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Biomedical subjects

G Gross

Publications and source records attributed to G Gross.

At least 181 records · Page 10Linked to original sources

Bladder distention as a cause of inferior vena caval obstruction in the newborn: demonstration with ultrasonography.

We report an unusual case of inferior vena caval (IVC) obstruction secondary to a tensely distended urinary bladder in an asphyxiated newborn. The use of portable real-time ultrasonography gave a reliable diagnosis of the correct etiology and ruled out more ominous possibilities, such as IVC thrombosis. This case presentation provides an interesting addition to the differential diagnosis of IVC obstruction, and once again emphasizes the valuable role of bedside ultrasonography in the neonatal intensive care unit.

Asphyxia Neonatorum↗

Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity.

To design and direct at will the specificity of T cells in a non-major histocompatibility complex (MHC)-restricted manner, we have generated and expressed chimeric T-cell receptor (TcR) genes composed of the TcR constant (C) domains fused to the antibody's variable (V) domains. Genomic expression vectors have been constructed containing the rearranged gene segments coding for the V region domains of the heavy (VH) and light (VL) chains of an anti-2,4,6-trinitrophenyl (TNP) antibody (SP6) spliced to either one of the C-region gene segments of the alpha or beta TcR chains. Following transfection into a cytotoxic T-cell hybridoma, expression of a functional TcR was detected. The chimeric TcR exhibited the idiotope of the Sp6 anti-TNP antibody and endowed the T cells with a non-MHC-restricted response to the hapten TNP. The transfectants specifically killed and produced interleukin 2 in response to TNP-bearing target cells across strain and species barriers. Moreover, such transfectants responded to immobilized TNP-protein conjugates, bypassing the need for cellular processing and presentation. In the particular system employed, both the TNP-binding site and the Sp6 idiotope reside almost exclusively in the VH chain region. Hence, introduction into T cells of TcR genes containing only the VHSp6 fused to either the C alpha or C beta was sufficient for the expression of a functional surface receptor. Apparently, the VHC alpha or VHC beta chimeric chains can pair with the endogenous beta or alpha chains of the recipient T cell to form a functional alpha beta heterodimeric receptor. Thus, this chimeric receptor provides the T cell with an antibody-like specificity and is able to effectively transmit the signal for T-cell activation and execution of its effector function.

Animals↗

Subclassification of alpha 1-adrenoceptor recognition sites by urapidil derivatives and other selective antagonists.

1. The affinities of urapidil derivatives and other antagonists for alpha 1-adrenoceptors labelled by [3H]-prazosin were determined on membranes of six different rat tissues. 2. Urapidil and its 5-acetyl-, 5-formyl- and 5-methyl-derivative displaced [3H]-prazosin from alpha 1-adrenoceptor binding sites in a concentration-dependent manner which varied with tissue. IC50 values were lower in vas deferens, hippocampus and cerebral cortex than in heart, liver and spleen. For 5-methyl-urapidil, binding to two distinct sites could be demonstrated with mean K1 values of about 0.6 and 45 nM. Saturation binding studies with [3H]-prazosin in the presence of 5-methyl-urapidil indicated a competitive type of interaction between 5-methyl-urapidil and [3H]-prazosin. 3. The proportion of [3H]-prazosin binding sites with high affinity for 5-methyl-urapidil was 58% in vas deferens, 69% in hippocampus, 41% in cerebral cortex and 23% in myocardium. In liver and spleen virtually no high affinity sites were found. These values were in good agreement with the percentages of binding sites with high affinities for WB-4101 and phentolamine, indicating that all these antagonists bind to the same subtype of alpha 1-recognition sites, whereas other alpha-antagonists like BE 2254, yohimbine and unlabelled prazosin did not discriminate between two binding sites. 4. Preincubating membranes of the cerebral cortex with chloroethylclonidine preferentially inactivated [3H]-prazosin binding sites with low affinity for 5-methyl-urapidil. 5. The antagonist potencies of 5-methyl-urapidil and WB-4101 against alpha 1- adrenoceptor-mediated contractile responses were higher in vas deferens than in myocardium. The alpha 1-mediated effects in vas deferens but not in the heart were highly susceptible to nitrendipine. 6. Using 5-methyl-urapidil, the existence of two distinct alpha 1-adrenoceptor recognition sites could be demonstrated which correspond to the proposed alpha 1A- and alpha 1B-subtypes. Since 5-methyl-urapidil is one of the ligands with most selectivity between these subtypes in binding studies it may serve as a valuable tool for such investigations.

