Search PubMed⌕ Search

Biomedical subjects

I Klein

Publications and source records attributed to I Klein.

At least 145 records · Page 8Linked to original sources
PubMed1987

Myosin content and myosin isoenzyme distribution in the heterotopic rat heart allograft.

Heterotopic cardiac transplants are vascularly perfused organs that can be used to study the regulation of myocardial protein content. Prior studies have demonstrated that cardiac isografts undergo marked atrophy with a decrease in weight and myosin content. In the present studies we have investigated the changes in size, myosin content and myosin isoenzyme distribution in the heterotopic cardiac allografts. Six days after transplantation allograft hearts were not spontaneously beating and histologically showed evidence of necrosis and cellular infiltration. Total heart weight (816 +/- 16 mg) and protein content (117 +/- 7 mg) were significantly greater in the allografts compared to in situ hearts (471 +/- 11 and 90 +/- 5 mg respectively, (P less than 0.01). In contrast to the increase in weight there was a simultaneous decrease in myosin ATPase (26%), the V1 isoform of the myosin isoenzyme (43%), and myosin content (53%) in the allograft heart. These studies demonstrate that similar to cardiac isografts, allograft hearts undergo a decrease in myosin content and a shift in myosin isoenzymes. In contrast to the marked atrophy of the cardiac isograft, the allograft heart weight is increased most likely due to rejection with cellular infiltration and an increased water content.

Adenosine Triphosphatases↗
PubMed1987

Pharmacokinetics of ethylenediaminemalonatoplatinum(II) (JM-40) during phase I trial.

Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-410) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60 min) infusion. Doses ranged from 20 to 1,200mg m-2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +/- 0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t1/2 alpha (10 and 13 min), t1/2 beta (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223 ml min-1), renal clearance (69 and 73 ml min-1) and metabolic clearance (183 and 154 ml min-1). During the first 6 h 27 +/- 9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29 +/- 13% and 60 +/- 13% over the first 6 h, 24 h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24 +/- 0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin.

Adult↗
PubMed1987

Effects of lithium on the endocrine system: a review.

Lithium has been established as a useful drug for the treatment of mood and behavior disorders. In addition to its therapeutic role in psychiatric disease it is important to recognize that it has diverse effects on endocrine function. These include the development of hypothyroidism and goiter in up to 10% of patients. Hyperthyroidism is a rare but reported side effect. Other abnormalities include hypercalcemia, diabetes insipidus, and altered carbohydrate metabolism. Depending on the clinical situation it is usually not necessary to discontinue lithium treatment, but appropriate intervention to correct the resulting endocrine abnormality may be indicated. This review emphasizes that psychiatrists and clinicians caring for patients given lithium need to be aware of the possible endocrine effects of this drug.

Blood Glucose↗
PubMed1987

Pharmacokinetics of carboplatin after i.v. administration.

Pharmacokinetics of the cisplatin analog carboplatin were studied in ovarian cancer patients who received short-term iv infusions of 290-370 mg/m2. Platinum (Pt) was determined by atomic absorption spectrometry in plasma ultrafiltrate up to 24 hours and in plasma and urine up to 5 days following infusion. Carboplatin was determined in plasma ultrafiltrate and in urine by high-performance liquid chromatography with electrochemical detection. The final half-life of total Pt in plasma was 5.8 +/- 1.6 days. Pharmacokinetics of carboplatin and ultrafilterable Pt (free Pt) were similar with respect to alpha-half-life (16 +/- 6 and 23 +/- 8 mins), beta-half-life (118 +/- 15 and 120 +/- 11 mins), area under curve/dose (18 +/- 5 and 17 +/- 4 min/m2/L), total-body clearance (101 +/- 21 and 107 +/- 19 ml/min), and volume of distribution Vss (9.9 +/- 1.3 and 10.0 +/- 1.4 L/m2). After 6 hours the cumulative urinary excretion of carboplatin and Pt was 41% +/- 14% and 68% +/- 7% of the dose, respectively. After 5 days the cumulative urinary excretion of Pt was 84% +/- 6%. Renal and metabolic clearances of free Pt from plasma were 81 +/- 17 and 26 +/- 11 ml/minute, respectively. The first-order rate constant for metabolic elimination of free Pt (KM = CLM/Vss) was 1.5 X 10(-3) +/- 0.6 X 10(-3) min-1, which is ten times lower than the value calculated from literature data for cisplatin (15 X 10(-3) +/- 1 X 10(-3) min-1). This means that the overall in vivo reactivity of carboplatin is ten times lower than that of cisplatin.

