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H Stark

Publications and source records attributed to H Stark.

At least 127 records · Page 7Linked to original sources
PubMed1995

Azines and diazines as potential histamine H3-receptor antagonists.

In search of structure-activity relationships among histamine H3-receptor antagonists the imidazole ring of known H3-receptor antagonists was replaced by different heteroaromatic ring systems. Thus, azines and diazines with ether (6-13) and carbamate (15-24) moieties as functional groups were synthesized. The obtained compounds did not show significant H3-receptor antagonist activity in vitro (rat brain cortex) or in vivo (mice brain). The new compounds were also screened for H1-receptor antagonist activity on the isolated guinea-pig ileum and for H2-receptor antagonist activity on the isolated spontaneously beating guinea-pig right atrium. The substances showed only weak antagonistic activity at both histamine receptors, H1 and H2.

Animals↗
PubMed1995

Unilateral hematometrocolpos associated with double uterus.

The case of twelve year old girl with double uterus, unilateral vaginal obstruction and ipsilateral renal agenesis is described. Excision of the imperforate vaginal septum resulted in drainage of the hematometrosalpingocolpos and complete disappearance of the large pelvic-abdominal mass. Such a mass in normally menstruating women may detract from the true diagnosis. Awareness of this relatively rare condition is the mainstay of prompt diagnosis which will prevent unnecessary and destructive surgery.

Child↗
PubMed1994

CD44 variant isoforms are preferentially expressed in basal epithelial of non-malignant human fetal and adult tissues.

CD44 is a transmembrane glycoprotein, which can exist in a multitude of isoforms due to alternative splicing of the pre-mRNA. We have generated monoclonal antibodies to several of these variant regions, which are encoded by 10 additional exons in the extracellular part of the molecule. CD44 variant isoforms have been reported to be involved in the malignant progression of rat and human tumours. The precise localization of CD44 variant isoforms in normal developmental and morphogenetic processes is essential for diagnostic studies of human tumorigenesis. Therefore, we have analysed a large number of different human tissues by immunohistochemistry for the expression of CD44 isoforms containing either exons 4v, 6v or 9v. Expression of exon 9v-isoforms was detected in almost all epithelia analysed, with a few exceptions. Exon 6v isoforms are expressed only in squamous and glandular epithelial, e.g. skin epidermis, sweat and sebaceous glands, oesophagus, ducts of the mammary gland, salivary and prostate glands. Detection of exon 4v-encoded isoforms was restricted to the epidermis and the oesophagus. Similar tissue distributions of CD44 variant isoforms were observed in 10-week-old fetal tissues. Since one of the ligands of CD44 is hyaluronic acid (HA), we also analysed the tissue distribution of HA synthetase. HA synthetase was detected in all tissues analysed, showing good correlation with the expression of the standard form of CD44, CD44s.

Adult↗
PubMed1994

Alpha 6 integrin distribution in human embryonic and adult tissues.

Alpha 6 integrin is an adhesion molecule that connects cells with extracellular matrix molecules of the laminin family. The laminin interaction seems to be essential for cell differentiation during embryogenesis and for the subsequent maintenance of tissue integrity in the adult. Alpha 6 integrin can also interact with laminin-independent cellular ligands and in this way plays a role in homing of leucocytes. Furthermore, in cancer biology alpha 6 integrin has an important role in metastasis and as a possible new prognostic factor; exact knowledge of alpha 6 integrin distribution in normal human tissues is therefore a crucial element. By immuno-histochemical methods we have screened alpha 6 integrin expression of representative human tissues from the adult and the embryonic organism. All tested epithelia were alpha 6 integrin positive, except for the endocrine cells of the pancreas and the adrenal glands. Heterogeneous staining was found on non-epithelial tissues. Strong staining was evident in peripheral nerves (Schwann cells), germ and Sertoli cells, endothelia, and smooth muscle cells of the myometrium. Weak staining was found in nerve cells of the stratum granulosum, the microglia, Kupffer's cells and stromal cells of the ovary. All fibroblasts, striated muscle cells and astrocytes were negative. The tissue distribution of alpha 6 integrin and the semi-quantitative estimation of their expression level should provide a better understanding of alpha 6 integrin function under normal and pathological conditions, in particular in tumour progression.

Adult↗
PubMed1994

Expression and modulation of CD44 variant isoforms in humans.

CD44 is a ubiquitous surface molecule that exists as a number of isoforms, generated by alternative splicing of 10 "variant" exons. Little is known about the expression and function of the variant isoforms, except that certain isoforms may play a role in cancer metastasis. We produced mAbs against CD44 variant regions encoded by exons 4v, 6v, and 9v, by immunizing mice with a fusion protein spanning variant exons 3v to 10v. A comprehensive analysis of human tissues revealed that CD44 variant isoforms were expressed widely throughout the body, principally by epithelial cells. However there was differential expression of CD44 variant exons by different epithelia. Most epithelia expressed exon 9v, but much fewer expressed 6v or 4v. The regions of epithelia that expressed the highest levels of the variant isoforms were the generative cells, particularly the basal cells of stratified squamous epithelium, and of glandular epithelium. CD44 variant isoforms were also expressed differentially by leukocytes, with CD44-9v expressed at very low levels and CD44-6v and 4v virtually absent. However, CD44-9v and CD44-6v were the main variants that were transiently upregulated on T cells after mitogenic stimulation and on myelomonocytic cell lines by TNF alpha and IFN gamma treatment. Some epithelial cell lines could preferentially upregulate CD44-6v upon IFN gamma incubation. These results show that CD44 variant isoforms are expressed much more widely than first appreciated, and that expression of the variant isoforms on some cell types can be modulated by particular cytokines.

