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H Hess

Publications and source records attributed to H Hess.

At least 19 recordsLinked to original sources

Extracardiac conduit fontan procedure: early and intermediate results.

OBJECTIVE: The extracardiac Fontan procedure, as compared with classic atriopulmonary connections, may have the potential for optimizing ventricular and pulmonary vascular function by maximizing the laminar flow principle, by the avoidance of intra-atrial suture lines and cardiac manipulation, and by minimizing cardiopulmonary bypass time. In this study the clinical results of this procedure are assessed. METHODS: From January 1990 until January 1997, 45 patients (33 males and 12 females) with a median age of 4.0 years (range 2.7-38 years) underwent an extracardiac Fontan procedure for univentricular physiology. The underlying diagnoses included tricuspid atresia (n=19), double-inlet left ventricle (n=11), and complex anomalies (n=15). Forty patients (89%) were in sinus rhythm. The median ventricular ejection fraction was 60%. In 37 patients (82%) the procedure was staged. RESULTS: Median cardiopulmonary bypass time was 72 min, with a decrease to a median time of 24 min in the last ten patients. Aortic cross-clamping was avoided in 33 patients (73%). The intraoperative Fontan pressure and transpulmonary gradient were low: 13.6+/-3.2 and 8.5+/-3.9 mmHg, respectively. Transient supraventricular tachyarrhythmias were observed in six patients (13%). There was no early or late mortality. At a median follow-up of 64 months (range 26-105 months), 39 patients (87%) were in NYHA class I, four (9%) were in NYHA class II, and two (4%) were in class III. Forty patients (89%) remained in sinus rhythm. The median ventricular ejection fraction was 59%. The median arterial oxygen saturation raised from 82% preoperatively to 97%. Functional class (P=0.02), maintenance of sinus rhythm (P=0.04), and preservation of ventricular function (P=0.05) was superior in patients who were appropriately staged. None of the patients had atrial thrombus, chronic pleural effusions, or protein losing enteropathy. CONCLUSIONS: In the majority of patients, the extracardiac Fontan procedure, when performed as a staged procedure, provides excellent early and midterm results in terms of quality of life, maintenance of sinus rhythm, and preservation of ventricular function.

Adolescent↗

Relative efficiency of microglia, astrocytes, dendritic cells and B cells in naive CD4+ T cell priming and Th1/Th2 cell restimulation.

We have compared the efficiency of central nervous system and peripheral antigen-presenting cells (APC) in T cell priming and restimulation. OVA peptide 323 - 339-dependent activation of DO11.10 TCR-transgenic naive CD4+ and polarized Th1 or Th2 cells was assessed in the presence of microglia and astrocytes from the neonatal mouse brain as well as dendritic cells (DC) and B cells purified from adult mouse lymph nodes. DC were the most efficient in inducing naive T cell proliferation, IL-2 secretion and differentiation into Th1 cells, followed by IFN-gamma-preactivated microglia, large and small B cells. Astrocytes failed to activate naive T cells. IFN-gamma-pretreated microglia were as efficient as DC in the restimulation of Th1 cells, whereas IFN-gamma-pretreated astrocytes, large and small B cells were much less efficient. Conversely, Th2 cells were efficiently restimulated by all the APC types examined. During T cell priming, DC secreted more IL-12 than microglia but similar amounts of IL-12 were secreted by the two cell types upon interaction with Th1 cells. The hierarchy of APC established in this study indicates that DC and microglia are the most efficient in the stimulation of naive CD4(+) T cells and in the restimulation of Th1 cells, suggesting that activated microglia may effectively contribute to Th1 responses leading to central nervous system inflammation and tissue damage. These potentially pathogenic responses could be counteracted by the high efficiency of astrocytes as well as microglia in restimulating Th2 cells.

Animals↗

Conversion of atriopulmonary or lateral atrial tunnel cavopulmonary anastomosis to extracardiac conduit Fontan modification.

