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Biomedical subjects

I Halbrecht

Publications and source records attributed to I Halbrecht.

At least 37 records · Page 2Linked to original sources

Sialic acid content and sialyltransferase activity in lymphocytes from neonates.

Venous blood from 24 healthy volunteers, 20-40 years old, and umbilical cord blood from 28 healthy full-term neonates, immediately after delivery, was used for the determination of lymphocyte sialic acid content and sialyltransferase activity. A significantly increased content of lymphocyte sialic acid and an increased sialyltransferase activity were observed in neonates as compared to adults. It is suggested that the increased sialic acid content of fetal lymphocytes may contribute to a possible masking effect of antigenic sites on fetal immunocompetent cells.

Adult↗

Primary tissue cultures of benign and malignant human thyroid tumors: effect of TSH.

Many thyroid carcinomas seem to be dependent upon the thyroid growth-promoting properties of the thyroid stimulating hormone (TSH). The purpose of the present investigation was to compare the in vitro effect of TSH on tissue cultures derived from malignant and benign thyroid tumors. The results indicate that TSH can affect the morphology and protein synthesis of primary tissue cultures derived from benign and malignant thyroid tumors differently. The addition of TSH to cultures derived from benign tumors resulted in a reorganization of follicle-like structures of the monolayer and in a reduction of protein synthesis. In contrast to this, monolayers derived from carcinomas of the thyroid were not able to reorganize and their protein synthesis was not inhibited in the presence of TSH. For a better understanding of TSH suppressive therapy, we suggest testing the influence of TSH on a large number of tissue cultures derived from benign and malignant tumors of the thyroid.

Culture Techniques↗

Alpha-interferon and fragility at 16q22. A study on 15 selected controls and 146 selected patients.

Inducibility or enhancement of fragility at 16q22 by alpha-interferon has been found in a Danish laboratory and in our laboratory. Several other studies were not able to confirm these findings. We present the results of a large study on peripheral blood lymphocytes of 15 selected controls and 146 selected patients treated in vitro by alpha-interferon. In some of our patients parallel studies with distamycin A were performed. Both interferon and distamycin A induced the same fragility, but only in some patients. Both agents were not consistently able to enhance a spontaneously expressed 16q22 fragility. 16q22 is the location of the metallothionein genes, whose transcription is induced by interferon. The induction of the metallothionein gene transcription and the 16q22 fragility, however, do not seem to be directly related. To explain our findings we advance the hypothesis that fragility at 16q22 may be a modification induced by virus(es) with selective tropism for cells which are differently influenced by a pleiotropic action of interferon.

Chromosome Fragility↗

Differences in sensitivity to melphalan between con A-activated and nonactivated human T-cell subsets.

In vitro treatment with melphalan (L-PAM, L-phenylalanine mustard), 2 micrograms/2 X 10(6) cells, significantly decreased the total number of E-rosette-positive (E+) T lymphocytes from peripheral blood (PBL) of healthy human donors as well as those of the OKT4 (precursor suppressor/helper/inducer T cells) and OKT17 populations (suppressor cells within the OKT4 subset). The OKT8 population (cytotoxic/mature suppressor cells) was not affected by a similar L-PAM treatment. The sensitivity of concanavalin A (Con A)-activated E+ T-cell populations to subsequent L-PAM treatment in vitro was different from that of Con A-untreated T cells: Thus, L-PAM treatment did not affect the expression of OKT3 and OKT4 antigens, increased the percentage of OKT17 cells, and inhibited the expression of OKT8 antigen. Depletion of OKT8 from Con A-activated E+ T cells (OKT4+-OKT8(-)-OKT17+) did not affect their suppressive activity on PHA stimulation in L-PAM-treated as well as untreated cells. Further depletion of OKT17+ cells from the OKT4+-OKT8(-)-OKT17+ subset (OKT4+-OKT8(-)-OKT17-) abolished the suppressive effect on PHA stimulation. Suppressive activity of the OKT4+-OKT8(-)-OKT17- subset was again evident after treatment of this population with L-PAM. The results obtained indicate that the sensitivity to L-PAM treatment of various T-cell phenotypes is changed by Con A activation and that after depletion of specific T suppressor cells L-PAM seems affect the immunoregulatory circuit within the Con A-activated OKT4 subset.

Antigens, Surface↗

Inversion (16)(p13q22) in tumor cells of sigmoid colon.

We report on the cytogenetic findings in direct preparations of two tumors of the sigmoid colon. Respectively, they had a near-triploid and a near-tetraploid constitution and relative numerical and other inconstant chromosomal imbalances. The only constant chromosomal structural anomaly apparently was inversion of chromosome #16, inv(16)(p13q22), which was found in all the cells examined. This rearrangement has been found to be associated with a type of acute myelomonocytic leukemia type M4. We suggest that an etiologic clastogenic (and oncogenic) agent responsible for this rearrangement may eventually be the cause of various kinds of malignancy.

