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Biomedical subjects

E Kalman

Publications and source records attributed to E Kalman.

At least 19 recordsLinked to original sources
PubMed2001

Screening for cerebroprotective agents using an in vivo model of cerebral reversible depolarization in awake rats.

The need to screen cerebroprotective compounds without anesthetic interference prompted the development of a model using hypoxic rats. In this model two outcome measures were used: (1) the time to reach isoelectric electroencephalogram (iEEG), caused by nitrogen gas inhalation in the test chamber, and (2) the time for behavioral recovery measuring the latency of restoration of the head-withdrawal reflex upon vibrissae stimulation. We report here data of blood chemistry, cerebral tissue oxygen measurements, a definition of a proposed scoring system, and the pharmacological results of RGH-2202. The findings with RGH-2202 are used here to show the utility of the screening method. Events during hypoxia: Arterial and venous pO(2), pCO(2), and pH, and brain tissue pO(2)significantly declined. Significant correlations were established among the pO(2)of cerebral tissue, blood, and the test chamber. RGH-2202 significantly and dose-dependently shortened the iEEG time; the compound's Effective Dose(30)was 227.8 mg kg(-1). Events during recovery: Immediately after the iEEG, when the atmosphere in the chamber was replaced with room air, the arterial, venous and brain tissue pO(2)increased above the control level and subsequently recovered to baseline levels. Behavioral recovery occurred before blood chemistry was otherwise normalized. RGH-2202 significantly and dose-dependently shortened the recovery time; the Effective Dose(30)was 8.71 mg kg(-1). The available data define and support the physiological basis of this practicable rat-screening model.

Administration, Oral↗
PubMed2001

The evolution of care for the chronically critically ill patient.

The post acute health care system has evolved its infrastructure to accommodate the growing complex medical patient population, a direct result of the expanded capability in supporting critically ill patients in the ICU setting. When patients fail to wean from mechanical ventilation in the ICU, there is often less emphasis on continuing these efforts, and patients appear better served in specialized units dedicated to weaning patients from mechanical ventilation. Long-term acute care hospitals also provide an ideal environment to support patient care for other complex medical illnesses, including populations with oncologic, cardiovascular, and infectious disease. The LTAC hospital seems best adapted to this role. Its infrastructure includes significant physician support and the blending of immediate and long-term care services and provides an ideal opportunity to serve this resource-intensive group. An emphasis on the transition from acute illness to recovery serves to define the role and mission of this important entity and highlights the specialized nature of the LTAC hospital.

Cost of Illness↗
PubMed2000

Cells producing cathepsins D, B, and L in human breast carcinoma and their association with prognosis.

Lysosomal proteinases, cathepsins D, B, and L have been associated with malignant tumor progression and with prognosis in various human carcinomas. In the current study, the immunohistochemical localization of cathepsins in tumor cells was correlated with cathepsin protein concentration in breast carcinoma cytosols from 77 patients. Significant correlation was found for cathepsin D (P < .041) and borderline correlation for cathepsin B (P < .055) but not for cathepsin L. We hypothesize that the poor correlation of cysteine cathepsins was attributable to the fact that they were present not only in malignant epithelial cells, but also in infiltrating macrophages and stromal fibroblasts. In addition, tumor-surrounding myoepithelial cells (42% of tumors) and myofibroblasts (26% of tumors) as well as endothelial cells of neovasculature (10% of tumors) all stained specifically for cathepsin B. Two thirds of tumors co-expressed cathepsins B and L in tumor cells, whereas only 17% of tumors co-expressed all 3 cathepsins. Intense immunostaining for cathepsin D of tumor cells was observed in tumors at high TNM stage and tumors having positive lymph nodes. The expression of cathepsin B was independent of established prognostic factors, whereas intense cathepsin L staining in tumor cells was associated with high histological grade. With respect to prognosis of patient survival, only tumor cell-associated cathepsin D (P = .042) and myoepithelial cell-associated cathepsin B (P = .061) showed borderline significance. Cathepsins B and L immunostaining in tumor cells was not prognostic. In contrast, cytosolic levels of cathepsin B correlated with higher rate of relapse. Taken together, these results show the diversity in the cellular distribution of cathepsins in human breast carcinoma, presumably reflecting specific regulation and function of each of the cathepsins during tumor progression.

Adult↗
PubMed1999

Immunochemical analysis of cathepsin B in lung tumours: an independent prognostic factor for squamous cell carcinoma patients.

