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Biomedical subjects

E Hochuli

Publications and source records attributed to E Hochuli.

At least 19 recordsLinked to original sources

Immobilization of monoclonal antibodies for affinity chromatography using a chelating peptide.

A procedure was developed for oriented immobilization of monoclonal antibodies on a solid support. The technique involves the specific oligosaccharide-directed covalent modification of the monoclonal antibody (mAb) with the chelating peptide, Lys-Gly-(His)6, in conjunction with immobilized metal ion affinity chromatography. Chelating peptide-mAb conjugates with a molar ratio of 2.2 retained full antigen binding activity. On immobilization of the modified antibodies on a nickel affinity resin, the molar antigen binding ratio was 1.4. The high antigen binding capacity is indicative of oriented immobilization providing maximum access for the antigen. The described method can be used for the preparation of high-capacity immunosorbents for affinity chromatography and it is applicable for all immunoglobulin classes.

Antibodies, Monoclonal

[Prognostic and therapeutic significance of steroid receptors in invasive breast cancer].

It is generally accepted that breast cancer with positive steroid receptors has a better prognosis than with negative receptors. The aim of this study was to analyse the influence of the oestrogen (ER) and progesterone (PR) receptors regarding disease-free interval (DFI) and overall (oa) survival of 441 patients operated on in the Department of Gynaecology of the University Hospital of Zürich. Analysis of the subgroups separated according to menopausal status showed the following results: Premenopausal patients (n = 135): Only PR have a significant influence on the oa-survival (p = 0.0370), not the ER. The DFI was independent of ER and PR positive findings. Postmenopausal patients (n = 306): In this group only the ER has a significant influence (p = 0.0296) on the oa-survival, not the PR. Both steroid receptors did not have any influence regarding DFI. Metastases and local recurrence occur pre- and postmenopausaly approximately at the same time, independent of the quality of the steroid receptors. The better oa-survival despite the same DFI can be explained by a better response to the therapy by patients in the premenopause with positive PR status and patients in the postmenopause with positive ER status.

Antineoplastic Combined Chemotherapy Protocols

[Prognosis of local-regional recurrence in breast carcinoma].

992 primary breast cancers were treated at the Gynaecological Department of the University Hospital of Zürich between 1971 and 1988. Local recurrence (LR) has occurred in 131 patients up to now after a median follow-up of 5.1 years. 75% of the LR manifested the first three years after operation. Especially the locoregional (axillary) recurrences occurred early. The frequency of LR was independent of the menopausal status and the steroid receptors, but was dependent on the initial axillary nodal status and the tumor size. Patients with nodal involvement had recurrences significantly more often (74 of 372 = 20%) than those without (34 of 469 = 7%). LR of patients with tumors smaller than or equal to 2 cm occurred in 7%, in patients with tumors greater than 2 cm in 17%. The 5-year survival of all patients and the patients with a LR was 80% and 57% respectively. The longer the disease-free interval, the better the prognosis of survival. The findings suggest, that especially an early LR can not be looked at as merely a local problem but rather as a signal of a systemic manifestation of the disease.

Breast Neoplasms

[Risk factors in breast carcinoma].

A group of 992 breast cancer patients (risk group, R) was compared with a group of 482 patients hospitalized for non oncologic reasons and matched for age and year of hospitalization (comparison group, C). The findings confirm the following factors as risk factors for breast cancer: nulliparity (R 28.8%, C 17.5%, p less than 0.001), late first birth (over 34 years of age) (R 11.4%, C 5.1%, p less than 0.001), diabetes mellitus (R 7.0%, C 3.8%, p = 0.017), hypertension (R 25.7%, C 18.1%, p = 0.0016), alcohol (R 9.4%, C 5.9%, p = 0.03), positive family history (R 14.8%, V 5.3%, p less than 0.001) and breast surgery for benign disease (R 13%, C 7.5%, p = 0.002). Frequently mentioned risk factors such as early menarche and late menopause did not emerge as risk factors in our study. Cigarette smoking did not show a protective effect but even tended to be more frequent in the risk group. Multiparity (more than 2 births) was protective (R 22.1%, C 32.4%, p less than 0.001). The findings on hormonal replacement therapy (R 7.1%, V 17.0%, p less than 0.01) might have been influenced by a selection bias (hospitalization of patients in the comparison group because of complications of hormonal replacement therapy such as bleeding) and are thus not fully conclusive. It can at least be said that hormonal replacement therapy is not more frequent in the risk group.