Adenocarcinoma↗

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↗

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↗

The immunomodulating effect of theophylline on lymphocytes from chronic lymphocytic leukemia patients.

The in vitro immunomodulating effects of theophylline on E-rosette formation, phytohemagglutinin (PHA) response, and Ig surface receptors of B lymphocytes were studied on fresh as well as on preincubated lymphocytes from patients with B cell chronic lymphocytic leukemia (CLL). In 11 out of 14 CLL patients, 24 hours preincubation at 37 degrees C significantly enhanced E-rosette formation. Subsequent treatment of preincubated cells with appropriate concentrations of theophylline further enhanced E-rosette formation in 11 cases. On fresh lymphocytes the enhancing effect of theophylline on E-rosette formation was not significant. The same was true for PHA stimulation; in 5 out of 7 cases the mitogen enhanced the stimulating effect of preincubation and had no significant effect on fresh lymphocytes from CLL patients. Preincubation significantly reduced the percentage of surface immunoglobulin positive B cells from CLL patients in all cases studied, and theophylline treatment had an additional effect on this phenomenon. No such effect of theophylline on fresh B cells from CLL patients could be observed. Preincubation had no significant effect on control lymphocytes. The effect of theophylline on control lymphocytes as compared to lymphocytes from CLL patients was completely different for T as well as for B lymphocytes. E-rosette formation from control lymphocytes (fresh and preincubated) was significantly inhibited in the presence of theophylline. No significantly enhanced responsiveness to PHA could be observed after treatment of fresh or preincubated lymphocytes with theophylline. Preincubation and theophylline treatment had no significant effect on the percentage of Ig positive B cells from control lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

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↗

Prostaglandin E2 and cyclic nucleotides in plasma and urine of colonic cancer patients.

Prostaglandin E2 and cyclic nucleotide levels were measured in plasma and urine of 14 patients with colonic cancer. The measurements were performed 1 day before and 8 days after the removal of the tumor by operation. There was no difference between the plasma PGE2 levels (in form of the 13, 14-dihydro-15-keto metabolite) before and after the operation, but they were significantly higher than the level of a control group. No differences before and after operation were found between plasma cyclic AMP (cAMP) levels, plasma cyclic GMP (cGMP) levels, urinary cAMP levels and urinary cGMP levels. All the cyclic nucleotide concentrations were within the normal range. No correlation could be found between the stage of the tumor spread and any of the substances analyzed. The conclusions are that plasma PGE2 and plasma and urinary cyclic nucleotides do not originate from the colonic tumor tissue, and that these substances cannot be used as tumor markers.

Adenocarcinoma↗

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↗

Familial syndrome with some features of the Langer-Giedion syndrome, and paracentric inversion of chromosome 8, inv 8 (q11.23----q21.1).

A family is reported with an autosomal dominant inherited syndrome presenting some of the typical features of the tricho-rhino-phalangeal syndrome type II (TRP II) or Langer-Giedion syndrome. The critical region for the expression of the syndrome seems to be at band 8q24.1. In the affected members of the family reported here, anomaly of chromosome 8 was noted, involving however the proximal part of the 8 long arm, which was interpreted as a paracentric inversion. Whether the anomaly is causally or only casually related to the syndrome is a matter of discussion.

Adolescent↗

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↗

Sialic acid in newborn and maternal lymphocytes: preterm deliveries.

Sialic acid was determined in newborn and maternal lymphocytes immediately after preterm deliveries of 34 and 35 weeks of gestation. The results were compared with those found in full-term deliveries. In contrast with full-term deliveries, in preterm deliveries a significant increase in sialic acid in maternal as compared to newborn lymphocytes was found. However, the mean cumulative value of sialic acid for maternal and newborn lymphocytes was similar in both groups. In addition to this, sialic acid concentrations seem to be sex-dependent and higher mean cumulative values for maternal and newborn lymphocytes could be found for male as compared to female newborns after full- as well as after preterm deliveries.

Female↗

Synergistic effect of N-acetyl-D-glucosamine (NAG) on mitogenic, antigenic and allogeneic stimulation of normal human lymphocytes.

The effect of N-acetyl-D-glucosamine (NAG) on in vitro stimulated human peripheral blood lymphocytes was investigated. NAG was added to lymphocyte cultures stimulated by the mitogen PHA, the antigen PPD or to one-way-stimulated mixed lymphocyte cultures from unrelated donors. The results indicate that NAG (1-2 micrograms/ml) in appropriate experimental conditions has an enhancing effect on DNA and protein synthesis induced by PHA, PPD and allogeneic cells. Addition of NAG (1-2 micrograms/ml) to unstimulated lymphocyte cultures had no effect on DNA or protein synthesis.

Acetylglucosamine↗