In order to evaluate the possible role of the proteolytic enzyme cathepsin B (cath B) in human non-small cell lung cancer (NSCLC) we examined cath B concentrations (cath B(C)) and activities (cath B(A)) in homogenates of 127 pairs of lung tumour tissues and corresponding non-tumourous lung parenchyma. Total cath B activity (cath B(AT)) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B(A7.5)) were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The immunostaining pattern of cath B was determined in 239 lung tumour tissue sections, showing the presence of the enzyme in tumour cells (cath B(T-I)) and in tumour-associated histiocytes (cath B(H-I)). The median levels of cath B(AT), cath B(A7.5) and cath B(C) were 5.6-, 3.2- and 9.1-fold higher (P < 0.001), respectively, in tumour tissue than in non-tumourous lung parenchyma. Out of 131 tissue sections from patients with squamous cell carcinoma (SCC), 59.5% immunostained positively for cath B, while among the 108 adenocarcinoma (AC) patients 48.2% of tumours showed a positive reaction. There was a strong relationship between the levels of cath B(AT), cath B(A7.5), cath B(C) and cath B(T-I) in the primary tumours and the presence of lymph node metastases. Significant correlation with overall survival was observed for cath B(T-I) and cath B(A7.5) (P < 0.01 and P < 0.05, respectively) in patients suffering from SCC. In these patients positive cath B in tumour cells (cath B(T-I)) and negative cath B in histiocytes (cath B(H-I)) indicated significantly shorter survival rate compared with patients with negative cath B(T-I) and positive cath B(H-I) (P < 0.0001). In contrast, in AC patients, both, positive cath B(T-I) and positive cath B(H-I), indicated poor survival probability (P < 0.014). From these results we conclude that the proteolytic enzyme cath B is an independent prognostic factor for overall survival of patients suffering from SCC of the lung.

Adenocarcinoma↗
PubMed1996

Cathepsins D, B, and L in transformed human breast epithelial cells.

To investigate the regulation of lysosomal enzymes during carcinogenesis, we measured cathepsins (Cats) D, B, and L in MCF-10F, which is a human breast epithelial cell line, and cells evolved after treatment with carcinogen and transfected with c-Ha-ras oncogene. The clones used in this study, MCF-10FTras, D3, D3-1, and D3-1Tras, expressed no estrogen receptors and gradually increased invasive potential, while oncogene-transfected lines were also tumorigenic in SCID mice [16, 19]. Cats D, B, and L were determined in the cells and in cell media using enzyme-linked immunosorbent assay (ELISA), specific enzyme activity measurements, and immunocytochemistry. The major intra- and extracellular lysosomal proteinase in these cells was Cat D (30-180 pm/mg), followed by Cat B (2-10 pm/mg) and Cat L (1-5 pm/mg). An inverse relationship between intracellular Cat D levels and invasive potential of carcinogen-treated and c-Ha-ras oncogene-transfected cell lines was observed. No significant changes in extracellular concentration of Cat D precursor in this series of cell lines was observed. Intracellular levels of Cats B and L were unchanged or slightly lower in carcinogen-treated D3 and D3-1 cells, as well as in MCF-10FTras. On the other hand, in D3-1Tras cell line, evolving from c-Ha-ras transfected D3-1 line, 3.5 fold and 4.4 fold increases in Cat B and Cat L, respectively, but a 2 fold decrease in Cat D, were observed compared to the parental cell line. Immunocytochemical staining showed a granular, polarized perinuclear and cytoplasmic staining of cathepsins in all cell lines. Cysteine proteinases stained more frequently and more intensely in D3-1Tras compared to other lines, confirming the immunochemical assays. We hypothesize that several molecular events, caused by a carcinogen and an oncogene such as c-Ha-ras, are needed to increase Cat B and Cat L, but not Cat D, expression. Therefore, the cysteine and aspartic lysosomal proteinases are differentially expressed in the breast cell lines with more invasive phenotype.

Breast↗
PubMed1995

Cathepsins D, B and L in breast carcinoma and in transformed human breast epithelial cells (HBEC).