OBJECTIVE: Obstruction of the atriopulmonary anastomosis or the lateral atrial tunnel cavopulmonary anastomosis in the Fontan circulation for univentricular physiology may result in dilation of the right atrium or the right atrial free wall that is incorporated in the lateral atrial tunnel, respectively. Secondary detrimental sequelae may consist of supraventricular dysrhythmias, thromboembolism, right pulmonary vein compression, pleural effusions, and protein-losing enteropathy. Conversion of these Fontan connections to an extracardiac conduit cavopulmonary anastomosis may improve central systemic venous flow patterns and provide clinical improvement in these patients. METHODS: Eighteen patients (7-40 years old) with atriopulmonary anastomosis (n = 15) or obstructed lateral atrial tunnel cavopulmonary anastomosis (n = 3) presented at 5.7 +/- 3.9 years with moderate to severe right atrial dilation (n = 15), Fontan pathway obstruction (n = 12), atrial dysrhythmia (n = 13), pleural effusion (n = 8), right atrial thrombus (n = 3), right pulmonary vein compression (n = 3), and protein-losing enteropathy (n = 3). All patients underwent conversion to an extracardiac conduit cavopulmonary anastomosis. RESULTS: Two of the three patients with protein-losing enteropathy died (2/18; 11%) on the 30th and 52nd postoperative days. At a mean follow-up of 19 months, the remaining 16 patients had marked (n = 11) or moderate (n = 5) clinical improvement. The SaO2 improved from 90.7 +/- 5.3% to 96.0 +/- 4.1%. None of the patients had obstruction in the systemic venous pathway. In the 13 surviving patients with previous atriopulmonary anastomosis there was a drastic reduction in right atrial size. Four of 13 patients with atrial dysrhythmias converted to sinus rhythm. The right pulmonary vein compression as present in three patients resolved after conversion. Pleural effusions disappeared in four patients. CONCLUSIONS: Conversion to an extracardiac cavopulmonary connection may lead to clinical improvement in patients with atriopulmonary or lateral atrial tunnel Fontan connection associated with specific target conditions such as obstruction, pulmonary vein compression, right atrial enlargement, atrial dysrhythmia, or atrial thrombus. The conversion operation should not be unduly delayed to prevent irreversible deterioration of clinical status with chronic rhythm disturbances or protein-losing enteropathy. The benefit of the conversion operation is questionable in patients with poor clinical condition and protein-losing enteropathy.

Adolescent↗

Early repair of coarctation of the aorta.

BACKGROUND: Repair of coarctation of the aorta with hypoplasia and elongation of the proximal aortic arch is a technically demanding procedure with a substantial rate of recurrent stenosis at the coarctation repair site. In addition, a high incidence of hypertension has been reported in patients who underwent repair beyond infancy. PATIENTS AND METHODS: Between January 1991 and June 1997, 52 patients (34 neonates and 18 infants with a median age of 37 days; range 2 days to 8 months) with a mean peak systolic upper to lower extremity resting gradient of 33.5 +/- 18.9 mmHg underwent repair of aortic coarctation. The echocardiographically measured median diameter of the aortic arch immediately distal to the innominate artery was 5.4 mm (range 4.0 to 8.1 mm). Eight patients (15%) were considered hypertensive. In 41 patients, through a left thoracotomy, an end-to-side anastomosis was constructed between the descending aorta and the undersurface of the proximal aortic arch. In 12 of these patients (who all had a hypoplastic and elongated aortic arch) this procedure was preceded by the construction of an extended side-to-side left carotid-subclavian arterioplasty. The remaining 11 patients, all with hypoplasia of the aortic arch, had concomitant complete repair of intracardiac anomalies through a median sternotomy. In 8 of these patients, in addition to anastomosis of the descending aorta to the undersurface of the proximal aortic arch, the ascending aorta and aortic arch were augmented with a pulmonary homograft patch. RESULTS: One neonate with associated Shone's syndrome died (2%) on the first postoperative day. There was no late mortality. Early postoperative complications included recurrent laryngeal nerve injury in 1 patient and prolonged chest tube drainage in 4 patients. At a median follow-up of 55 months (range 15 to 92 months), only 3 patients (5. 7%) developed a recurrent stenosis at the coarctation repair site. The remaining 48 patients are free of recurrent stenosis by echocardiography and clinical examination. None of the patients had systemic hypertension. CONCLUSIONS: 1. Coarctation repair consisting of resection of all ductal tissue with end-to-side anastomosis of the descending aorta to the undersurface of the (proximal) aortic arch, if necessary combined with a side-to side left carotid-subclavian arterioplasty, may lead to excellent results. 2. This technique can be applied with low mortality and morbidity via a left thoracotomy if the proximal aortic arch is at least 5 mm in diameter. 3. In view of the low mortality, the low incidence of restenosis at the coarctation repair site, and the absence of substantial morbidity including the development of hypertension, we advocate repair of aortic coarctation at neonatal age or in early infancy to avoid the detrimental sequelae of delayed repair of coarctation, in particular hypertension.

