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Biomedical subjects

G Gross

Publications and source records attributed to G Gross.

At least 217 records · Page 12Linked to original sources

Enhancement of translational efficiency by the Escherichia coli atpE translational initiation region: its fusion with two human genes.

The cDNA sequences encoding mature human interleukin 2 (IL2) and beta-interferon (INF beta), respectively, were fused with various translational initiation regions and inserted into two different types of expression vector. The relative levels of expression of the two genes and the functional stability of their respective mRNAs were examined in vivo in Escherichia coli hosts. The addition of the 30-bp sequence, found immediately upstream of the E. coli atpE gene Shine-Dalgarno (SD) sequence, to the translational initiation regions of IL2 and INF beta increased the expression of both these genes by a factor of 6-10. Thus this sequence, which naturally acts within the E. coli atp operon to enhance the translational initiation frequency of the atpE gene, can increase the expression of other genes in E. coli. It may exemplify a specific type of recognition signal for the E. coli translational apparatus.

Base Sequence↗

Systemic treatment of condylomata acuminata with recombinant interferon-alpha-2a: low-dose superior to the high-dose regimen.

Fourteen patients with chronic genital warts were entered in a pair-matched crossover trial of recombinant interferon-alpha-2a. They received daily doses of either 1.5 X 10(6) U or 18 X 10(6) U interferon for one week by the subcutaneous route (abdominal skin). After an observation period of 4 weeks in case of no change or partial response, patients of the low-dose group were given 18 X 10(6) U and those of the high-dose group 3 X 10(6) U daily for another 7 days. Eight of 14 patients had a complete remission by the end of the therapy-free interval of 4 weeks, 5 patients of the low-dose group and 3 patients of the high-dose group. Acute side-effects consisted of a transient influenza-like syndrome. Remissions have been maintained for 6 to over 10 months. The data implicate that recombinant interferon-alpha-2a is highly effective in patients with human papillomavirus-related genital warts and that the low-dose regimen is at least equivalent to the high-dose treatment.

Adult↗

Classification and prognosis of schizophrenic disorders in light of the Bonn follow-up studies.

In the Bonn Schizophrenia Study (Huber et al., Monogr. Gesamtgebiete Psychiat., vol. 21, Springer, Berlin 1979) 113 cases fulfilled the criteria for four types of schizo-affective and/or cycloid psychoses. Each of these subgroups had a significantly more favorable long-term prognosis than that of the Bonn sample as a whole. Several prognostically favorable factors found in the Bonn Study are identical to criteria used to classify schizo-affective, schizophreniform and cycloid psychoses, e.g., acute onset, endogenomorph-depressive symptoms, and psychoreactivity. In the Bonn main sample of 502 schizophrenics, 22% demonstrated complete recovery and 40% more or less noncharacteristic types of remission (pure asthenic defect); 56% were socially recovered, two thirds reaching their premorbid level and one third remaining below it. The 12 different types of course are described. There are four course type groups, the prognostically favorable (types I-III), the relatively favorable (types IV-VI), the relatively unfavorable (types VII-IX), and the unfavorable group (types X-XII), each embracing about one quarter of all schizophrenics. The long-term prognosis is dependent on factors such as primary personality, school success, precipitating factors and certain psychopathological initial symptoms and syndromes. The results support the assumption that early treatment, including that of the prodromes, improves the long-term prognosis or at least the chance of complete remission of the subgroup with peracute and acute onset. In spite of the more favorable long-term outcome of the schizo-affective psychoses the results cannot justify the nosological differentiation and classification of these and related psychoses as an independent disease entity but only as different prognostically favorable types of endogenous psychoses. In this respect it is possible to make a distinction between a nuclear group of schizophrenia and a different group with a better prognosis, variously termed schizophreniform, schizo-affective or psychogenic psychoses, which with respect to prognosis is an intermediate group.

Adult↗

Systemic treatment of mollusca contagiosa with inosiplex.

