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Biomedical subjects

I Klein

Publications and source records attributed to I Klein.

At least 163 records · Page 9Linked to original sources
PubMed1985

Contraction regulates myosin synthesis and myosin content of cultured heart cells.

Cultured neonatal rat heart cells are a useful model for studying the regulation of myocyte growth. The myosin content of heart cells increases between days 1 and 4 in culture. To determine if contraction per se can regulate myocyte growth, myosin content and protein synthesis were compared in spontaneously contracting and noncontracting cultured heart cells. Myosin content, assayed as the total myosin ATPase activity per culture dish, was significantly increased in contracting cells after 3, 4, and 5 days in culture. Protein synthesis was measured by incorporation of [14C]lysine into total cell protein and into sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved myosin. Contraction stimulated both total cell protein content and protein synthesis by day 3 in culture. Compared with heart cells arrested with 50 mM KCl, myosin synthesis was significantly increased by 96, 112, and 46% at days 2, 3, and 4, respectively. Similar results were observed when myosin content and protein synthesis in contracting myocytes were compared with cells arrested with either 25 mM KCl or 10(-5) M verapamil. The present studies suggest that contraction increases the myosin content in cultured heart cells and that this increase is mediated via a stimulation of myosin synthesis in association with cell growth.

Adenosine Triphosphatases↗
PubMed1984

Unusual manifestations of hypothyroidism.

Thyroid hormone exerts direct effects on essentially all of the organ systems of the body. Hypothyroidism is a frequently diagnosed endocrine disorder that has characteristic clinical signs and symptoms. In addition to these common manifestations, however, there are many additional manifestations of hypothyroidism that are less commonly acknowledged and include involvement of the hematologic, muscular, cardiac, and rheumatologic systems. It is important to recognize that these other organ systems may be involved and that the resulting disease states can dominate the clinical picture. As with the classic manifestations of hypothyroidism, these unusual manifestations respond to thyroid hormone replacement therapy. Thus, the importance of recognizing these signs and symptoms, as a result of hypothyroidism, is evident. This article emphasizes these less common manifestations of the patient with hypothyroidism, and, in addition, discusses the possible pathophysiologic mechanisms by which thyroid hormone deficiency can lead to organ system dysfunction.

Adult↗
PubMed1984

Pharmacokinetics of free and total platinum species after short-term infusion of cisplatin.

Pharmacokinetic studies were performed in ten patients who received short-term (4-15-min) infusions of cisplatin. Computerized nonlinear least-squares analysis (NLIN) and an adapted curve-stripping approach (CSTRIP) were used to characterize total-platinum concentration-time curves. The overall curves showed a rapid initial phase and a prolonged terminal phase, separated by a phase with secondary peaks attributed to the existence of an enterohepatic recirculation. Up to Day 5, NLIN analysis revealed three exponential phases, with half-lives of 14.4 mins, 273.7 mins, and 5.3 days, respectively. However, a significant consistent divergence (P less than 0.005) was found between the observed and predicted curves during the intermediate phase, not justifying the use of an exponential function during this phase. The shape of the intermediate curve was strongly suggestive of a second influx in the plasma compartment, the amount of which was estimated by the CSTRIP approach (1.4% +/- 0.5% of the administered dose). Free-platinum levels declined in a biphasic manner (half-lives: 9.7 +/- 0.2 and 40.4 +/- 2.5 mins; n = 3). After administration of 100 mg/m2 of cisplatin, maximum platinum levels in rbcs ranged from 0.51 to 0.58 micrograms/ml and were reached within 90-150 mins. Thereafter, rbc platinum levels declined in a biphasic fashion, with a terminal half-life, for the interval Days 5-15, of 36-47 days. The binding of platinum to both plasma and proteins and rbcs in vitro (using patients' own blood) was slow, biphasic, and irreversible.

Adult↗
PubMed1984

Clinical and chemical assessment of thyroid function during therapy with amiodarone.