Aorta, Thoracic↗

New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2.

The POU transcription factor Oct-4 is expressed specifically in the germ line, pluripotent cells of the pregastrulation embryo and stem cell lines derived from the early embryo. Osteopontin (OPN) is a protein secreted by cells of the preimplantation embryo and contains a GRGDS motif that can bind to specific integrin subtypes and modulate cell adhesion/migration. We show that Oct-4 and OPN are coexpressed in the preimplantation mouse embryo and during differentiation of embryonal cell lines. Immunoprecipitation of the first intron of OPN (i-opn) from covalently fixed chromatin of embryonal stem cells by Oct-4-specific antibodies indicates that Oct-4 binds to this fragment in vivo. The i-opn fragment functions as an enhancer in cell lines that resemble cells of the preimplantation embryo. Furthermore, it contains a novel palindromic Oct factor recognition element (PORE) that is composed of an inverted pair of homeodomain-binding sites separated by exactly 5 bp (ATTTG +5 CAAAT). POU proteins can homo- and heterodimerize on the PORE in a configuration that has not been described previously. Strong transcriptional activation of the OPN element requires an intact PORE. In contrast, the canonical octamer overlapping with the downstream half of the PORE is not essential. Sox-2 is a transcription factor that contains an HMG box and is coexpressed with Oct-4 in the early mouse embryo. Sox-2 represses Oct-4 mediated activation of i-opn by way of a canonical Sox element that is located close to the PORE. Repression depends on a carboxy-terminal region of Sox-2 that is outside of the HMG box. Expression, DNA binding, and transactivation data are consistent with the hypothesis that OPN expression is regulated by Oct-4 and Sox-2 in preimplantation development.

Amino Acid Sequence↗

[Poisoning in small children--assessing the incidence and intervention. II. What is effective in prevention?].

A study was started a) to assess the incidence self-poisoning in pre-school children and b) to evaluate the impact of an emergency set containing activated carbon and an antifoam. Cooperation was established with the regional legal sickness funds, the regional physician association, and two pharmaceutical companies. Incidence and extent of unintentional self-poisoning among pre-school children are to be determined. The impact of an emergency specimen given to parents of one year old children is evaluated. Families with children aged 1 to 4 year living in boroughs of Berlin are the population at risk. Study period for measuring the incidence is from January 1995 to June 1998. Cases are all accidents of poison ingestion by children of the at-risk-population. Intervention was performed between July 1995 and June 1996. The sets were handed out to parents of children born in 1994. 85% of the selected parents could be interviewed. It was studied whether the behaviour of parents in accidents of poisoning differed between those given an emergency set compared to those who had none. Data were mainly collected by telephone interviews. In this paper the theoretical aspects of the psychological effect of the intervention are discussed.

Child, Preschool↗

Characterization of the adjuvant effect of IL-12 and efficacy of IL-12 inhibitors in type II collagen-induced arthritis.

A destructive joint disease can be induced in susceptible DBA/1 mice by immunization with type II collagen emulsified with oil and either killed Mycobacterium tuberculosis or IL-12 as adjuvant. Cellular and humoral anti-collagen immune mechanisms appear to be involved in the pathogenesis of arthritis. We have characterized the adjuvant effect or IL-12 in more detail and addressed the question whether mycobacteria might act via the induction of endogenous IL-12. Injections of IL-12 into collagen-immunized DBA/1 mice promoted the development of IFN-gamma-producing CD4+ T cells and strongly upregulated the production of complement-fixing IgG2a and IgG2b antibodies resulting in severe arthritis. Neutralization of IFN-gamma in vivo largely inhibited the increase in antibody synthesis and prevented joint disease in IL-12-treated mice. However, collagen-specific IFN-gamma synthesis by T cells was further enhanced in these animals. Furthermore, IL-12 treatment promoted the development of IFN-gamma-producing T cells but failed to enhance antibody synthesis and to induce arthritis in C57BL/6 or BALB/c mice immunized with collagen in oil. These results indicate that the induction (by IL-12) of a strong collagen-specific T-cell response alone is not sufficient to trigger arthritis. Attempts to show a role for endogenous IL-12 in DBA/1 mice immunized with collagen with mycobacteria as adjuvant gave no reliable results. Whereas anti-IL-12 treatment delayed the onset and ameliorated the disease in some experiments, it failed to do so in other experiments, or, control reagents also had some effect. A slight inhibition of collagen-specific IgG2a synthesis was observed in most experiments in the sera of anti-IL-12-treated mice. Taken together, the results show that exogenous IL-12 can promote arthritis via its direct effect on T cells and its effect on antibody production, which is at least in part IFN-gamma-dependent. On the other hand, whether or not endogenous IL-12 is involved in the adjuvant effect of mycobacteria needs further clarification.