The ensuing regression of mollusca contagiosa in 7 of 9 children, 6 of whom were suffering from atopic dermatitis, was observed during systemic treatment with inosiplex. In our report the involutional process of mollusca contagiosa did not differ clinically from the inflammatory course observed in spontaneous healing. It is supposed that inosiplex enhances underlying defective immunological mechanisms which lead to a restoration of the host defence.

Adolescent↗

[Urogenital and anal papillomavirus infections].

Recently virologists and clinicians have focused attention on infections with human papillomaviruses (HPV). This is due to the ubiquity, the increasing frequency and the possible association of these viruses with the development of squamous cell carcinomas of the skin and of the mucous membranes of the respiratory, gastrointestinal, genitourinary and anorectal tracts. HPV represent a very heterogeneous group of DNA tumor viruses. By means of molecular-biological techniques, more than 40 HPV types have been recognized. In the urogenital and anal tract, papillomaviruses have been associated with venereal warts (condylomata acuminata), which have been known and recognized as a sexually transmitted disease since the Romans. Furthermore, an association has been made recently between HPV and nonpapillomatous, sometimes macular lesions: flat condylomata of the uterine cervix and of the vagina, flat condylomatous lesions and pigmented papules. The latter are localized at the mucocutaneous borders and at the skin of the lower genital tract and of the perianal and crural region. Like epidermodysplasia verruciformis, only some virus types (HPV 16, HPV 18) are regularly found in malignant, invasive squamous cell carcinomas of the genital tract, whereas others (HPV 6, HPV 11, HPV 2, HPV 10, HPV 31) are associated preferentially with benign papillomas and dysplasias. In view of the different possible oncogenic potential of the individual genotypes, early determination of the virus type probably has not only diagnostic but also prognostic value. As HPV 16 DNA is regularly present in bowenoid papulosis (flat condylomatous lesions and pigmented papules of the male genital tract), a natural reservoir has been found from which these viruses could be transmitted to the sexual partner. Knowledge of the HPV-associated clinical pictures is therefore the prerequisite for diagnosis and treatment of both the patient and his sexual partner. Clinical observation, cytology and virus typing from genital smears of both partners represent preventive methods that may contribute to the early detection of genital cancer.

Anus Neoplasms↗

[Virus infections of the skin and mucous membranes and malignant tumors].

The relationship between virus infections of the skin and mucosae and the development of malignant tumors is discussed. Guided by seroepidemiological data, virus infections with herpes simplex have been associated with the development of cervical carcinoma, genomes specific for HSV, however, have only occasionally been detected in malignant tumor tissue from the cervix. In contrast, DNA specific for papilloma virus could be identified to a high percentage in cervical cancerous and precancerous tissue as well as in bowenoid papulosis in both sexes. Aside from oncogenic papilloma virus, malignant degeneration seems to be dependent on both endogenic cofactors such as immunodeficiency and exogenic cofactors like sunlight or additional virus infections.

Bowen's Disease↗

[Sexual transmissibility of papillomaviruses].

Papillomavirus infections in the genitoanal region are detectable by the demonstration of type-specific HPVDNA (DNA-DNA hybridization, in situ hybridization on cell smears) or by a peroxidase-antiperoxidase assay using formalin-fixed paraffin sections for demonstration of common structural antigens of papillomaviruses. Using these methods an epidemiological study on sexual partners with genitoanal papillomavirus infections has been initiated.

Bowen's Disease↗

Stabilisation of human interferon beta synthesis in Escherichia coli by zinc ions.

Human interferon beta synthesized in Escherichia coli is unstable and toxic for the bacterial cell. Zinc ions are able to stabilise interferon beta in E. coli probably by inhibiting the action of cell internal proteinase(s) which affect the half-life of this foreign protein. As a result up to one order of magnitude more active IFN-beta can be detected in Zn2+-treated E. coli cells.

Cloning, Molecular↗

Bowenoid papulosis. Presence of human papillomavirus (HPV) structural antigens and of HPV 16-related DNA sequences.

