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Biomedical subjects

J Huber

Publications and source records attributed to J Huber.

At least 199 records · Page 11Linked to original sources

HER-2 amplification, steroid receptors and epidermal growth factor receptor in primary breast cancer.

Amplification of HER-2 oncogene was analysed in DNAs obtained from 291 primary human mammary carcinomas. 52/291 (18%) were found to contain amplified HER-2 oncogene. Moderate amplification (2- to 5-fold) was noted in 36/291 (12%). Thirteen tumors (4.5%) had a copy number of 5 to 10. A 10- to 20-fold and greater than 20-fold amplification was observed in 2 and 1 patient, respectively. Sample sizes allowed the determination of estrogen receptor (ER) and progesterone receptor (PgR) levels in 253/291 primary breast cancers. HER-2 gene amplification was noted in 14% of ER+ patients and in 28% of ER- patients, respectively (P = 0.02). Similarly a significantly greater number of PgR- primary mammary carcinoma exhibited an amplification of the HER-2 gene compared to PgR+ cases (22% vs. 16%, P = 0.01). Although statistically not significant, tumors with HER-2 gene amplification were found to have lower levels of ER and PgR. No association of HER-2 amplification with the androgen receptor and EGF receptor was observed. Present data combine to suggest that tumor progression is more stringently controlled by the oncogene upon loss of hormone dependency. Differences found in HER-2 amplification between steroid receptor positive and negative tumors could be helpful to define a specific subset of women to whom adjuvant therapy should be directed.

Breast Neoplasms↗

Structural study of long arm fragments of laminin. Evidence for repetitive C-terminal sequences in the A-chain, not present in the B-chains.

The outer segments of the long arm of laminin have recently been shown to mediate attachment of many cell types and to stimulate neurite outgrowth. For a structural characterization of this part of the molecule we prepared, by limited elastase digestion of laminin, fragments E3 and E8, previously identified as a globular heparin-binding domain and as a 35-nm-long rod with a terminal globule, respectively. Fragment E3 is a domain adjacent to fragment E8. Both structures together comprise the complete terminal half of the long arm. Our data confirm current models, which predict that the C-terminal segments from all three chains contribute to its structure. The B chains terminate at the end of the rod like domain, while the large terminal globule is formed by A-chain structures only. In addition to fragment E3, two new fragments T1 and T2 obtained by tryptic cleavage of fragment E8 were characterized as substructures of the globular domain. Screening of a mouse cDNA library with synthetic oligonucleotides allowed isolation of an 1.8-kb cDNA clone encoding 547 C-terminal amino acids of the A chain and some 196 nucleotides of the 3'-untranslated region including a single polyadenylation site. The clone contained portions of domain T2 and the complete heparin binding domain E3 which was thus identified as the most C-terminal domain of the A chain. Sequence alignment indicated that the terminal globule is formed by homologous repeats of some 140 residues having no counterpart in the B chains.

Amino Acid Sequence↗

Acute thymus involution in infancy and childhood: a reliable marker for duration of acute illness.

To evaluate the relationship between histologic parameters and clinical data, we studied thymus histology in 234 fetuses and young children who died after a short period of acute illness. Thymus weight and volume percentages of interstitium, cortex, and medulla were significantly related to prenatal or postnatal status and age of the patient. Thymus weight was related to the duration of acute illness only in prenatal patients. The histology, categorized in five grades according to appearance of macrophages (with a starry-sky aspect) in the cortex, increase of interlobular interstitium, and lymphodepletion of the cortex, correlated significantly with the duration of acute illness and not with any other clinical parameter. This finding enables the pathologist to estimate the duration of acute disease before death.

Adolescent↗

[Serum proteins in vaginal and abdominal hysterectomy].

Postoperative changes in various acute-phase-proteins (alpha 1-antitrypsin, c-reactive protein), alpha 2-macroglobulin, haptoglobin, transferrin, c3-c4-complement and myoglobin as well as four endocrine parameters (TBG, SHBG, prolactin and cortisol) were studied in forty healthy women divided into two groups. Each group consisted of 20 women who underwent either vaginal or abdominal hysterectomy. Differences between both groups related to both operative methods, seen in determination of 2-acute-phase-proteins, alpha 1-antithrypsin, CRP and the muscle specific myoglobin where established, whereby no statistically significant differences were apparent concerning the other parameters and hormones.

Acute-Phase Proteins↗

[Serum proteins and hormones in vaginal and abdominal hysterectomy].

Postoperative changes in various acute-phase-proteins (alpha 1-Antitrypsin, c-reactive protein), alpha 2-Macroglobulin, haptoglobin, transferrin. c3-c4-complement and myoglobin as well as endocrine parameters were studied in forty healthy women in two groups. Women with malignant neoplasms were excluded. Each group consisted of 20 women who underwent either a vaginal or abdominal hysterectomy. Differences between both collectives could be seen in determinations of alpha 1-antitrypsin, CRP and myoglobin, where decreases were significantly higher in the laparotomy group than in the vaginal operation group.

Acute-Phase Proteins↗

[The beta-endorphin level in climacteric women].

UNLABELLED: Hot flushes are not caused by a hypergonadotrophinemia. Peaks of gonadotrophin in the serum do not coincide with the cutaneously measured hot flushes. There is an occurrence of hot flushes in hypophysectomized women as well. GnRH and other neurotransmitters (beta-endorphin?) effect the thermoregulation. - HYPOTHESIS: During the climacteric period changes of neurotransmitters, a decrease of catecholestrogens, a decrease of alpha-2-adrenoceptor activity and the ceasing of the ovarian steroid production lead to changes of the endogenous opiate activity and thus to disturbances of the thermoregulation resulting in the occurrence of hot flushes. Low beta-endorphin levels in the peripheral plasma, which increase again after a treatment with estrogens, are found during the climacteric period. On the other hand women with severe hot flushes as an expression of a stress event show enormously increased beta-endorphin values, which normalize again after a hormone substitution therapy, effected by still unknown neuroendocrinological feedback mechanisms.