Adjuvants, Immunologic↗

High doses of interleukin-12 inhibit the development of joint disease in DBA/1 mice immunized with type II collagen in complete Freund's adjuvant.

Collagen-induced arthritis (CIA) is an (autoimmune) joint disease readily elicited in DBA/1 mice by immunization with type II collagen (CII) emulsified with complete Freund's adjuvant. It is a destructive arthritis involving about 50% of the limbs and occurs with an incidence of 70% to 100%. In this study we evaluated the effect of mouse recombinant interleukin-12 (mrIL-12) on CIA. Administration of mrIL-12 at high doses (1 micrograms/mouse, daily) for 2 or 3 weeks delayed the onset and reduced the incidence of CIA. Furthermore, the severity of CIA was much milder and in most cases restricted to single digits of the paws. Short-term administration of high doses of IL-12 exerted some, but less pronounced, disease-suppressing effect. In contrast, 10-fold lower doses of IL-12 given during the first 3 weeks, or high doses of IL-12 administered therapeutically proved to be ineffective. Only those regimens of IL-12 treatment that ameliorated CIA were associated with a down-regulation of the CII-specific antibody response. A strong inhibition of CII-specific IgG1 antibodies (10- to 20-fold) and a moderately (2- to 6-fold) suppressed IgG2b response was observed, whereas the level of CII-specific IgG2a antibodies remained high. Taken together, the results indicate that some initial events in the induction of CIA in DBA/1 mice injected with CII emulsified with CFA are suppressed by treatment with high doses of IL-12.

Animals↗

Peripheral arterial occlusions: local low-dose thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA).

OBJECTIVE: To study the efficacy and risks of local thrombolytic therapy of peripheral arterial occlusions using rt-PA. DESIGN: This open study was performed in one clinic in Munich, Germany. METHODS: 288 patients suffering from occlusions of the lower limb arteries were subjected to 336 treatments performed with a permanently controlled technique. In a short pilot study 10mg rt-PA/h were administered for 5 h but in the majority of the cases only 2.5mg/h were administered for a maximum of 5 h. The average total dose of rt-PA was 2.97mg and the average time for lysis was 78 min. RESULTS: 43 (84.3%) out of 51 embolic occlusions and 168 (71.5%) out of 235 thrombotic occlusions were recanalised with a cumulative patency of 95% and 79.7% respectively after 2 years. One systemic bleeding occurred in the pilot study with 10mg rt-PA/h whereas with the 2.5mg/h dosage no systemic bleeding or embolism occurred in the 315 treatments. There were no deaths during hospitalisation. Six major and two forefoot amputations were necessary. Thirteen patients required a bypass operation and one an embolectomy. The advantages of our controlled technique are: short duration of treatment, small doses of activating agent, an accurately directed pathway with the possibility of dilating stenoses during the same session, no danger of systemic bleeding or embolism and, therefore, good prospects of success with minimal risk. CONCLUSION: The use of rt-PA for local lysis substitutes the inadequate tissue activator available for effective spontaneous lysis and is, therefore, almost physiological. The effect of a very low dose of rt-PA was as good as that of higher doses.

Adult↗

IL-12 promotes cellular but not humoral type II collagen-specific Th 1-type responses in C57BL/6 and B10.Q mice and fails to induce arthritis.