Carboplatin↗
PubMed1986

Protein binding of five platinum compounds. Comparison of two ultrafiltration systems.

Amicon Centriflo CF50A cones and Amicon MPS-1 micropartition systems with YMT filters were compared for the preparation of ultrafiltrates of plasma samples containing cisplatin, spiroplatin, JM-40, carboplatin or iproplatin. The MPS-1 system equipped with YMT membranes showed less adsorption of the platinum compounds than CF50A cones and allowed more rapid processing of smaller plasma volumes. In vitro binding to human plasma proteins measured with YMT filters after 24 h of incubation was 94%, 89%, 83%, 31% and 0 for cisplatin, spiroplatin, JM-40, carboplatin and iproplatin, respectively. These values corresponded with the initial half-lives in plasma and the decomposition half-lives of intact drug in plasma ultrafiltrate as measured by HPLC. It is suggested that the degree of protein binding is related to the stability of the leaving groups.

Adsorption↗
PubMed1986

Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of cisplatin.

Pharmacokinetic studies were performed in 51 patients who received cisplatin infusions. Two treatment regimens (single-day or daily for 5 days) and three infusion schedules (for 4 to 15 minutes, 2 to 3 hours, or 24 hours) were used. The daily dose of cisplatin varied from 20 to 120 mg/m2. The kinetics of total platinum studied up to day 5 revealed differences only during the initial period after the infusion. Peak levels were both dose and schedule dependent and initial t1/2 values in the decay curves were only schedule dependent (mean values: 13 minutes for rapid infusions, 40.3 minutes for 2 to 3-hour infusions, and 220.5 minutes for 24-hour infusion). The t1/2 values between days 1 and 5 were neither dose nor schedule dependent (mean 5.0 to 7.3 days). Concentrations of free platinum declined biexponentially after the rapid and 2 to 3-hour infusions, but they declined monoexponentially after 24-hour infusions. Final t1/2 values ranged from 26.0 to 78.8 minutes. In patients with normal renal and hepatic function, the free platinum AUC was identical for cisplatin infusions of different duration when equal doses were given. Free platinum clearance correlated with creatinine clearance (P = 0.017). The uptake of platinum in red blood cells was rapid, and peak concentrations correlated with the free platinum AUC (P = 0.0006), independent of the infusion schedule. The decay of platinum levels in red blood cells was biphasic. The mean terminal t1/2 for the interval between days 5 and 15 was 29.8 days. This suggests a breakdown of red blood cells that results from cisplatin dosing.

Adult↗
PubMed1986

Pharmacokinetic comparison of cisplatin in solution with common lyophilized cisplatinum (Platinol).

Total platinum kinetics were studied after the administration of two formulation products of cisplatin: the lyophilized form and a ready-to-use solution. Twelve patients received both preparations during two successive cycles in a randomized crossover study. Platinum concentrations in plasma and urine were measured by atomic absorption spectrometry. Data were analyzed by means of a mixed-effect analysis of variance. Areas under the concentration-time curves up to 96 h were increased (p = 0.026) and slopes of the elimination phase were decreased (p = 0.035) during cycle 2 when compared with cycle 1. However, no difference in these two parameters was observed when comparing the two formulations. Three-day urinary platinum excretion was not related to either the treatment cycle or the formulation used. Because of its convenience of use and reduced risk of aerosolization, the ready-to-use formulation seems preferable.

Aged↗
PubMed1986

Effects of thyroid hormone on cardiac size and myosin content of the heterotopically transplanted rat heart.

