Oestrogen toxicity in the ferret.
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Animals↗
Biomedical subjects
J Hart
Publications and source records attributed to J Hart.
Gene mapping and somatic cell hybrid analysis of the role of human lymphocyte function-associated antigen-3 (LFA-3) in CTL-target cell interactions.
LFA-3 is expressed on a wide variety of human cell lines, including those which have been used as recipients for gene transfer of human class I gene products, whereas a murine counterpart is either absent or significantly different such that the anti-LFA-3 monoclonal antibody (MAb) does not bind. By using a somatic cell genetic approach, we demonstrate that LFA-3 is not a major histocompatibility complex-encoded molecule, and that its gene locus maps to human chromosome 1. When LFA-3 and HLA-A2 are coexpressed on the mouse cell surface, anti-LFA-3 MAb interfered with specific recognition and lysis of these target cells by human CTL capable of lysing HLA-A2-expressing mouse transfectants. A significant contribution of the LFA-3 molecule to CTL reactivity was not observed, however, because the presence of LFA-3 did not restore recognition by CTL clones previously found incapable of lysing HLA-A2-expressing mouse transfectants, nor was it required by those human CTL that could lyse mouse cell transfectants. Thus, we have used genetic techniques to demonstrate that LFA-3 may serve a role in CTL-target cell interactions at the target cell level, but is not a molecule absolutely required for human allospecific CTL recognition of HLA antigens expressed on mouse cells. We suggest that LFA-3 may not participate directly in CTL function under normal circumstances, but delivers a more general inhibitory signal only when provoked by bound MAb.
Animals↗
Different inducibility and possible significance of several concomitant "fragile sites" in two brothers.
Concomitance of four fragile sites (at 16p13, 16q22, 16q23, Yq12) in the lymphocyte cultures of two brothers is reported. The expression of each of these fragile sites was enhanced (or induced) by different culture conditions. Some of the inducing conditions are already known and others are reported here for the first time. The meaning of the fragile sites is discussed and a possible viral etiology suggested. Concomitance of some of them may be a potential causal factor for deletions, translocations, or inversions.
Chromosome Fragile Sites↗
Hepatotoxicity of the synthetic oestrogen hexoestrol in the female rat.
The synthetic oestrogen hexoestol is hepatotoxic to the female rat. Twenty-five animals were treated daily with hexoestrol at a dose of 60 mg/kg. Twenty-five more acted as controls. Five animals from each group were killed after 4, 12, 20, 30 and 40 days of treatment to permit serial evaluations of liver histopathology to complement serum biochemical investigations. There were no mortalities during the study and only modest external signs of toxicity. All the treated rats showed reductions in body weight and appetite and gains in liver weight. This latter effect was due to both cellular hypertrophy and hyperplasia. The principle finding of the liver histopathology was fatty change. This affected scattered individual cells, mainly in the midzonal region. All of the serum parameters of toxicity--which consisted of bilirubin, total protein, albumin, glycoprotein, alpha 2-macrofoetoprotein, and alkaline phosphatase--indicated liver impairment. Most of these also showed time-related changes consistent with an initial phase up to Day 20 of marked liver dysfunction superseded by a more adaptive phase thereafter. The hepatotoxicity described here seems sufficient to explain blood clotting defects observed elsewhere in oestrogen-treated rats.
Alkaline Phosphatase↗
Familial fragile site found at the cancer breakpoint (1)(q32). Inducibility by distamycin A, concomitance with fragile (16)(q22).
A normal baby was cytogenetically examined immediately after birth for the possible presence of a fragile (16)(q22), which had been found in her mother and in her retarded sister with a 46,XX;46,XX,del(16)(q22) mosaic karyotype. Distamycin A was added to the cultures to enhance the fragile (16)(q22) expression. The response of the baby to the action of distamycin A in vitro was much greater than that of her family members. A fragile (16)(q22) was induced in many cells as well as a fragile (1)(q32), which was also found in her mother. This fragile site, which is known to be a cancer breakpoint, has not been reported so far either to be familial or to be inducible by distamycin A. The concomitance of fragile (1)(q32) with fragile (16)(q22) and their possible significance are considered.
Cells, Cultured↗
Lactate dehydrogenase and alkaline phosphatase isoenzymes and protein-bound sialic acid in regenerating rat liver.
Lactate dehydrogenase (LDH) and alkaline phosphatase (AP) isoenzyme patterns and protein-bound sialic acid content were compared between normal, regenerating rat liver 10 days after partial hepatectomy and fetal rat liver. For this purpose, liver from ten adult rats and two pools of ten fetal livers each were examined. Isoenzymes were separated by electrophoresis on cellulose acetate and their percent distribution calculated after quantitation by densitometry of the bands. LDH-5 and LDH-4 combined represented in all the tissues examined 90%-94% of the total activity. LDH-5/LDH-4 ratios were nearly equivalent in the normal and regenerated liver (7.14, 6.41), but substantially lower in fetal liver (2.50). Two bands of AP were visualized in electropherograms. AP-1/AP-2 ratio was lower in regenerated liver (1.57) as compared to normal liver (2.27) and still lower in fetal liver (1.06). Protein-bound sialic acid was, on protein basis, slightly but not significantly higher in regenerated liver (1.71 microgram/mg protein) than in normal liver (1.43), and significantly higher in fetal liver (1.87). The relatively small differences in isoenzyme patterns and in protein-bound sialic acid between regenerated and normal liver as compared to those between fetal and normal tissue add support to the view that the cells in regenerated liver are not of embryonic origin.