Adrenergic alpha-Antagonists↗

Alpha 1-adrenoceptors: the ability of various agonists and antagonists to discriminate between two distinct [3H]prazosin binding sites.

Recently, it has been demonstrated that two distinct alpha 1-adrenoceptor binding sites showing high and low affinity for WB-4101 (2-(2,6-dimethoxyphenoxy)ethyl-aminomethyl-1,4-benzodioxane) and 5-methyl-urapidil can be distinguished. In the present study we examined the ability of several agonists and antagonists to discriminate between these alpha 1-adrenoceptor binding sites. [3H]Prazosin binding to membranes of rat liver, heart, cerebral cortex and hippocampus was inhibited monophasically by butanserine, I-BE 2254 (2-(3-(4-hydroxy-3-iodophenyl)ethylaminomethyl)tetralone-hydrochloride), prazosin, rauwolscine and verapamil. In contrast, competition curves of adrenaline, oxymetazoline, amidephrine and YM-12617 (5-[2-[[2-(o-ethoxy-phenoxy)ethyl]-amino]propyl]-2- methoxybenzenesulfonamide HCl) were best described by a model of two binding sites. Chloroethylclonidine (CEC), a compound shown to irreversibly eliminate binding sites with low affinity for WB-4101, increased the proportion of high affinity binding sites for oxymetazoline and amidephrine, whereas the binding data for prazosin and adrenaline remained unchanged. These results indicate that amidephrine, oxymetazoline and YM-12617, but not the other drugs tested discriminate between different alpha 1-adrenoceptor recognition sites labelled by [3H]prazosin.

Adrenergic alpha-Agonists↗

Basic symptoms in schizophrenic and affective psychoses.

The study compares schizophrenic and affective psychoses with regard to basic symptoms. 30 patients in schizophrenic pre-, intra-, and postpsychotic basic stages and 30 patients in endogenous-depressive phases were examined according to the Bonn Scale for the Assessment of Basic Symptoms. The most important result is that certain cognitive basic symptoms and cenesthesias which are decisive for the development of florid productive-psychotic phenomena are found more frequently in the group of schizophrenias.

Adult↗

Recurrent vulvar Buschke-Löwenstein's tumor-like condylomata acuminata and Hodgkin's disease effectively treated with recombinant interferon-alpha 2c gel as adjuvant to electrosurgery.

The local application of recombinant interferon-alpha 2c hydrogel (1 x 10(6) IU IFN-alpha 2c per g) given as an adjuvant after electrosurgery led to a complete cure of previously recalcitrant untreatable giant Buschke-Löwenstein's tumor-like condylomata acuminata of a 19-year-old patient suffering from Hodgkin's disease (stage II/II). Interferon-alpha 2c hydrogel given as adjuvant with surgery may have more direct antiproliferative and antiviral activities than immunomodulating defects. This combined topical application is an effective and safe treatment which is recommended especially in immunocompromised individuals suffering from genital HPV disease nonresponsive against systemic interferon and conventional therapy modalities.

Adult↗

Bowenoid papulosis. Classification as a low-grade in situ carcinoma of the epidermis on the basis of histomorphologic and DNA ploidy studies.

