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Biomedical subjects

G Köhler

Publications and source records attributed to G Köhler.

At least 163 records · Page 9Linked to original sources

The contribution of constant region domains to the binding of murine IgM to Fc mu receptors on T cells.

IgM hybridoma constant region domain deletional mutants were used to investigate the domain requirements for binding of murine IgM to Fc mu receptors (Fc mu R) on normal murine T lymphocytes. Parental Sp 6:18 (mu, kappa; anti-trinitrophenyl) and its mutant proteins or their trinitrophenyl-antigen immune complexes were tested for their ability to inhibit the binding of pentameric IgM to Fc mu R on T lymphocytes. Inhibition was observed with ligands containing multiple copies of the third constant region domain. Inhibition did not occur with ligands missing the third constant region domain. In addition, a battery of rat monoclonal antibodies specific for individual murine IgM constant region domains was tested for the ability to inhibit the binding of pentameric murine IgM to Fc mu R on normal murine T lymphocytes. Total inhibition was observed with the antibodies directed to different epitopes located in C mu 3, but significant inhibition was not observed with antibodies directed to C mu 1, C mu 2, or C mu 4. Studies with domain deletional mutants and anti-domain antibodies have independently provided strong evidence that the C mu 3 domain plays a major role in the binding of IgM to Fc mu R on T lymphocytes and that C mu 1, C mu 2, and C mu 4 are not essential for binding. These studies have also provided evidence that valency and avidity influence the binding of IgM to T lymphocytes that express Fc mu R.

Antibodies, Monoclonal↗

The molecular interactions with helper T cells which limit antigen-specific B cell differentiation.

Helper T (Th) cell-dependent activation requirements for 2,4,6-trinitrophenyl (TNP)-specific resting B cells obtained from mice transgenic for Sp-6 mu, kappa genes were analyzed. Carrier-specific T cell help required linked recognition of TNP carrier and was functionally restricted by the B cell major histocompatibility complex. However, histoincompatible T cell-B cell conjugates formed by bridging surface immunoglobulin and Th cell receptor for antigen (TcR) through TNP-conjugated anti-TcR antibodies resulted in the efficient differentiation of TNP-specific B cells. Thus, Th cell-dependent cognate recognition of B cells is not obligatory. Specific conjugate formation could be obviated by using unconjugated fragments of anti-TcR antibodies. If dimeric, these fragments supported the Th cell-dependent differentiation of co-cultured histoincompatible resting B cells. Unconjugated monomeric fragments were ineffective, demonstrating the necessity for TcR cross-linking. Resting B cells from Sp-6+ mice rendered TNP-conjugated monomeric fragments of anti-TcR antibodies effectively multivalent, thereby satisfying conditions for the activation of co-cultured Th cells. The results demonstrate that Th cells do not transduce activation signals through TcR recognition of B cell membrane-associated ligand which limit the induction of B cell differentiation. Cross-linking of TcR on Th cells is required, sufficient and can be induced through interaction with the antigen-specific B cell surface.

Animals↗

Spontaneous esophagotracheal fistula resulting from ulcer in heterotopic gastric mucosa.

In a 50-yr-old male patient, a spontaneously perforating peptic ulcer located in a patch of heterotopic gastric mucosa in the upper part of the esophagus led to the development of an esophagotracheal fistula. The histologic workup revealed, in addition to ulcer necroses and granulation tissue, glands of the fundic type, with chief and parietal cells. On the basis of histologic results, the fistula was successfully occluded with the aid of a fibrin adhesive applied endoscopically. After the second session, the patient immediately became free of symptoms. Under medical treatment with an H2-receptor blocker, the patient has been completely symptom-free for 1 yr.

Choristoma↗

[Behavior of T-lymphocytes during the normal menstrual cycle].

FSH, LH, estradiol-17 beta, progesterone, and T-lymphocytes were examined daily in 12 biphasic cycles of 6 healthy women (age 19-29 years). T-lymphocytes were estimated by the alpha-naphthyl-acetate-esterase-reaction as T-cell-marker. There was a significant reduction of T-cells in the first and a nonsignificant reduction in the second cycle phase. The suppressions were related to the high estradiol levels in the follicular as well as the luteal phase. If there is a causative connection and whether the whole immune system is depressed or other regulatory mechanisms interfere isn't quite clear.

Adult↗

[New progestational hormones].

The pharmacology and the application in oral hormonal contraceptives of four new progestogens--gestodene, desogestrel, norgestimate, and dienogest--are described in a survey. Although derived from 19-norethisterone these progestogens exhibit in clinical dosages no androgenic effects. Both in animal and in human tests gestodene possesses the highest progestogenic potency followed by levonorgestrel, desogestrel, norgestimate, and dienogest. The monophasic preparations with the new progestogens (femovan--gestodene, marvelon--desogestrel, cilest--norgestimate, certostat--dienogest) are safe contraceptives and the incidence of bleeding disturbancies amount to about 5%. After administration of these monophasic contraceptives the concentration of SHBG in serum increases and as a result of this the level of free testosterone decreases. Further a favourable effect on lipid metabolism is observed. In spite of a different progestogen content these combination pills are almost without influence on biochemical parameters and carbohydrate metabolism.

