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Biomedical subjects

J Hald

Publications and source records attributed to J Hald.

At least 19 recordsLinked to original sources
PubMed2000

Control of endodermal endocrine development by Hes-1.

Development of endocrine cells in the endoderm involves Atonal and Achaete/Scute-related basic helix-loop-helix (bHLH) proteins. These proteins also serve as neuronal determination and differentiation factors, and are antagonized by the Notch pathway partly acting through Hairy and Enhancer-of-split (HES)-type proteins. Here we show that mice deficient in Hes1 (encoding Hes-1) display severe pancreatic hypoplasia caused by depletion of pancreatic epithelial precursors due to accelerated differentiation of post-mitotic endocrine cells expressing glucagon. Moreover, upregulation of several bHLH components is associated with precocious and excessive differentiation of multiple endocrine cell types in the developing stomach and gut, showing that Hes-1 operates as a general negative regulator of endodermal endocrine differentiation.

Amino Acid Sequence↗
PubMed1996

Spontaneous human squamous cell carcinomas are killed by a human cytotoxic T lymphocyte clone recognizing a wild-type p53-derived peptide.

A cytotoxic T lymphocyte (CTL) clone generated in vitro from the peripheral blood of a healthy HLA-A2-positive individual against a synthetic p53 protein-derived wild-type peptide (L9V) was shown to kill squamous carcinoma cell lines derived from two head and neck carcinomas, which expressed mutant p53 genes, in a L9V/HLA-A2 specific and restricted fashion. Thus, the normal tolerance against endogenously processed p53 protein-derived self-epitopes can be broken by peptide-specific in vitro priming. p53 protein-derived wild-type peptides might thus represent tumor associated target molecules for immunotherapeutical approaches.

Carcinoma, Squamous Cell↗
PubMed1995

Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck.

Tumour-infiltrating lymphocytes (TIL) and tumours from six patients with squamous cell carcinomas of the head and neck (SCCHN) were investigated. The six tumours all expressed major histocompatibility complex (MHC) class I antigens both in vivo and as tumor cell lines grown in vitro. In addition, the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+ and CD8+ T cells, but generally contained few CD56+CD3- cells of the natural killer (NK) phenotype. CD8+ T cells dominated the individual TIL cultures from five of the six patients and showed significant autologous tumour cell lysis. In TIL cultures derived from four of these tumour-reactive TIL cultures, killing could be partially blocked by an anti-MHC class I mAb. TIL cultures reacting with autologous tumour cells also showed strong TCR/CD3-redirected cytotoxicity when assayed against hybridoma cells expressing anti-TCR/CD3 mAb as well as natural-killer(NK)-like activity. A number of TIL cultures devoid of autologous tumour cell lysis were capable of lysing the natural-killer(NK)-sensitive K562 cell line suggesting that the SCCHN cells themselves are resistant to NK-like lysis. In conclusion, TIL cultures from head and neck carcinomas contain T cells which, upon expansion in vitro, can lyse autologous tumour cells in a MHC-class-I-restricted fashion. Thus, the results of the present study document that carcinomas of the head and neck in some patients are infiltrated by cytotoxic T cell precursors potentially capable of rejecting the autologous tumour.

Adult↗
PubMed1994

In vivo infiltration of mononuclear cells in squamous cell carcinoma of the head and neck correlates with the ability to expand tumour-infiltrating T cells in vitro and with the expression of MHC class I antigens on tumour cells.

A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well with their ability to expand in vitro in the presence of high-dose interleukin-2 (2000 U/ml). High MHC class I antigen expression on tumour cells was found to be positively correlated with p53 overexpression, suggesting that p53-derived peptides, wild-type or mutated ones, presented by MHC class I antigens, are potential targets for MHC-restricted cytotoxic T cells in head and neck squamous cell carcinomas. However, lack of correlation between peritumoural T cell infiltration in vivo and T cell expansion in vitro, on the one hand, and p53 overexpression on tumour cells, on the other hand, suggests absence of p53-peptide-specific T cells in the patients. Eight out of ten expanded tumour-infiltrating lymphocyte (TIL) cultures showed T-cell-mediated cytotoxicity. "Promiscuous" cytotoxic T cell activity against the natural-killer-cell-sensitive K562 target cell line was observed in three out of ten TIL expansion cultures.