This study reviews 39 cases of anogenital bowenoid papulosis lesions in 22 individuals of both sexes that were analyzed clinically, histologically, immunocytochemically, and virologically. Macroscopically, three different types of lesions were demonstrated: erythematous macules; papules (lichenoid and/or pigmented papules); and leukoplakialike lesions. Microscopically, bowenoid papulosis fulfills the criteria of a squamous cell carcinoma in situ. Much like oral precancers, three distinct growth patterns (flat, endophytic, and exophytic) could be differentiated, which did not correlate with the clinical aspect of the lesions. In only two (5.12%) of the 39 cases of bowenoid papulosis could structural antigens of papillomaviruses be detected immunocytochemically (peroxidase-antiperoxidase technique). The DNA from 12 lesions that were analyzed for the presence of papillomavirus-specific sequences hybridized stringently in all cases with the human papillomavirus 16 specific DNA probe labeled with phosphorus 32.

Adolescent↗

Thyroid-dependent alterations of myocardial adrenoceptors and adrenoceptor-mediated responses in the rat.

Cardiovascular alterations in hypo- and hyperthyroidism have been ascribed to changes of noradrenergic neurotransmission. In the present study the influence of thyroid hormones on adrenoceptors in the rat heart was further characterized. The effect of artificial hypothyroidism (induced by feeding 6-propyl-2-thiouracil, PTU) and hyperthyroidism (induced by daily injections of triiodothyronine, T3) on myocardial adrenoceptor binding, catecholamines, some physiological responses, and their interdependence was examined. The density of myocardial beta-adrenergic binding sites (3H-dihydroalprenolol, 3H-DHA) was reduced after PTU (by 38%) and enhanced after T3 treatment (by up to 82%). The increase was dose- and time-dependent and reversible within 4 days. No changes of the affinity of 3H-DHA to its binding sites were observed. Only L-T3 and L-T4 proved to be active, D-T3 and reverse T3 had no effect. The rise in beta-adrenoceptor density caused by T3 was prevented by concomitant administration of cycloheximide, indicating its dependence on protein synthesis. The density of myocardial alpha 1-adrenergic binding sites (3H-prazosin) was significantly reduced in the PTU group (by up to 28%) and even more distinctly by T3 treatment (by up to 50%). KD values remained unaltered. The noradrenaline content and turnover of rat hearts was significantly reduced by T3-induced hyperthyroidism. PTU treatment had no influence on content and turnover of noradrenaline. Plasma noradrenaline as well as adrenaline levels in freely moving rats were increased by PTU treatment 9- and 5-fold, respectively. In T3-injected animals no significant changes were measured. The density of adrenoceptors is known to be inversely correlated with catecholamine levels in several organs. Neither alpha- nor beta-adrenoceptor changes in the myocardium of dysthyroid rats could be attributed to such a homologous regulation, since they still occurred after chemical sympathectomy with 6-hydroxydopamine and adrenalectomy.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Lesioning of serotoninergic and noradrenergic nerve fibres of the rat brain does not decrease binding of 3H-clonidine and 3H-rauwolscine to cortical membranes.

alpha 2-Adrenoceptors located presynaptically on nerve terminals are known to modulate the release of neurotransmitters from noradrenergic and serotoninergic neurons. The pre- and/or postsynaptic localization of binding sites for alpha 2-adrenergic radioligands, the agonist 3H-clonidine and the antagonist 3H-rauwolscine, was investigated in the rat cerebral cortex by the use of specific neurotoxins. Intracerebroventricular injections of 6-hydroxydopamine (6-OH-DA) and 5,7-dihydroxytryptamine (5,7-DHT) were used to destroy the noradrenergic and serotoninergic neurons, respectively, and the success of the treatment was controlled by measurement of tritium accumulation in cortex slices incubated with 3H-noradrenaline or 3H-serotonin. In cortical membranes, 3H-rauwolscine bound to a single site (KD about 5 nmol/l; Bmax 217-247 fmoles/mg protein), whereas 3H-clonidine bound to a high affinity site (KD 0.6-1.4 nmol/l) and a low affinity site (KD 6-10 nmol/l). The total number of high plus low affinity 3H-clonidine binding sites was about two thirds of the number of 3H-rauwolscine binding sites. 6-OH-DA treatment significantly increased the number of high affinity 3H-clonidine binding sites without reducing the number of high plus low affinity binding sites, indicating a denervation supersensitivity. KD- as well as Bmax-values for 3H-rauwolscine remained unaltered after 6-OH-DA-treatment. Since an increase in postsynaptic alpha 2-adrenoceptors due to 6-OH-DA-administration might have masked a loss of presynaptic alpha 2-adrenergic binding sites, rats were chronically treated with high doses of clonidine in order to prevent a possible supersensitivity of postsynaptic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