Adult

Timing of breast cancer surgery within the menstrual cycle: influence on lymph-node involvement, receptor status, postoperative metastatic spread and local recurrence.

Prompted by a report of Hrushesky et al. stating that women operated upon for breast cancer during their perimenstrual period showed a higher risk for developing future metastases than women operated upon during their mid-cycle, we examined the patients with breast carcinoma who were treated at the Gynaecological University Hospital Zürich between 1971 and 1988 with respect to the influence of menstrual cycle phase on certain factors. 104 patients underwent perimenstrual surgery, i.e., between days 1 and 6 or days 21 and 36 of the cycle. 120 women had mid-cycle surgery (i.e., days 7-20 of the cycle). In contrast to the experience of Hrushesky et al., we found no significant differences in the survival curves. The same was true when the proliferative phase (days 1-14; n = 109) was compared with the secretory phase (days 15-32; n = 108). We tested the different groups for homogeneity and found that 54% of the patients with perimenstrual surgery showed axillary lymph node involvement, whereas in the midcyclic group only 38% showed positive nodes. We have no plausible explanation for this difference. These findings indicate that there might be certain cycle-related differences with respect to lymph node status but that they do not affect survival. Hence, timing surgery to the menstrual cycle is not mandatory for the time being.

Breast Neoplasms

Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). I. Producing organism, fermentation, isolation and biological activity.

Anantin, a peptide binding to the receptor of the atrial natriuretic factor (ANF) was isolated from a strain of Streptomyces coerulescens. The molecule consists of 17 natural L-amino acids which form a peptidic ring system. It has a MW of 1,871.0. The chemical composition is C90H111N21O24. The compound was found to bind competitively to ANF-receptors from bovine adrenal cortex (Kd = 0.61 microM). Furthermore, it dose-dependently inhibited the ANF-induced intracellular cyclic guanosine monophosphate accumulation in bovine aorta smooth muscle cells. At the same concentration no agonistic effects were detectable in these cells. Thus, anantin is considered to be the first microbially produced antagonist of the cardiac hormone, ANF.

Adrenal Cortex

[Effectiveness of gynecologic preventive examinations--perspectives].

Genital cancer and breast cancer cases were compiled from the data base of the Swiss working group of the Departments of Gynecology and Obstetrics. The total number of 390,000 cases was divided in two three-year periods (1983-1985 and 1986-1988) and then compared. With the exception of cervical cancer cases, which showed a significant increase of Stage 0/CIN III and a significant decrease of the more advanced stages, we noted a more or less unchanged distribution of the other cancer stages in respect of the manifestations. Screening methods allowing early diagnosis are still not used with appropriate technique and frequency, especially in the postmenopausal age.

Breast Neoplasms

Adenocarcinoma of the uterine cervix. An analysis of 84 cases between 1970 and 1988.

Of 1284 cases with cervical carcinoma of Stages 0-IV treated at the Gynaecological University Hospital CH-Zurich between 1970 and 1988, 84 (6.5%) were adenocarcinomas; whereas a previous study performed at our clinic between 1950 and 1970 had only revealed an incidence of 3.2%. Compared with the 1200 cases of squamous cell carcinoma during the period from 1970 to 1988 it is of interest that patients with adenocarcinomas are slightly older (median value: 48 years, squamous cell carcinoma: 44 years) and that there is a temporary postmenopausal decrease in incidence: whereas there were 29 cases in the 45- to 54-year age group and 12 in the 65- to 74-age group, only 3 cases occurred in the 55- to 64-age group. Of the 38 women undergoing radical hysterectomy, 9 (24%) showed metastases in the pelvic lymph nodes. Of 115 squamous cell carcinomas operated in the same way, 15 (13%) were metastatic, which corresponds to a value of 3.65 (p = 0.057) in the chi-square test and is just below significance different. No metastases could be evidenced in any of the 28 adnexa removed bilaterally. The general appearance of the adenocarcinoma largely corresponds to that of its squamous cell counterpart of the cervix, although there are certain indications, confirmed by some references, as to poorer prognosis, earlier formation of lymph node metastases and slightly reduced radio-sensitivity.