Amino Acid Sequence↗
PubMed1994

Novel histamine H3 receptor antagonists: affinities in an H3 receptor binding assay and potencies in two functional H3 receptor models.

1. We determined the affinities of ten novel H3 receptor antagonists in an H3 receptor binding assay and their potencies in two functional H3 receptor models. The novel compounds differ from histamine in that the aminoethyl side chain is replaced by a propyl or butyl chain linked to a polar group (amide, thioamide, ester, guanidine, guanidine ester or urea) which, in turn, is connected to a hexocyclic ring or to an alicyclic ring-containing alkyl residue [corrected]. 2. The specific binding of [3H]-N alpha-methylhistamine to rat brain cortex membranes was monophasically displaced by each of the ten compounds at pKi values ranging from 7.56 to 8.68. 3. Inhibition by histamine of the electrically evoked tritium overflow from mouse brain cortex slices preincubated with [3H]-noradrenaline was antagonized by the ten compounds and the concentration-response curve was shifted to the right with apparent pA2 values ranging from 7.07 to 9.20. 4. The electrically induced contraction in guinea-pig ileum strips (which was abolished by atropine) was inhibited by the H3 receptor agonists R-(-)-alpha-methylhistamine (pEC50 7.76), N alpha-methylhistamine (7.90) and imetit (8.18). The concentration-response curve of R-(-)-alpha-methylhistamine was shifted to the right by thioperamide (apparent pA2 8.79) and by the ten novel compounds (range of pA2 values 6.64-8.81). 5. The affinities and potencies were compared by linear regression analysis. This analysis was extended to thioperamide, the standard H3 receptor antagonist, which is also capable of differentiating between H3A and H3B sites. Comparison of the apparent pA2 values in the two functional H3 receptor models yielded a regression coefficient of 0.77 (P<0.02). When the pA2 of the drugs in the mouse brain cortex were compared to the pXj for H3 sites (ten novel compounds) and for H3A sites (thioperamide), a significant correlation (r = 0.87; P<0.001) was obtained. There was, however, no significant correlation when the pKi of thioperamide for H3B sites was used instead (r = 0.52). In a similar manner, comparison of the pA2 in the guinea-pig ileum with the pKi in the binding assay yielded a significant correlation(r = 0.70, P <0.05) only when the pKi of thioperamide for H3A sites was used but not when its pKi forH3B sites was considered (r = 0.17, NS).6 On the basis of these results, structure-activity relationships for the novel H3 receptor antagonists,and the nature of the H3 receptors in the guinea-pig ileum and mouse brain, are considered.

Animals↗
PubMed1994

[125I]iodoproxyfan, a new antagonist to label and visualize cerebral histamine H3 receptors.

Iodoproxyfan, i.e., 3-(1H-imidazol-4-yl)propyl-(4-iodophenyl)-methyl ether, is a novel potent and selective histamine H3 receptor antagonist. [125I]Iodoproxyfan binding to membranes of the rat striatum was reversible and saturable. Specific binding defined with 1 microM (R)-alpha-methylhistamine corresponded to 65% of the total at 30 pM. Scatchard analysis indicated a Kd of 65 pM and maximal binding capacity of 78 fmol/mg of protein. The specificity of [125I]Iodoproxyfan binding to H3 receptors was demonstrated by its pharmacological profile. A series of H3 receptor agonists inhibited [125I]iodoproxyfan binding with a similar maximal effect and with the expected order of potency and stereoselectivity ratio. H3 receptor antagonists inhibited the specific binding with the expected Ki values. In the presence of guanylnucleotides, 40% of sites exhibited a approximately 40-fold lower affinity for histamine, indicating that the H3 receptor belongs to the superfamily of G protein-coupled receptors and revealing the existence of two populations of sites. Well contrasted autoradiographic pictures of total [125I]iodoproxyfan binding to sections of the rat brain were obtained in a short time and over a low nonspecific binding. The heterogenous distribution of H3 receptors with high labeling of anterior cerebral cortex, ventral striatum and other limbic areas was confirmed. In addition, a clearly distinguishable laminated pattern of labeling was evidenced in the cerebral cortex and hippocampal formation. Hence, this new probe should be useful for sensitive assay and localization of the H3 receptor.

Animals↗
PubMed1994

A trap system for the isolation of amino acid sequences inducing GPI anchor addition.

