Search PubMed⌕ Search

Biomedical subjects

H Ikenberg

Publications and source records attributed to H Ikenberg.

At least 37 records · Page 2Linked to original sources

Human papillomavirus DNA in invasive carcinoma of the vagina.

The presence of human papillomavirus (HPV) DNA in invasive carcinomas of the vagina, in their lymph node metastases, and in corresponding normal tissue was investigated by Southern blot hybridization with 32P-labeled HPV DNA. Tumor tissue from ten of 18 patients with vaginal carcinoma contained HPV DNA. Three of the 18 patients had a history of cervical neoplasia more than 14 years before the diagnosis of vaginal carcinoma. Five of 15 primary squamous cell carcinomas, one primary adenocarcinoma, and a vulvar recurrence of a vaginal squamous carcinoma contained HPV 16. A primary squamous carcinoma yielded HPV-related sequences. The HPV copy number varied from 0.5 to 50 per cellular genome. Four histologically positive inguinal lymph nodes from three patients contained HPV DNA. In six tumor-free control tissues from four patients, no HPV DNA was detected. No relationship was established between HPV positivity, HPV type, or copy number of the tumor and the grade of differentiation or keratinization or the clinical stage. After a median follow-up of 13 months, five of nine HPV-positive patients were alive without recurrence, whereas all seven HPV-negative patients had died because of disease. The results of this study indicate a possible major role of HPV in the development of vaginal cancer.

Adult↗

Localization of human epidermal growth factor receptor in cervical intraepithelial neoplasias.

Immunohistochemical staining of epidermal growth factor receptor (EGF-R) with a monoclonal antibody was performed in 43 biopsies of cervical tissue. The distribution of the receptors in normal cervical tissue differs from that of cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma of the cervix. Whereas the staining reaction in normal squamous epithelium was confined to the basal and deep parabasal cell layer, in all cervical intraepithelial neoplasias, with or without human papilloma virus association, a homogeneous EGF-R staining reaction could be observed throughout the entire lesion. This means that the dysplasia cells of a CIN I-III, like the tumor cells of a squamous cell carcinoma, have a raised EGF-R content, which in the normal squamous epithelium is usually only found in the basal and deep parabasal cells that are capable of dividing. No EGF-R staining reaction could be detected in the higher, differentiated cell layers of the normal squamous epithelium of the cervix.

Adult↗

[Detection of human papilloma virus (HPV) DNA in vulvar cancers].

Using Southern Blot hybridization 18 invasive malignant tumours of the vulva and 2 intraepithelial vulvar neoplasias were tested for the prevalence of HPV-DNA. In 6 of 11 primary squamous carcinomas, including one carcinoma of the Bartholinic gland, HPV 16 could be identified. Contrarily, in all seven recurrent vulvar tumours examined, including 5 squamous carcinomas, 1 fibrosarcoma and 1 zylindroma, no HPV-DNA was found. No correlation existed between HPV status of the tumours and grade of differentiation or keratinization, or the tumour-stage and lymph-node status. In one tumour-invaded lymph-node HPV 16 was detected as in the corresponding primary tumour. 12 samples from tumour free abdominal skin considered as corresponding normal tissue specimens were negative for HPV-DNA. A correlation between clinical course of the disease and HPV status of the primary tumours was not observed.

Biopsy↗

[CO2 laser therapy and typing of human papilloma virus in follow-up studies of cervix intraepithelial neoplasms].

In 104 woman patients with cervical intraepithelial neoplasia (CIN) I-III who had been treated between 1981 and May 1986 in the dysplasia consulting-room of the Department of Gynecology by means of conisation effected by laser, we checked on therapeutic success via cytology and colposcopy as well as by human papilloma virus (HPV) typing. In 90.3% of the cases 1.25 laser treatments sufficed for healing of the lesion. Relapses occurred mainly in severe intraepithelial neoplasias with identified HPV 16/18. Incidence of HPV was reduced from 56% before therapy to 13.3% after therapy. This shows that laser therapy can be regarded as an effective treatment of the causes of the disease even in CIN associated with HPV. The markedly increased relapse rate in CIN III (24%) makes a reliable follow-up mandatory especially in such cases.

Cervix Uteri↗

Human papillomavirus standardization and DNA cytophotometry in cervical intraepithelial neoplasia.

Human papillomavirus (HPV) standardization and DNA cytophotometry were carried out in 29 cases of cervical intraepithelial neoplasia (CIN) grades I-III. A prognostically unfavorable DNA distribution pattern with an aneuploid stemline was found in 14 of the 16 dysplasias with HPV types 16 and 18, while in 11 of 13 dysplasias with HPV types 6 and 11 there was a favorable DNA distribution with a euploid-polyploid stemline. Among 178 colposcopically, cytologically and histologically confirmed cervical lesions, there was a statistically significant incidence of HPV 16/18 infections in severe dysplasias and carcinomas, while HPV 6/11 was found predominantly in mild cervical lesions. It seems that CIN can be divided into high- and low-risk lesions not only by the degree of severity and the DNA distribution pattern but also by HPV typing.