Animals↗
PubMed1993

Nasopharyngeal carcinoma in an HIV-positive patient causing severe morbidity and early death.

A nasopharyngeal carcinoma was the first event in an otherwise symptom free HIV person. No reports of simultaneous nasopharyngeal carcinoma and HIV infection are known to us. A 46-year-homosexual man was admitted to the ENT department with a three week history of pain in the throat referred to the left ear. He was found to have an irregular tumour in the nasopharynx with a lymph node metastasis to the left side of the neck. The poor response to radiotherapy and the very aggressive progress after treatment raised suspicion of a co-existing disease process. The risk of sexually transmitted HIV was confirmed post mortem and could explain the rapid progression of the tumour. No anti-HIV treatment was given concurrently with radiotherapy.

Carcinoma, Squamous Cell↗
PubMed1991

Human temporal bone findings in acquired hypothyroidism.

Histological studies of the auditory organ in patients with acquired hypothyroidism are scarce. Thus the aim of the present study was to examine the temporal bones and the brain in subjects with hypothyroidism. Four temporal bones and two brains from clinically and biochemically hypothyroid subjects were removed and evaluated by light microscopy determine to the morphological changes and deposition of neutral and acid glycosaminoglycans. An audiogram from one of the patients showed a sensorineural hearing loss, which could be ascribed to occupational noise exposure. The study revealed histological changes compatible with age and infectious disease. No accumulation of neutral or acid glycosaminoglycans could be demonstrated in the temporal bones, or in the brains.

Adipose Tissue↗
PubMed1987

Autoantibodies against spermatozoal antigens detected by immunoblotting and agglutination. A longitudinal study of vasectomized males.

Sera taken pre- and post-operatively at regular intervals within a year from 16 men undergoing vasectomy were analysed for autoantibodies against spermatozoal proteins by immunoblotting. The reaction patterns were compared with the results of sperm agglutination tests. Immunoblotting revealed the presence of autoantibodies against various spermatozoal polypeptides in all sera taken pre-operatively and post-operatively. On average, seven polypeptides showed reaction. During the post-operative period two patients developed spermatozoal agglutinins in moderate titers (greater than 16) but in immunoblotting no change in band reactivity was observed for these two patients. However, scanning of the immunoblotting results revealed that one of the patients, although without sperm agglutinins, during the post-operative period showed an increasing band colouring of a polypeptide of Mr 31,500, reflecting an increased level of the corresponding antibodies.

Adult↗
PubMed1983

Barium peritonitis. Experience of five pediatric cases.

Barium peritonitis secondary to perforation of the gut is an infrequent complication of radiological G-I tract examinations. It is thought to imply a high mortality rate. However, this conception seems to be based on data obtained during the early 1950's. More recent case reports and small series indicate a more favourable prognosis depending on effective antibiotics and successful maintenance of severely ill patients. The scant information concerning the fate of pediatric cases warranted presentation of the experience of 5 patients, who all survived. Our approach to treatment and the suggested use of barium studies, in particular barium enema, in obscure abdominal emergency cases are offered.

Administration, Oral↗
PubMed1982

Lack of effect of indomethacin on ordered growth of the femur in rats.

The effect of indomethacin on ordered growth in length and width of the femur was studied in 48 adolescent rats given 2 mg/kg/day of the drug, a regimen previously shown to inhibit fracture healing. The animals were given either indomethacin suspension, or the vehicle alone, orally for 6 weeks. All the animals tolerated the treatment well. During drug treatment the femur distal to the intertrochanteric crest grew about 7 mm in length. Indomethacin plasma levels were about 1 microgram/ml in the indomethacin-treated animals. Indomethacin did not inhibit ordered growth in either length or width. This indicates that indomethacin does not inhibit the normal homeostasis of the skeletal system in adolescent rats.

Animals↗