Infrarenal heterotopic cardiac isografts maintain structural and functional integrity. We have used this transplantation model to further explore the mechanisms of thyroid hormone-induced cardiac hypertrophy. Thyroid hormone administration, 1-thyroxine (T4) 10 micrograms/animal per d, led to a significant 30% increase in total heart weight and a 40% increase in the myosin content of the in situ heart when compared with control. In contrast, T4 treatment was without effect on the heart weight, protein content, rate of protein synthesis, or calculated myosin content of the heterotopic, nonworking heart. Heterotopic hearts demonstrated a significant decrease in the percentage of the V1 myosin isoenzyme from 95% to 61%. This shift occurred in euthyroid animals but was prevented by T4 treatment. These results suggest that thyroxine-induced cardiac hypertrophy is mediated indirectly via changes in cardiac work. Myosin isoenzyme expression can be altered by changes in work load but is still responsive to increased levels of thyroid hormone.

Adenosine Triphosphatases↗
PubMed1986

Interaction of cisplatin and carboplatin with sodium thiosulfate: reaction rates and protein binding.

Toxicity of cisplatin can be decreased by concomitant administration of sodium thiosulfate, which perhaps chemically inactivates this platinum compound. We studied the disappearance of cisplatin and carboplatin in aqueous solutions of thiosulfate at 37 degrees C by means of liquid chromatography. At initial concentrations that were similar to therapeutic concentrations in plasma, both drugs disappeared, with half-lives of 66 and 537 min for cisplatin and carboplatin, respectively. At higher thiosulfate concentrations, as found in urine, the respective half-lives were 3.7 and 33.8 min. These values suggest that direct chemical interaction in the plasma compartment has limited therapeutic consequences, whereas the anti-toxic effect of thiosulfate might be explained by the rapid inactivation of cisplatin in the kidneys. Reaction products of cisplatin and thiosulfate bound instantaneously and mainly reversibly to plasma proteins. Protein-bound cisplatin was not released by added thiosulfate--which may explain why thiosulfate, to be effective, must be given in advance of and during cisplatin administration.

Carboplatin↗
PubMed1986

Prospective evaluation of thyroid function in patients with systemic sclerosis (scleroderma).

A consecutive series of 77 ambulatory, clinically euthyroid patients with systemic sclerosis was evaluated for clinical, chemical and serologic evidence of thyroid disease. Measurements of baseline serum thyroid function tests and the thyroid stimulating hormone response to thyrotropin releasing hormone (TRH) were made. We classified 18 (23%) patients as abnormal, including 8 (10%) who were chemically hypothyroid and 10 (13%) with normal baseline studies but an exaggerated response to TRH injection. The remaining 59 (77%) patients were euthyroid by all measurements. Antithyroid antibodies were present in only 4 of 8 (50%) of the hypothyroid group. There were no differences between the 3 patient groups with regard to the extent of scleroderma, the presence of internal organ involvement, or the frequency of common signs or symptoms of hypothyroidism. Abnormal thyroid function in systemic sclerosis is frequent, often unsuspected clinically, and may occur without markers of autoimmune thyroid disease.

Adult↗
PubMed1985

Development of heart cells in culture: studies using an affinity purified antibody to a myosin light chain.

Cultured neonatal rat heart cells can be used to study the factors that regulate cardiac contractility and myocyte development in vitro. An antibody to the 26,000 dalton light chain of myosin (MLC1), has been produced and purified on a Sepharose 4B affinity column prepared with rat heart myosin. When primary cultures of myocytes are studied by indirect immunofluorescence using this antibody a predictable pattern of myofibrillar structure is observed to develop over 72 h. This myosin cytoskeleton is highly organized and the myosin fibrils exhibit cross striations. The antibody does not stain non-muscle heart cells and there is no evidence for myocyte division in culture. The qualitative immunofluorescent pattern of myosin organization is the same in both spontaneously beating and in non-contracting cells.

Animals↗
PubMed1985

Regulation of the growth of nonmuscle heart cells in culture.