Climacteric↗

Pharmacokinetics of cyproterone acetate and its main metabolite 15 beta-hydroxy-cyproterone acetate in young healthy women.

Cyproterone acetate (CPA) and 15 beta-hydroxy-cyproterone acetate (15 beta-OH-CPA) have been quantitated in human plasma by a selective, automated HPLC assay in 8 young female subjects. Subjects received a single oral dose of 100 mg CPA and four weeks later, a single intramuscular dose of 300 mg CPA. Plasma levels in seven subjects could be evaluated pharmacokinetically. After intramuscular administration maximum CPA serum levels of 191 +/- 49 ng/ml were reached between 2 and 3 days. Postmaximal levels declined with a half-life of 4.3 +/- 0.7 days. After oral administration maximal serum levels of 255 +/- 110 ng/ml were measured between 2 and 3 h. CPA levels decayed biphasically with a terminal half-life of 3.6 +/- 1.3 days. Bioavailability after oral administration was nearly complete (88 +/- 20%). Metabolite levels were below CPA levels until 4 days (i.m.) and 6 h (p.o.) and exceeded CPA levels later on. 15 beta-OH-CPA levels declined with half-lives similar to those of corresponding CPA levels, indicating that terminal half-life of the metabolite in serum reflects its rate of formation rather than its rate of elimination. Areas under the metabolite serum level curves after intramuscular and oral administration were 10 to 15% higher than the corresponding areas for unchanged CPA. Since CPA and 15 beta-OH-CPA contribute to the antiandrogenetic efficacy there is good reason to assume that the intramuscular administration of CPA might be equally effective in the therapeutical use as the oral administration.

Administration, Oral↗

[Phospholipase A2 levels during labor].

Determinations of phospholipase A2 activity 2 hours after spontaneous start of uterine contractions in 14 women showed higher values than immediately post partum. The reason of this increase of enzyme activity inducing prostaglandin synthesis is not known yet.

Cesarean Section↗

Multicenter evaluation of a chromogenic substrate method for photometric determination of prothrombin time.

A multicenter study of a chromogenic substrate method for photometric determination of prothrombin time was conducted in order to evaluate its clinical application. Seven laboratories participated in the study using a total of 742 plasma samples from 417 patients on oral anticoagulant therapy, 261 healthy subjects and 64 patients with different diseases especially of the liver as well as 30 patients with hereditary deficiency of coagulation factors II, V, VII, X. The chromogenic PT method was compared to a standardized coagulometric PT assay which uses the same sensitive human placenta thromboplastin calibrated against international reference preparations. A high correlation of the prothrombin ratio values of the chromogenic and the coagulometric assay was obtained in 402 plasma samples (r = 0.940; y = 1.02x - 0.1). The study showed that the chromogenic PT reagent is sensitive to deficiency of the coagulation factors of the extrinsic pathway but not affected by heparin up to 1 IU/ml because of the heparin antagonist added. The precision (coefficient of variation) of the photometric method ranged between 0.6 and 3% (intraassay CV) and between 1.4 and 5.8 (interassay CV). The International Sensitivity Index (ISI) obtained for the used lot was 1.09. The therapeutical range in percentage activity for patients in a stable phase of an anticoagulant therapy was found to be from 15 to 27 percent of normal. The results of the clinical evaluation proved the good comparability of the new chromogenic PT test with coagulometric methods, its high factor sensitivity, good reproducibility and easy performance.

Anticoagulants↗

Fetal and neonatal mortality: a matter of care? Report of a survey in Curaçao, Netherlands Antilles.

A detailed clinicopathological analysis of 223 consecutive fetal and neonatal deaths was carried out in Curaçao during 1984 and 1985; this included careful histological examination of 210 infants (94%). The crude death rate was 34.2 per 1000 total births. Malformation was the principal cause of death in 28 cases, antepartum haemorrhage in 19, hypertension in 25, and asphyxia in 35. Death was caused by problems of preterm birth in 68 cases. No specific cause could be found for 34 deaths. Improvement in the quality of obstetric care might substantially reduce both fetal and neonatal death rates.

Birth Weight↗

[Neuroendocrine changes in the climacteric].

In order to investigate the relationship between hot flushes and LH-peaks, we applied GnRH-Analogon for pharmacological hypophysectomy. Although the gonadotropin serum levels could be normalized, none of the women showed a cessation of the flushes. Therefore it can be assumed that not gonadotropins, but neurotransmitters are involved in the development of flushes. The determination of the serum-level of vasointestinal peptide in the course of a TRH-test showed high VIP levels only in two climacteric women. To verify the suspected relation of VIP to the climacterium, a larger collective of women has to be checked.

Climacteric↗

[Endocrinology of mastopathy and small breast cancer].

The role of hormones in the cancerogenesis of breast cancer is still discussed. It is not clear at the moment if sexual hormones are primarily or secondarily in wall in cancerogenesis. Beside the discussion it is clear that estrogen, progesterone, androgens, prolactin and thyroxin have influences on the physiology and pathophysiology of the breast tissue. Furthermore the isoforms of these hormones and also the sexual hormone, binding-protein could be of interest. At last also the receptor evaluation becomes of interest in the etiology and therapy of breast cancer.

Breast Neoplasms↗