Clinical and chemical variables of thyroid function were studied in 26 patients with symptomatic ventricular tachyarrhythmias before and during long-term oral treatment with amiodarone. The mean (+/-SEM) pretreatment thyroxine (T4) level in the 26 patients was 7.32 +/- 0.33 micrograms/dL, and increased notably to 10.15 +/- 0.47 micrograms/dL by 30 to 120 days after treatment. The free thyroxine index (FT4I) was also notably elevated. Clinical hyperthyroidism or goiter did not develop, but clinical hypothyroidism occurred in four patients during and in one patient after discontinuation of amiodarone treatment. Notable titers of antithyroid antibodies were found in the serum of two of the five and a family history of thyroid disease was present in three of the five hypothyroid patients. An elevation of both the T4 level and the FT4I above the normal range is an expected finding in patients receiving amiodarone and does not by itself indicate hyperthyroidism. Patients with positive antithyroid antibodies or a family history of thyroid disease prior to treatment with amiodarone may be at an increased risk of hypothyroidism developing when treated with this drug.

Adult↗
PubMed1983

Colchicine stimulates the rate of contraction of heart cells in culture.

Microtubules have been demonstrated in intact heart muscle as well as in cultured myocytes. To better understand what role these filaments may be playing in the regulation of cardiac function we have used the microtubule disrupting agent colchicine and examined its effect upon the rate of beating of rat heart cells. Colchicine, but not the inactive stereoisomer lumicolchicine, increased the myocyte rate of spontaneous contraction in a dose dependent manner. This effect was clearly distinguishable from the positive chronotropic effect of isoprenaline and unlike isoprenaline was not blocked by propranolol. Colchicine was without effect on the in vitro activity of adenylate cyclase assayed in a myocyte homogenate. The binding of 3H-colchicine to cultured heart cells increased with a time course consistent with the increase in heart rate. Subcellular distribution and sephadex gel chromatography demonstrated that approximately 30% of the cell associated colchicine comigrated with tubulin. Measurements of total myocyte tubulin by 3H-colchicine binding indicated that tubulin represents about 0.04% of the total heart cell protein.

Adenylyl Cyclases↗
PubMed1983

Trifluoperazine inhibits the contraction of cultured rat cardiac cells and the phosphorylation of myosin light chain.

Cultured, spontaneously beating heart cells were used to study the role of calmodulin in regulating cardiac contraction. Trifluoperazine (TFP), an antipsychotic drug that binds to calmodulin, reversibly inhibited myocardial contraction. This effect occurred over a TFP concentration range of 5-100 muM with half maximal activity at approximately 15 muM TFP. When the phosphoprotein profile of TFP-treated cells was compared with control cultures, there was a significant decrease in (32)P content of the 20,000-D myosin light chain. As measured by two-dimensional gel electrophoresis, the fraction of phosphorylated myosin light chain decreased from 0.31+/-0.06 in control to 0.16+/-0.05 in TFP-treated cells (P < 0.05). This inhibition of protein phosphorylation was relatively selective, as two other phosphoproteins ( approximately 41,000 and 36,000 D) were unaffected, and a third protein ( approximately 28,000 D) showed an increase in (32)P activity. In contrast, the cessation of spontaneous beating by 50 mM KCl did not reproduce these changes. This inhibition of contraction mediated by TFP associated with alterations in the phosphorylation of certain cardiac phosphoproteins suggests a role for calmodulin and for the myosin light chain in the regulation of cardiac cell contraction.

Animals↗
PubMed1983

Spirogermanium: effects on hematopoietic stem cells and survival of normal and tumor-bearing mice.

The effect of spirogermanium (SG) on hematopoietic stem cells, tumor burden, and survival times was investigated in C3H mice with transplanted mammary carcinoma. Compared to normal mice, the number of hematopoietic stem cells, or colony-forming units per spleen (CFU-S), was lower in the marrow of tumor-bearing mice. Spirogermanium at 15 and 30 mg/kg was not toxic to the normal hematopoietic cells in the marrow of either normal or tumor-bearing mice. In contrast to animals treated with cyclophosphamide, SG did not decrease the tumor growth rate or prolong the survival times of tumor-bearing C3H mice. Doses of 35-40 mg/kg SG did not prolong the survival times or decrease the tumor burden of AKR/J mice with a long-passaged lymphoma. These studies demonstrate that SG has minimal inhibitory effects to the marrow of normal mice and may promote the maintenance of normal marrow cells in tumor-bearing animals. However, in two different transplanted tumor cell lines, SG did not inhibit tumor growth or prolong host survival time.