The nature of bowenoid papulosis was investigated by a comparative investigation of 12 biopsy specimens of this lesion, 19 biopsy specimens of Bowen's disease, 14 biopsy specimens of squamous cell carcinoma and 10 biopsy specimens of seborrheic keratosis. In addition to conventional histomorphologic and cytomorphologic studies, nuclear DNA measurements on single cells isolated from tissue blocks were performed using a TV image analysis system combined with an automatic microscope. Two parameters, the "5c exceeding rate" (5cER) and the "2c deviation index" (2cDI), were computed from the single-cell DNA values to arrive at a "DNA diagnosis" and a "DNA malignancy grade" (DNA-MG). All specimens of bowenoid papulosis and Bowen's disease were morphologically diagnosed as in situ carcinomas of the epidermis; a DNA diagnosis of malignant was rendered in all of these specimens due to the detection of aneuploid nuclei (5cER greater than or equal to 1). DNA diagnoses of malignant were also rendered on all specimens of squamous cell carcinoma (100% sensitivity) while DNA diagnoses of benign were rendered in all specimens of seborrheic keratosis (100% specificity). The mean DNA-MG for bowenoid papulosis (0.69) was significantly lower than that for Bowen's disease (1.04) and squamous cell carcinoma (1.15). The mean morphologic (Broder's) grade of malignancy was also lower for bowenoid papulosis than for Bowen's disease and squamous cell carcinoma. HPV 16 DNA was detected in 10 of 12 specimens of bowenoid papulosis. Thus, the results of DNA image cytometry and morphologic investigation suggest that bowenoid papulosis is a low-grade carcinoma in situ of the epidermis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The concept of basic symptoms in schizophrenic and schizoaffective psychoses.

This paper presents the psychiatric aspects of the concept of basic symptoms (BS), especially history, actual position and tendencies of development of the doctrine of BS, phenomenology and clinical picture of basic stages, the Bonn Scale for the assessment of dynamic and cognitive basic deficiencies (BSABS) and the importance of this concept for early diagnosis, therapy, prevention and rehabilitation. The patients experience and communicate the BS as deficiencies and are able to cope with, adapt and compensate for them. The BS were termed as basic symptoms because they represent the basis of the productive-psychotic symptomatology. Follow-up studies of cases with the suspicion diagnosis "prodrome of schizophrenia" based on BSABS rating, revealed that the subgroup passing over in schizophrenic psychoses after an average of 6.3 years showed significantly higher scores of cognitive BS at the time of index investigation. It now seems possible to impede increase of cognitive BS already present in prepsychotic prodromal states before reaching the threshold of transition into productive-psychotic symptomatology. Long-term development is more favorable if therapy commences as early as possible including the prepsychotic basic stages and also taking into consideration BS which were, until now, disregarded in DSM-III. Summarizing our findings of the last 30 years we suggest that the BS-concept may be an approach to overcome the dichotomy of negative and positive psychopathology in schizophrenia.

Cognition Disorders↗

Coliphage lambda to terminator lowers the stability of messenger RNA in Escherichia coli hosts.

The effects of the transcription terminators to and tfd on the overall high-level expression of a human interferon-beta gene (IFN-beta) in Escherichia coli hosts were compared. Deletion mapping shows that mRNA lability is caused by sequences at or near the lambda terminator to stem-loop structure. Extensive RNA secondary structure in this region indicates a potential RNase III cleavage/binding site. In RNase III- E. coli hosts, IFN-beta synthesis is indeed considerably enhanced. The bacteriophage tfd terminator does not confer this mRNA labilization phenomenon. In all cases, RNA level and stability correlate with the level of IFN-beta synthesized in the cell. In the system described, ongoing translation stabilizes mRNA only moderately.

Bacteriophage lambda↗

Alternative mechanisms for gene activation induced by poly(rI).poly(rC) and Newcastle disease virus.