DBA/1 (H-2q) and C57BL/6 (H-2b) mice develop an intermediate immune responses when immunized with chicken type II collagen (CII) emulsified with incomplete Freund's adjuvant (IFA). Only a few animals develop a mild form of arthritis. As reported before and confirmed herein, administration of IL-12 to DBA/1 mice immunized with CII in IFA strongly enhances the cellular and humoral (auto)immune response to CII and induces severe destructive joint disease with an incidence of 80-100%. In contrast, the same treatment did not promote joint disease in C57BL/6 mice. Characterization of the IL-12 effect on the CII-specific immune response of C57BL/6 mice revealed that IL-12 promoted the development of CII-specific T cells producing IFN-gamma in DBA/1 and C57BL/6 mice equally well. However, whereas treatment with IL-12 in DBA/1 mice strongly up-regulated the synthesis of CII-specific antibodies, especially of the IgG2a and IgG2b subclasses, it rather slightly down-regulated the CII-specific IgG2a and IgG2b synthesis in C57BL/6 mice. This may indicate that the effect of IL-12 on the CII-specific antibody synthesis is of crucial importance in the pathogenesis of type II collagen-induced arthritis (CIA). The failure of IL-12 to up-regulate IgG2a and IgG2b synthesis in C57BL/6 mice is specific for CII as antigen and not a general property of this strain because the keyhole limpet hemacyanin-specific antibody response is up-regulated by IL-12 in C57BL/6 mice. Furthermore, it is not the H-2b haplotype of C57BL/6 mice but rather the genetic background (DBA/1 versus BL/6 or BL/10) that limits the effect of IL-12 on the CII-specific antibody response because IL-12 treatment of CII-immunized B10.Q (H-2q) mice also failed to induce arthritis and to enhance CII-specific IgG2a and IgG2b synthesis. However, as in the two other strains, injection of IL-12 promoted the development of splenic T cells producing IFN-gamma upon activation with CII. These results indicate that an enhancement of the cellular and humoral anti-CII response by IL-12 is required for inducing arthritis.

Animals↗

Administration of interleukin 12 in combination with type II collagen induces severe arthritis in DBA/1 mice.

The induction of arthritis in DBA/1 mice usually requires immunization with the antigen type II collagen emulsified with Mycobacterium tuberculosis in oil. Here we describe that interleukin 12 (IL-12) can replace mycobacteria and cause severe arthritis of DBA/1 mice when administered in combination with type II collagen. Immunization of DBA/1 mice with type II collagen emulsified in oil alone resulted in a weak immune response, and only a few animals (10-30%) developed arthritis. Administration of IL-12 for 5 days simultaneously with each immunization strongly enhanced the anti-type II collagen immune response. Collagen-specific interferon gamma (IFN-gamma) synthesis by ex vivo activated spleen cells was enhanced 3- to 10-fold. IFN-gamma was almost completely produced by CD4+ T cells. Furthermore, the production of collagen-specific IgG2a and IgG2b antibodies was upregulated 10- to 100-fold. As a consequence, the incidence of arthritis in the group of mice immunized with collagen plus IL-12 was very high (80-100%). The developing arthritis was severe, involving approximately 50% of all limbs with strongly increased footpad thickness in most cases. Furthermore, histological examination revealed massive, mainly polymorphonuclear cell infiltration, synovial hyperplasia, cartilage and bone destruction, as well as new bone formation. In many cases, this resulted in the complete loss of joint structure. Neutralization of IFN-gamma in vivo prevented the development of arthritis in collagen-immunized and IL-12-treated mice. In conclusion, our data show that in vivo administered IL-12 can profoundly upregulate a T helper I-type autoimmune response, resulting in severe joint disease in DBA/1 mice.

Animals↗

Interleukin-12 profoundly up-regulates the synthesis of antigen-specific complement-fixing IgG2a, IgG2b and IgG3 antibody subclasses in vivo.