Contraceptives, Oral, Hormonal↗

[Development and responsibilities of clinical obstetrics and gyne- cology in the 19th century at the Greifswald University--a contribu- tion on the 110 year existence of the clinic of gynecology and obstetrics].

At the university of Greifswald clinical obstetrics developed at the beginning of the 19th century with priority for education of physicians and midwives. For further support of education in the middle of the century an obstetrical outpatients' department has been founded. Approximately at the same time gynaecological diseases were treated in both institutes so that the teaching combination obstetrics and gynaecology gradually came into existence and medical attendance and scientific work became more importance. There was a similar process at other German universities in the last century.

Germany↗

[Antiprogestins].

In a survey it is reported on the antiprogestins mifepristone (RU 486) and gestrinone (R 2323). Thanks to its high reversible affinity for progesterone receptor mifepristone stops progesterone activity at its target organs. Mifepristone also inhibits ovarian progesterone synthesis. This antiprogesterone was tested clinically with different results for following indications: postcoital contraception, luteolysis, early abortion, ectopic pregnancy, missed abortion, cervix priming, and breast cancer. Gestrinone has antiestrogenic, antiprogesterone, and weak androgenic properties. These effects are related to the affinity for estrogene-, progesterone- and androgene receptor. A suppressory action on gonadotropins has been observed in therapeutic dosages. On the basis of its properties gestrinone is used for treatment of endometriosis, leiomyomas, benign breast diseases and also for contraception.

Estrenes↗

[Is there is seasonal incidence of acute adnexitis?].

188 cases of endoskopic proven acute adnexitis were examined regarding to a seasonal accumulation. There was a trend to a higher incidence of the acute adnexitis in general and of the gonorrhoeal one in particular in the sunny months. A gonorrhoea was detectable in 14.9%, and 55% of the patients were nulliparous women. The conclusions related to prophylaxis of infertility are discussed.

Adult↗

[Endometriosis and basal temperature].

Basal body temperature of 168 cycles have been measured in 20 infertile women (age 21-31 years) with endometriosis. There were 10.1% anovulatory cycles, and in 22.5% of the 151 biphasic cycles the hyperthermic phase lasted less than 11 days. A late decline of basal body temperature after the onset of menstruation was recorded in 34.5% and may be only limitedly indicative of endometriosis. In 64.9% of all cycles basal body temperature was somewhat elevated and/or proved one or more temperature peaks in the follicular phase. Perhaps this may be indicative of endometriosis. Nevertheless the so-called endocrinologic infertility requires endoscopy for accurate diagnosis.

Adult↗

[Esophagotracheal fistula caused by an ulcer in heterotopic gastric mucosa of the cervical esophagus. Diagnosis and endoscopic therapy].

A tracheo-esophageal fistula occurred spontaneously in a 50-year-old man. At endoscopy it was found to be due to a perforated ulcer localized in heterotopic gastric mucosa in the cervical esophagus. Histological examination revealed ulcer necrosis and granulation tissue, as well as glands of the stomach type with chief and other cells. Malignant or specific genesis was excluded. Based on the histological finding, the attempt was successfully made of closing the fistula with fibrin glue in two sittings. All symptoms ceased immediately after the second sitting. Later radiological and endoscopic examinations no longer demonstrated either the fistula opening nor a fistulous tract.

Choristoma↗

Targeting cytotoxic T cells to antigen-specific B lymphocytes.

A recent development in immunomanipulation involves the targeting of cytotoxic T lymphocytes (CTL) to cell-bound antigens using bispecific antibodies. These antibodies have been engineered such that specificity is directed against the T cell receptor (TCR) or TCR-associated T3 molecules, as well as against the chosen antigen. The present study was aimed to force interactions between T and B cells by bridging their receptors. F23.1 antibodies, which are specific for gene products of the TCR V beta 8 gene family, were conjugated with TNP (2,4,6-trinitrophenyl) and this construct was used to bridge the receptors of V beta 8+ T cells with the receptors of TNP-specific B cells. The bridging was demonstrated by direct killing of both a TNP-specific B hybridoma and of blast cells from mice transgenic for mu, kappa of the TNP-specific antibody Sp6. Further, F23.1-TNP constructs in conjunction with V beta 8+ CTL were shown to specifically deplete Ig-secreting B cells from Sp6 transgenic mice. Conjugates of TCR-specific antibodies and antigen are theoretically useful in vivo to either deplete or expand B cells of a given specificity by coupling their receptors to the TCR of CTL or T helper cells, respectively.

Animals↗

Assembly and secretion of heavy chains that do not associate posttranslationally with immunoglobulin heavy chain-binding protein.