Alkaline Phosphatase↗
A procedure for handling complaints against general practitioners.
Patient dissatisfaction with the care they receive in general practice is sometimes expressed as a formal complaint. We report our experience with an hierarchical complaints procedure. The annual rate of complaints received by the area medical director of a local health centre serving 11 500 patients was 100 per 10 000 registered patients. The medical officer for the region (regional population 160 000) received 4 complaints per 10 000 patients. The regional Public Complaints Committee received 0.1 complaint per 10 000 patients per year and the Israeli National Health Service Ombudsman received 0.2 complaints per 10 000 patients per year from the same region. Almost all dissatisfaction relating to style of practice was dealt with at the local level, while complaints relating to matters of substance or ethics quickly reached the higher authorities. The complaints procedure was thus shown to distinguish between temporary breakdowns of the doctor-patient relationship and inadequacies of the system of care and to handle the relevant complaints appropriately.
Adult↗
Declination has not been defeated.
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Humans↗
Serum lipoproteins in Israeli "Bnei Israel" Indians.
Serum lipoprotein concentrations differ markedly in the various ethnic groups which compose Israel's immigrant population. A group of subjects belonging to a community of "Bnei Israel" Indians, consisting of 21 women and 16 men between the ages of 30 and 60 years, was studied 10 years after immigration. The women had lipoprotein levels comparable with the Israeli-born population. The men had significantly lower mean cholesterol levels and significantly higher HDL/total cholesterol ratios and a tendency for lower triglycerides than an age-matched Israeli-born group, and a higher HDL/LDL cholesterol ratio than the women of the same origin. These results are consistent with the observed low incidence of coronary heart disease in Israeli Bnei Israel men who appear to have a "healthier" lipoprotein profile than the women in this community.
Adult↗
Phospholipids chiral at phosphorus. Use of chiral thiophosphatidylcholine to study the metal-binding properties of bee venom phospholipase A2.
It has been shown recently by 31P nuclear magnetic resonance (NMR) that phospholipase A2 (PL A2) from bee venom shows a high degree of stereoselectivity toward the "isomer B" of 1,2-dipalmitoyl-sn-glycero-3-thiophosphocholine (DPPsC) [Bruzik, K., Jiang, R.-T., & Tsai, M.-D. (1983) Biochemistry 22, 2478-2486]. We now report a quantitative kinetic study of PL A2 using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and (RP)-, (SP)-, and (RP + SP)-DPPsC by a spectrophotometric assay. The substrates were mixed with Triton X-100 to form mixed micelles, and steady-state kinetic theories were applied. The enzyme was activated by Ca2+, which induced a conformational change of the enzyme, as shown by UV difference spectra. The apparent dissociation constant of Ca2+/PL A2 is 2.5 mM. In the presence of Ca2+, large substrate specificity and stereospecificity in Vmax (in mumol min-1 mg-1) were observed: DPPC, 1850; (RP)-DPPsC, 7.6; (RP + SP)-DPPsC, 64; (SP)-DPPsC, 0.044. On the other hand, relatively small variation in Km was observed, which suggests that the interfacial interaction is relatively nonspecific among the substrates studied. (SP)-DPPsC and Cd2+ were shown as competitive inhibitors for the hydrolysis of DPPC by Ca2+/PL A2. Binding of Cd2+ with apo-PL A2 was also demonstrated by UV difference spectra, with a dissociation constant of 0.59 mM. Activation of apo-PL A2 by Cd2+ was unequivocally demonstrated for (SP)-DPPsC by use of 31P NMR. The Vmax values of Cd2+/PL A2 were DPPC/(RP)-DPPsC/(SP)-DPPsC = 17.6/0.069/0.0044 mumol min-1 mg-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Cytogenetic study of patients with carcinoma of the colon and rectum: particular C-band variants as possible markers for cancer proneness.
A possible involvement of chromosomal heterochromatic polymorphisms in propensity to cancer has been considered and discussed by several investigators who studied groups of patients presenting with different forms of malignancy. We report a cytogenetic study on the circulating lymphocytes of patients suffering from colorectal carcinoma, most of whom were of European origin. Significantly increased incidence of polymorphisms of chromosomes #1 and #9 was found, especially partial inversions (PI). Emphasis is given to the problem of selecting adequate controls, which must be as homogeneous as possible.
Adenocarcinoma↗
In vitro selective effect of melphalan on human T-cell populations.