An increased expression of lysosomal enzymes, cathepsin (Cat) D, Cat B and Cat L, was observed in various human tumours and after in vitro cell transformation. To establish possible co-ordination in their expression, all three cathepsins were determined in human breast tumours and in transformed human breast epithelial cells (HBEC). In breast carcinoma (n = 120) all three cathepsins, determined immunochemically and by enzymatic activity, were increased compared to normal breast tissues. The activities, correlated with the corresponding protein masses for Cat D (r = 0.77, p < 0.01), but not for Cat B and Cat L. Significant increase in Cat B activity was observed in stage II compared to stage I tumours, and Cat L activity in stage III compared to stage II tumours, but no significant correlation of cathepsin protein with tumour stage (TNM) was established. No significant correlation between Cat D and the cysteine cathepsins B and L was observed. Similarly, Cat D, Cat B and Cat L levels did not correlate in the in vitro system, e.g. in the five transformed HBEC, such as evolved after dimethylbenz(a)anthracene treatment and c-Has-ras oncogene transfection of diploid MCF-10F cell line (Calaf et al., 1993). Transformed cells showed increased anchorage-independent growth and invasive capability (MCF-10 < MCF-10FTras < D3 < D3-1 < D3-1Tras). The intracellular level of Cat D was not related to cell invasiveness, while total cellular Cat B and Cat L increased 13 fold and 4 fold, respectively, in the most invasive cell line, D3-1Tras compared to MCF-10F.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A large deletion in the connection subdomain of murine leukemia virus reverse transcriptase or replacement of the RNase H domain with Escherichia coli RNase H results in altered polymerase and RNase H activities.

The functional relationship between the polymerase and RNase H domains of reverse transcriptase (RT) was investigated by studying the activities of AKR murine leukemia virus (MuLV) enzymes. In addition to the wild type, an RNase H-minus RT missing the entire RNase H domain and two other mutants having abnormal polymerase:RNase H ratios were expressed. These mutants include (i) a chimeric protein in which the MuLV RNase H domain was replaced by the entire Escherichia coli RNase H sequence and (ii) an RT with a 126 amino acid deletion in a region analogous to the "connection" subdomain in the p66 subunit of human immunodeficiency virus type 1 RT (Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A., & Steitz, T. A. (1992) Science 256, 1783-1790). With the wild-type RT, the major RNase H cleavage reaction was coordinated with DNA synthesis and occurred at a position corresponding to 15 nucleotides from the 3'-terminus of the DNA primer. Additional cleavages closer to the 5'-end of the RNA were explained in terms of a model relating binding of the RNA.DNA hybrid substrate and enzyme structure. The chimeric RT behaved like E. coli RNase H, exhibited 300-fold higher RNase H activity than wild-type RT, and was limited in its ability to synthesize DNA. Qualitative and quantitative changes in the polymerase and RNase H activities of the deletion mutant were also observed. The RNase H domain appeared to function independently of the polymerase domain, supporting the idea that the proper spatial relationship between the two active centers was disrupted by the mutation. Taken together, our results indicate that alteration of the normal polymerase:RNase H ratio can have profound effects on both polymerase and RNase H cleavage activities, as expected for an enzyme with two interdependent domains.

Animals↗
PubMed1990

Anorexia resulting from fear of vomiting in four adolescent girls.

Four adolescent girls were referred for psychiatric assessment because of suspected anorexia nervosa. Although all of them had lost at least 15% of their body weight, investigation showed that they did not meet the criteria for anorexia nervosa. In all cases, refusal to eat resulted from fear of vomiting following a viral illness and not from a desire to lose weight. Their family configurations and personal histories showed many similarities, including constricted range of affect and a notable lack of anger. With counseling and, in one case, psychotropic medication, the patients recovered promptly.

Adolescent↗
PubMed1978

Present status of the infant of very low birth weight treated in a referral neonatal intensive care unit in 1974.

In 1974, 250 infants with birth weights of 1500 g or less were referred to the Intensive Care Unit at the Hospital for Sick Children, Toronto. Sixty-six per cent survived. Prospective follow-up studies of the survivors have been completed over a minimum of two years. Infants at highest risk for handicapping defects (about 85%) are those who survived intracranial haemorrhage during the neonatal period. Neurological defects encountered in these children were severe--hydrocephalus, spastic quadriplegia, hemiplegia or microcephalus--and were usually associated with low psychometric scoring. The second highest risk group were small for gestational age infants. Of these, 53% were significantly handicapped at two years of age, and 43% had developmental quotients of less than 80. These defects could not be related to postnatal events. The third category at high risk were infants with birth weights of 1000 g or less. Among these, 30% had a significant handicap by two years of age. The outcome in the remainder of the sample was generally good. These results suggest that the decreased mortality of the very premature infant is associated with an increased number of relatively normal survivors and that the infants at highest risk for subsequent defects can be identified at or shortly after birth.

Cerebral Hemorrhage↗