Animals↗
PubMed1983

Skin tags: a cutaneous marker for colonic polyps.

The relation between adenomatous colonic polyps and the development of adenocarcinoma of the colon is well established. An association between skin tags and colonic polyps in patients with acromegaly has also been reported. To ascertain if skin tags are a cutaneous marker for colonic polyps independent of the presence of acromegaly, 100 men referred for colonoscopy were studied. Forty-six patients had colonic polyps and 37 also had skin tags; the correlation was highly significant (p less than 0.005). The sensitivity and specificity of the presence of skin tags serving as a cutaneous marker for adenomatous colonic polyps were both greater than 75%. Thus, at least in this population, skin tags may serve as a means for identifying patients at increased risk for having colonic polyps.

Colonic Neoplasms↗
PubMed1983

[Clinical experimental studies of postoperative infusion analgesia].

30 postoperative patients, who had undergone abdominal gynaecological surgery with standard general anaesthesia were randomly divided into three groups and received, in the recovery ward, a continuous infusion of either pentazocine, piritramid, or ketamine. The patients rated their pain on a 15 cm pain analogue score. Group I pentazocine: Mean dosage on the day of operation 0.12 mg/kg/h, 0.1 mg/kg/h on the first and only 0.07 mg/kg/h on the second postoperative day. Pentazocine blood levels were on average 50 micrograms/l. Group II piritramid: Mean dosage on the day of operation 0.038 mg/kg/h, 0.024 mg/kg/h on the first and 0.019 mg/kg/h on the second postoperative day. Blood levels of piritramid were not determined because there is no satisfactory assay available. Group III ketamine: mean dosage on the day of operation 0.32 mg/kg/h, 0.28 mg/kg/h on the first and 0.29 mg/kg/h on the second postoperative day. Ketamine blood levels lay between 120 and 180 micrograms/l. The three analgesics did not cause any important haemodynamic or respiratory side effects. Pentazocine and piritramid were the most effective analgesics, ketamine was the least effective with a high incidence of side effects.

Adult↗
PubMed1982

Pharmacokinetics of free platinum species following rapid, 3-hr and 24-hr infusions of cis-diamminedichloroplatinum (II) and its therapeutic implications.

The pharmacokinetics of free platinum species derived from cis-diamminedichloroplatinum (II) (cisplatin) was studied in three patients who received the drug as a single agent for the first time at equal doses (100 mg/m2) but with different infusion times. In rapid, 3-hr and 24-hr infusions, peak levels of free platinum were 8.62, 1.96 and 0.27 microgram Pt/ml respectively; half-lives of disposition calculated 0-30 min after the end of each infusion were 17.4, 22.7 and 26.2 min respectively. Free platinum availability, measured as the area under the curves of the free platinum concentration, was the same for the three modes of administration (290, 321 and 325 micrograms Pt/min/ml-1 respectively). This observation supports the clinical impression that antitumour activity of cisplatin is not dependent on the method of administration.

Aged↗
PubMed1982

Evidence for cellular mediated immunity in an animal model of autoimmune pituitary disease.

The anterior pituitary gland can be involved in an inflammatory reaction mediated by lymphocytes that leads to various degrees of dysfunction. In seven rabbits immunized with homologous pituitary tissue in complete Freund's adjuvant, a focal lymphocytic infiltrate, and increased fibrosis was observed in five. These changes were patchy in distribution and limited to the anterior pituitary. No inflammation was observed in five control animals. When incubated with pituitary extract, partially purified lymphocytes from four of the five animals with altered pituitary histology demonstrated a significant (p less than 0.05) stimulation of 3H-thymidine incorporation. Measures of antipituitary antibodies using indirect immunofluorescence were negative in experimental as well as control animals. The present studies characterize the histologic changes and suggest that cellular immunity plays a role in the pathogenesis of experimentally induced autoimmune pituitary disease.

Animals↗