We designed a trap system to isolate different amino acid sequences which could target proteins to the cell surface via GPI anchor transfer. This selection procedure is based on the insertion of various sequences which regenerate a functional GPI anchor signal sequence and therefore provoke re-expression at the surface of a reporter molecule. Using this trap for cell surface targeting sequences, we could show the importance of the defined elements essential for GPI anchor addition. Such a system could be used for an exhaustive analysis of the carboxyl terminus structural requirements for GPI membrane anchoring.

Amino Acid Sequence↗
PubMed1993

Gaucher's disease and mesangiocapillary glomerulonephritis in childhood--a coincidence?

A 6-year-old boy, presenting with a nephritic syndrome, was diagnosed as suffering from Gaucher's disease (GD) and mesangiocapillary glomerulonephritis (MCGN). GD was suspected because of aseptic necrosis of the femoral heads on X-ray and later confirmed by bone marrow aspiration and a lack of glucocerebrosidase activity in white blood cells; MCGN was documented on renal biopsy. The child was treated with prednisone, dipyridamole and aspirin, and recovered completely clinically. A second biopsy was not performed. The connection between these two rare diseases, and between nephritis and GD in general, is discussed.

Basement Membrane↗
PubMed1993

[Occurrence of CD44 and its isoforms under orthological and pathological conditions].

Variant isoforms of CD44 have been strongly implicated in malignant transformation and cancer metastasis. To ascertain the pattern of expression of these isoforms in human normal, fetal and tumor tissues (breast carcinomas, renal cell carcinomas, malignant melanomas, colon carcinomas, non-Hodgkin-lymphomas, neuroblastomas and brain tumors), we generated monoclonal antibodies against CD44 variant regions. Monoclonal antibodies were produced against variant regions encoded by exons 4v, 6v and 9v. CD44 variant isoforms are expressed on normal epithelial cells in a different pattern. Regions of epithelia that expressed the highest levels of the variant isoforms were those with a high rate of cell division. CD44 variant isoforms were not expressed by all investigated tumors (not by malignant melanomas, brain tumors and neuroblastomas). It is interesting that the expression of CD44 isoforms in non-Hodgkins lymphomas and colon carcinomas shows possibly a correlation with malignancy.

Antibodies, Monoclonal↗
PubMed1993

[Responsible prescription of hearing aids].

A case report serves to document that sufficient cerebral circulation is mandatory for sustaining function of the brain. If impulses from the ear are not processed within the areas of the brain normally doing this, prescription of a hearing aid will not improve the capacity to perceive in a patient being hard of hearing. In these cases, one should rather examine the state of the cerebral circulation.

Aged↗
PubMed1992

Severe tubular resistance to aldosterone in a child with familial juvenile nephronophthisis.

A 9.5-year-old girl, whose early symptoms were polyuria and growth retardation, is described. During the progression of her disease, hyperkalaemia developed out of proportion to the degree of renal insufficiency. Her fractional excretion of sodium increased from 3.3% to 35%, and her fractional excretion of potassium decreased from 55% to 22%. The plasma aldosterone level and plasma renin activity (PRA) were very high--290 ng/ml and 100 ng/dl per hour, respectively (normal range for this age 2.6-20.8 ng/ml and 1.2-2.7 ng/ml per hour, respectively). In an attempt to reduce these hormone levels, an acute and sustained saline load, captopril and peritoneal dialysis were used. Only the sustained saline load normalized the PRA, and only peritoneal dialysis sufficiently suppressed the plasma aldosterone level. Successful renal transplantation normalized both plasma aldosterone and PRA. This girl presents the unusual occurrence of pseudohypoaldosteronism type I, during the course of familial juvenile nephronophthisis.

Aldosterone↗
PubMed1992

[Documentation of glaucomatous visual field defects in threshold and suprathreshold perimetry].

In contrast to normal subjects, the individual stimulus threshold for differential light sensitivity (DLS) in glaucoma patients fluctuates considerably. The sensitivity and the size of the defect are correlated: with a higher individual stimulus threshold, i.e. when sensitivity deteriorates, the number of defects decreases. Conversely, when the individual stimulus threshold drops, i.e. when sensitivity improves, the number of defects recorded increases. The trend is the same with extensive Grade 3 defects. This correlation between sensitivity and defect size means that the number and depth of individual defects change constantly, due to the fluctuation of the individual stimulus threshold. In follow-up examinations test positions with permanent defects (a defects) can be distinguished from those where defects have been detected several times, but not permanently (b defects) and, respectively, only once in 2 1/2 years (c defects). Defects must therefore be classified not only according to depth, but also according to behaviour at individual test positions. Such a classification can be accomplished by tabulating all newly numbered test positions and the defects identified there. After 5 visual field examinations the defects are then classified as a, b, or c defects. They are then identified by colour symbols and transferred to a test position chart representing a synopsis of 5 visual fields. The chart not only permits exact topographical analysis but also furnishes information on certain structural features of the glaucomatous visual field: stable nuclear areas of a defects surrounded by fluctuating peripheral defects (b defects) or concomitant c defects. After a further 1 1/2-2 years, 5 more follow-ups are summarized, classified and transferred to a follow-up test position chart. Comparison of these two test position charts furnishes information of major prognostic value.

Aged↗