Papillomavirus infection of the anogenital region: correlation between histology, clinical picture, and virus type. Proposal of a new nomenclature.

The clinical and histologic picture of 84 anogenital condylomatous and condyloma-like lesions of both sexes were analyzed in an effort to establish a correlation to the different papillomavirus (PV) types. The presence of human papillomavirus (HPV)-specific DNA sequences was confirmed through molecular hybridization and the presence of PV structure antigens was verified in thin sections by means of a group-specific anti-PV-antiserum using the peroxidase-antiperoxidase (PAP) technique. Three distinct clinical forms harboring distinct HPV types were distinguished: (1) Condylomata acuminata in which HPV-6 DNA was present in 37 of 59 samples and HPV-11 DNA in only 13 of 59 samples. HPV-16 DNA was not detected at all and 9 condylomatous lesions remained unclassified. (2) Flat condyloma-like lesions, where HPV-6 and HPV-11 were associated with lesions of low epidermal atypia in 8 and in 2 of 18 cases, respectively, and where HPV-16 was associated exclusively with 6 of 18 such lesions with severe atypia, called bowenoid papulosis. (3) Pigmented papules where HPV-16 was detected twice in lesions of bowenoid papulosis and HPV-11 in 2 of the benign pigmented lesions. The fourth clinical manifestation of genital papillomavirus infections--the so-called condylomata plana--was not available for virologic analysis. Histologically 5 different koilocytotic features were determined which could not be correlated either with one of the clinical pictures or with a specific PV type. HPV-16, however, was found frequently in non-koilocytotic lesions exhibiting the features of severe epithelial atypia known in bowenoid papulosis. The existence of PV structure antigens in these lesions could not be verified using the indirect immunoperoxidase--PAP-technique--in contrast to the koilocytotic lesions where clear evidence of the presence of HPV was proved in 36 of 56 (64.3%) of the cases.

Animals↗

Epidermal growth factor receptors in different skin tumors.

Specific binding of 125I-labeled epidermal growth factor (EGF) was measured in 62 skin tumors of different severity. Within a group of 28 benign tumors, 11 of 15 condylomata acuminata were receptor positive, whereas the investigated mesenchymal tumors and normal skin as a control were receptor negative. 6 of 18 basal cell epitheliomas bound EGF specifically. In the group of precancerous and malignant skin tumors, 7 of 8 squamous cell carcinomas had the highest number of EGF binding sites and a high affinity state, whereas 5 malignant melanomas were receptor negative. The clinical relevance of these findings is not yet clear due to the short follow-up of the patients.

Binding Sites↗

Psychopathology of basic stages of schizophrenia in view of formal thought disturbances.