Heavy chain-binding protein (BiP) associates posttranslationally with nascent Ig heavy chains in the endoplasmic reticulum (ER) and remains associated with these heavy chains until they assemble with light chains. The heavy chain-BiP complex can be precipitated by antibody reagents against either component. To identify sites on heavy chain molecules that are important for association with BiP, we have examined 30 mouse myelomas and hybridomas that synthesize Ig heavy chains with well characterized deletions. Mutant Ig heavy chains that lack the CH1 domain could not be demonstrated to associate with BiP, whereas mutant Ig heavy chains with deletions of the CH2 or CH3 domain were still able to associate with BiP. In two light chain negative cell lines that produced heavy chains with deletions of the CH1 domain, free heavy chains were secreted. When Ig assembly and secretion were examined in mutants that did not associate with BiP, and were compared with normal parental lines, it was found that the rate of Ig secretion was increased in the mutant lines and that the Ig molecules were secreted in various stages of assembly. In one mutant line (CH1-) approximately one-third of the secreted Ig molecules were incompletely assembled, whereas the Ig molecules secreted by the parental line were completely assembled. Our data show the CH1 domain to be important for association with BiP and that when this association does not occur, incompletely assembled heavy chains can be secreted. This implies a role for BiP in preventing the transport of unassembled Ig molecules from the ER.

Animals↗

[Postcoital contraception with dienogest].

Fifty eight fertile female volunteers between 20 to 45 years were enrolled in a clinical trial to evaluate the efficacy and tolerance of the progestin dienogest (17 alpha-cyanomethyl-17 beta-hydroxyestra-4,9-dien-3-one, VEB Jenapharm Jena GDR) as a postcoital contraceptive. An oral dose of 2 mg dienogest was administered immediately after each coitus. The 58 women reported 872 intercourses during 302 cycles. Frequency of ingestion was on average 3 times per cycle. Pregnancy occurred in 14 women corresponding to a Pearl-index of 55.6. The observed pregnancy rate referring to all intercourses was 1.6 per cent. The incidence of expected pregnancies in relation to the coital exposures was 4.04 per cent. As a result the risk of pregnancy was reduced 2.5 times by dienogest. Menstrual disorders occurred in 18.9 per cent in regard of the total numbers of cycles. The results and an overview of literature suggest that neither dienogest nor other progestins are suitable as a sole contraceptive method when used as a postcoital agent. They are only indicated as a risk-reducing method after so-called "contraceptive emergencies".

Adult↗

[Therapy of endometriosis with dienogest].

Dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one, VEB Jenapharm, Jena, GDR), an orally active 19-nortestosterone derivative, was used firstly in the treatment of endometriosis. 57 patients (age 17-45 years) have been entered into the study. The diagnosis was confirmed by laparoscopy or laparotomy in 56 cases and in one case clinically. All patients have been treated with 2 mg dienogest per day in a progestin only regimen over a period of 6 month. The day after completing the course of dienogest therapy 51 patients underwent laparoscopy for control. On this basis endometriotic lesions had completely disappeared in 66.7%; in 80.4% a marked improvement was noted, but no effect was visible in 19.6% of the implants. Eighty-four per cent of the women reported symptomatic improvement. The efficacy of dienogest was correlated negative with the age of the treated women. The major side effects were spottings and decrease of libido. Blood pressure as well as mean body weight remained unaltered. No patient discontinued dienogest therapy due to side effects.

Adolescent↗

[Estrogen receptor status in breast carcinoma. Results of comparative immunohistochemical and biochemical studies].

Comparative biochemical and immunohistochemical investigations on receptors were performed on 100 breast cancers of different types. The biochemical analysis was carried out by means of radioimmunoassay (RIA) and immunohistochemical detection was performed with monoclonal antibodies against nuclear receptor protein (ER-ICA, Abbott Lab.). The semiquantitative evaluation is based on a histological score considering a graduated staining intensity and the percentage of positively reacting cells. The results of the two methods corresponded in 92% in positive and in 68% in negative receptor detection. The age-dependence is confirmed. The nuclear grading and histological grading show that the number of estrogen receptors gradually decreases with increasing degree of malignancy of the carcinomas. The advantage of immunohistochemical receptor assay consists in the microscopic investigation of homogeneous and heterogeneous degrees of intensity as well as in the possibility of determining receptor status in very small breast cancers, in punch biopsies and in tumours in which the tumour parenchyma is largely necrotic, sclerosed or surrounded by large amounts of mucus.

Adult↗

Experiences with a new priming score for estimation of efficiency of PGF2 alpha-gel for cervical maturation in first trimester induced abortion.

A new priming score for estimation of the efficiency of a cervix priming with prostaglandins (PG) prior to first trimester induced abortion is presented. The score consists of five points: 1 = No effect or partial dilatation of the cervix, further mechanical dilatation is very difficult. 2 = Partial dilatation of the cervix, further mechanical dilatation is moderately difficult. 3 = Partial dilatation of the cervix, further mechanical dilatation is effortless. 4 = Cervix is open for pregnancy age, no further mechanical dilatation is required. 5 = Abortion. A total of 340 primigravidae requiring a termination of first trimester pregnancy took part in a prospective study for testing the score. The cervix priming was performed by a single intracervical application of 2.5 mg PGF2 alpha-gel. Regarding the score, this regimen was found to be in 89.1% effective. In 8.5% a partial and in 2.4% no effect was recorded. Because the recommended score is related to the age of pregnancy, it is suitable for comparison of different prostaglandins and other methods for cervix priming prior to pregnancy termination.

Abortion, Induced↗