Adenocarcinoma

[Labor without prenatal care--an unnecessary challenge].

A group of 431 patients who had given birth, but had not attended regular check-ups during their pregnancy, are compared with a cumulative comparative group. The data is from a databank, belonging to the Swiss gynaecological working group. The following results are striking: Very young women, relatively older childbearing women, a noticeably high number of unmarried women and women from the Mediterranean countries. The number of women with heavy nicotine abuse is significant. The general progress of the pregnancy is however not noticeably different from the comparative group. The premature birth rate is higher in the group without pregnancy check-ups, as are birth deficiences and clinical foetal distress. Particularly noticeably is the high number of perinatal deaths. The pointlessness and the possible reasons for lack of regular pregnancy check-ups are discussed.

Adolescent

Large-scale chromatography of recombinant proteins.

When recombinant proteins are expressed in bacterial cells and subsequently grown in fermentation tanks, there remains the problem of recovering the product in pure form. The empirical knowledge gained upon recovery of recombinant proteins indicates that a one-step purification process is very unlikely to succeed. However, combinations of modern techniques, such as immunoaffinity chromatography or immobilized-metal affinity chromatography, with classical techniques, such as ion-exchange chromatography, seem to be suitable for large-scale recovery of recombinant proteins.

Chromatography, Affinity

New metal chelate adsorbent selective for proteins and peptides containing neighbouring histidine residues.

A novel nitrilotriacetic acid adsorbent has been prepared for metal chelate affinity chromatography. The new resin is a quadridentate chelate former and specially suitable for metal ions with coordination numbers of six, since two valencies remain for the reversible binding of biopolymers. It has been found to chelate Cu2+ and Ni2+ strongly and to be superior to the known iminodiacetic acid adsorbent. Charged with Ni2+, it was evaluated for the ability to bind peptides and proteins containing neighbouring histidine residues. The remarkable specificity found makes it an attractive addition to the range of adsorbents for metal chelate affinity chromatography.

Adsorption

Specificity of the immunoadsorbent used for large-scale recovery of interferon alpha-2a.

After immunoaffinity chromatography, interferon alpha-2a synthesized in bacteria is not homogeneous. Beside oligomers and monomers, a fragment of molecular weight 15,000 was observed. Amino acid analysis and the determination of the amino terminal amino acid sequence of the fragment indicate that this polypeptide represents an interferon alpha-2a molecule lacking the 22 terminal amino acids. In order to define the epitope on the interferon alpha-2a molecule recognized by the immunoadsorbent, the binding to the immunoadsorbent of interferon alpha-2a fragments prepared by cyanogen bromide cleavage was studied. The results suggest that cyanogen bromide fragments Arg 22-Met 59 and Lys 112-Met 148 are recognized. Since the oligomers, the monomers and the fragment of molecular weight 15,000 of interferon alpha-2a share these sequences, the different forms are as expected co-purified on the immunoadsorbent.

Amino Acid Sequence

[Laparoscopy in gynecology and obstetrics].

Thanks to the statistics of the Arbeitsgemeinschaft Schweizerischer Frauenkliniken (Swiss Gynecological Clinics' Working Group) it has for the first time become possible to report on larger numbers of laparoscopies performed in Switzerland. In contrast to most international statistical records, data relating to this subject are gathered prospectively; there is no doubt that this improves the quality of the data. The authors report on a total of 18,186 laparoscopies performed in 1983/84/85, in 50% of the cases for sterilization. The various sterilization methods employed are discussed. As far as diagnostic laparoscopies are concerned, the indications and techniques are described. Serious intraoperative complications occurred in 15 cases, which corresponds to one serious complication in every 1,212 laparoscopies. Fortunately, not a single patient died as a direct result of the laparoscopy. The results are compared with those in the international literature. With regard to late-onset morbidity it is evident that there are more complications with the more complex procedure of diagnostic laparoscopy.

Female