Adult↗

[Alpha interferon in condylomata acuminata and juvenile diabetes mellitus].

Persistent condylomata acuminata in a 21-year-old patient with diabetes mellitus were treated with highly purified interferon-alpha (IFN-alpha) obtained by recombinant DNA technology. Daily dose was 1.5 X 10(6) IU, given subcutaneously. Already during treatment the condylomata regressed. Two weeks after the end of therapy, i.e. after a total dose of 10.5 X 10(6) IU IFN-alpha, all condylomata had completely receded. Blood glucose levels remained constant with concomitant insulin therapy. Toxic side-effects or antibodies to IFN-alpha were not observed.

Adult↗

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↗

[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↗

[Generalized verrucosis in familial T-helper cell deficiency. Treatment with interferon and Tigason].

We report on a 17-year-old patient suffering from generalized verrucosis. This diagnose had been confirmed by means of light microscopy, electron microscopy, and DNA hybridisation (HPV type 2). The study of immunological parameters revealed reduced numbers of T-lymphocytes, especially of helper-T-cells. Skin tests with recall antigens were normal. Three brothers of our patient showed slight reduction of helper-T-cells. Treatment with topical retinoic acid was not effective. Treatment with alpha-interferon i.m. intralesionally was effective in the beginning, but two weeks after onset of therapy no further improvement could be achieved. Discontinuation of therapy was followed by a relapse. Tigason which was given thereafter led to flattening of the warts but failed to bring about complete regression within the following four months.

Adolescent↗

Human papillomavirus type 16 related DNA in an anaplastic carcinoma of the lung.

Twenty-four biopsy specimens from various histologic types of human carcinomas in the lung were analyzed for the presence of human papillomavirus (HPV) DNA. DNA from the individual specimens was tested for the presence of homologous sequences to HPV genotypes 1, 2, 4, 8, 9, 10, 11, 13, 16 and 18. One anaplastic carcinoma in the lung contained multiple copies of DNA hybridizing under stringent conditions to HPV 16 DNA. The latter DNA has been found to be frequently associated with human genital cancer (cervical, penile, and vulval cancer) and genital Bowen's disease. The HPV 16 positive lung tumor originated from a 61-year-old female patient who underwent hysterectomy due to cervical cancer 9 years earlier.

Base Sequence↗

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↗

Interferon therapy for bronchial papillomatosis controlled by papillomavirus-DNA hybridization.

In biopsy specimens from a patient with tracheal and bronchial papillomatosis, human papillomavirus (HPV) type 11 DNA was identified. Treatment with leukocyte interferon was initiated, and the results of therapy was monitored by molecular hybridization of biopsy specimens with phosphorus 32-labeled HPV type 11 DNA after interferon application. There was no improvement of the clinical course, although two of five biopsy specimens showed a considerable reduction in the amount of HPV type 11. We discuss the reasons for the insufficient effect of therapy and propose molecular hybridization as an additional method for therapy control in viral diseases.

Bronchial Neoplasms↗

Analysis of oral papillomas, leukoplakias, and invasive carcinomas for human papillomavirus type related DNA.

Five papillomas, five leukoplakias, and six carcinomas were investigated for the presence of papillomavirus group-specific antigens and viral DNA. Viral proteins were identified with genus-specific papillomavirus antibodies. Cloned human papillomavirus (HPV) 11 and 16 DNA were used as probes in Southern blot hybridization at conditions of different stringency in order to determine viral DNA. Four of five papillomas, four of five leukoplakias, and three of six carcinomas reacted with HPV DNA probes and revealed some stained cells after exposure to HPV antibodies. HPV type 16 was found in one carcinoma and HPV type 11 was demonstrated in another case of carcinoma.

Adult↗

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↗

Demonstration of HPV-16 genomes in the nuclei of cervix carcinoma cells.

Specimens of 4 different cervical cancers, 1 flat condyloma of the cervix, 1 condyloma acuminatum, 1 morbus Bowen of the skin and 1 skin wart were subjected to in situ hybridization using human papilloma virus type 16 (HPV-16) DNA nick translated with 3H-TTP as a probe. Within each cervical cancer biopsy we found a certain number of tumor cell clusters with clearly labelled nuclei, while sections of the other skin lesions did not reveal any accumulation of grains within their nuclei. Southern blot hybridization of the DNA extracted from the 4 cervical carcinomas with 32p-labelled HPV-16 DNA gave a positive reaction in 3 tumors. Non-reactivity in the 4th biopsy might be due to a low concentration of HPV-genomes within the total extracted DNA of this tissue part.

Biopsy↗

[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↗

[Focal epithelial hyperplasia (Heck disease). Contribution on its viral origin].

Demonstration of human papilloma virus DNA (HPV-DNA) in the lesions of focal epithelial hyperplasia in an 11-year-old Turkish girl provides further proof of its viral cause. In this case characterization of HPV-DNA showed a reaction with that of type 13 and 18. This previously undescribed variant is probably the expression of a new HPV type.

Child↗