After poly(rI).poly(rC) induction of FS-4 fibroblasts, both human interferon-beta (IFN-beta) mRNA and an additional induced RNA class (12S RNA) hybridize to a genomic cosmid clone containing the human IFN-beta gene as well as 35 kbp of flanking sequences. However, this coinduced 12S RNA does not originate from regions in the neighborhood of the IFN-beta gene, but hybridizes to the genomic cosmid clone via repetitive Alu-family sequences. While IFN-beta mRNA rapidly decays after reaching a maximum 2-4 h after induction, this 12S RNA is stably maintained in the fibroblast cell for more than 16 h. Contrary to IFN-beta mRNA, the level of the 12S RNA is not further elevated by superinduction conditions (cycloheximide treatment) during poly(rI).poly(rC) induction. However, subsequent to treatment with the weaker viral inducer Newcastle disease virus (NDV) both IFN-beta and the 12S RNA transcripts are induced to a higher level in the presence of cycloheximide. Cell-free translation of hybrid-selected 12S RNA leads to detection of an induced protein of 14 kDa. cDNA cloning reveals that the 12S RNA contains part of an Alu-family sequence in the 5'-untranslated region. The 12S RNA is probably not an RNA polymerase III transcript and codes for a protein of 9 kDa (as monitored by in vitro cell-free translation). This discrepancy in molecular mass can be attributed to a retarded migration of the protein in SDS/PAGE.

Amanitins↗

Alterations of cellular lipids in rat thymocytes during cell cycle progression.

This study provides information on the lipid content and composition of rat thymocytes during cell cycle progression. Cultured rat thymocytes were stimulated by concanavalin A and interleukin-2 to enter the cell cycle and to proliferate. At indicated intervals during a 96 h culture, cells were analyzed for lipid content and lipid synthesis. A growth-related 3.8-fold increase in the cellular cholesterol and a 2.8-fold increase in the phospholipid content was observed after 48 h of culture. Cholesterol synthesis, measured by [14C]acetate incorporation, increased 34-fold, whereas the synthesis of the other lipids was enhanced only 15-fold. Concerning the percentage distribution of the total fatty acids, arachidonic acid showed a significant decline between 24 and 72 h of culture, being mainly caused by the release of arachidonic acid from phosphatidylcholine. Addition of actinomycin D, an inhibitor of DNA replication, prevented the decline of cellular arachidonic acid content in a dose-dependent manner. These data suggest that both the pronounced rise of the cholesterol content as well as the decline of arachidonic acid content are closely linked to cell proliferation.

Acetates↗

Human pancreatic secretory trypsin inhibitor (PSTI) produced in active form and secreted from Escherichia coli.

As a basis for a protein design project, we decided to produce the human pancreatic secretory trypsin inhibitor (PSTI) in its active form. Total gene synthesis was carried out efficiently by (i) computer design of the gene fragments, (ii) synthesis of the oligodeoxynucleotides by the segmental support method, and (iii) assembly of double strands under optimized ligation conditions. Fusion to the ompA gene signal peptide led to secretion of processed PSTI in various constructions, with or without additional amino acids (aa) at the N-terminus. The secreted proteins (56 to 63 aa) were biologically active, suggesting that the three cysteine bridges were correctly formed. Surprisingly, after induction the product was found almost exclusively in the culture medium. Variants of PSTI with Asp or Asn at aa positions 21 and 29 [sequences published by Greene et al., Methods Enzymol. (1976) 813-825, and by Yamamoto et al., Biochem. Biophys. Res. Commun. (1985) 605-612] showed the same Ki for both human and porcine trypsin.

Amino Acid Sequence↗

5-Methyl-urapidil discriminates between subtypes of the alpha 1-adrenoceptor.

The affinity of 5-methyl-urapidil for alpha 1-adrenoceptors was determined from the inhibition of [3H]prazosin binding on membrane of different rat tissues. In hippocampus, vas deferens and heart 5-methyl-urapidil displaced [3H]prazosin in a biphasic manner with mean pKI values between 9.1 and 9.4 for the high-affinity site and 7.2 to 7.8 for the low-affinity site. Only the low affinity site was found in spleen and liver. At present, 5-methyl-urapidil is the antagonist which most clearly discriminates between alpha 1-adrenoceptor subtypes.

Adrenergic alpha-Antagonists↗