteocalcin gene and the absence of vitamin D receptor mRNA in the cells. Quin-2-loaded ROS 17/2.8 and ROS 24/1 cells were treated with 1 alpha,25-(OH)2D3 in the presence and absence of extracellular calcium and with the inactive epimer, 1 beta,25-dihydroxyvitamin D3 [1 beta,25-(OH)2D3]. The 1 alpha,25-(OH)2D3 increased cytosolic calcium in the ROS 17/2.8 and 24/1 cells after 5 minutes in a dose-responsive manner and in the presence and absence of extracellular calcium. Pretreatment of both cell lines with 1 beta,25-(OH)2D3 for 30 s blocked the hormone-induced rise in cytosolic calcium. The rapid effects of 1 alpha,25-(OH)2D3 on ROS cells with and without the vitamin D receptor and the ability of the inactive epimer to inhibit these effects indicate that the signaling system mediating the hormone's rapid actions is not the classic vitamin D receptor.

Aminoquinolines

Disruption of the cytoskeleton with cytochalasin D induces c-fos gene expression.

The treatment of exponentially growing HeLa cells and quiescent WI-38 cells with cytochalasin D, which disrupts the cytoskeletal microfilaments, results in a rapid and marked increase in the transcription of the c-fos protooncogene with a concomitant increase in c-fos mRNA steady-state levels. Transcription of rRNA, HLA-B7, and H4 histone genes was not significantly affected by the drug treatment. These results suggest that the nucleus can respond to signals related to the structural organization of the cytoskeleton and selectively adjust the regulation of gene expression.

Cytochalasin D

Lack of effect of peroral acyclovir for the treatment of acute infectious mononucleosis.

Perorally administered acyclovir was evaluated in the therapy of acute infectious mononucleosis in a multicentered, randomized, double-blind, placebo-controlled trial. A total of 120 patients received 600 mg of acyclovir or placebo five times daily for 10 days. All patients were entered into the study within 7 days of symptom onset and had a positive Monospot test. Analysis of mean values and time to resolution of fever, lymphadenopathy, weight change, hepatomegaly, splenomegaly, liver function tests, atypical lymphocytes, hours of bed rest, sense of well-being, and return to normal activities revealed no significant differences. There was a trend toward suppression of Epstein-Barr virus excretion in the oropharynx in acyclovir recipients. No toxicity was detected in patients treated with acyclovir. Under the conditions of the study, there was no evidence that treatment with perorally administered acyclovir affected the course of infectious mononucleosis.

Acyclovir

Hydrostatic pressure influences histone mRNA.

Exposure of HeLa S3 cells to high hydrostatic pressure (6.89 x 10(3) to 6.89 x 10(4) kPa: 1000 to 10,000 lbfin-2) reduced core and H1 histone mRNA levels as determined by hybridization to specific histone DNA probes. At 4.14 x 10(4) kPa for 10 min core histone and H1 histone mRNA levels were reduced 32-38% and 56%, respectively. At 30 min postdecompression core mRNA levels returned to atmospheric control levels while H1 histone mRNA levels continued to be suppressed. Levels of macromolecular synthesis were monitored under hydrostatic pressure with radioactive precursors of RNA, DNA and protein. Macromolecular synthesis was shown to be suppressed in a dose-dependent manner with increasing magnitude and duration of pressure. To determine the influence of pressure on histone mRNA stability, actinomycin D (10 micrograms ml-1) was used to block RNA synthesis. Relative amounts of H4 and H1 mRNA were determined at atmospheric pressure and following treatment with actinomycin D (10 micrograms ml-1), pressure (4.14 x 10(4) kPa) and a combination of pressure and actinomycin D. This study shows that a synthesis component and a stability component are involved in the pressure-induced reduction of core histone mRNA. At 4.14 x 10(4) kPa for 15 min, there was a 42% reduction in core histone mRNA of which approximately one third was due a suppression of transcription and two thirds to a loss of mRNA stability. The pressure-induced reduction in histone mRNA is attributed to the instability of endogenous histone mRNA and a reduction in transcription/processing of new histone mRNA.

HeLa Cells

[Clinical aspects of acute cytomegalovirus infection in adults without immune deficiency].

The clinical pictures of 11 adults with cytomegalovirus-infection were analyzed. Characteristic symptom was fever of unknown origin lasting up to 50 days. Indications of an accompanying hepatitis were found in all patients and confirmed by increased serum levels of the transaminases which for al short time exceeded 5 mumols/s/l (AST) and 8 mumols/s/l (ALT) only in 2 patients. Mononucleosislike pictures, however, have not been seen. One patient developed neurological symptoms. The diagnosis was made by demonstrating IgM and IgG antibodies by way of the fluorescence antibody test. An antiviral therapy has not been introduced.

Adult

Do limited changes in phosphate intake modulate 1,25(OH)2D3 levels in early renal failure?

A high dietary phosphate load relative to GFR is thought to explain, at least in part, diminished renal 1-alpha hydroxylase activity in early renal failure (RF). To assess the role of dietary phosphate/GFR ratio in more detail, we examined the response of 1,25(OH)2D3 concentration to a controlled isolated reduction of dietary phosphate intake for up to 10 days with no change of Ca, Na and energy intake. We studied 7 healthy controls (2 male, 5 female, median age 45 years) and 6 non-nephrotic patients with early renal failure (RF) (3 males, 3 females, median age 55 years; median Cin 60.5ml/min/1.73 m2; 41-69). During an initial 3-day period of controlled diet with usual phosphate intake no difference of UVPi (median 27.6 mmol/day, 18.9-43.8) was found between controls and RF. A diet with 15 mmol Pi/day (confirmed by duplicate meal analysis) significantly reduced median UVPi (controls: 27.7 to 11.9 mmol/d; RF 27.4 to 14.1 mmol/d) with no change of median UVCa. Median day to day variation of 1,25(OH)2D3 levels (by RIA) in controls was 15.4%. Lowering dietary phosphate intake did not significantly change median 1,25(OH)2D3 levels in controls (45.7 vs. 38.3 pg/ml) and patients with RF, respectively (23.5 vs. 19.1 pg/ml). No changes of intact iPTH values were found. The experiment had a 68% power to detect a 15% change and a 99% power to detect a 30% change at a significance level of p less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol

Phagocytosis activity of polymorphonuclear cells of normal persons and dialysis patients is influenced by different dialysis membranes.

Leukocyte (PMN) functional capacity has been investigated through evaluation of phagocytosis of opsonised yeast cells in a radiometric test system. The PMN of dialysis patients (DP) had a slightly lower ability to ingest opsonised yeast cells in comparison with normal persons (NP), suggesting that an intrinsic cellular defect may exist. Under the influence of six membranes (cellulose acetate, regenerated cellulose, modified cellulose, cuprophane, polysulphone, and polymethylmethacrylate) the phagocytosis index decreased significantly between 10 and 17% in NP and between 13 and 23% in DP. There is a clear correlation with the membrane surface area. These results are not explained by the number of dead leukocytes (4-6.5% in DP and also in NP independently of membrane contact). The direct membrane effect could be responsible for the diminished phagocytic activity of leukocytes in NP and DP. Aqueous extracts of membranes alone resulted in no change of the phagocytic ability of PMN. Extracellular or 'uraemic factors' were excluded by the test procedure. The killing rate of yeast cells by PMN in NP and DP was not influenced in any of the membranes tested.

Adult