Psychopathological, nosological, and prognostic aspects of basic stages and basic symptoms, in particular consideration of formal thought disorders, are outlined. In view of the far-reaching overlap of the psychopathological pictures of the pre- und postpsychotic basic stages a Bonn Scale for the Assessment of Basic Symptoms (BSABS) including all types of basic stages was constructed. Subjective cognitive thought disorders were recorded from 69% of the patients in pure defective states, from 78% in postpsychotic reversible basic stages and from 67% in prodromes. In contrast to incoherence of thoughts, including the symptoms of the endogenomorphic-schizophrenic axial syndrome (Berner), these thought disorders are registered only on the basis of the reports of the patients and not through observation by the investigator. The difference between subjective and objective thought disorders is presumably only conditioned primarily by differences in the degree and secondarily by the psychopathological quality of the disorders. If the criteria concerning formal thought disorders and affective blunting of the schizophrenic axial syndrome or of SANS (Andreasen) are fulfilled, as a rule the patient loses the ability of perceiving, communicating, and coping with the disorders, and at the same time there is a break from an only quantitative to a qualitative abnormal phenomenon. The presence or absence of subjective or objective formal thought disorders in the beginning of the disease had no significant influence on the long-term outcome in the main sample of the Bonn study. Proceeding from the initial psychopathological syndromes 54% of the female hebephrenics with the most unfavorable long-term prognosis showed incoherence of thoughts in the first 2 years of the illness; in contrast, incoherence was seen in only 16% of the male hebephrenics for whom the long-term outcome did not differ from that of the whole sample. This and other data of the Bonn schizophrenia study seem to argue in favor of the assumption that typical incoherence of thoughts might be valuated as a criterion of unfavorable prognosis only when the phenomenon appears within the context of a hebephrenic initial syndrome in the beginning of the schizophrenic disease.

Cognition Disorders↗

[In vitro and in vivo studies with interleukin 2 (IL-2) and various immunostimulants in a patient with AIDS].

We report on a lethal course of an acquired immunodeficiency syndrome (AIDS) in a young female patient. She had spent her vacancies six years before diagnosis in Haiti, where a sexual intercourse with a Haitian man had occurred. Leading clinical symptoms consisted of recurrent Herpes simplex infections of the genital and perianal region as well as unexplained high temperatures. There were some typical laboratory and immunologic features of this disease with leukopenia, hypergammaglobulinemia, cutaneous anergy, a reduction of peripheral T-lymphocytes (OKT 3) and an almost complete loss of OKT 4 (helper cells) positive lymphocytes. The mitogenic response upon stimulation with allogeneic cells (MLC) or with the mitogens PHA, Con A and PWM was significantly reduced. There was no measurable interleukin-2 (IL-2) secretion of peripheral blood lymphocytes. Several immunostimulators (thymopentin, inosiplex, bestatin) were tested in lymphocyte proliferation assays in vitro. The mitogenic response could not be enhanced by neither of these substances. A clinical trial with Delimmun (inosiplex) for 14 days did not show any clinical or immunologic improvement in this patient. The intravenous application of high dose immunoglobulin G was without any observable effect. The proliferation inducing capacity of a highly purified IL-2 preparation on the AIDS cells in vitro led us to a clinical trial with this substance. We applied 100 Bödeker units of IL-2 per kg body weight and day subcutaneously for 16 days. A therapeutical effect, however, could not be observed. Cell marker analyses did not show significant changes in lymphocyte subpopulation composition under IL-2 therapy. There was an increase in the spontaneous cell proliferation 14 days after start of IL-2 therapy. The PHA- and IL-2 response of the AIDS cells, however, was unchanged. It cannot be excluded that an administration of IL-2 in earlier stages of AIDS may have beneficial effects.

Acquired Immunodeficiency Syndrome↗

[Bowenoid papulosis and carcinoma in situ of the cervix uteri in sex partners. An example of the transmissibility of HPV-16 infection].

The development of bowenoid papules in a 20-year-old man and a carcinoma in situ of the portio uteri of the 22-year-old female sexual partner is reported. In both lesions HPV-16 DNA could be detected by molecular biological means. This observation led us to the conclusion that HPV 16 had been transmitted sexually. The same seems to be true for HPV-11-induced condylomata acuminata, which appeared on the external genitalia of both patients after recuperation from the HPV-16-induced lesions and conisation treatment. The clinical significance of this observation and its consequences for dermatologists and gynecologists are discussed.

Adult↗