The influence of the cytokine interleukin-12 (IL-12) on humoral immune responses was studied in vivo. CBA/J mice immunized with protein antigens (keyhole limpet hemocyanin, phospholipase A2) adsorbed to aluminum hydroxide (Alum) develop a Th2-like immune response characterized by the production of large amounts of IgG1 as well as some IgE but little IgG2a, IgG2b and IgG3 antibodies. IL-12 is a cytokine that promotes the development and the activation of Th1 cells. Th1 cells are involved in the induction of cellular immunity, which is characterized by low or absent antibody production. On the other hand, some Th1-like immune responses are associated with a strong antibody production of the IgG2a, IgG2b and IgG3 subclasses. Thus, we investigated whether treatment with IL-12 would down-regulate the humoral immune response or stimulate antibody production of the IgG2a, IgG2b and IgG3 subclasses. We observed that: 1) administration of IL-12 to mice together with protein antigens adsorbed to Alum strongly enhanced the humoral immune response by increasing the synthesis of antigen-specific antibodies of the IgG2a, IgG2b and IgG3 subclasses 10- to 1000-fold. The synthesis of IgG1 was not or only slightly (2-5-fold) enhanced, whereas that of the IgE isotype was suppressed. 2) These effects of IL-12 were observed when high (10 micrograms, 100 micrograms) or low doses (0.1 microgram) of antigen were used for immunization. 3) Titration of IL-12 in vitro revealed that IgG2a is strongly up-regulated over a wide dose range of IL-12 (10 to 1000 ng/day). 4) The effects of IL-12 in vivo are at least partially interferon (IFN)-gamma-dependent because an anti-IFN-gamma mAb in combination with IL-12 prevented most of the enhanced IgG2a production. 5) Mice receiving IL-12 showed a strong up-regulation of IFN-gamma but no inhibition of IL-5 synthesis by spleen cells activated ex vivo with antigen. These results suggest that IL-12 is a potent adjuvant for enhancing humoral immunity to protein antigens adsorbed to Alum, primarily by inducing the synthesis of the complement-fixing IgG subclasses 2a, 2b and 3.

Aluminum Hydroxide↗

The protein complexity of the cytoskeleton of bovine and human sperm heads: the identification and characterization of cylicin II.

The cytoskeletal calyx of mammalian sperm heads surrounding the basolateral part of the nucleus contains two kinds of basic proteins: Calicin, a polypeptide of approximate M(r) 60,000 as estimated from SDS-PAGE, and the group of the very basic cylicins (pI > 10.0), formerly designated as "multiple-band polypeptides." Recently, bovine cylicin I has been cDNA cloned and identified as a new type of a cytoskeletal protein, which contains numerous Lys-Lys-Asp tripeptides accumulated in nine central repetitive units predicted to form alpha-helices. We now report the cDNA cloning and localization of a second species of cylicin, bovine cylicin II, present in bovine and human sperm heads: Cylicin II (488 amino acids, M(r) 53,561, pI 10.55) shows the same prominent molecular characteristics as cylicin I, including a high content of charged amino acids, the abundance of Lys-Lys-Asp tripeptides, and repetitive units of presumably alpha-helical configuration, but also presents some differences. As with cylicin I mRNA, the 2.6-kb mRNA has also been shown to be specifically expressed in testis. The possible existence of a larger cylicin multigene family and its contribution to the cytoskeleton and the morphogenesis of the sperm head are discussed.

Amino Acid Sequence↗

Molecular nature of calicin, a major basic protein of the mammalian sperm head cytoskeleton.

In the mammalian sperm head the nucleus is tightly associated, in many species in its posterior part, with a large and dense nonfilamentous cytoskeletal structure, the calyx, whose major proteins are basic, representing a novel category of cytoskeletal element. Using specific antibodies, biochemical methods, and cDNA cloning we have characterized one of these calyx proteins, previously termed calicin, in bull and man. The polypeptide of 588 amino acids (Mr of 66,889; IEP 8.1) is very similar in the two species and is encoded by a approximately 2.2-kb mRNA that has been detected only in testis but not in any other tissue or cell culture examined. Sequence analysis has revealed that calicin is homologous to the kelch protein of the ring canal structure of Drosophila ovaries. In particular, it contains three consecutive repeating units of 48 amino acids each which are homologous to the so-called "beta-strand folds" occurring in proteins of the kelch family, including the actin cross-linking protein scruin of Limulus sperm and a series of other eukaryotic, bacterial, and viral proteins. Moreover, the amino terminal domain of calicin contains a region of about 100 amino acids homologous to an extended motif shared by the kelch protein as well as various zinc finger and poxvirus proteins. The possible role of calicin as a morphogenic cytoskeletal element in spermiogenic differentiation is discussed, also in relation to the demonstrated absence or altered arrangement of calicin in frequent forms of human teratozoospermia such as "round-headed" or other "postacrosomal sheath defect" sperm malformations.

Amino Acid Sequence↗

[Promoting breast feeding and the public health service].