In vitro treatment with 2 micrograms/2 X 10(6) cells melphalan (L-PAM: L-phenylalanine mustard) significantly decreased the total number of T lymphocytes from peripheral blood (PBL) of healthy human donors and of the OKT4 population (precursor suppressor/helper/inducer) T cells as defined by monoclonal antibodies OKT3 and OKT4, respectively. No changes in the OKT+8 lymphocyte population (cytotoxic/mature suppressor cells) were observed following the same treatment. Preincubation of PBL with L-PAM at concentrations that do not affect the rate of DNA synthesis in PHA-stimulated lymphocytes inhibited the generation of T suppressor lymphocytes by ConA, as shown by their effect on PHA stimulation. Treatment of allogeneic PBL with L-PAM had no effect on mature suppressor T cells already induced by ConA, as shown by incubation of PBL with L-PAM after incubation with ConA.
Antibodies, Monoclonal↗
The reduction of inter- and intra-observer variability for defining regions of interest in nuclear medicine.
The use of region-of-interest (ROI) techniques to quantify data obtained in radionuclide images is commonplace. However, the reproducibility of quantitation due to inter- and intra-observer variations using particular methods of deriving ROIs is often not appreciated. We examined such variations in the results obtained by four independent observers of varying experience using four methods of depicting a ROI about an organ. The set of image data consisted of renal scans with varying target-to-background ratios, and the ROI facilities included two edge-detection methods. The results indicated that, once observers were experienced with edge-detection methods, a lower inter- and intra-observer variation could be achieved, although the technique of 'shrinking' a ROI about a subjectively chosen display level was reasonably satisfactory. In terms or reproducibility, the least satisfactory method of depicting a ROI was the commonly used manually guided 'bug' around arbitrarily chosen display levels representing the boundary of an organ.
Humans↗
The mouse spot test: results with a new cross.
The fertility and sensitivity of a new cross using male PDB (a/a b/b d/d p/p) and non-agouti female NMRI (a/a c/c) mice have been assessed. This cross results in embryos which are heterozygous at the same coat colour loci as are present in the embryos from the classical TxC57Bl/6 cross, commonly used in the mammalian spot test. The fertility of this new cross reflects the good breeding performance of the NMRI females. The typical litter size at the age when the F1 are examined for coat colour mosaics is 9-10, and this, together with the high pregnancy rate, results in substantial economies in the number of treated animals. The sensitivity of the cross to treatment with ethylnitrosourea, procarbazine, isoniazid, cyclophosphamide and 4-nitroquinoline oxide has been shown to compare well with other published results. If further evaluation of this cross confirms these preliminary results, then the cross can be used to reduce numbers of experimental animals without loss of sensitivity.
4-Nitroquinoline-1-oxide↗
Cloning and expression of the metE gene in Escherichia coli.
A lambda-transducing phage was isolated that contains the metE gene. This gene codes for N5-methyl-H4-folate:homocysteine methyltransferase (EC 2.1.1.14), an enzyme that catalyzes the terminal reaction in methionine biosynthesis. A 9.1-kb EcoR1 fragment of this phage, containing the metE gene, was then cloned into pBR325. This plasmid, pJ19, was used to transform Escherichia coli strain 2276, a metE mutant, and restore the MetE+ phenotype. Although the transformed cells produced large amounts of the metE protein in vivo, in vitro studies using pJ19 as template showed low synthesis of the metE protein.
Bacteriophage lambda↗
On the meaning of fragile sites in cancer risk and development.
In the last few years, there has been increasing concern about the possible involvement of fragile sites in cancer risk and development. Patients with malignancies and family histories of cancer who presented with constitutional fragile sites are reported here. These findings are discussed with regard to the familial risk for cancer and the tissue specificity of the malignancy in relation to the different fragile sites. The hypothesis is advanced that these may be sites of viral DNA modification, probably representing areas where genes that are important for the metabolism of the virus are located. On the other hand, these genes may well be cellular (proto)oncogenes. We believe that fragile sites may increase the risk for cancer, not by being break-prone points at oncogene locations, but through more complex mechanisms that are not easy to predict.
Chromosome Banding↗
Concomitance of urogenital with lymphoid and intestinal malignancies: more than a coincidence.
Concomitance of different primary malignant neoplasms in the same individual has been observed and explained by several possible mechanisms. For urogenital malignancies in concomitance with lymphoid or with intestinal malignancies some data indicate that common etiologic factor(s) with pleiotropic effects may be involved. Concomitance of these particular different primary malignant neoplasms must therefore be kept in mind in the evaluation of patients' conditions.
Aged↗
X-ray microanalysis of normal human neutrophils, lymphocytes, monocytes and platelets.
Elemental X-ray microanalysis of normal peripheral blood neutrophils, lymphocytes, monocytes and platelets was carried out with a scanning electron microscope fitted with an X-ray analytical system. Each cell type was characterized by its own spectrum. Nucleus containing cells displayed a high phosphorus level, while platelets showed a low peak of this element. The elevated level of sulfur observed in platelets, neutrophils and monocytes may result from their cytoplasmic granules which contain sulfur-rich substances. The highest amount of calcium was detected in the platelets. The results indicate that X-ray microanalysis may be applied for the detection of the elemental content of blood cells.
Blood Platelets↗