Primary cultures of neonatal rat hearts contain both striated muscle (myocytes) as well as nonmuscle heart cells (NMHC). Although myocytes do not divide in culture, NMHC do increase in number. The growth of NMHC is dependent on the concentration of serum in the media over a range of 1 to 10%. When compared to growth in 10%, cells in 1% serum have a prolonged doubling time and reach a maximum density that is 70% less. Thus, 1% serum which supports normal myocyte development is a useful culture media to also maintain muscle heart cell homogeneity by its failure to support optimum NMHC division.

Adenosine Triphosphatases↗
PubMed1985

Measurement of myosin adenosinetriphosphatase and myosin content in cultured heart cells.

An assay specific for myosin ATPase in whole-cell extracts of cultured heart cells has been developed. Myosin ATPase is measured by the production of Pi from ATP in the presence of high ionic strength (0.5 M KCl) at pH 9.1. Enzyme activity is maximal with 10 mM CaCl2 and completely inhibited with 5 mM MgCl2. Spontaneously beating myocytes grown in the presence of 10% newborn calf serum and 0.1 mM 5-bromo-2'-deoxyuridine show a significant rise in myosin ATPase between Days 1 and 4 in culture. The measurement of myosin ATPase allows for the quantitation of cellular myosin content, and can be used to assess changes in myosin content that occur during growth, development, and cellular repair.

Adenosine Triphosphatases↗
PubMed1985

Biliary excretion of platinum in rats after administration of cisplatin and aqua(1,1-bis(aminomethyl)-cyclohexane)sulfatoplatinum(II) (spiroplatin, TNO-6).

Three groups of 6 rats were treated with cisplatin (3 mg/kg, bolus and 3-h infusion) and spiroplatin (3 mg/kg, bolus) by infusion in the right external jugular vein. The mean amounts of platinum +/- c.v. excreted in the bile during the first 6 h after the start of administration were 0.32 +/- 0.19% and 0.39 +/- 0.29% of the dose after bolus injection and 3-h infusion of cisplatin, respectively, and 3.77 +/- 3.32% of the dose after spiroplatin. The values were not significantly different between the 2 cisplatin administration modes (P greater than 0.05), but were between the spiroplatin and cisplatin bolus groups (Wilcoxon two-sided rank test, P less than 0.01). These data are related to pharmacokinetic parameters in man.

Animals↗
PubMed1985

Phase I study and pharmacokinetics of intraperitoneal carboplatin.

In the early stages of this phase I study the tolerance of carboplatin intraperitoneally was good. Pharmacokinetic profiles suggest a possible therapeutic advantage for giving the drug intraperitoneally for the treatment of tumour nodules situated in the peritoneum. The extent of penetration of carboplatin through tumour nodules has not yet been assessed but tumour nodules are being processed for nuclear activation analysis.

Antineoplastic Agents↗
PubMed1985

Self reactive delayed type hypersensitivity (DTH) induced in mice by syngeneic lymphoblasts.

Normal and x-irradiated A mice injected with syngeneic concanavalin A (Con A)-induced lymphoblasts revealed after challenge with syngeneic lipopolysaccharide (LPS)-induced lymphoblasts delayed type hypersensitivity (DTH) measured both by footpad swelling and by 125IudR accumulation. Mice injected with allogeneic Con A-induced lymphoblasts and challenged with syngeneic LPS-induced lymphoblasts or vice versa, also generated an appreciable DTH response. In contrast, Con A-induced blast cells of human origin (xenogeneic cells) generated a considerably less effective DTH. The DTH response was more profound and consistent in x-irradiated mice, suggesting that irradiation sensitive cells control this response. The syngeneic DTH response was efficiently transferred to naive recipients with Thy-1+, nylon wool passed cells. The establishment of the DTH activity was associated with the lymphoblasts own (differentiation?) antigens and not with contaminants attached to the cells, such as Con A or fetal calf serum. The results were compared with similar results reported by other groups and the biological significance of all findings was evaluated.

Animals↗