This paper deals with the establishment of the National Breastfeeding Committee at the Robert-Koch-Institut and its activities. As the highest level scientific and advisory board for the German Federal Health Ministry the institute obtained permission from the state authorities to carry out a survey of the local health offices. A finding of this survey was that the different health offices apparently place different priorities on advising mothers in regard to breastfeeding. Some health offices offer medical counselling and others indicate that their counselling is carried out by non-medical personnel. In some cases the health offices reported a supply but no demand. We believe that the public health services should at least provide information on breastfeeding counselling in the community and on training opportunities for counsellors. The National Breastfeeding Commission will collect such information and provide it to the health offices and also give advice in the case of problems with regard to breastfeeding.

Breast Feeding↗

Activating anti-idiotypic human anti-mouse antibodies for immunotherapy of ovarian carcinoma.

Human anti-mouse antibodies (HAMA) are observed frequently after immunoscintigraphy with monoclonal antibodies (MoAb) directed against CA-125. As the authors have shown previously, HAMA can cause false-positive CA-125 values in routine CA-125 immunoradiometric assay (IRMA) tumor-marker assays (in one case, up to 900 days after immunoscintigraphy). In 32 patients, the authors found a HAMA frequency of 34% (11/32: 3/7 after the first administration, 6/13 after the second, and 2/2 after the third). Ten patients developed extremely high CA-125 levels after undergoing the CIS IRMA assay (up to 80,000 U/ml) in parallel to a significant HAMA increase. The use of different assays, or HAMA removal before in vitro testing, can solve this problem. After a new CA-125 assay containing antibodies that recognize different epitopes on the CA-125 antigen (Biomira Tru-Quant OV) was applied, only mildly increased assay results or normal levels were measured. Most of HAMA-positive patients demonstrated a predominantly anti-idiotypic response, determined with two different HAMA assays. Seven patients with anti-idiotypic HAMA responses after OC-125 immunoscintigraphy remained free of tumor or had stable disease (2-42 or more months), contrary to their poor prognoses that had been made based on the underlying stages of their tumors. All of these patients are currently doing well (Karnofsky Index > 70%) and show no significant tumor progression. In light of their extremely poor prognoses (5-year survival rates of 3-5% in recurrent International Federation of Gynecology and Obstetrics III/IV stages), without further chemotherapy, these courses are extremely unusual. Preliminary in vitro experiments lead to the postulation that anti-idiotypic HAMA may trigger an antitumor effect either by suppressing the growth of CA-125-expressing cancer cells directly, or by activating the patient's immune response via induction of Ab3. Similar results are observed after immunoscintigraphy with a technetium-99m-labeled anti-CA-125 monoclonal antibody (B43.13), which the authors now also use for immunotherapy of ovarian cancer patients by repeated injections, hoping that induction of anti-idiotypic HAMA will be beneficial for prolonged survival of patients with ovarian carcinoma.

Animals↗

Oct-4 transcription factor is differentially expressed in the mouse embryo during establishment of the first two extraembryonic cell lineages involved in implantation.

Oct-4 is the earliest expressed gene known to encode a transcription factor which is developmentally regulated during mammalian embryogenesis. In order to understand the role of Oct-4 in early murine embryogenesis, we carried out an analysis of the temporal and spatial pattern of protein expression. We report the presence of Oct-4 protein in cultured cells and murine embryos as determined by immunohistochemistry using confocal microscopy. Oct-4 protein is present in both embryonic stem cells and embryonal carcinoma cells, but is down-regulated following differentiation of these cells by culture in the absence of leukemia inhibitory factor or in the presence of retinoic acid, respectively. In embryos, the protein is found at low levels in unfertilized eggs and is localized predominantly to the pro-nuclei upon their formation following fertilization. The protein is present in the nuclei in all cleavage stages, but following differentiation of the trophectoderm at the blastocyst stage, Oct-4 protein is only expressed in the inner cell mass. The pattern of protein expression to this stage correlates well with previously reported in situ hybridization results; however, a striking difference was seen in primitive endoderm cells which had begun to differentiate and migrate along the inner surface of the trophectoderm. In direct contrast to RNA localization studies which demonstrate that there are only low levels of Oct-4 transcripts in primitive endoderm cells, protein expression in these early migrating cells is higher than in the inner cell mass.

3T3 Cells↗